Abstracts of the 19th International Congress on Neuromuscular Diseases 7th – 11th July 2026

Dr. Ljelja Muaremoska Kanzoska1 , Prof. Todor Arsov2 1 University clinic for pediatric diseases, Skopje, North Macedonia. 2 Faculty of Medical Sciences, University “Goce Delchev”, Shtip, North Macedonia Background: RANBP2 -associated acute necrotizing encephalopathy type 1 (ANE1) is an infection-triggered neuroinflammatory disorder caused by monoallelic pathogenic RANBP2 variants, typically inherited in an autosomal-dominant pattern with incomplete penetrance and strikingly variable intrafamilial clinical expressivity. While often labeled as “encephalopathy,” survivors commonly experience abrupt, high-burden acquired motor–bulbar dysfunction, with variable respiratory involvement, translating into substantial rehabilitation needs. We aimed to define the spectrum of motor–bulbar disability and rehabilitation burden within a single RANBP2 -ANE1 pedigree carrying the shared pathogenic variant c.1754C>T (p.Thr585Met), and to report IL-6 receptor blockade (tocilizumab) as escalation therapy in one family member. Methods: Retrospective descriptive review of six affected children from one family carrying the familial RANBP2 variant c.1754C>T (p.Thr585Met), presenting with clinical and imaging features consistent with ANE1. Analysed variables included infection trigger, acute neurological phenotype, supportive and immunomodulatory interventions, and functional outcomes emphasizing mobility, bulbar impairment (swallowing/communication), and respiratory dependence. Results: Clinical expression included a spectrum from fulminant disease with fatal outcomes to survival with severe persistent disability, but also asymptomatic (non-penetrant) cases. Functional trajectories included early death after rapid neurological decline; survival with major cognitive and motor sequelae; severe permanent spastic motor disability requiring long-term rehabilitation; and an extreme respiratory-care trajectory with progression to chronic unresponsive state and prolonged mechanical ventilation following influenza-triggered ANE1. Collectively, these outcomes delineate a neuromuscular spectrum from loss of independent ambulation, contracture risk, dysphagia, and respiratory dependence - despite differing acute presentations, illustrating variable expressivity within a single family. The most recent (sixth) case is a 3.5-year-old girl from the extended family who developed severe acute encephalopathy with prominent unilateral pyramidal deficit after laboratory-confirmed influenza A infection, with neuroimaging typical for ANE and molecular confirmation of the familial RANBP2 variant. She received antiviral therapy and standard immunomodulation with escalation to single-dose tocilizumab (12 mg/kg). After IL-6 blockade, rapid improvement in consciousness and interaction was observed. She is currently on multidisciplinary rehabilitation program with standard physiotherapy and specialized dysphagia-focused therapy. Conclusion: RANBP2 associated ANE1 can manifest as a wide spectrum of rapid-onset motor–bulbar symptoms with variable respiratory involvement and major disability burden. Early recognition (family history and prompt imaging) and rapid molecular confirmation allow early treatment (immunomodulatory) escalation. In that context, IL-6 receptor blockade escalation was associated with meaningful early neurological recovery allowing early rehabilitation. Presymptomatic testing of family members enables anticipatory counseling and prompt clinical management with treatment escalation.

Prof. Edoardo Malfatti APHP, Paris, France. INSERM, Paris, France Background: Myopathies encompass a broad spectrum of both inherited and acquired neuromuscular disorders. Interpreting muscle biopsies requires the analysis of a wide and expensive battery of histochemical and immunohistochemical techniques by experienced neuropathologists. Next-generation sequencing and serological diagnosis have changed the indication for muscle biopsies, limiting both access and interpretation skills in European Neuromuscular Reference centers (ERNC). Nevertheless, they remain indispensable to identify and characterize inflammation, to validate pathogenicity when variants of uncertain significance are identified on genetic testing, or when novel genes are discovered. Methods: We propose an algorithm for the analysis of muscle biopsies using digital pathology. In an initial machine-learning phase, Hematoxylin–Eosin (H&E) stained whole-slide images of muscle sections were analyzed using an automated myofiber segmentation workflow that integrates QuPath, Cellpose and a home made developed pipeline to enable quantitative assessment of muscle histology. Results: Our analysis demonstrates the efficacy of our algorythm to identify : 1)a higher fiber size variability distribution in all patterns compared to controls; 2) a significantly higher nuclear internalizations in dystrophic, inflammatory, and neurogenic patterns; 3) the presence of Inflammatory infiltrates, identified as areas of increased nuclear density, that were significantly higher in inflammatory myopathies compared to controls. Conclusion: These preliminary results highlight the potential of artificial intelligence as a valuable tool for next-generation myopathology, supporting standardized, quantitative, and reproducible analysis of muscle biopsies. Ongoing work aims to expand and validate the approach on larger cohorts, paving the way toward machine-assisted interpretation of digitally scanned muscle sections and the development of AI-driven first-line diagnostic support in muscle pathology.

Dr. Renato Mantegazza 1 , Dr. Saiju Jacob 2 , Dr. Tuan Vu 3 , Dr. Ali Habib 4 , Dr. Hiroyuki Murai 5 , Dr. John Vissing 6 , Dr. Aziz Shaibani 7 , Dr. Todd Levine 8 , Dr. Yessar Hussain 9 , Dr. Andreas Meisel 10 , Dr. Rodrigo Pavani 11 , Dr. Umesh Chaudhari 11 , Dr. Neda Jalali 11 , Dr. Michelle DeVeaux 11 , Dr. Karoline A Meagher 11 , Dr. Steven Sherman 11 , Dr. Eric Bachman 11 , Dr. Dipti Pawaskar 11 , Dr. Amal Souttou 11 , Dr. Lorah Perlee 11 , Dr. James F Howard Jr 12 1 Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 3 University of South Florida Morsani College of Medicine, Tampa, FL, United States. 4 University of California Irvine, Orange, CA, United States. 5 International University of Health and Welfare, Narita, Japan. 6 University of Copenhagen, Copenhagen, Denmark. 7 Nerve and Muscle Center of Texas, Houston, TX, United States. 8 Bob Bové Neuroscience Institute, Scottsdale, AZ, United States. 9 Austin Neuromuscular Center, Austin, TX, United States. 10 Charité-Universitätsmedizin Berlin, Berlin, Germany. 11 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States. 12 University of North Carolina, Chapel Hill, NC, United States Background: Generalised myasthenia gravis (gMG) is characterized by auto-antibody complement activation, which causes damage to the neuromuscular junction. The phase 3 NIMBLE trial ( NCT05070858 ) evaluated subcutaneous cemdisiran (an siRNA inhibiting hepatic C5 production) and subcutaneous pozelimab (a monoclonal antibody targeting C5) as monotherapies or in combination in adults with gMG. Methods: NIMBLE is a double-blind, placebo-controlled trial. A total of 288 adults with gMG were randomised to receive cemdisiran (600 mg every 12 weeks), pozelimab (200 mg every 4 weeks [Q4W]), combination (pozelimab 200 mg Q4W + cemdisiran 200 mg Q4W), or placebo. The primary and key secondary efficacy endpoints (n=239, database lock August 6, 2025) were assessed using change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores at Week 24. Other secondary efficacy endpoints included change from baseline at Week 24 in Myasthenia Gravis Composite (MGC) and Myasthenia Gravis Quality of Life (MGQoL15r) scores, and achievement of a ≥3-/≥5-point reduction in MG-ADL/QMG scores from baseline to Week 24. Safety was assessed in 281 patients in the double-blind treatment period (DBTP) (database lock December 10, 2025). Results: NIMBLE met its primary and key secondary endpoints. Results are expressed as least-squares mean (LSM) and SE. In participants assigned to cemdisiran (n=64) and combination (n=67), the LSM (SE) change in the primary endpoint (MG-ADL) was –4.5 (0.4) and –4.0 (0.4), with placebo-adjusted differences of –2.3 ( P =0.0005) and –1.7 ( P =0.0086). LSM (SE) change in the key secondary endpoint (QMG) was –4.2 (0.6) and –3.3 (0.6) for cemdisiran and combination, respectively, with placebo-adjusted differences of –2.8 ( P =0.0015) and –1.9 ( P =0.0348). In the cemdisiran and combination arms, the LSM (SE) change from baseline at Week 24 in MGC total score was –7.8 (0.9) and –6.0 (0.9), with placebo-adjusted LSM differences of –4.3 ( P =0.0009) and –2.6 ( P =0.0481) ( Table 1 ). In the cemdisiran and combination arms, the LSM (SE) change from baseline at Week 24 in MGQoL15r total score was –4.7 (0.8) and –4.3 (0.8), with placebo-adjusted LSM differences of –2.4 ( P =0.0348) and –2.0 ( P =0.0825) ( Table 1 ). In MG-ADL, 76.6% (cemdisiran) and 65.7% (combination) of participants achieved ≥3-point reductions, while 48.4% (cemdisiran) and 35.8% (combination) of participants achieved ≥5-point reductions in QMG. Assessment of terminal complement inhibition was 76.6% in the cemdisiran monotherapy arm and 99.6% in the combination arm. Cemdisiran was generally well-tolerated, with TEAEs occurring in 74.7% (59/79), 81.6% (40/49), 81.5% (66/81) and 81.9% (59/72) of participants in the cemdisiran, pozelimab, combination and placebo arms, respectively. No serious infections, meningococcal infections or deaths occurred during the DBTP; there were 2 deaths (pneumonia [cemdisiran], septic shock [combination]) in participants on concomitant immuno-suppressive therapies after the DBTP. Conclusion: Cemdisiran, both as monotherapy and in combination with pozelimab, significantly improves clinical signs and symptoms in people with gMG and was generally well-tolerated. Quarterly subcutaneous administration of cemdisiran provides effective symptom relief and enhanced quality of life, with partial complement inhibition.

Dr. Valentina Vera 1 , Dr. Elena Rossini 1 , Dr. Stefania Morino 2 , Dr. Luca Leonardi 2 , Prof. Giovanni Antonini 1 , Dr. Antonio Lauletta 1 , Dr. Francesca Forcina 1 , Dr. Laura Tufano 1 , Dr. Demetrio Marando 1 , Dr. Matteo Garibaldi 1,2 , Dr. Fionda Laura 2 1 Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), SAPIENZA University of Rome, Rome, Italy. 2 Neuromuscular and Rare Diseases Centre, Neurology Unit, Sant’Andrea Hospital, Rome, Italy Background: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder characterized by fluctuating muscle weakness and fatigability. In recent years, the therapeutic landscape of generalized MG (gMG) has been transformed by the introduction of targeted biological therapies, including complement inhibitors (CI) and anti–neonatal Fc receptor (FcRn) agents which have demonstrated rapid and sustained efficacy in patients with refractory or poorly controlled disease. Evidence from randomized clinical trials and real-world studies has largely been derived from patient populations receiving background non-steroidal immunosuppressive therapies (NSISTs), frequently in combination with corticosteroids. However, the clinical relevance of continuing concomitant NSIST therapy in patients treated with targeted agents remains uncertain. This study aimed to evaluate whether background NSIST use influences clinical scale outcomes, corticosteroid reduction, and disease stability in patients with gMG receiving targeted therapies. Methods: We conducted a single-center, retrospective, observational study at the Neurology Unit of Sant’Andrea Hospital, Rome. Forty-one patients with gMG who initiated treatment with CI or FcRn inhibitors were included. Collected data included demographic and clinical characteristics, thymic pathology, comorbidities and concomitant therapies. Clinical assessments were conducted at baseline and during follow-up using the MG Activities of Daily Living (MG-ADL) scale and the Quantitative MG (QMG) score. Achievement of Minimal Symptom Expression (MSE), MG Foundation of America Post-Intervention Status (MGFA-PIS), and changes in corticosteroid dosage from baseline to last available follow-up were also evaluated. Treatment discontinuations and treatment-related adverse events were additionally recorded. Results: Patients were stratified according to concomitant use of NSIST: 20 patients were receiving background NSIST (Group 1) whereas 21 patients were not (Group 2). The distribution of complement inhibitors and anti-FcRn therapies was balanced between the two groups. Baseline demographic characteristics werewere overall comparable. Disease duration at initiation of biologic therapy and mean follow-up duration were similar between groups (17.47±20.59 vs 15.9±9.12 months). At baseline, mean MG-ADL scores were comparable between Group 1 and Group 2 (9.10±4.36 vs 8.24±3.38) as were baseline corticosteroid dosages (22.17±13.81 mg vs 22.06±16.43). Mean baseline QMG scores was slightly higher in Group 1 compared to Group 2 (14.00±5.14 vs 10.86±4.82). MG-ADL and QMG scores showed a statistically significant improvement for both groups at every time point compared to baseline. No significant differences in clinical scale improvement during follow-up were observed comparing the two groups. The achievement of MSE, improvement in MGFA-PIS and reduction in mean corticosteroid dose from baseline to the last available follow-up did not differ significantly between the two groups. Treatment discontinuation occurred in 5 of 20 patients in Group 1 and 7 of 21 patients in Group 2. Conclusion: Our pilot analysis indicates that concomitant use of NSIST does not appear to be associated with greater improvement in clinical outcomes, enhance corticosteroid-sparing effects or increased disease stability. These findings suggest that, in the context of highly effective targeted therapies, background NSIST may not confer additional benefit for all patients. Larger, prospective studies are needed to better define the role of concomitant chronic immunosuppression and to optimize treatment strategies in gMG.

Dr. Roeland Vanhauwaert 1 , Ms. Kelly Ho 2,3 , Dr. Richard Webster 4 , Dr. Sally Spendiff 2 , Dr. Julien Oury 5 , Ms. Lieselot De Clercq 1 , Ms. Rani Coppejans 1 , Mr. Bernhardt Vankerckhoven 1 , Dr. Yin Dong 4 , Prof. Hanns Lochmülller 2,6,7 , Prof. Steven J. Burden 8 , Prof. Lore Mariën 9 1 argenx, Ghent, Belgium. 2 Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada. 3 University of Ottawa, Ottawa, Canada. 4 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. 5 Tevard Biosciences, Cambridge, United States. 6 The Ottawa Hospital, Ottawa, Canada. 7 Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada. 8 Massachusetts General Hospital, Harvard University, Boston, United States. 9 Agenx, Ghent, Belgium Background: Congenital myasthenic syndromes (CMS) are caused by impaired neuromuscular junction (NMJ) function, with subtypes arising from mutations in genes including DOK7, Agrn, ColQ  and CHRNE .   Adimanebart (ARGX-119) is a humanized agonistic monoclonal antibody that specifically binds and activates muscle-specific kinase (MuSK) to stimulate acetylcholine receptor (AChR) clustering and synaptic differentiation. Adimanebart demonstrated improved NMJ function and decreased muscle weakness and fatigability in a DOK7 CMS mouse model. Here, we investigated an adimanebart derivative, 3B2, in CMS mouse models deficient in agrin ( Agrn nmf380 ), the collagen tail of acetylcholinesterase ( ColQ –/– ), or AChR (Chrne –/– ; CHRNG + ). Methods: Agrn–, ColQ–, and AChR–CMS were modelled using Agrn nmf380 , ColQ knockout ( ColQ –/– ), and Chrne –/– CHRNG + mice, respectively. Mice received 3B2 (20 mg/kg for first dose, 10 mg/kg thereafter) or isotype control antibody by intraperitoneal injection on post-natal days 5, 15, and 35 ( Agrn nmf380 ), days 22, 29, 36, 43, 50, and 57 ( ColQ –/– ), or weekly from week 2–12 (Chrne –/– CHRNG + ). Mice were euthanized and tissues harvested on day 50 ( Agrn nmf380 ), day 66 ( ColQ –/– ), or week 13 (Chrne –/– CHRNG + ). Efficacy was assessed by survival duration, weight-gain, muscle strength, and muscle fiber size. Results: All 3B2-treated Agrn nmf380 mice (n=6) survived and demonstrated increases in body weight over time consistent with wild-type mice (n=6). Of the isotype control-treated Agrn nmf380 mice (n=6), only one survived to study end, increases in body weight plateaued after 15 days. In ColQ –/–  (3B2, n=13; isotype, n=12; wild-type, n=12) and Chrne –/– CHRNG + mice (3B2, n=9; isotype, n=13), no difference in body weight was observed between 3B2 or isotype control mice. Muscle strength significantly improved with 3B2 in Agrn nmf380   versus isotype control-treated mice, as assessed by time to fall in hindlimb suspension on days 7–8 and forelimb grip strength at days 23 and 40. No difference in muscle strength was observed between 3B2 and isotype control-treated ColQ –/–  and Chrne –/– CHRNG + mice, as assessed by fore- and hindlimb grip strength at days 32, 45, and 65 ( ColQ –/– ), inverted hanging wire time at days 26, 40, and 54 ( ColQ –/– ), or screen hang time throughout the study (Chrne –/– CHRNG + ). Quadriceps and gastrocnemius muscle fiber area were significantly greater in Agrn nmf380 mice treated with 3B2 versus isotype control, and similar to wild-type mice, while no differences in soleus muscle fiber area were seen between groups. There was no difference in soleus muscle fiber size between treatment groups in ColQ –/– mice. Combining 3B2 with pyridostigmine and salbutamol did not improve phenotypic measures compared with pyridostigmine and salbutamol alone in Chrne –/– CHRNG + mice. Conclusion: Administration of 3B2 prevented mortality, restored body weight and muscle fiber size to wild-type levels, and improved muscle strength in an Agrn-CMS mouse model, but did not rescue the CMS phenotype in mouse models of ColQ and AChR deficiency. These data suggest differential effects of adimanebart, dependent upon pathophysiology of CMS subtypes and the expected adimanebart mechanism of action.

Dr. Elena Cortes-Vicente Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Background: Myasthenia Gravis (MG) was initially considered a disorder in women under 40 years of age. Patients have been generally classified into 2 subgroups according to age at onset: early-onset MG, when they are under 50 at disease onset, and late-onset MG, when they are aged 50 or older at onset. However, in recent decades the incidence has increased in both men and women over 65. This group have been defined as very-late-onset MG patients. Methods: We designed an observational cross-sectional multicenter study based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed. Results: This study was published in Neurology in 2020 (Cortés-Vicente E, et al. Neurology 2019;00:1-10. doi:10.1212/WNL.0000000000008903). We studied a total of 939 patients from 15 hospitals: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men (p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti-acetylcholine receptor (anti-AChR) antibodies (p < 0.0001) was higher and fewer patients had thymoma (p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening (p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset (p = 0.002), they required fewer drugs (p < 0.0001) and were less frequently drug-refractory (p < 0.0001). Conclusion: Patients with MG are primarily very-late-onset with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, their outcome is usually good when diagnosed and treated properly.

Miss Elena Karkkainen , Mr. Aleks Carver, Miss Jess Page, Miss Laura Simms, Miss Stephanie Tanner, Ms. Dionne Moat, Mr. Robert Muni Lofra, Assoc. Prof. Chiara Marini Bettolo Newcastle University - John Walton Muscular Dystrophy Research Centre, Newcastle Upon Tyne, United Kingdom Background: The UK SMA Patient Registry, established in 2008, represents a well-defined cohort of individuals living with Spinal muscular atrophy (SMA) in the United Kingdom and Ireland. The registry has 688 participants: 474 adults (≥16 years); 214 paediatric (<16 years). The registry is a valuable tool for the collection of SMA data through patient-reported outcome measures (PROMs). PROMs capture the SMA patients’ perspectives about their quality of life and the impact of their condition.In April 2022, the registry implemented a range of PROMs in order to contribute to Managed Access Agreement (MAA) data collection supporting the national regulatory review of recently emerged SMA treatments Nusinersen and Risdiplam, aiming to collect PROMs data from 100 patients receiving each respective treatment. Methods: In April 2022, the registry implemented the following PROMs: - EQ-5D-5L - EQ-5D-Y-3L - Patient Global Impression of Severity (PGI-S) - Patient Global Impression of Improvement (PGI-I) - SMA Independence Scale – Upper Limb Module (SMAIS-ULM) - Free-text box. The registry simultaneously launched a pilot study in collaboration with the national Adult SMA REACH and SMA REACH UK clinical networks to support the collection of PROMs data through the registry. Results: Since their implementation, PROMs questionnaires have been completed by 257 adults and by the caregivers of 106 paediatric patients in the registry. In total, the registry has collected 3764 entries to PROMs questionnaires. In collaboration with the UK’s national SMA REACH clinical networks, PROMs data collected from patients receiving SMA treatment has been aligned with SMA REACH clinical data and submitted to UK regulatory authorities for consideration as part of the treatment reviews. Participants’ first submission of PROMs data post treatment initiation will be presented in comparison to their most recent submission of PROMs data post treatment initiation. Conclusion: The PROMs data presented indicates that participants reported stabilised or improved scores when comparing their first PROMs entry post treatment initiation to their most recent PROMs entry post treatment initiation. The registry’s presented data proves that PROMs add value to clinician-reported outcomes and offer a different perspective, demonstrating that it is worth continuing the effort of collecting the patient voice.

Dr. Amirul Asyraf Ab Ghapar 1,2,3 , Dr. Yukiko Tsuji 1 , Dr. Aicee Dawn Calma 1,2 , Dr. Nathan Pavey 1,2 , Dr. Mehdi A.J van den Bos 1 , Prof. Steve Vucic 1,2 , Assoc. Prof. Parvathi Menon 1,2 1 Brain and Nerve Research Centre, Concord Repatriation General Hospital, NSW Sydney, Australia. 2 Department of Neurology, Concord Repatriation General Hospital, NSW Sydney, Australia. 3 Neurology Subdivision, Ministry of Health Malaysia, Putrajaya, Malaysia Background: Diagnostic delay in ALS results from delayed recognition, further complicated by phenotypic heterogeneity and comorbidities that mimic ALS in an ageing population. Advances in therapeutic interventions have increased interest in biomarkers that enable early and accurate diagnosis of ALS. The previously described ALS Diagnostic Index (ALSDI) combines cortical and peripheral neurophysiological measures with selected demographic variables and has demonstrated good diagnostic utility in ALS. This study prospectively assessed the diagnostic utility of the ALSDI alongside the current Gold Coast Diagnostic Criteria (GCC). Methods: Participants with a progressive upper and lower motor neuron (LMN) disorder or pure LMN disorder were prospectively recruited and underwent transcranial magnetic stimulation (TMS) using the paired-pulse threshold tracking technique to record short-interval intracortical inhibition (SICI) averaged over 1–7 ms. Examiners were blinded to participants’ history and investigation results. Clinical, peripheral neurophysiological, and demographic data were collected concurrently to score the GCC and ALSDI. Participants with an established diagnosis at progress evaluation by the census date were included in the study. Results: One hundred and sixty-nine patients were comprehensively evaluated, with 105 participants having a final diagnosis of ALS and 64 with other neuromuscular disorders (NMD). The GCC demonstrated a diagnostic accuracy of 84% (sensitivity 87.6%, specificity 78.1%), comparable to the ALSDI accuracy of 80.5% (sensitivity 86.7%, specificity 70.3%). Combining both diagnostic indices resulted in a substantial improvement in diagnostic certainty, with excellent specificity of 96.9%, sensitivity 76.5%, and odds ratio (OR) 89.4; 95% CI 19.6–407.9. This combined approach performed equally well in participants with ≤12 months or >12 months of symptoms, in those with limited functional disability (ALSFRS-R >38), and in those with spinal onset disease, who form the majority of ALS and NMD cases (Table 1). Conclusion: The GCC provides general neurologists with a good diagnostic tool for ALS. This study shows that combining the GCC with the ALSDI significantly increases diagnostic specificity across early and late disease and a range of functional disability, making it a potentially valuable tool for use at ALS centres to confirm ALS diagnosis.

Dr. Nicolas Dubuisson 1,2 , Dr. Claire Bergstrom Johnson 1 , Dr. Roberto Bellanti 1 , Dr. Mateusz Makuch 1 , Dr. Robert Prior 3 , Dr. Mariya Misheva 1 , Assoc. Prof. Simon Rinaldi 1 1 Oxford University, Oxford, Oxford, United Kingdom . 2 Cliniques Universitaires St-Luc, Brussels, Belgium . 3 KULeuven, Leuven, Belgium Background: Multifocal motor neuropathy (MMN) is a chronic immune-mediated, purely motor, neuropathy characterized by the presence of GM1 antibodies. Currently, the underlying immune processes, particularly the role of B-cell clonality and GM1 antibodies, remain incompletely understood. This study aims to better characterize the origin and pathogenic potential of GM1 antibodies to inform more targeted therapies. Methods: A cohort of 35 MMN patients was clinically characterized using MRC-SS, ONLS, and MMN-RODS. The presence of paraproteins and light-chain restriction was evaluated using serum protein electrophoresis (SPEP), ELISA and high-resolution mass spectrometry. PBMCs from MMN patients vs controls were analysed by flow cytometry, followed by bulk and single-cell sorting and in vitro culture to assess GM1-specific IgM production. Finally, the pathogenic potential of patient-derived antibodies was investigated using human iPSC-derived neuromuscular organoids. Results: The clinical course of MMN confirmed an initial response to treatment, followed by an inevitable functional decline after approximately seven years of therapy. Serologically, GM1 antibodies were detected in 57% of patients, and evidence of B-cell clonality was observed in 35% of cases. Mass spectrometry identified additional IgM paraproteins in 30% of MMN patients and do it more frequently than in disease controls (ALS patients). Anti-GM1 reactivity was present in both IgD⁺ and IgD⁻ memory B-cell subsets, suggesting an early origin of autoreactivity involving both central and early peripheral checkpoint dysfunction, and is not dependent on germinal centre driven somatic hypermutation. Single-cell B-cell receptor sequencing data will soon be available to test this hypothesis. In human iPSC-derived neuromuscular organoids, patient-derived IgM impaired muscle contraction, supporting a direct pathogenic role. Conclusion: MMN is characterized by a B-cell–mediated autoimmune response with evidence of clonality and GM1 antibody pathogenicity. The latter arise from memory B-cell compartments and bind motor axons while activating complement. These findings provide insight into disease induction and persistence mechanisms and support the development of targeted B-cell therapeutic strategies.

Dr. Barbara Risi 1,2 , Dr. Michele Giovanni Croce 3 , Dr. Silvia Nicolosi 4 , Dr. Nicola Carapella 5 , Dr. Daniele Velardo 6 , Prof. Anna Pichiecchio 3,4 , Prof. Giacomo Pietro Comi 7,8 , Prof. Stefania Corti 6,7 , Dr. Sabrina Ravaglia 9 , Prof. Massimiliano Filosto 10,1 1 NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy. 2 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 3 Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy. 4 Advanced Imaging And Artificial Intelligence Center, Neuroradiology Department, IRCCS Mondino Foundation, Pavia, Italy. 5 Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy. 6 Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. 7 Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 8 IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy. 9 Neuromuscular Unit, IRCCS Fondazione Mondino, Pavia, Italy. 10 Department Of Clinical And Experimental Sciences, University of Brescia, Brescia, Italy Background: Inclusion body myositis (IBM) is the most common acquired myopathy in older adults and is typically characterized at onset by slowly progressive, asymmetric weakness of the knee extensors and/or deep finger flexors. However, atypical presentations may occur, as recognized in the updated diagnostic criteria, leading to diagnostic delay or misdiagnosis. These include early involvement of facial muscles, dysphagia, axial or proximal weakness, and foot drop, which may mimic neuromuscular junction disorders, motor neuron disease, or idiopathic inflammatory myopathies. We describe two Italian female patients with an early-onset, long-lasting, atypical form of IBM. Methods: We retrospectively analyzed two patients evaluated at two different Italian tertiary neuromuscular centers. Clinical data, laboratory results, and instrumental findings were collected. A review of the literature on atypical IBM was also performed. Results: The clinical, laboratory, and instrumental characteristics, as well as treatment responses, of the two patients are summarized in Table 1. Neurological examination of patient 1 (P1; 53 years old) revealed slight difficulty walking on heels, inability to rise from a squatting position, severe weakness of the orbicularis oculi and oris muscles (MRC 3/5) and of the neck flexors (MRC 4−/5), inability to whistle, mild macroglossia, dysphagia requiring thickened liquids and a soft diet, dysarthria with a nasal voice, and mild left eyelid ptosis. Moderate weakness of finger extension/abduction (MRC 4−/5) and of thigh flexion and leg extension (MRC 4/5) was also noted [IBM-FRS: 34/40]. Neurological examination of patient 2 (P2; 51 years old) revealed difficulty rising from a squatting position, severe weakness of all facial muscles (MRC 3/5) and neck flexors (MRC 2/5), with dysphagia requiring a softened diet. Despite normal muscle strength, mild atrophy of the distal portion of the quadriceps femoris was evident on examination [IBM-FRS: 31/40]. Conclusion: Facial diplegia appears to be a rare presentation of IBM, accounting for approximately 4% of atypical cases (Alamr et al.). The few cases described in the literature almost exclusively involve female patients with symptom onset in their fifties or sixties. Unlike our patients, three previously reported cases required early non-invasive ventilation (Salam et al.). Data on clinical evolution are limited, except for one case in which finger flexor weakness developed within seven years of disease onset (Cummins et al.). Robust data are also lacking regarding MRI characteristics in patients with this atypical presentation—although in some reported cases a typical pattern of thigh involvement has been observed, as in both of our patients—as well as regarding the prevalence of anti-cN1A antibody positivity. The cases described here provide additional insights into symptom onset—which may occur at a younger age, as in patient P1—clinical presentation, and disease progression in IBM. Notably, neither patient developed the classical pattern of muscle weakness over an approximately ten-year disease course. In the presence of such atypical presentations, complementary investigations—particularly muscle MRI of the thigh and forearm—are essential to support the diagnosis.

Dr. Enzo Pellacani , Dr. Ana Marina Silva, Dr. Alessandra Tolentino, Dr. Roseli Corazzini, Dr. David Feder, Dr. Alzira Carvalho Centro Universitário FMABC, Santo André, Brazil Background: Myxovirus resistance protein A (MxA) is a surrogate marker for Type I Interferon (IFN1) activation. Its expression, particularly in a perifascicular pattern, is currently regarded as a highly specific hallmark of Dermatomyositis (DM) (1–3) . Systemic Lupus Erythematosus (SLE) is also driven by an IFN1 signature. However, the expression of MxA in Lupus Myositis (LM) remains controversial, with conflicting data regarding its sensitivity and staining patterns (3–5) . We report a case of Lupus Myositis (LM) presenting with patchy MxA staining. We aim to question the prevailing view that MxA is consistently negative in SLE, highlighting that Type I Interferon activation in Lupus can occasionally mirror the immunohistochemical profile of DM. Methods: A 46-year-old man presented to the neuromuscular service, exhibiting a clinical picture of symmetrical, proximal tetraparesis, associated with ophthalmoparesis, ptosis, intense dysphagia, and severe fatigue. Laboratory tests showed elevated Creatine Phosphokinase (CK) and Aldolase levels. Electromyography (EMG) was consistent with myopathic disease, leading to a suspicion of inflammatory myopathy. The patient fulfilled the 2021 ACR/EULAR criteria for SLE, achieving 80% strength recovery under prednisone and methotrexate. Muscle biopsy showed mild-to-moderate fiber size variation, increased internalized nuclei, and rare regenerating fibers. It featured a single fascicle with reduced fiber caliber, more evident in the periphery. Immunohistochemical (IHC) study revealed positive immunoexpression for C5b9 (sarcolemmal granular pattern) in normal-appearing fibers, along with positive and patchy MxA expression, across the whole fascicle. Given the association of a clinical SLE diagnosis and the evident patchy MxA positivity pattern, without significant lymphomonocytic infiltrate or necrosis, and with only questionable perifascicular atrophy, a diagnosis of LM was consolidated. Results: SLE and DM share an IFN1 signature (1–4) . While Nishino et al. emphasize MxA as a highly specific marker for DM (often comparing it against SLE controls), the variable expression reported by Xing et al. in a larger LM cohort suggests a more complex landscape, raising the question of whether these discrepancies reflect distinct disease entities or variations in the intensity of a shared interferonopathy (1–4) . We demonstrate MxA positivity in a patient fulfilling current ACR/EULAR criteria for SLE, lacking classic DM clinical features. Shared interferon mechanisms between DM and SLE may limit MxA specificity, suggesting that diagnosis should not rely solely on this marker's positivity. Conclusion: MxA expression in LM raises the possibility that Type I Interferon activation is a shared feature across a broader spectrum of autoimmune myopathies, rather than a unique hallmark of DM. The patchy pattern, unlike the classic perifascicular presentation, adds complexity to the diagnostic landscape. This case invites us to reconsider the rigid categorization of autoimmune myopathies based on staining alone, suggesting that histological boundaries between these entities might be more fluid than previously thought, potentially representing variations within a common “interferonopathy” mechanism. This case suggests that finding MxA expression should not automatically default to a DM diagnosis, but rather prompt clinicians to maintain a broader differential diagnosis, ensuring that subtle SLE-specific stigmata are not overlooked, acknowledging that these diseases may exist on a shared pathophysiological spectrum.

Assoc. Prof. Juliana Gurgel Giannetti , Assoc. Prof. Nelio Januario, Mrs Anna Marina, Mrs Lucina Milanez, Mrs Ana Carolina Moura, Ms. Nara Carvalho, Ms. Carolina Assis, Assoc. Prof. Keyla Cunha, Assoc. Prof. Ana Lucia Starling Universidade Federal de Minas Gerais, BELO HORIZONTE, Brazil Background: Newborn screening (NBS) for 5q spinal muscular atrophy (SMA) has been implemented in many countries following the availability of disease-modifying therapies (DMTs). However, implementing a statewide NBS program for 5q SMA in Minas Gerais, Brazil was challenging due to its large population of approximately 20 million inhabitants, about 20,000 monthly births, and its extensive territory covering 586,528 km² across 853 municipalities.The aim of this study is to present preliminary data from the first 18 months of the 5q SMA newborn screening program in Minas Gerais, Brazil. Methods: NBS for 5q SMA was implemented in January/February 2024 within the public health system of Minas Gerais and the data was analyzed until July 2025. Sample collection is performed at primary health care units between the 3rd and 5th day of life. Screening is carried out using RT-PCR, and confirmatory testing is performed by MLPA both performed in a central laboratory at Federal University of Minas Gerais. Following the positive result, the first medical consultation and follow-up are conducted at the Hospital das Clínicas UFMG) including neurological evaluation, motor and bulbar scales (Chop intend, OrSAT), crying vital capacity, and Bayle scale III. The DMT is initiated on the same day of the first consultation. Results: Over 18 months, 312,816 samples were screened, and 26 patients with 5q SMA were identified, corresponding to an estimated incidence of approximately 1:12,546. Regarding SMN2 copy number, 17 patients had 2 copies, 6 had 3 copies, 2 had 4 copies, and 1 patient had 1 copy. At the first evaluation, all patients with 3 or 4 four copies were asymptomatic and among the 17 patients with 2 SMN2 copies, 6 were classified as asymptomatic, 9 as oligosymptomatic and 2 as symptomatic. DMT was provided to 23 patients with 2 or 3 SMN2 copies, in accordance with national therapeutic protocol. The mean age at treatment initiation was 17.7 days of life, all patients started with Risdiplam. Regarding motor outcomes 11 patients completed 12 to 18 months of treatment (n=11; 8 with 2 SMN2 copies; 3 with 3 with SMN2 copies) and all achieved the ability to sit and crawl. Within this group, among those with 2 SMN2 (n=8), 50% (4/8) achieved independent ambulation and 50% (4/8) walked with support. In contrast, all patients with 3 SMN2 copies (n=3) achieved independent ambulation. Bulbar function was preserved in all treated patients (n=23) with 100% (23/23) maintaining exclusively orally feeding. Concerning respiratory function only one symptomatic patient with 2 SMN2 (1/23) has required NIV which was started at the first consultation. Conclusion: This is the first newborn screening program for 5q SMA implemented in a large Brazilian state, and it is also the first one in South America. The organization of this program has proven to be successful and sustainable within the public health system, with excellent clinical outcomes, including motor gains, absence of bulbar and respiratory involvement (except for one symptomatic patient with 2 SMN2 copies).

Ms. Mei Wun Cheung 1 , Dr. Sophelia Hoi Shan Chan 2,3 , Miss Angel Wing Lam Tung 1 , Dr. Stephen Wing Wai Chan 1 , Mr. Ming Chung Poon 1 1 Allied Health Department (Physiotherapy) of Hong Kong Children's Hospital, Hong Kong SAR, China. 2 Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, China. 3 Paediatric Neurology Team, Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, China Background: Spinal muscular atrophy (SMA) is a neuro-degenerative disease characterized by progressive muscle weakness, atrophy and paralysis. SMA with two SMN2 copies (SMA type 1) typically have disease onset before 6 months of age and rarely achieve independent sitting. Most died before age 2. Disease-modifying treatments have significantly altered their natural disease course. In Hong Kong, SMA newborn screening (NBS) started in 2022, enabling early diagnosis and treatment initiation for better clinical outcomes. Real-world data on post-treatment outcomes of NBS-diagnosed SMA are needed. This study aims to evaluate the clinical outcomes of patients with NBS-diagnosed SMA carrying two SMN2 copies after being treated with disease-modifying therapies. Methods: We collected demographic and clinical data – age, sex, symptom-onset age, treatment-initiation age, and clinical status including feeding, breathing, musculoskeletal, and motor function - at pre-treatment and post-treatment follow-ups, according to protocol. Motor functions were evaluated using (1) Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), (2). Bayley-4 Motor Scale (Growth Scale Value, GSV), (3) HINE-2. (4) Motor milestone achievement age. Data collection spanned from 2022 to November 2025. All patients received same standard of care including regular multidisciplinary evaluation and physiotherapy. Results: Four eligible patients were included. One remained pre-symptomatic; others showed symptom onset on days 1, 4, and 15 of life. All started disease-modifying treatment between two weeks and one month of life, with three being symptomatic at treatment initiation. Follow-up ranged over at least one year. Motor assessments showed noticeable improvements: CHOP-INTEND scores increased by a mean of 34.75±12.63; Bayley fine-motor, gross-motor GSV increased by 37.75 ±14.31 and 24.5 ±8.74 respectively; HINE-2 increased by 19±4.97 points. Three patients (75%) achieved independent sitting before age 1, two (50%) achieved independent standing by 15 and 29 months, and one (25%) achieved independent walking by 33 months. Independent standing/walking occurred earlier than crawling. Three (75%) maintained oral feeding, one (25%) required gastrostomy feeding. Two (50%) started nocturnal non-invasive ventilation (NIV). Two (50%) had mild scoliosis before age 2 with spinal brace. All (100%) had pronated feet in standing. Conclusion: NBS allowing early initiation of disease-modifying treatments improves the muscle strength and motor functions of SMA with 2 SMN2 copies. In our three patients with treatment started at the symptomatic stage, delay in motor milestone related to transitional maneuvers such as rolling, crawling, and floor to stand, was observed, suggesting truncal and proximal instability. They also developed respiratory, feeding and musculoskeletal complications. Proactive physiotherapy training on transitional maneuvers, respiratory maintenance, and early introduction of hydrotherapy, is recommended. An advanced initiation of treatment within the first week of life may increase the likelihood of treatment prescribed at a pre-symptomatic stage in affected babies with 2 SMN2 copies diagnosed through NBS. A global effort to develop a new standard of care including rehabilitation strategies and early introduction of spinal brace and foot orthosis for the new phenotype of SMA in the era of disease-modifying treatments, is urgently needed.

Klaus Daniel Martin Background: The question of the extent to which electrical stimulation of a peripheral nerve achieves a functional improvement in a motor function has not yet been sufficiently clarified. We therefore examined 19 patients who received direct peroneal nerve stimulation with central foot drop with the question of the functional gain of foot lifting. Methods: The extent and force of foot lifting and the functional gait pattern were evaluated in 19 patients who received an implantable peroneal nerve system. This was done 40 months after implantation by determining the strength level according to Janda and with the help of gait tests such as gait endurance, speed and the risk of falling. Results: The force level of the Janda foot lift increased by a value of 2 on average. The six min gait endurance test increased from 197±39 m to 390±40 m in 78% while using the implant. Gait speed measured over 20 m increased in average in 43.6 %, the time needed decreased from 32.1±9.8 s without to 19.4±4.3 s by using electrical stimulation of a peripheral nerve. Gait steadiness improved, measured by the Timed Up and Go (TUG) test in 34.4%. Conclusion: Electrical stimulation of a motor nerve can lead to a significant improvement in the function controlled by this muscle. This certainly depends on the complexity of the function and thus how many nerves and thus muscles have to be controlled and what range of movement and thus functionality is desired.

Dr. Margaux Poleur 1 , Mr. Guillaume Parinello 2 , Dr. Eva Vrščaj 3 , Ms. Camille Bisson 2 , Dr. Céline Cluzeau 2 , Dr. Aurore Daron 1 , Asst. Prof. Lena Szabo 4 , Prof. Damjan Osredkar 3 , Dr. Paul Strijbos 5 , Mr. Damien Eggenspieler 2 , Prof. Laurent Servais 6,7 1 University department of neurology, Citadelle, Liege, Belgium. 2 Sysnav, Vernon, France. 3 University Children's Hospital, Ljubljana, Slovenia. 4 Pediatric Center, Semmelweis University, Budapest, Hungary. 5 F. Hoffmann-La Roche Ltd., Basel, Switzerland. 6 Neuromuscular Reference Center, Department of Pediatrics, University Hospital Liege & University of Liege, Liege, Belgium. 7 University of Oxford, Oxford, United Kingdom Background: Early treatment of patients with Duchenne muscular dystrophy (DMD) is considered critical to maximize the effect of disease-modifying treatments. However, traditional clinical outcome measures are challenging to administer to patients younger than 4 years of age, as they have limited ability to understand and follow instructions. Wearable digital health technology (wDHT) enables passive collection of ambulation data in daily living. A digital endpoint, stride velocity 95 th centile (SV95C), derived from data collected by the Syde ankle-worn sensor, was qualified as primary endpoint by the European Medicines Agency in ambulant patients with DMD from the age of 4 years. We hypothesized that this sensor could be worn and provide a robust and sensitive measure of ambulatory function in individuals between 1 and 4 years of age. Methods: Ambulant patients and healthy volunteers below 4 years old were enrolled in an ongoing 3-year longitudinal multicentric study, ActiLiege-Next. Patients were asked to wear two ankle sensors daily for the first 3 months and subsequently for 1 month every 3 months. Controls were instructed to wear the same sensors daily for 1 month every 6 months. Two digital variables were computed: SV95C and number of strides per hour (nb strides/h). Their reliability was assessed by comparing 2 consecutive two-week periods within each recording month using intraclass correlation coefficient (ICC). Ability of the measure to differentiate patients from controls was evaluated using a Mann Whitney U test. Longitudinal changes were assessed using Wilcoxon signed-rank test. Steroids effect was tested by comparing the slope of evolution before and after steroids initiation. Results: Twenty-eight patients were enrolled (median age [range]: 35 months [16-47]), and twenty-seven healthy boys (32 months [13-48]). Five patients were on steroids before or upon enrolment, and as of August 2025 seven initiated steroids during follow-up. Most participants were adherent to wearing the sensors, with more than 85% recording at least 50 hours of data at baseline, 6, 12 and 18 months. SV95C reliability was excellent, with intraclass correlation coefficients ≥0.97 for patients and ≥0.92 for controls at all time points, whereas reliability of nb strides/h varied between 0.60 and 0.93. Mean baseline SV95C was significantly higher in controls than in patients (p<0.001). Longitudinal analyses showed a greater increase in SV95C among controls than among patients at 12 months, with mean change from baseline of 0.51 m/s for controls (n=17), and 0.24 m/s for patients naive to steroids (n=12), respectively. For the 7 patients initiating steroids during follow-up, median SV95C increase was 0.17 m/s/year before starting steroids and 0.47 m/s/year after starting steroids. Conclusion: These results suggest that SV95C can differentiate patients from healthy boys and quantify treatment effect even in small cohorts. Together, these findings validate SV95C as a robust measure of ambulation and support its use for evaluating treatment efficacy in clinical trials for all ambulant patients with DMD including those younger than 4 years old. All available data will be presented at the congress.

Dr. Chiara Brusa 1,2 , Dr. Kate Waters 2,3 , Dr. Adnan Manzur 2 , Dr. Stephanie Robb 2 , Dr. Shira Rabinowicz 2 , Dr. Pinki Munot 2 , Dr. Mariacristina Scoto 1,2 , Prof. Giovanni Baranello 1,2,4 , Prof. Francesco Muntoni 1,2,4 , Dr. Anna Sarkozy 1,2 1 Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 2 Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children, London, United Kingdom. 3 Psychological Services, Great Ormond Street Hospital for Children, London, United Kingdom. 4 National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom Background: Duchenne Muscular dystrophy (DMD) may have a variable neurocognitive and neurobehavioural phenotype, largely related to the location of the DMD gene mutation. Intellectual disability affects 1/3 of DMD patients, while other frequent neurodevelopmental comorbidities include attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Mood (anxiety, depression) and obsessive-compulsive disorder (OCD) symptoms, and behavioural problems are also common. Despite the increasing attention to the involvement of the central nervous system (CNS) in DMD, treatment of brain comorbidities remains an unmet need in this population, especially as regards to the role of psychopharmacological therapies for severe symptoms. We aim to provide an update on the use of psychopharmacological treatments in a paediatric cohort of DMD patients. Methods: Retrospective review of clinical notes of DMD patients aged 0-18 years seen at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London. We reviewed the use and type of psychopharmacological medications that are largely prescribed by external services, in particular the Child and Adolescent Mental Health Services (CAMHS) local to the patient. Results: At the time of the study, the GOSH neuromuscular patients’ database included 252 DMD patients aged 0-18 years and, out of these, 13/252 (5%) were receiving a psychopharmacological therapy, either a CNS stimulant (5/13) for ADHD, or a selective serotonin reuptake inhibitor (8/13) for mood disorder/OCD. Median age at initiation of treatment was 13 years (range 9-16), with median duration of treatment being 2 years 5 months (range 5 months – 7 years 9 months). No side effects were reported by patients or families, nor observed during regular neuromuscular and cardiac follow-ups. All patients and/or caregivers verbally reported a perceived benefit with improvement of symptoms throughout the duration of treatment. Conclusion: Data from this study expand the knowledge on the use of psychopharmacological therapies for paediatric patients with DMD and show preliminary, limited evidence of a positive profile both in terms of safety and efficacy once prescribed. Multicentre prospective studies are required to collect more robust data and develop evidence-based recommendations for this population to ensure a prompt start of psychopharmacological medications when required.

Dr. Ieva Glāzere 1,2,3 , Dr. Gundega Ķauķe 1,3 , Dr. Marija Roddate 1 , Dr. Staņislavs Mironovs 1,3 , Assoc. Prof. Viktorija Ķēniņa 1,2 1 Pauls Stradins Clinical University Hospital, Department of Neurology, Centre of Rare Neurological Disorders, Riga, Latvia. 2 Riga Stradins University, Department of Biology and Microbiology, Riga, Latvia. 3 Pauls Stradins Clinical University Hospital, Department of Neurology, Laboratory of Neurophysiology, Riga, Latvia Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neuropathy, often challenging to diagnose due to its ability to mimic other peripheral nerve disorders, both – immune and hereditary. Typical CIDP can present acutely in up to 10-15% of patients with rapid progresssion within 4 weeks and initially could be diagnosed with Guillain Barre syndrome (GBS). Additionally, various recently diagnosed disorders in the same patient may perplex the diagnosis even more. Methods: A retrospective analysis of one clinical case was conducted at Pauls Stradiņš Clinical University Hospital, by reviewing medical records, performed between 2020 and 2026. A written informed consent was obtained by authors from the patient prior to submission of the case report. Results: We present a clinical case with a previously healthy 37-year-old female who initially manifested with acute onset sensory disturbances and motor weakness in both lower legs. Her symptoms progressed over the time of two weeks until she was unable to walk without aid. Notably, she did not report vision disturbances, facial weakness, shortness of breath or dysarthria, but did have a tingling sensation in her tongue. Two weeks prior to the hospitalisation her son has had a varicella zoster infection. Neurological examination revealed symmetrically reduced muscle strength in her limbs, with a Medical Research Council (MRC) score of 4/5 in both upper limbs proximally, and 3/5 in both lower limbs proximally, 2/5 distally. Additionally, she exhibited absent tendon reflexes, impaired superficial and deep perception in all limbs. Therefore, a preliminary diagnose of GBS was made. Lumbar puncture was performed, cerebrospinal fluid (CSF) workup showed extremely elevated protein level (4.6 g/L), with normal cell count. Spinal MRI results revealed massive contrast enhancement in cauda equina. Screening of infectious diseases, as well as other autoimmune/systemic disorders was negative. The patient received 5 plasma exchange procedures, which resulted in good clinical response – legs distally 3/5, proximally – 4/5. Four weeks later she returned to the hospital with reoccurring weakness, particularly in legs. She received intravenous immunoglobulin treatment (IVIG, 2g/kg) as a treatment related relapse. Explicit re-examination of the patient was performed, and an early stage (T1N0M0) breast cancer (Grade 2 ductal carcinoma) was diagnosed. She underwent surgical removal and was started on Tamoxifen 20 mg per day. The patient recovered neurologically with mild sensory disturbances in feet and no motor deficit. She was asymptomatic for four years, since 2025 she started to experience frequent leg muscle cramps, 6 months later the weakness of the lower legs re-appeared (MRC 2/5) and re-evaluation was completed. Nerve ultrasound revealed enlarged cervical roots and multiple nerves in arms and legs. Nerve conduction studies supported the diagnosis of CIDP. The IVIG treatment was started, which stabilised the patient and improvement her clinical symptoms. Conclusion: CIDP can clinically manifest with subacute onset motor weakness and sensory disturbances, and in the presence of newly diagnosed cancer, it can mimic paraneoplastic polyneuropathy. It is essential to perform a wide work-up, including nerve ultrasound, and re-evaluated patients history data to provide timely precise diagnosis and treatment.

Asst. Prof. Marcus Vinicius Pinto Mayo Clinic, Rochester, United States Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is frequently misdiagnosed, particularly in its atypical clinical phenotypes. Accurate identification is critical as delays in recognizing inflammatory neuropathies increase patient morbidity and mortality. Recent clinical advancements have led to the classification of autoimmune nodopathies (e.g., targeting Neurofascin-155, Contactin-1) as a distinct group of disorders separate from CIDP, requiring unique therapeutic approaches due to their poor response to standard intravenous immunoglobulin (IVIg) therapy Methods: This lecture will review the diagnosis and management of CIDP and autoimmune nodopathies. Results: CIDP is diagnosed through a combination of clinical phenotypes (typical vs. variants) and rigorous nerve conduction studies that identify non-uniform demyelination, including multifocal slowing, conduction block, and temporal dispersion. Autoimmune nodopathies (targeting proteins like NF155 and CNTN1) are now classified as separate clinical entities and are no longer considered CIDP variants. While IVIg remains the established first-line therapy for CIDP, autoimmune nodopathies are typically resistant to IVIg. There have been no randomized clinical trials specifically for autoimmune nodopathies to date, but clinical experience indicates promising results with the use of corticosteroids and rituximab Conclusion: Successful management of demyelinating neuropathies relies on integrating clinical phenotypes with rigorous EAN/PNS diagnostic guidelines. Clinicians must remain vigilant for “red flags” and CIDP mimics—such as POEMS syndrome, amyloidosis, and vasculitic neuropathy—especially in cases refractory to initial immunotherapy. Early differentiation of autoimmune nodopathies is essential to implementing effective, targeted B-cell depletion therapies.

Prof. Elise Duchesne 1,2,3,4 , Mr. Marc-Olivier Dugas 1 , Prof. Cynthia Gagnon 1,5 , Mr. Elie Fiogbé 1,5 , Prof. Eric Lukas Voorn 6 1 Groupe de recherche interdisciplinaire sur les maladies neuromusculaires (GRIMN), Centre intégré universitaire de santé et de services sociaux du Saguenay–Lac-Saint-Jean, Saguenay, Quebec, Canada. 2 École des sciences de la réadaptation, Faculté de médecine, Université Laval, Quebec City, Quebec, Canada. 3 CHU de Québec - Centre de Recherche de l'Université Laval, Quebec City, Quebec, Canada. 4 Centre Interdisciplinaire de Recherche en Réadaptation Et Intégration Sociale (CIRRIS), Institut de Réadaptation en Déficience Physique de Québec, Quebec City, Quebec, Canada. 5 Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada. 6 Amsterdam UMC location University of Amsterdam, Department of Rehabilitation Medicine, Amsterdam, Netherlands Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant neuromuscular disease caused by an expansion of a (GCN) trinucleotide repeat (11-18 repeats) in the PABPN1 gene, encoding the poly(A)-binding protein nuclear 1. Although research has traditionally focused on the cardinal symptom of dysphagia, emerging evidence, including work from our group and others, demonstrates substantial skeletal muscle impairment and mobility limitations in OPMD. As exercise-based rehabilitation gains momentum in neuromuscular diseases, objective characterization of cardiorespiratory fitness (CRF) and evaluation of aerobic training feasibility in OPMD are urgently needed. However, the validity of cardiopulmonary exercise testing (CPET) and the potential benefits of structured aerobic exercise remain unknown in this population.  Objectives : To (1) establish CPET validity in individuals with OPMD; (2) characterize CRF and mobility-related limitations relative to normative values; and (3) examine the feasibility, adherence, safety, and preliminary functional effects of a 12-week individualized home-based aerobic training program. Methods: Ambulatory adults with genetically confirmed OPMD underwent CPET and standardized mobility performance tests, including the 30-Second Chair Stand Test (30CST), 6-Minute Walk Test (6MWT), and maximal 10-Step Stair Tests for ascent and descent. CPET validity was determined using predefined physiological criteria. Participants electing to train completed a 12-week individualized home-based aerobic program following a polarized training model, consisting of two weekly low-intensity sessions and one weekly high-intensity session. Exercise intensity zones were individualized based on the first ventilatory threshold, determined from baseline CPET, and prescribed and monitored using heart-rate targets. Outcomes were assessed pre- and post-intervention. Feasibility metrics included adherence, retention, adverse events, and participant satisfaction. Results: Sixteen participants were enrolled; CPET was valid in 14 (88%), demonstrating that maximal exercise testing is achievable in most individuals with OPMD. Mean VO₂peak and maximal heart rate reached 99.2% and 103.2% of predicted values, respectively, indicating preserved central aerobic capacity. In contrast, peak power output (66.7% of predicted), 30CST (50.6%), and 6MWT performance (65.8%) were markedly reduced, revealing a pronounced dissociation between aerobic capacity and lower-limb functional performance. Of participants initiating the training program, 60% completed the intervention with excellent adherence (98.6% of prescribed sessions). Withdrawals were due to time constraints (20%) or unrelated medical issues (20%). Peak power output improved by 24.7% following training. No adverse events occurred, and participant satisfaction was high. Conclusion: To the best of our knowledge, this study is the first to establish CPET validity and comprehensively characterize CRF in OPMD, shifting the clinical focus beyond dysphagia to include systemic and functional limitations. Our findings provide initial evidence that individualized home-based aerobic training is feasible, safe, and capable of improving functional performance in OPMD. These results support the integration of aerobic exercise into clinical management and inform the design of future interventional trials in this underrepresented neuromuscular disease.

Prof. Kleopas Kleopa The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus Background: Emerging gene therapies for CMT inherited neuropathies include virally or non-virally mediated gene replacement, addition, silencing, or editing of genetic material. For most CMT neuropathies, gene- and disease, or even mutation-specific therapy approaches targeting lower motor and sensory neurons and their axons, or myelinating Schwann cells throughout the PNS are needed. While the efficiency of gene therapies to improve disease phenotypes has been demonstrated in cellular and in vivo rodent disease models, delivery approaches to human peripheral nerves remain to be optimized. Safety and scale-up biodistribution studies in bigger animal models, mostly non-human primates, have provided further insights into the translatability of the proposed administration routes and vector doses. Innovative delivery vehicles are currently in development, while insights from ongoing preclinical and clinical trials for other neurological and neuromuscular disorders will inform better safety strategies. Improving the risk-benefit ratio of gene therapies will facilitate future transformative treatments for CMT patients.

Dr. Vincenza Spallone University of Rome Tor Vergata, Rome, Italy Background: GLP1 receptor agonists (GLP1-RAs) represent a new class of drugs with multi-faceted beneficial effects on glycaemic control, overweight, cardiovascular and renal outcomes of diabetes. The advent of double or triple incretin agonists represents another strong opportunity to achieve almost unthinkable therapeutic goals in people with diabetes. Given the unmet need of a pathogenetic treatment for diabetic polyneuropathy (DPN), there is growing interest in exploring a potential place of GLP1-RAs in DPN, in addition to their potential effects on central neurological diseases. Preclinical studies have documented neuroprotective and significant antinociceptive effects of GLP1-RAs, thus providing the premises for clinical trials with the primary outcome of DPN or neuropathic pain. In preclinical studies GLP1-RAs provide a multimodal neuroprotection (by limiting inflammation through inhibition of NF-κB and MAPK pathways and reduction of pro-inflammatory cytokines), oxidative stress, and mitochondrial dysfunction, promoting Schwann cell survival and neurite growth, and reducing astrocyte and microglial activity. They may also activate μ-opioid receptors via increased IL-10 and β-endorphin in microglia thus suppressing pain-related synaptic transmission in the spinal dorsal horn. Prospective observational studies documenting a reduction in incidence of DPN in parallel with the increased adoption of GLP1-RAs in people with diabetes are lacking, though these drugs are linked with favourable changes in oxidative stress biomarkers and proteomic signatures of neuropathic pain. Moreover, few small controlled clinical trials of 6-18 months duration — including even fewer double-blind, placebo-controlled studies — have investigated the effects of GLP1-RAs on DPN measures but none demonstrated clear superiority over comparators. Therefore, current evidence from these small trials does not support a disease-modifying effect of GLP1-RAs on DPN. This presentation will briefly review preclinical findings in animal models of DPN and highlight clinical trial results, including ongoing research on dual and triple incretin agonists and combinations of GLP1-RAs with amylin agonists. Both GIP and amylin receptors are expressed in the peripheral nervous system, with limited preclinical evidence suggesting benefits for nerve repair and nociception regulation. Reduced relative risk of DPN development has been described with the GLP-1R/GIP dual agonist tirzepatide, and a trial with GLP1-RA semaglutide and amylin receptor agonist cagrilintide is currently underway for patients with type 2 diabetes and painful DPN. On the other hand, some cases of peripheral neuropathies have been reported in individuals with diabetes or obesity as possible consequences of GLP1-RAs-associated significant weight loss and rapid improvement in glycaemic control. These neuropathies resemble lumbosacral radiculoplexus neuropathy or treatment induced diabetic neuropathy, with inflammation and microvasculitis as possible causes. Although rare, these comorbidities of GLP1-RAs warrant awareness and surveillance.

Assoc. Prof. Antony Winkel 1,2 , Dr. Andrew Clarke 1,2 1 Sunshine Coast Health, Sunshine Coast, Australia. 2 Griffith University, Sunshine Coast, Australia Background: Multifocal motor neuropathy (MMN) is an immune-mediated neuropathy that typically requires high doses of intravenous immunoglobulin (IVIG). Pending trials underway currently for novel therapeutic agents, other treatment options are very limited, with traditional immunotherapies used in CIDP often ineffective in this condition. High-dose IVIG carries a known thrombotic risk, though hyperviscosity and associated ischaemia is rarely reported. Methods: Here we report a case of a 46 year old lady who, following the diagnosis of MMN and institution of IVIG therapy, required additional management for secondary digital ischaemia likely due to an increase of plasma viscosity due to IVIG in conjunction with an IgM-kappa paraprotein. The management is discussed. Results: The patient, a 46-year-old otherwise well lady presented in November 2021 with subtle left finger drop without sensory symptoms. Over several months this progressed to a radial motor deficit in the left hand, without sensory findings on examination, and then left median motor dysfunction and left fibular motor dysfunction followed. Nerve conduction studies and EMG showed focal motor changes with patchy conduction block at non-entrapment sites in these nerves and MRI with contrast showed T2 hyperintensity and contrast enhancement of the brachial plexus extending into the left radial nerve through the arm. A diagnosis of multifocal motor neuropathy with conduction block (MMN) was made and IVIG induction at 2g/kg produced significant improvement, with maintenance titrated to 1g/kg 2-weekly to maintain optimal motor function. An IgM-kappa paraprotein was detected as part of the initial work up, and Haematology review diagnosed monoclonal gammopathy of uncertain significance (MGUS) after further assessment, including bone marrow sampling. It was considered likely, however, that the immune dysregulation associated with the paraprotein may have contributed to the MMN. In July of 2023 the patient presented with new, subacute digital ischaemia in the hands with distal ulceration and dusky fingertips. Arterial supply to the upper limbs was normal on CT angiography and doppler ultrasound, and screening for other causes of thrombophilia or hyperviscosity were normal. Total IgG was elevated at 18-20 g/L. The known IgM-kappa paraprotein was stable at 3-4g/L, with no manifestations of haematological malignancy or plasma cell dyscrasia after repeat Haematology assessment. A secondary Raynaud's type phenomenon due to increased plasma viscosity from IVIG and the paraproteinaemia was considered. Intravenous phosphodiesterase infusion improved the digital ischaemia and allowed transition to oral therapy. Digital botulinum toxin was added as a second--line vasodilator, with further improvement and resolution of the ischaemia. A trial of rituximab was provided over 24 months given the M-protein, in the hope that this may allow IVIG dose-reduction. Unfortunately, no benefit was seen. Currently, the patient remains on her high-dose IVIG with 3-monthly botulinum and oral sildenafil, with good MMN symptom-control and no active digital ischaemia. Conclusion: This case illustrates the challenges of MMN in the setting of limited therapeutic options and significant other-organ dysfunction contributed to by high-dose IVIG and comorbidity. Trials of novel therapeutic agents, especially focusing on complement pathways, are welcomed as a potential alternative option in future for similar cases.

Dr. Emilie Retailleau, Dr. Clément Guémy , Prof. Pascal Laforet, Prof. Guillaume Nicolas Hopital Raymond Poincaré, Garches, France Background: Early identification of a genetic etiology of rhabdomyolysis is essential for optimized patient management and prevention of complications. However, establishing this diagnosis remains challenging, owing to the lack of readily available bedside diagnostic tools and the current reliance on increasingly large genetic panels with complex interpretative issues. The long exercise test (LET), performed as part of electrophysiological assessment, reflects muscle responsiveness to excitation and reproduces patient symptoms following sustained muscle contraction. Its diagnostic value has been well established in periodic paralysis and congenital myotonia, and more recently in McArdle disease. However, its role in the diagnostic workup of rhabdomyolysis has not yet been studied. Methods: We retrospectively analyzed the clinical, biological, genetic, and electrophysiological data of 43 patients with a history of rhabdomyolysis followed in three hospitals of the Assistance Publique–Hôpitaux de Paris (AP-HP). Particular attention was paid to LET results according to the etiology of rhabdomyolysis. Results: In patients with a single episode of rhabdomyolysis and a negative genetic panel, where an acquired origin was suspected, LET results were normal. In contrast, 72.4% of patients with an identified genetic cause showed significant abnormalities. An early decrement was observed in glycogen storage diseases and VLCAD deficiency, whereas a late decremental response was found in LCHAD deficiency and channelopathies ( RYR1, RYR3, CACNA1S ). Rather, patients carrying variants of uncertain significance in genes associated with channelopathies showed normal LET results. Patients with CPT2 deficiency showed more heterogeneous abnormalities. Conclusion: These findings suggest that the long exercise test may provide additional diagnostic arguments in the evaluation of rhabdomyolysis, particularly when metabolic myopathies or channelopathies are suspected. It may also contribute to the interpretation of variants of uncertain significance identified through genetic testing.

Dr. Gordana Kovacevic 1,2 , Dr. Slavica Ostojic 1,2 , Assoc. Prof. Adrijan Sarajlija 3,2,4 , Assoc. Prof. Nina Maric 5,6 , Dr. Nikola Ilic 3 , Dr. Mihail Basa 7 1 Neurology Department, Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia. 2 Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 3 Clinical Genetics Outpatient Clinic, Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia. 4 Faculty of Medicine, University of Eastern Sarajevo, Foca, Bosnia and Herzegovina. 5 Clinic for Children Diseases, University Clinical Center of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina. 6 Medical Faculty, University of Banjaluka, Banja Luka, Bosnia and Herzegovina. 7 Department of pulmology,Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia Background: Mutations in the RYR1 gene are common genetic findings in patients with congenital myopathies. The clinical symptoms of RYR1-related myopathies are very heterogenous, spanning from mild motor delay symptoms to severe neonatal hypotonia and respiratory insufficiency. The use of next-generation sequencing (NGS) has significantly contributed to accurate diagnosis. However, phenotypic variability and the frequent identification of variants of uncertain significance (VUS) continue to pose significant diagnostic challenges, especially when muscle magnetic resonance imaging (MRI) or histopathological muscle examination are unavailable. Aim of this study is to characterize the clinical and genetic variability of suspected RYR1-related myopathies in pediatric patients and to assess the diagnostic value and limitations of next-generation sequencing, particularly in cases with variants of uncertain significance. Methods: We retrospectively analyzed clinical, genetic, and histopathological data of seven pediatric patients with suspected RYR1 -related myopathy. Four patients harbored pathogenic or likely pathogenic RYR1 variants, each presenting with distinct clinical phenotypes. Three additional patients carried RYR1 VUS and exhibited clinical features compatible with congenital myopathy. Muscle biopsy was performed in two patients prior to the availability of genetic testing, while muscle MRI was not accessible. In patients with VUS, muscle biopsy was not performed due to parental refusal or recently obtained genetic results. In one family, a RYR1 variant of uncertain significance was identified in an affected sibling; however, the same variant was absent in a younger sibling with comparable hypotonia and delayed motor development. Consequently, whole genome sequencing was performed. Results: Among patients with pathogenic RYR1 variants, clinical presentations ranged from childhood-onset motor delay with hip-girdle weakness and central core disease on biopsy, to severe neonatal hypotonia with ophthalmoplegia, bulbar and respiratory weakness requiring invasive ventilation, contractures, and centronuclear myopathy on biopsy. Other phenotypes included neonatal hypotonia with axial, and proximal weakness, and ligamentous laxity, as well as milder hypotonia with delayed motor development and proximal weakness. Patients with RYR1 VUS also demonstrated variable phenotypes: congenital clubfoot with hypotonia and myopathic facies; mild axial weakness with ligamentous laxity, and delayed motor development with proximal muscle weakness.   In one of these patients, extended NGS revealed a homozygous VUS in the FXR1 gene. Segregation analysis confirmed the presence of the FXR1 variant in both parents and the affected sibling, leading to a diagnosis of autosomal recessive FXR1-related congenital myopathy .   In the absence of a muscle biopsy or MRI, definitive correlation between genotype and phenotype remained inconclusive in the remaining two cases. Conclusion: Our cohort demonstrates the marked clinical and genetic heterogeneity of RYR1-related myopathies in pediatric patients. Although next-generation sequencing plays a central role in identifying RYR1 variants, diagnostic uncertainty persists in a subset of patients, particularly with VUS, when comprehensive investigations cannot be completed. Limited access to MRI, biopsy, and extended genetic testing restricted definitive genotype–phenotype correlation. Nevertheless, selected cases demonstrate that extended NGS and family segregation studies can clarify the diagnosis, including non-RYR1 congenital myopathies. An integrated diagnostic strategy that combines careful clinical assessment, genetic testing, and muscle biopsy—when feasible—remains essential for accurate diagnosis in suspected RYR1-related myopathies.

Dr. Natalie Winter 1,2 , Dr. Henrik Lauer 3 , Ms. Victoria Johnson 1 , Ms. Julia Wittlinger 1 , Dr. Stephanie Männlin 1 , Prof. Jonas Kolbenschlag 3 , Prof. Alexander Grimm 1 , Dr. Johannes Heinzel 3 1 University Hospital Tuebingen, Tuebingen, Germany. 2 Hertie Institute for Clinical Brain Research, Tuebingen, Germany. 3 BG Klinik Tuebingen, Tuebingen, Germany Background: Traumatic transection of the median and ulnar nerves may result in persistent functional deficits despite timely surgical repair. High-resolution nerve ultrasound enables direct visualization of fascicular integrity and morphologic nerve parameters and may complement clinical and electrophysiological assessments. The relationship between sonographic findings, clinical sensory and motor function, and long-term patient-reported outcomes remains insufficiently characterized. Methods: Patients with traumatic transection of the median and/or ulnar nerve treated by primary end-to-end neurorrhaphy were invited for follow-up evaluation. Assessments included nerve– and muscle ultrasound, nerve conduction studies, electromyography, and standardized clinical examination including motor strength grading and two-point discrimination testing. Patient-reported outcomes were assessed using the Michigan Hand Questionnaire (MHQ) and the Short Form-36 (SF-36). Ultrasound evaluation focused on fascicular continuity and cross-sectional area (CSA) at the repair site. Associations between ultrasound, clinical, and questionnaire outcomes were analyzed. Subgroup analyses were performed for median and ulnar nerve injuries. Results: A total of 24 patients (6 women, 18 men) with 27 nerve injuries were included (9 median nerves, 18 ulnar nerves); three patients had combined median and ulnar nerve injuries. Mean age at follow-up was 44.0 ± 17.8 years. The mean interval between surgical repair and follow-up assessment was 3.2 ± 2.1 years. Ultrasound-assessed fascicular continuity showed significant correlations with multiple patient-reported outcome measures. Higher fascicular continuity was associated with lower pain levels on the MHQ (Kendall’s tau = −0.419, p = 0.015) and with a higher MHQ total score (tau = 0.415, p = 0.011). Within the SF-36 domains, fascicular continuity correlated significantly with Energy/Fatigue (tau = 0.583, p < 0.001), Emotional Well-Being (tau = 0.427, p = 0.014), Social Functioning (tau = 0.513, p = 0.005), Pain (tau = 0.401, p = 0.024), and General Health (tau = 0.375, p = 0.033). Cross-sectional area (CSA) at the neurorrhaphy site showed no significant correlation with MHQ or SF-36 scores, muscle strength grading, or sensory function. In a subgroup analysis of median nerve injuries, fascicular continuity showed no significant correlation with abductor pollicis brevis muscle strength or with sensory measurements; however, abductor pollicis brevis strength correlated significantly with the MHQ final score (tau = 0.569, p = 0.041). In the ulnar nerve subgroup, fascicular continuity correlated significantly with the MHQ final score (tau = 0.417, p = 0.046). Across the cohort, better two-point discrimination (minimum distance) correlated significantly with higher MHQ final scores (tau = 0.442, p = 0.038). Conclusion: Fascicular continuity assessed by nerve ultrasound is associated with relevant patient-reported quality-of-life outcomes after median and ulnar nerve repair, whereas morphometric parameters such as CSA show limited functional relevance. Motor strength and sensory discrimination emerge as important clinical correlates of hand-related patient-reported outcomes, underscoring the complementary value of sonographic, motor, and sensory assessments in the long-term evaluation of peripheral nerve repair.

Prof. Josef Finsterer Neurology and Neurophysiology Center, Vienna, Austria Background: Mutations in CHRNA1 are responsible for postsynaptic CMS and occur either as slow channel syndrome or fast channel syndrome. Slow channel CMS due to CHRNA1 variants responds favorably to pyridostigmine. A patient with slow-channel CMS due to a new CHRNA1 variant that responds favorably to 3,4-diaminopyridine (3,4-DAP) has not yet been reported. Methods: Case Report Results: The patient is a 36-year-old woman who was diagnosed with non-specific CMS at the age of one year when she presented clinically with signs of somnolence, weakness and facial dysmorphism. She later also developed limb weakness, with the upper limbs being more severely affected. Heat, low humidity, late menstruation, high fever and stress aggravated the muscle weakness. Only at the age of 17 was pyridostigmine started, which partially improved the muscle weakness. The diagnosis was genetically confirmed when the new, heterozygous variant NM_001039523 :c.1396G>A in CHRNA1 p.(Gly466Arg) was detected at the age of 30. Since then, 3,4-DAP was administered, which further improved the muscle weakness. Conclusion: CHRNA1-associated slow-channel CMS may respond favorably not only to pyridostigmine but also to the additional administration of 3,4-DAP; patients with CHRNA1-associated CMS can live for years without treatment, especially in early life; CMS should be diagnosed without delay to avoid putting people at risk of receiving medication that could potentially worsen their phenotype

Dr. Andrew Oldham 1 , Dr. Tan P. Pham 2 , Ms. Dina Elsouda 2 , Ms. Eugénie Kluczka 3 , Dr. Jader Baima 4 , Mr. Ian Keyzor 5 , Dr. Mark Roberts 1 1 Salford Royal NHS Foundation Trust, Salford, United Kingdom. 2 Astellas Pharma, Inc., Northbrook, IL, United States. 3 Sysnav, Vernon, France. 4 Astellas Gene Therapies, San Francisco, CA, United States. 5 Astellas Pharma Europe Ltd., Addlestone, United Kingdom Background: In Pompe disease, acid alpha-glucosidase deficiency leads to lysosomal glycogen accumulation, causing progressive neuromuscular degeneration over time. Despite improvements in standard of care (SOC) with enzyme-replacement therapy (ERT), some individuals experience continued muscular and respiratory decline. The 6-minute walk test (6MWT) is the current gold standard endpoint in trials of ambulatory individuals with neuromuscular disorders; however, this measure is challenging for those with significant motor impairments and may not accurately reflect treatment effect. The stride velocity 95th centile (SV95C) is a clinical outcome assessment (COA) endpoint that quantifies an individual’s fastest stride speed over a defined period. SV95C is captured using a wearable device, such as the Syde ® device (Sysnav, Vernon, France), enabling continuous monitoring of daily movement. SV95C is the first wearable digital COA qualified by the European Medicines Agency as a primary endpoint for use in trials of neuromuscular diseases, as an alternative to 6MWT (Servais et al, 2023). STEP, a non-interventional, longitudinal, observational pilot study aims to assess the validity and reliability of SV95C (captured using the Syde ® device) in measuring physical and motor function in participants with late-onset Pompe disease (LOPD). Methods: Approximately 22 adult ambulant participants (≥18 to <65 years) with genetically diagnosed LOPD treated with ERT for ≥2 years will be enrolled from the UK. Eligible participants will continue to receive ERT as usual. Participants will be followed for approximately 12 weeks, with visits scheduled relative to participant’s ERT infusion schedule ( Figure ). Functional performance tests and clinician-reported outcomes (ClinROs) will be assessed on-site (Visits 1, 4); patient-reported outcomes (PROs) will be assessed on-site (Visits 1, 4) and at-home (Visits 2, 3). Participants will be required to wear the Syde® device daily while awake during weeks 1–4 and 9–12. PROs and ClinROs will be assessed using generic and Pompe disease-specific questionnaires. The relationship between SV95C and 6MWT (and other functional performance tests, PROs, and ClinROs) will be tested using regression analyses, correlation and interclass correlation analyses, and Bland-Altman tests. Results: The primary outcome is to evaluate the relationship, including equivalence and correlation, between SV95C and 6MWT. Secondary/exploratory outcomes include evaluating the relationship between SV95C and other functional performance tests (100-meter walk timed test, 4-stair climb), PROs and ClinROs, assessing test-retest reliability, validity (including convergent and known-group validity) and responsiveness of SV95C using functional performance tests and PROs and ClinROs, describing participants’ responses for PROs and ClinROs, assessing changes in fatigue and physical function between intervals of ERT by comparing SV95C and PROs by number of days since last ERT infusion, describing participants’ baseline demographic and clinical characteristics, and evaluating adherence to and usability of the Syde ® device. Conclusion: This study will assess whether SV95C, as measured by the Syde ® device, is a valid and reliable endpoint for measuring physical and motor function in participants with ambulant LOPD. The findings may help reduce trial participation burden and expand options for evaluating the impact of therapies for individuals with LOPD.

Miss Ana Moraes, Dr. Paula Fratini, Mr. Enzo Pellacani , Dr. Alzira Carvalho Centro Universitario FMABC, Santo André, Brazil Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally and play essential roles in muscle differentiation, regeneration, and metabolism. A specific subset, known as myomiRs, is predominantly expressed in muscle tissue and has been implicated in the regulation of key pathways involved in neuromuscular diseases (NMDs). Due to their stability in biological fluids, myomiRs have gained attention as potential non-invasive biomarkers for diagnosis, prognosis, and therapeutic monitoring. This review aimed to demonstrate current knowledge on the role of myomiRs in major NMDs, particullary Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), limb-girdle muscular dystrophy (LGMD), McArdle disease, and myofibrillar myopathy (MFM), emphasizing their biological significance and clinical potential. Methods: A narrative literature review was conducted using indexed databases to identify studies addressing myomiR expression, function, and clinical implications in neuromuscular diseases. Results: The analysis demonstrated that specific myomiRs, such as miR-1, miR-133a/b, miR-206, miR-29b, miR-31, and miR-486, are differentially expressed among these disorders, participating in processes like muscle degeneration, regeneration, fibrosis, and inflammation. In DMD, several myomiRs are upregulated, reflecting ongoing muscle damage and regeneration, while in DM1, the downregulation of miR-1, miR-133a/b, and miR-29b contributes to defective muscle maturation and fibrosis. In contrast, miR-206 and miR-223-3p are increased as part of a compensatory regenerative response. For LGMD, miR-143-3p and miR-486 are elevated and may serve as circulating biomarkers. Only one study has evaluated the role of myomiRs in McArdle disease, underscoring the scarcity of available data and the need for further research to clarify their diagnostic and pathogenic relevance. Conclusion: MyomiRs are central to the molecular mechanisms of NMDs and stand out as accessible biomarkers for diagnosis, monitoring, and therapeutic evaluation. Their emerging use as non-invasive endpoints in clinical trials underscores their translational relevance and the need to expand research across the different NMDs.

Dr. Yan Huang Nantong University, Nantong, China Background: Regulatory T cells (Tregs), which secrete transforming growth factor (TGF)-β and interleukin (IL)-10, have essential role in anti-inflammatory and neurotrophic functions. Herein, we explore the neuroprotection of Tregs in Parkinson's disease (PD) by adoptive transfer of Tregs. Methods: Tregs, isolated by magnetic sorting, were activated in vitro and then were adoptively transferred to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice. Neuroinflammation, dopaminergic neuronal loss and behavioral changes of PD mice were evaluated. Live cell imaging system detected a dynamic contact of Tregs with MN9D cells that were stained with CD45 and galectin-1, respectively. Results: Tregs prevented MPTP-induced dopaminergic neuronal loss, behavioral changes, and attenuated the inflammatory reaction in the brain. When blockade the LFA-1 activity in Tregs or the ICAM-1 activity in endothelial cells, the percentage of Tregs in substantia nigra (SN) decreased. CD45 and galectin-1 were expressed by Tregs and MN9D cells, respectively. CD45-labeled Tregs dynamically contacted with galectin-1-labeled MN9D cells. Inhibiting CD45 in Tregs impaired the ability of Tregs to protect dopaminergic neurons against MPP + toxicity. Similarly, galectin-1 knockdown in MN9D cells reduced the ability of Tregs neuroprotection. Adoptive transfer of Tregs protects dopaminergic neurons in PD mice by a cell-to-cell contact mechanism underlying CD45-galectin-1 interaction. Conclusion: Treg Cells can attenuate neuroinflammation and protect dopaminergic neurons in MPTP-induced Parkinson's disease mice.

Dr. Carlo Antozzi Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy Background: Myasthenia Gravis (MG) is a chronic autoimmune disease of the neuromuscular junction characterized clinically by fluctuating weakness of voluntary muscles; the degree of fluctuations ranges from mild to severe worsening up to impending (IMC) or full myasthenic crisis (MC) with respiratory insufficiency requiring mechanical ventilation. The standard of care for clinical relapses/IMC-MC includes, apart from changes to ongoing pharmacological therapy, immunomodulation with plasmaexchange (PLEX) or high dose intravenous immunoglobulins (IVIG) effective in a proportion of patients. However, some patients may have medical contraindications to apheresis or inadequate vascular access; PLEX is also not available everywhere; IVIG are expensive and often in short supply. Moreover, high-dose steroids may carry an increased risk of infection or sepsis, which is a poor prognostic factor for patients in MC. Despite these limitations, PLEX and IVIG, together with corticosteroid, have a consolidated role in the management of MG relapses. During the last decade, considerable advances have been made in research and approval of targeted therapies such as complement or neonatal Fc (FcRn) inhibitors which have now entered clinical practice. Methods: Literature review and experience from real world use of targeted therapies in MG Results: Clinical experience started with eculizumab for refractory MG and efgartigimod, followed by the approval or ravulizumab and zilucoplan as complement inhibitors, and rozanolixizumab and nipocalimab as FcRn inhibitors. Apart from the different mechanisms of action, route of administraion, and treatment protocols (chronic versus cyclic regimens), targeted therapies share some features that suggest their role in the treatment of severe MG deteriorations and MC. Indeed, they provide rapid improvement (in general within two weeks in the majority of patients) and are free of the side effects of corticosteroids. Randomized clinical trials did not include MG patients in IMC/MC, hence no information is available from these studies. Nevertheless, case reports and small series are emerging in the medical literature regarding the use of efgartigimod in MC with clinical improvement observed during the first treament cycle; in this context, timing adjustments must be taken into consideration when combining FcRn inhibitors with PLEX or IVIG. Regarding complement inhibition, experience with eculizumab observed clinical improvement often within one week; in some patients improvement can be observed even within 24 hours, a condition of “super-responsiveness” observed also with ravulizumab. Conclusion: The evidence to guide the choice between anti-complement or anti-FcRn inhibition in severe MG deterioration is still limited. Apart from issues related to autoantibody specificities (anti-acetylcholine vs MuSK), decisions must be made taking into account each patient previous history (particulary the frequency of relapses and need for rescue therapy), comorbidities, and risk of infection, as well as the need to set a strategy as a form of “bridging therapy” or as a long-term maintenance treatment. Despite the available evidence, both complement and FcRn inhibitors have been included in the recent updates of several national guidelines for the management of MG also in case of severe deterioration.

Dr. Emna Farhat , Prof. Ilhem Ben Youssef-Turki, Prof. Najoua Miladi Tunis El Manar University, Tunis, Tunisia Background: Neuromuscular disorders (NMD) constitute a major health care burden in the north African region (NAR) due to their continuing high frequency related to the high degree of consanguinity. The access to basic diagnostic tools such as muscle biopsy and molecular biology remains limited in the region. The discovery of innovative life-saving drugs for diseases like spinal muscular atrophy has raised hopes among clinicians. Despite continued efforts in developing regional specific diagnosis strategy, patient registries and multidisciplinary clinical management according to international standards of care, the treatment of NMD has not changed and patients continue to be treated symptomatically. The access to new targeted therapies remains limited in the NAR. Very few patients have benefited from these treatments, most within the framework of a compassionate access program, with a lack of a concrete regional strategy to improve their availability. This is probably due to the absence of structures dedicated to research/clinical trials and the lack of NMD specialists trained in this particular field, in addition to the limited economic development. The Mongi Ben Hamida National Institute of Neurology of Tunisia, founded in 1973, was the first neuromuscular centre of the NAR, with a laboratory specialized in muscle pathology and research laboratories dedicated to neurogenetics and neurosciences. In this presentation, we will discuss the difficulties and challenges of accessing NMD disease modifying treatments in the NAR, and the potential solutions for advancing a global and adapted strategy to put in place, in order to participate first of all at programs of clinical trials for these drugs, and secondary to make them accessible for all patients.

Prof. Sonia Nouioua 1 , Dr. Abdelmadjid Abdelkrim 1 , Dr. Ouissem Benchaabi 1 , Dr. Sihem hallal 2 , Dr. Ferroudja Ramdane Cherif 1 , Dr. Sihem Abdelhak 1 1 Department of neurology EHS Cherchell, Tipaza, Algeria. 2 central laboratory CHU Mustapha, Algiers, Algeria Background: Contiguous gene deletion syndromes (CGDS) are rare genomic disorders caused by deletions of large DNA segments involving contiguous genes, leading to the co-occurrence of apparently unrelated multi-systemic clinical features. A typical example is the Xp21 contiguous gene deletion syndrome which includes deletions of DMD, Glycerol kinase (GK), NR0B1 (DAX1) and results in a complex phenotype combining Duchenne muscular dystrophy, glycerol kinase deficiency and congenital adrenal hypoplasia. Methods: We present the clinical, biochemical and molecular characterization of a 6-year-old male. The patient presented with a complex phenotype comprising Duchenne muscular dystrophy (DMD), profound intellectual disability and secondarily signs of adrenal insufficiency. The diagnostic workup included neurological examination, biochemical and endocrine profiling, neuroimaging, nerve conduction studies and electromyography (ENMG), muscle biopsy and genetic testing using next-generation sequencing (NGS) Results: A 6-year-old male born to consanguineous parents at term with no significant neonatal complications apart from a neonatal infection at the age of 20 days without sequelae, presented with a global development delay (independent sitting acquired at 15 months, first ambulation at 24 months, severe language delay), frequent hypoglycemia and vomiting, proximal lower limbs weakness and failure to thrive. On admission he had poor general condition with lethargy and severe dehydration. Clinical examination revealed profound intellectual disability with autistic features; language was never acquired correctly and his vocabulary was limited to a few isolated words, with associated strabismus. He exhibited a classic DMD phenotype, including pelvic girdle muscles weakness, a waddling gait, calf pseudohypertrophy, Gowers, scapula alata signs and scoliosis. The biochemical test showed markedly increased levels of Creatine-kinase (CK) exceeding 9500 IU/L with elevated liver enzymes, adrenal insufficiency characterized by high ACTH levels (>2000 pg/mL) while cortisolemia was within the normal range. Lipid profiling revealed a pseudo hypertriglyceridemia with low HDL. ENMG demonstrated myopathic patterns and the muscle biopsy confirmed the dystrophic process. The cardiac examination by transthoracic echocardiogram showed no dilated cardiomyopathy but revealed a patent foramen ovale, and abdominopelvic ultrasound demonstrated absent adrenal glands consistent with adrenal hypoplasia congenita. The etiological workup for cognitive impairment, including brain MRI, EEG, TSH and phenylalanine levels were unremarkable. Genetic analysis by NGS identified a large contiguous deletion of approximately 11 Mb on the short arm of the X chromosome, spanning the Xp21.1–Xp21.3 region and encompassing IL1RAPL1, NROB1 (DAX1), GK, and DMD genes. This rare pathogenic deletion correlates with the observed complex phenotype of DMD, adrenal hypoplasia congenita, glycerol kinase deficiency, and profound intellectual disability with autism spectrum features. The patient was treated with hydrocortisone, fludrocortisone and oral salt supplementation, resulting in improvement of his general condition and metabolic stability. Conclusion: This case highlights the considerable medical and genetic complexity of Xp21 CGDS syndrome and provides a precise molecular explanation for the co-occurrence of profound intellectual disability, adrenal agenesis and muscular dystrophy. Clinicians should consider Xp21 syndromes in male children with adrenal insufficiency and muscular or metabolic signs. Early screening and genetic testing are essential for establishing an accurate diagnosis, implementing effective management, and providing informed counselling to the family.

Dr. Daryl Yin Keong Lo 1 , Dr. Elizabeth Ming Jing Tan 2 , Dr. Yee Sean Teng 3 , Dr. Kelvi Kaibin Kuan 4 , Dr. Zhibin Tan 1 1 Department of Neurology, National Neuroscience Institute (Singapore General Hospital Campus), Singapore, Singapore. 2 Department of Emergency Medicine, Singapore General Hospital, Singapore, Singapore. 3 Department of Internal Medicine, Singapore General Hospital, Singapore, Singapore. 4 Department of Emergency Medicine, Changi General Hospital, Singapore, Singapore Background: A 44-year-old lady presented to the emergency department with acute onset binocular diplopia associated with facial and limb paraesthesias 30 minutes after consumption of cooked sea whelk. Physical examination revealed alternating exotropia worse on right gaze, as well as difficulty sustaining upward gaze. There was isolated mild weakness of the bilateral orbicularis oculi. There was generalised hyporeflexia. Pinprick sensation was diminished over all fingertips. The rest of the neurological examination was normal. Bedside pulmonary function tests were normal. Magnetic resonance imaging of the brain, third cranial nerves and intracranial vessels was unremarkable. Acetylcholine receptor, muscle-specific kinase and ganglioside antibodies were negative. Thyroid function tests were normal. Nerve conduction studies and electromyography, performed on day four of symptoms as an early baseline, were normal. Toxicology testing for paralytic shellfish toxins was not immediately available. Methods: The patient was managed supportively in the high dependency unit. She showed a rapid improvement of symptoms with initial resolution of her visual and sensory symptoms by day three, followed by resolution of orbicularis oculi weakness on day four, allowing for discharge from hospital. Interval ophthalmology examination at six weeks confirmed improvement of her exotropia. Results: Paralytic shellfish poisoning is the most common form of biotoxin poisoning which occurs after the consumption of contaminated shellfish. It occurs due to the accumulation within shellfish of a neurotoxin known as saxitoxin, which cannot be destroyed by gastric acid or through food preparation. Saxitoxin blocks voltage-gated sodium channels and modifies channel gating of potassium channels, leading to a rapid onset of neurological symptoms, typically within 30 minutes to 3 hours of shellfish consumption. Sensory disturbances such as tingling and numbness typically occur first, usually starting over the tongue and lips then spreading to the face and distal extremities. Other sensory deficits involving distal touch, vibration and position sense are also possible. In severe cases, there can be ataxia, dysphagia, flaccid paralysis and respiratory failure. Nerve conduction study (NCS) findings may be normal or show abnormalities resulting from the transient ion channel blockade, with resolution of abnormalities within two to three weeks. Laboratory testing for saxitoxin requires specialised expertise and is not readily available. The diagnosis is hence clinical and other diagnoses with similar presentations should be excluded. Food-borne botulism is distinguished by absence of sensory involvement, presence of cholinergic symptoms and a slower temporal onset. Acute inflammatory demyelinating polyneuropathy has neurophysiological abnormalities which persist for weeks, with positive anti-ganglioside antibodies and elevated CSF protein. Amnestic shellfish poisoning is distinguishable by prominent encephalopathy with severe memory loss, whilst neurotoxic shellfish poisoning causes neuroexcitatory effects rather than paralysis. Ciguatera has characteristic cold allodynia, whereas tetrodotoxin poisoning may feature fixed mydriatic pupils. Treatment is supportive. Recovery occurs between two days to two weeks, although prolonged symptoms lasting up to three months may occur. Most patients recover fully, however mortality is up to 10% and typically occurs within 12 hours of symptom onset. Conclusion: This case illustrates the importance of bedside clinical assessment in diagnosing saxitoxin poisoning – a rare syndrome with potentially serious neurological manifestations.

Miss Elena Karkkainen , Miss Jess Page, Miss Laura Simms, Mr. Aleks Carver, Ms. Dionne Moat, Dr. Robert Muni Lofra, Asst. Prof. Chiara Marini Bettolo Newcastle University - John Walton Muscular Dystrophy Research Centre, Newcastle Upon Tyne, United Kingdom Background: Adult SMA REACH a Re search and C linical H ub that established a collaborative clinical network in 2020 across 18 clinical sites in the UK, patient advocacy groups, regulators, and industry. It also established a longitudinal observational real-world data (RWD) collection study, collecting clinical data and outcome measures from adult SMA patients in the UK. SMA treatments Nusinersen and Risdiplam are available through Managed Access Agreements (MAA); Adult SMA REACH is responsible for capturing and reporting data to UK regulatory authorities to support their review of drug efficacy. The final data cuts for both MAA’s have now passed and Adult SMA REACH is in a position to grow; as a ready-made infrastructure to inform research questions in the UK, it is already currently supporting a number of initiatives. The aims of Adult SMA REACH are to better understand the natural history of adult SMA, evolving phenotypes and the impact of new therapies. Data is collected from clinical sites via a centralised online database. Using innovative data modelling techniques, we created an automated software for data validation, consistency checks, completeness analysis and treatment tracking. This allows us to continuously monitor evolving datasets, maximising the quality of collected data. Anonymised data can be provided to support research following submission of a data request which must receive approval from the steering committee. Methods: Data is collected from clinical sites via a centralised online database. Using innovative data modelling techniques, we created an automated software for data validation, consistency checks, completeness analysis and treatment tracking .This allows us to continuously monitor evolving datasets, maximising the quality of collected data. Anonymised data can be provided to support research following submission of a data request which must receive approval from the steering committee .Data request forms are available on request from the Adult SMA REACH team . Results: As of 10 /03 /2025, Adult SMA REACH contains data on more than 460 patients with more than 2200 visits entered .Of the total patients, 418 have provided consent for their data to be used in academic research . Visits entered have an average completeness of 87 %across mandatory data items . Conclusion: Data collected via Adult SMA REACH has supported research related to access to care; analysis of age at diagnosis, prevalence, and mortality; baseline characterisation of adults; and safety/efficacy analyses of available treatments. In addition to this, it is supporting the SMA Care UK initiative which aims to update and implement the Standards of Care for SMA patients. A pregnancy sub-study has also recently been established to characterise the effects of Nusinersen on pregnant women and the infants born to them. Adult SMA REACH is a valuable infrastructure to support SMA research, ultimately optimising patient care, advancing therapy approvals and broadening the understanding of the disease.

Prof. Bum Chun Suh 1 , Prof. Won Tae Yoon 1 , Prof. Sang-Beom Kim 2 1 Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of. 2 Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea, Republic of Background: Facial involuntary movements encompass a broad clinical spectrum, from brief twitching to sequelae of Bell’s palsy, hemifacial spasm, and blepharospasm. These phenomena may arise from peripheral nerve irritation, aberrant reinnervation, or central hyperexcitability. The blink reflex assesses the trigemino-facial pathway and may help clarify underlying mechanisms. This study evaluated the diagnostic contribution of extended blink reflex recordings in patients presenting with facial involuntary movements. Methods: We conducted a retrospective review of patients who underwent blink reflex testing between January 2024 and July 2025. Beyond the conventional zygomatic branch recording, additional electrodes were placed over the buccal and mentalis muscles to detect signs of abnormal reinnervation. Because these muscles do not typically respond to supraorbital stimulation, any elicited response was interpreted as hyperexcitability. Results: Eighty-eight patients (mean age 56.1 ± 14.8 years; 65.9% female) were included. Seven had a prior history of facial palsy (ipsilateral 3, contralateral 2, bilateral 2). Abnormal reflex activity was observed in the buccal muscle in 34.1% of patients (ipsilateral R1 33%, ipsilateral R2 31%, contralesional-stimulation R2 25%) and in the mentalis muscle in 30% (24/80). Facial nerve compressive lesions were identified on MRI in 7/79 patients (8.8%), all of whom demonstrated hyperexcitability on blink reflex testing. Conclusion: Extended blink reflex testing that includes buccal and mentalis recordings may serve as a valuable adjunct in assessing facial involuntary movements. Both additional muscle channels showed similar sensitivity in detecting aberrant reinnervation. Neuroimaging is recommended when hyperexcitable responses are present. Contralesional R2 responses, in particular, may indicate broader facial motor neuronal hyperexcitability rather than localized ephaptic transmission.

Dr. Matteo Azzimonti 1 , Dr. Francesca Magri 2 , Dr. Daniela Piga 1 , Dr. Guido Del Vecchio 3 , Dr. Marco Stroppi 3 , Assoc. Prof. Giorgio Conte 3 , Prof. Stefania Corti 2,4 , Assoc. Prof. Dario Ronchi 1,4 , Prof. Giacomo Pietro Comi 1,4 1 Neurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 2 Neuromuscular and Rare Diseases Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlino, Milan, Italy. 3 Neuroradiology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 4 Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy Background: Stroke-like lesions (SLLs) in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) show a non-random regional distribution across the brain, but the biological basis of this selective vulnerability remains unclear. Using a brain-wide transcriptomic–neuroimaging approach, we investigated how regional gene expression profiles relate to lesion susceptibility. Methods: Five patients with MELAS due to m.3243A>G mutations and availability of at least one MRI acquired during the acute phase of a stroke-like episode were enrolled. Acute SLLs were identified and segmented on FLAIR sequences, and binarized lesion masks were averaged across patients to generate a lesion probability map (LPM). Spatial cross-correlation between the LPM and the expression of 2,802 genes related to disorders of energy metabolism (Open Targets Platform, EFO: Orphanet_79200) was evaluated using the Allen Human Brain Atlas (AHBA) and the MENGA platform (p<0.001, R²≥0.15). Cell-type-specific expression was assessed using the Darmanis human brain transcriptome database. Results: Thirteen acute MRI scans from unique stroke-like episodes were analysed. The LPM showed a non-random spatial distribution of SLLs, with preferential involvement of occipital, parietal and temporo-polar regions. Higher lesion probability was associated with higher expression of SLBP (R²=0.725, p<0.001), a gene involved in histone mRNA processing and highly expressed in metabolically active tissues, suggesting that regions with higher intrinsic metabolic demand are more vulnerable to SLLs. In addition, higher expression of genes involved in neurovascular unit regulation, including SGCG (R²=0.667, p<0.001) and POSTN (R²=0.628, p<0.001), was associated with increased lesion probability, highlighting the role of mitochondrial microangiopathy in SLL pathogenesis. Conversely, lower expression of TMEM127 (R²=0.617, p<0.001), a negative regulator of mTOR and HIF-α signaling, characterized more vulnerable regions, suggesting that altered metabolic and hypoxic stress responses contribute to regional susceptibility. Conclusion: In MELAS, stroke-like lesions preferentially affect brain regions with higher metabolic activity, greater dependence on neurovascular unit integrity, and reduced capacity to respond to hypoxic stress. This imaging–transcriptomic approach provides a framework for identifying molecular mechanisms and potential therapeutic targets underlying stroke-like episodes in MELAS.

Prof. Kazuma Sugie 1,2,3 , Dr. Tomo Shiota 1 , Dr. Minako Yamaoka 1 , Dr. Ai Yamanaka 1 , Dr. Tomohito Ohashi 1 , Dr. Rui Shimazaki 1 , Dr. Yukako Nishimori 1 , Dr. Hitoki Nanaura 1 , Dr. Nobuyuki Eura 1 , Dr. Takao Kiriyama 1 , Prof. Eiichiro Mori 4 , Prof. Shuhei Nakamura 2,5 , Prof. Ichizo Nishino 3 1 Department of Neurology, Nara Medical University, Nara, Japan. 2 Center for Autophagy and Anti-Aging Research, Nara Medical University, Nara, Japan. 3 Department of Neuromuscular Research, National Institute of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan. 4 Department of Future Basic Medicine, Nara Medical University, Nara, Japan. 5 Department of Biochemistry, Nara Medical University, Nara, Japan Background: Danon disease is a rare X-linked dominant disorder characterized by vacuolar cardiomyopathy and skeletal myopathy, resulting from deficiency of lysosome-associated membrane protein-2 (LAMP-2). Although the disease is clinically severe, its epidemiological profile and genotype–phenotype correlations remain incompletely defined, particularly at the population level. Methods: To refine the national landscape of Danon disease in Japan, we expanded upon a nationwide questionnaire survey conducted in 2018, which had targeted 2,617 hospitals. Newly diagnosed and subsequently reported patients were incorporated into the present analysis. Comprehensive review of clinical records, muscle pathology, and molecular genetic testing of the LAMP2 gene was undertaken. Results: Since the previous survey, 13 additional patients (9 males and 4 females) from 9 unrelated families were identified, yielding a total cohort of 52 individuals (26 males and 26 females) from 29 families. Hypertrophic cardiomyopathy and electrocardiographic abnormalities were highly prevalent. Of the 23 deceased patients, 22 (96%) succumbed to either progressive heart failure or sudden cardiac death, underscoring the central role of cardiac involvement in disease prognosis. Heart transplantation, currently the only disease-modifying intervention, had been performed in two patients and was deemed urgently necessary in six others. Histopathological examination of skeletal muscle uniformly revealed autophagic vacuoles with sarcolemmal characteristics. Genetic analysis disclosed 23 distinct LAMP2 mutations across the 29 families, with approximately half of probands harboring de novo variants. Mutations were broadly distributed from exon 1 through exon 9; notably, three families carrying the exon 9B deletion mutation (c.1097_1098delAA), which selectively affects the LAMP-2B isoform, exhibited remarkably attenuated or absent cardiomyopathy. Conclusion: Cardiac involvement remains the principal determinant of survival in Danon disease, accounting for nearly all disease-related mortality. However, the strikingly benign clinical course associated with the exon 9B mutation indicates that disruption of the LAMP-2B isoform alone may confer a uniquely mild phenotype. These findings provide important insights into the molecular basis of phenotypic heterogeneity in Danon disease and have direct implications for prognosis and patient management.

Dr. Niklas Huntemann 1 , Dr. Axel Haarmann 2 , Prof. Heidrun H. Krämer 3 , Prof. Tim Hagenacker 4 , Dr. Tobias Hegelmaier 5 , Dr. Norma Krümmer 6 , Prof. Christiane Schneider-Gold 7 1 Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 2 University Hospital Würzburg, Würzburg, Germany. 3 Justus Liebig University of Giessen, Giessen, Germany. 4 Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany. 5 Hannover Medical School (MHH), Hannover, Germany. 6 Klinikum Altenburger Land, Altenburg, Germany. 7 St. Josef Hospital, Ruhr-University of Bochum, Bochum, Germany Background: Generalized myasthenia gravis (gMG) is an autoimmune disorder driven by pathogenic immunoglobulin G (IgG) autoantibodies that disrupt neuromuscular transmission, leading to fluctuating muscle weakness. Efgartigimod, a human Fc IgG1 fragment administered in individualized cyclic treatment courses, blocks the neonatal Fc receptor (FcRn) and accelerates IgG degradation, thereby lowering circulating pathogenic antibody levels. Given that prolonged exposure to pathogenic autoantibodies might amplify neuromuscular junction (NMJ) damage in gMG, prompt FcRn blockade provides a theoretically compelling approach to preserve NMJ integrity and translate into sustained clinical improvement. Real-world evidence on the efficacy and safety of initiating efgartigimod shortly after diagnosis remains limited, prompting the present investigation. This study assessed the clinical efficacy and safety of early treatment intensification with efgartigimod in gMG, defined as therapy initiation within 24 months of diagnosis. Methods: We conducted a retrospective, multicenter cohort study across seven German specialized MG centers and identified patients who received their first efgartigimod dose within the predefined 24-month period following diagnosis. Outcome measures comprised established MG scores as well as safety parameters. Data were collected retrospectively at baseline (BL) and at Months 1, 3, 6, and 12. Patients with at least two follow-up visits were included. Because individualized dosing cycles can cause fluctuations in the mentioned outcome parameters, the best response observed for each patient during follow-up was used for analysis. Results: Our cohort comprised 23 gMG patients with a mean latency from diagnosis to first efgartigimod administration of 10.6 months (SD ± 7.7 months). Early initiation of FcRn blockade in the disease course led to rapid and sustained therapeutic benefits; MG-Activities of Daily Living (MG-ADL) scores improved from 8.3 ± 4.3 to 3.4 ± 2.3 after 1 year, with a mean maximal individual reduction of −5.7 ± 3.3 points ( P < .001). By Month 12, mean Quantitative Myasthenia Gravis (QMG) score declined from 11.3 ± 6.0 to 3.2 ± 2.8 ( P = .0001). At the best individual follow-up visit, 87% of patients achieved a Patient Acceptable Symptom State according to QMG criteria (≤3 points; BL: 35%; P = .0007) and 45% with respect to the MG-ADL (≤2 points; BL: 5%; P = .0039). Clinically meaningful improvement occurred in 87% (QMG) and 73% (MG-ADL) of patients, while minimal symptom expression was achieved in nine (41%) patients. Consistent with these findings, quality of life increased substantially with MG Quality of Life-15 scores, declining from 32.4 ± 10.8 to 19.6 ± 14.0 ( P = .0002). Evidence of steroid sparing was demonstrated by a reduction in mean daily prednisolone doses from 25.5 ± 18.7 mg to 5.9 ± 3.8 mg ( P = .0005). Efgartigimod treatment was well tolerated, with no withdrawals and no emergence of new safety signals. An updated analysis will be presented at the congress. Conclusion: Early efgartigimod initiation in gMG was associated with rapid and durable clinical improvement and high responder rates, while substantially reducing corticosteroid dosage. This retrospective multicenter real-world analysis indicates that targeting pathogenic IgG via FcRn blockade early in the disease course can yield meaningful benefits, potentially preventing disease progression and structural NMJ damage.

Assoc. Prof. Alexander Grimm 1 , Dr. Katharina Kneer 2 , Dr. Helene Hurth 3 , Assoc. Prof. Martin Schuhmann 3 , Dr. Nathalie Winter 2 , Dr. Jan-Hendrik Stahl 2 1 University hospital of Neurology, Tübingen, Germany. 2 University hospital of Neurology, Tuebingen, Germany. 3 University hospital of Neurosurgery, Tuebingen, Germany Background: CIDP variants and neuralgic amyotrophy (NA) may present with similar symptoms that make differentiation difficult, i.e. focal palsies, sensory disturbances and pain. We therefore compared imaging tools, electrophysiology, disease course, and treatment response in treatment-naive and newly diagnosed patients suffering from either of these disorders. Methods: CIDP and NA with primary brachial plexus and arm nerve involvement were included in our study. All patients underwent CSF and blood analysis, MR neurography, high-resolution ultrasound (HRUS), and electrophysiological studies (EDx). HRUS was performed on the median, the ulnar, the radial nerve along its course, as well as from nerve roots C5 and C6. All patients were initially treated with steroids. Results: We included 22 patients (11 CIDP and 11 NA patients). MRI neurography of the brachial plexus was considered abnormal in 9 NA and 7 CIDP patients, whereas HRUS abnormalities could be differentiated in generalized and diffuse enlargements, seen in 11 NA patients, and focal enlargement, seen in 2 CIDP patients. Peripheral nerve enlargement affected proximal nerve segments in both patient groups equally, nerve enlargement in distal nerve segments was more often seen in CIDP patients, but did not statistical significance. Lumbal puncture was unremarkable in 11 patients (7 NA, 4 CIDP), proteinaemia was seen in 5 patients (2 NA, 3 CIDP) and pleocytosis in 2 patients, both with CIDP. The differences were not statistically significant. Surprisingly, in 8/10 focal variants of CIDP, EDx was not demyelinating but rather axonal. In NA, EDx was always predominantly axonal (p>0.05). 9/10 CIDP patients initially improved to repeated steroid pulse, however ongoing treatment switched to IVIG or others was needed in 8/10 patients. 7 out of 11 patients with relapsing-remitting NA did not sufficiently improve to repeated steroids in all affected nerve segments (p<0.001 compared to CIDP), constrictions and fascicular entwinements were found in all NA patients and were limited to this patient group. Conclusion: Differentiation between NA and focal CIDP variants remains clinically challenging. MRI and HRUS often show similar abnormalities, whereby a diffuse and generalized enlagement is more often seen in NA patient. Further, differentiation between both disease entities may be possible by identifying distal nerve enlargement or nerve constrictions in a relapsing treatement course.

Dr. Tanya Banerjee , Dr. Karthik Vinay Mahesh, Dr. Ritu Shree, Dr. Abeer Goel, Prof. Manish Modi Post Graduate Institute of Medical Education and Research, Chandigarh, India Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy with variable clinical, electrophysiological, and radiological manifestations. Nerve root hypertrophy has been described in CIDP but is typically mild to moderate. Marked or “giant” nerve root enlargement resembling plexiform neurofibromas is uncommon and may lead to diagnostic confusion. Severely raised cerebrospinal fluid (CSF) protein levels with pseudofroin’s syndrome and papilledema and secondary complications such as hydrocephalus are rarely reported in this context. Methods: We describe a case series of three patients presenting with relapsing or progressive sensorimotor lower motor neuron quadriparesis who fulfilled electrophysiological criteria for CIDP. All patients underwent detailed clinical evaluation, nerve conduction studies, CSF analysis, spinal magnetic resonance imaging (MRI), myeloma and inflammatory work-up to rule out secondary causes of CIDP, antibody testing for nodal and paranodal antibodies where available, and genetic testing to exclude hereditary neuropathies. Treatment responses and clinical outcomes were assessed following immunotherapy. Results: The case series comprised of two males and one female aged 49–55 years. None of them had diabetes mellitus. All three patients demonstrated marked enlargement of spinal nerve roots on MRI, involving cervical and/or lumbosacral regions, with appearances initially reported as plexiform neurofibromas in two of the cases. One patient additionally showed extensive involvement of intercostal and cranial nerves, including bilateral trigeminal and lower cranial nerves. CSF analysis revealed strikingly elevated protein levels in all patients (range 487–1116 mg/dL), with albuminocytological dissociation and features of pseudofroin’s syndrome, including papilledema. One patient developed communicating hydrocephalus with seizures and altered sensorium, which resolved solely after ventriculoperitoneal shunting combined with immunotherapy. Neurofascin-140 antibodies were positive in one patient, while antibody testing was negative or not performed in the remaining cases, highlighting immunological heterogeneity among the cases. Genetic testing, including whole exome sequencing where performed, did not support a hereditary neuropathy despite radiological mimicry. All patients showed clinically meaningful responses to immunotherapy, including corticosteroids, intravenous immunoglobulin, mycophenolate mofetil, rituximab, and cyclophosphamide, with improvement from severe disability to assisted or independent ambulation. Conclusion: This case series expands the recognized clinical and radiological spectrum of CIDP by highlighting extreme nerve root hypertrophy mimicking neurofibromatosis, severe CSF hyperproteinorrachia with pseudofroin’s syndrome, and extremely rare secondary complications such as hydrocephalus. Awareness of this presentation is critical to avoid misdiagnosis and delays in treatment. These findings underscore the importance of considering CIDP in patients with giant nerve root enlargement and reinforce the role of timely immunotherapy in preventing irreversible neurological morbidity.

Prof. Stefania Corti 1,2 , Dr. Andrea D' Angelo 1 , Dr. Francesca Beatrice 1 , Dr. Chiara Cordiglieri 3 , Dr. Matteo Miotto 4 , Prof. Simona Lodato 4,5 , Dr. Delia Gagliardi 2 , Prof. Giacomo Comi 1,2 , Dr. Federica Rizzo 2 , Prof. Linda Ottoboni 1,2 1 University of Milan, Milan, Italy. 2 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy. 3 INGM, Milan, Italy. 4 Humanitas University, Pieve Emanuele, Italy. 5 Humanitas Hospital, Rozzano, Italy Background: The advent of SMN-restoring treatments has fundamentally changed SMA prognosis, yet clinicians still face uncertainty regarding optimal intervention timing. A deeper grasp of how neurodegeneration unfolds temporally and when neurons remain responsive to therapy is crucial for improving patient outcomes. This study aims to delineate the temporal boundaries of therapeutic efficacy for SMN2-targeting compounds and to uncover novel disease mechanisms in spinal muscular atrophy (SMA) through patient-derived spinal cord organoid models. Methods: Three-dimensional spinal cord organoids were derived from iPSCs obtained from SMA patients, employing a scaffold-free differentiation approach. Spontaneous electrical activity and network coordination were assessed through multielectrode array (MEA) technology. Transcriptomic profiling via RNA sequencing captured gene expression dynamics at sequential differentiation stages. The risdiplam-like SMN2 splicing modifier RO7021707 was applied at distinct developmental timepoints to characterize the window of therapeutic responsiveness. Results: SMA organoids displayed marked electrophysiological abnormalities, with diminished spontaneous firing and impaired synchronous network activity relative to healthy controls. Transcriptomic analysis uncovered widespread suppression of genes encoding ciliary structures, including core architectural proteins and transition zone components. This finding points to an unexpected contribution of ciliary dysfunction to cellular signaling impairment and neuronal vulnerability in SMA. RO7021707 administration revealed a distinct pattern of temporal sensitivity: treatment at intermediate differentiation stages yielded maximal SMN protein recovery alongside normalization of network function. Intervention at early stages produced partial functional improvement, whereas treatment at advanced stages conferred limited benefit. These observations establish that a discrete developmental period determines therapeutic responsiveness, with treatment efficacy closely linked to restoration of ciliary gene expression and recovery of coordinated network activity. Conclusion: These data reveal ciliary pathway disruption as a previously unappreciated element of SMA pathophysiology and establish specific developmental windows during which therapeutic intervention achieves optimal effect. The clinical relevance extends to treatment timing decisions, while the identification of ciliary abnormalities opens new avenues for therapeutic development. This organoid-based platform offers valuable opportunities for individualized treatment strategies in SMA and related motor neuron disorders.

Dr. Bruno Graziosi , Dr. Enzo Pellacani, Dr. Thainá Louise Rodrigues, Dr. Ana Marina Silva, Dr. Alessandra Tolentino, Dr. Roseli Corazzini, Dr. David Feder, Dr. Alzira Carvalho Centro Universitário FMABC, Santo André, Brazil Background: Congenital myasthenic syndromes (CMS) comprise a heterogeneous group of inherited disorders caused by pathogenic variants affecting presynaptic, synaptic, or postsynaptic components of neuromuscular transmission. Among postsynaptic CMS, myasthenic plectinopathy has emerged as an underrecognized entity associated with variants in PLEC , which encodes plectin, a large cytolinker anchoring intermediate filaments to sarcolemmal and synaptic membrane complexes. Plectin displays marked pleiotropy, and pathogenic PLEC variants have been associated with two OMIM-defined disorders: epidermolysis bullosa simplex with muscular dystrophy (OMIM #226670) and limb-girdle muscular dystrophy type 2Q (OMIM #613723). Although traditionally regarded as distinct nosological entities, increasing evidence suggests that PLEC-related disease represents a pleiotropic neuromuscular spectrum rather than rigidly separated categories. Classic limb-girdle muscular dystrophy is characterized by progressive scapulopelvic weakness, hyperCKemia, and overt dystrophic changes on muscle biopsy. In contrast, patients with PLEC-related CMS may present with an identical limb-girdle–predominant pattern of weakness but normal creatine kinase levels and only subtle or nonspecific biopsy findings. In such cases, a congenital myasthenic syndrome phenotypically mimics muscular dystrophy. The present report illustrates this overlap and supports a unified pleiotropic model of PLEC-related disease. Methods: An 11-year-old boy had been followed since two years of age for recurrent lumbar-predominant myalgia, intermittent erythematous skin lesions, constipation, and mild dysphagia. Cutaneous symptoms partially improved with antihistamines and topical corticosteroids. At five years of age, he developed extensive bullous eruptions requiring hospitalization without identifiable triggers. Over time, he developed symmetrical proximal muscle weakness affecting the shoulder and pelvic girdles (MRC grade 4−), with relative preservation of distal and axial muscles. Examination revealed positive Gowers’ sign, waddling gait, lumbar hyperlordosis, toe walking, frequent falls, and difficulty running. Mild unilateral ptosis was present, without ophthalmoplegia. Repetitive nerve stimulation showed no decremental response. A comprehensive myopathy gene panel was unremarkable. Whole-genome sequencing identified two heterozygous PLEC variants of uncertain significance in compound heterozygosity. Muscle biopsy revealed minimal, nonspecific dystrophic changes, insufficient to support a primary muscular dystrophy diagnosis, supporting congenital myasthenic plectinopathy. Results: This case expands the phenotypic spectrum of PLEC-related CMS by highlighting a limb-girdle–predominant presentation with minimal electrophysiological abnormalities and subtle myasthenic features. To date, only two cases have been reported describing this specific phenotypic overlap with available muscle biopsy data, reinforcing the pleiotropic nature of PLEC-related disease rather than strictly segregated nosological entities. Conclusion: Although the identified variants were classified as variants of uncertain significance, the strong genotype–phenotype correlation, exclusion of alternative etiologies, and consistency with previously reported PLEC-related CMS presentations support their probable pathogenic relevance. Recognition of such atypical phenotypes is clinically important, as PLEC-related disease may benefit from targeted therapy and requires multidisciplinary management. Taken together, these observations support a conceptual shift in which PLEC-related disorders should be approached as a unified pleiotropic disease spectrum encompassing structural, dystrophic, and neuromuscular transmission phenotypes, rather than rigidly separated diagnostic entities defined solely by traditional OMIM classifications.

Prof. Birouk Nazha 1 , Prof. Bouhouche Ahmed 2 1 Neurophysiology department, Hospital of specialities, Ibn Sina University Hospital, Mohamed V University, Rabat, Morocco. 2 Laboratory of neurogenetics, Hospital of specialities, Ibn Sina University Hospital, Mohamed V University, Rabat, Morocco Background: The TPM2 gene, encodes beta-tropomyosin an important molecule for thin filaments in skeletal muscles. TPM2 mutations are related to severe congenital myopathies and distal arthrogryposis. Some TPM2 mutations are responsible of milder phenotypes with congenital contractures and moderate muscle deficit. Methods: We identified by, Exom sequencing, a TPM2 mutation, p.Lys7del (K7del), in 2 unrelated Moroccan families with congenital myopathy and a distinctive clinical phenotype with mostly large joint contractures during early childhood and very moderate skeletal muscle weakness. Results: Patient 1: 65 years old male experiencing since early childhood, running difficulties with severe and progressive feet equinovarus. Clinical examination showed large joint contractures (ankles, elbows, knees with rigid spine). He was needing 1 cane for walking 500 m with difficulties in climbing stairs and slight proximal upper limbs weakness. Patient 2: 10 years old female who had generalized congenital muscles contractures that was improved by kinesitherapy. She had normal milestones development. She had difficulties in running and climbing stairs and was able to walk unlimited distance. Her examination showed limitation in all large joints’ amplitudes with rigid spine and limited mouth opening. She was improved by kinesitherapy and was stable at 24 years. Her father had the same clinical presentation with stable signs overs years. Both patients had normal CK and myogenic recruitment pattern with normal nerve conduction at ENMG examination. They had the same heterozygous TPM2 p.Lys7del mutation leading to the diagnosis of autosomal dominant congenital myopathy 23. Conclusion: The TPM2 p.Lys7del (delK7) mutation leads to the loss of a highly conserved lysine residue near the N-terminus of b-tropomyosin. Mokbel et al. (2013) reported similar patients with large joint contractures as prominent clinical feature. Studies of patient muscle suggested that the mutant protein doesn't incorporate well into the thin filaments of muscle sarcomeres and likely accumulates in nemaline bodies in muscle fibers, a hallmark of nemaline myopathy. Muscle fibers become overly sensitive to calcium, leading to sustained contraction and joint stiffness. It is interesting to consider delK7 TPM2 mutation as possible diagnosis in patients with muscle stiffness and joint contractures.

Prof. Josef Finsterer neurology and neurophysiology center, vienna, Austria Background: Early-onset Leigh syndrome is usually a genetically and phenotypically heterogeneous, severe, rapidly progressive mitochondrial disorder with a fatal outcome. Leigh syndrome is genetically heterogeneous as it is based on mutations in mtDNA or nDNA genes, which mostly encode subunits of respiratory chain complexes or assembly factors. It is phenotypically heterogeneous because it is genetically heterogeneous and due to the peculiarities of mitochondrial genetics. One of the more than 100 mutated genes responsible for Leigh syndrome is NDUFV1. Here we present an infant with Leigh syndrome who suffers from a novel heterozygous variant of NDUFV1, which is phenotypically characterized by a number of previously unknown features. Methods: Case Report Results: The patient is a four-month-old girl with Leigh syndrome due to the compound heterozygous variants c.1162+4A>C (previously described, inherited from the mother) and c.1138G>C (novel, inherited from the father) in NDUFV1. The mutation c.1162+4A>C is a non-canonical splice site variant that has been demonstrated to result in loss of function. Bioinformatic analysis supports that the missense variant c. 1138G>C has a deleterious effect on protein structure or function. The mutations manifested phenotypically with typical cerebral lesions on imaging, developmental delay, cognitive decline, epileptiform discharges in the electroencephalography without seizures, AV block II, agenesis of a subclavian vein, right heart failure, patent foramen ovale, pulmonary hypertension, hypoaldosteronism and abdominal hernias. Within five weeks of hospitalization, the disease took a progressive course and the patient died of infectious complications despite maximum treatment. Conclusion: This case shows that the described new heterozygous variant in NDUFV1 can occur with previously undescribed phenotypic features. It is important to diagnose mitochondrial disorders due to NDUFV1 mutations early in order not to miss the time for appropriate symptomatic treatment

Dr. Julie Yue Yuan 1 , Dr. Veronica Pini 2,1 , Prof. Stefano Carlo Previtali 2,3 , Prof. Francesco Muntoni 1,4 1 Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 2 Neuromuscular Repair Unit, Institute of Experimental Neurology, Ospedale San Raffaele, Milan, Italy. 3 Vita-Salute Sanraffaele University, Milan, Italy. 4 NIHR Great Ormond Street Hospital Biomedical Research Centre, London, United Kingdom Background: LAMA2-related muscular dystrophy (LAMA2-RD) is a severe congenital neuromuscular disorder caused by mutations in the LAMA2 gene, resulting in absent or defective laminin-α2 and leading to progressive muscle weakness, fibrosis, and impaired regeneration. Disease severity correlates with residual laminin-α2 expression: patients with complete deficiency typically present with a homogeneous, severe phenotype and rarely achieve independent ambulation, whereas those with residual protein show more variable and often milder disease. We identified a patient with an atypically mild LAMA2-RD phenotype despite complete laminin-α2 deficiency, who remains ambulant at 36 years of age. This individual carries a previously unreported genomic variant in the muscle transcription factor MEF2A , located within a poorly characterised region of the protein. MEF2A plays a central role in myogenesis and muscle homeostasis, and preliminary transcriptomic data indicate altered expression of MEF2A-dependent genes in this patient. This study investigates how the MEF2A variant influences cellular and molecular features of LAMA2-RD and evaluates its potential role as a genetic modifier and therapeutic target. Methods: Primary fibroblast and myoblast were established from atypical and LAMA2-RD patients and healthy controls. MEF2A subcellular localisation was analysed by immunofluorescence. Myogenic differentiation capacity will be evaluated. Expression of predicted MEF2A interactors and target genes was analysed by qPCR, with proteomic profiling underway. Results: Immunofluorescence analyses showed preserved nuclear localisation of MEF2A in patient-derived fibroblasts, suggesting that the MEF2A variant does not impair nuclear trafficking. These findings indicate that altered disease severity is unlikely to result from MEF2A mislocalisation. Patient-derived cellular models have been successfully established, enabling ongoing analyses of myogenic capacity, proliferation, apoptosis, and gene expression. Preliminary molecular profiling supports the presence of altered MEF2A-dependent transcriptional programmes in the mild phenotype patient. Proteomic and transcriptomic studies are in progress to identify MEF2A-interacting partners and downstream pathways associated with the variant. Conclusion: A previously unreported genomic variant in MEF2A is associated with an atypically mild LAMA2-RD phenotype despite complete laminin-α2 deficiency. Preserved nuclear localisation of MEF2A suggests that altered transcriptional regulation, rather than mislocalisation, may underlie disease modification. Ongoing molecular aim to define MEF2A-dependent pathways that influence disease severity. These findings highlight MEF2A as a potential therapeutic target for modifying disease progression in LAMA2-related muscular dystrophy.

Assoc. Prof. Alexander Grimm , Dr. Helene Hurth, Assoc. Prof. Martin Schumann, Dr. Katharina Kneer, Assoc. Prof. Jonas Kolbenschlag, Dr. Johannes Heinzel, Dr. Jan-Hendrik Stahl, Ms. Alexandra Hermes, Ms. Julia Wittlinger, Dr. Natalie Winter University hospital of Neurology, Tübingen, Germany Background: Neuralgic amyotrophy is a rare, but certainly underrecognized peripheral nerve disorder, mostly affecting the upper trunk of the brachial plexus, typically arising with severe shoulder pain followed by pareses of distinct muscles. We analyzed patients of our hospital presenting in the years 2022 to 2024. Methods: Patients were screened clinically, electrophysiologically and by ultrasound or MRI. Most patients - depending on time of presentation - received high dosage steroids, sometimes repeated and all of them received follow-up analyses. In some patients neurosurgical steps were needed Results: Results -1: 100 patients (7:3 male) have been included. 10% without severe pain. 92% received steroids (mostly 0,5g/die for 3 days). 5 persons had a relapsing remitting course with more than 3 episodes (no SEPT9 or PMP 22 mutation found). 81% of patients received nerve conduction studies (75% of these showed axonal damage including SNAP reduction), 80% PSA in the EMG. Overall 64% received MRI and ultrasound , 97% revealed nerve swelling of the plexus and of several peripheral nerves (i.e. n=34 supraclavicular and axillary nerve, n=27 AIN , rarer ones were the PIN, the long thoracic and others). 15 patients did not improve with treatment and showed nerve constriction and entwinement in 24 nerves (i .e. n=10 AIN fascicle, n=3 SSC ). After surgery paresis improved in 21/24 nerves Conclusion: NA is a mostly painful acquired, probably autoimmune inflammation of the epineurium, particularly affecting the upper trunk, i.e. the SSC or the lower trunk, AIN fascicle. In about 15% of cases scar tissue building leads to nerve constriction and surgery is needed, which then improves symptoms mostly. Ultrasound helps in depicting nerve pthology in the beginning and nerve constriction in refractory disaease

Prof. Senda Ajroud Driss Northwestern Univeristy, Chicago, United States Background: US patient organizations have made transformative contributions to neuromuscular disease research, therapy development, and clinical care over the past 20 years, fundamentally reshaping the landscape from basic research through FDA approval and clinical implementation. US patients’ organizations have been active on many fronts, they interact with legislators to change policies that directly affect neuromuscular patients, they engage with the FDA, they fund research and clinical infrastructure and play a role in care standardization and access to care not just locally but also globally. During the presentation, I will review the history of patients and patients’ organizations in the US their direct role in fundamentally changing the way we care for our patients and how they propelled us in the era of genetic therapies and precision medicine

Assoc. Prof. Edmar Zanoteli FMUSP, São Paulo, Brazil Background: Patients with autosomal inherited limb-girdle muscular dystrophies (LGMD) present with similar clinical and histological findings, with weakness predominating in the proximal portions of the limbs. Currently, at least 34 subtypes based on protein deficiency and genetic defect are included in its classification. Some of the most common forms of the disease are caused by common pathogenic mechanisms, including sarcolemmal glycoprotein deficiency (e.g. sarcoglycan complex), defects in the extracellular matrix (e.g. collagen 6, merosin, α-dystroglycan hypoglycosylation), sarcomere remodeling dysfunction (e,g, calpain-3), and sarcolemmal repair defects (e.g. dysferlin, anoctamin-5), among others. More recently, new disease mechanisms have been associated with LGMD phenotype. For example, different genes related to the Notch signaling pathway, known to maintain the quiescence of muscle stem cells, have been recognized as being associated with both congenital myopathy ( MEGF10 ) and LGMD ( POGLUT1, JAG2 ). Genes involved in RNA splicing or transport of small nuclear ribonucleoproteins (snRNPs) ( SNUPN ) have also been associated with LGMD phenotype. Patients with LGMD phenotype and pathogenic variants in HMGCR , which is related to mevalonate pathway, were recently described. Finally, variants in POPDC genes ( POPDC1 and POPDC3 ) that possess the evolutionarily conserved Popeye domain and are associated with protein traffic have been identified in patients with LGMD phenotype. In addition to improving the genetic diagnosis and phenotypic characterization of patients with muscular dystrophy, the identification and characterization of new pathophysiological mechanisms of LGMD may pave the way for treatments based on pathways that have therapeutic effects for multiple subtypes of the disease.

Dr. Asif Paker 1 , Dr. Shahram Attarian 2 , Dr. Hans-Peter Hartung 3,4,5,6 , Dr. Yi Lu 7 , Dr. Miguel Alonso-Alonso 1 1 Sanofi R&D, Neurology Development, Cambridge, MA, United States. 2 Neuromuscular Disease and ALS Reference Center, Timone University Hospital, Aix-Marseille University, CHU Timone, Marseille Cedex 05, France. 3 Department of Neurology, Faculty of Medicine, Heinrich-Heine-University, Düsseldorf, Germany. 4 Brain and Mind Center, University of Sydney, Sydney, NSW, Australia. 5 Department of Neurology, Medical University of Vienna, Vienna, Austria. 6 Department of Neurology, Palacky University Olomouc, Olomouc, Czechia. 7 Sanofi R&D, Evidence Generation and Decision Science, Cambridge, MA, United States Background: People living with chronic inflammatory demyelinating polyradiculoneuropathy(CIDP) experience fatigue, weakness and sensory abnormalities, affecting quality-of-life(QoL). Riliprubart, a first-in-class, humanized, IgG4-monoclonal antibody, selectively inhibits activated-C1s within the classical complement pathway and is self-administered subcutaneously via auto-injector. A Phase-2 trial( NCT04658472 ) evaluating riliprubart in CIDP demonstrated decreased fatigue-severity and improved QoL at week-48. Here we assess effect of riliprubart on fatigue, pain and QoL up to week-76. Methods: Open-label trial evaluating riliprubart across three groups: Standard-of-Care(SoC)-Treated(N=48), SoC-Refractory(N=18), and SoC-Naïve(N=12). Participants underwent 24-week treatment(Part-A), followed by optional treatment-extension(Part-B:52-weeks). At week-76, changes from baseline in health-related QoL were descriptively analyzed using EuroQol-Visual Analogue Scale(EQ-VAS; range 0-100, higher score indicate better outcomes) and health utility index value(range <0[as bad or worse than dead] to 1[full-health]), pain through EQ-5D-5L Dimension(range 1[no pain/discomfort] to 5[extreme pain/discomfort]), and fatigue using Modified Rasch-built Fatigue Severity Scale(R-FSS; range: 0-21, higher score indicate greater fatigue-severity). Results: At week-76, QoL, pain and fatigue were assessed in 37 SoC-Treated, 11 SoC-Refractory and 6 SoC-Naïve participants. Mean[SD] change from baseline in EQ-VAS(SoC-Treated:12.1[18.4], SoC-Refractory:19.1[21.8], SoC-Naïve:8.5[16.2]) and health utility index value(SoC-Treated:0.18[0.28], SoC-Refractory:0.21[0.18], SoC-Naïve:0.05[0.22]) suggested QoL improvement across all groups. Higher proportion reported no pain versus baseline(SoC-Treated:27.0%[10/37] vs 12.8%[6/47], SoC-Refractory:45.5%[5/11] vs 16.7%[3/18], SoC-Naïve:33.3%[2/6] vs 16.7%[2/12]). Mean[SD] R-FSS changes indicated reduced fatigue across SoC-Treated(-3.7[7.6]), SoC-Refractory(-2.2[9.5]), and SoC-Naïve(-3.3[4.2]) groups. Conclusion: Riliprubart indicated sustained decrease in fatigue and pain, and improved QoL in people with CIDP, along with clinical improvement. Two randomized, placebo-controlled Phase-3 studies(MOBILIZE, VITALIZE) are ongoing to confirm these findings.

Dr. Tara Hamilton , Dr. Orna O'Toole Cork University Hospital, Cork, Ireland Background: Poems is a rare condition. The prevalence is estimated to be approximately 0.3 cases per 100’000 people. It often can be difficult to diagnose and it is easily missed given the multiple different signs/symptoms that it can present with. Methods: We had a case of a 49 year old female who presented with abdominal distension and discomfort. She then represented with hypertension. She had a medical background of depression, Castleman's syndrome and right parotid gland resection in 2021 for pleomorphic adenoma. She has no family history of malignancy or hereditary neuropathies. She had a CTTAP as part of her investigations which revealed low level para aortic adenopathy and mild splenomegaly. Her serum protein electrophoresis showed an IgA lambda monoclonal band in the beta region. She had a bone marrow biopsy done which showed increased plasma cells in the lymphoid cluster. CD56 positivity was appreciated. In situ hybridization for kappa and lambda showed light restriction with dominant lambda positivity. Overall these features were consistent with a plasma cell neoplasm which appears to involve ∼10% of the overall marrow cellularity. VEGF levels then came back raised at 6975. She was started on daratumumab, lenalidomide and dexamethasone for her plasma cell dyscrasia. She then developed new sensory symptoms involving reduced sensation in her fingers and then her toes as well as a deeper muscle ache in both calves. Her neurological exam found reduced sensation in all modalities in upper limbs to the level of her metacarpophalangeal joint and in her lower limbs with slight asymmetry extending higher to the knee on the right versus mid-calf on the left. Her power was preserved, as were her reflexes. Her gait exam was normal. She had visible acrocyanosis in her fingers and toes. Results: She had nerve conduction studies done which showed evidence of a mixed neuropathy with demyelinating neuropathy. This along with her clinical picture of splenomegaly, Castleman's syndrome, elevated VEGF levels, acrocyanosis and an IgA lambda paraprotein supported a diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes). Her sensory symptoms were not bothersome enough to warrant medications. She is currently awaiting an autologous stem cell transplant. Conclusion: This case is a good example of how much work it takes and multiple disciplines are needed to help diagnose this POEMS syndrome. This patient had input from hematology, endocrinopathy, neurology and neurophysiology. The diagnostic criteria include major and minor criteria with mononeuropathy and monoclonal plasma cell proliferative disorder being mandatory criteria. These findings should prompt you to look for the other possible features of POEMS. The pathophysiology of POEMS is not fully understood. Treatment focuses on managing the monoclonal plasma cell proliferative disorder as was the case with our patient.

Ms. Lauren Roberts 1,2 , Dr. Gina Trakman 2 , Dr. Kate Furness 2 , Ms. Emily Farrugia 1,2 1 Northern Health, Melbourne, Australia. 2 La Trobe University, Melbourne, Australia Background: In contrast to Motor Neurone Disease, for which evidence-based guidelines exist, evidence regarding the risks and benefits of gastrostomy insertion and use in progressive neurological diseases, excluding Motor Neurone Disease, is lacking. As a result, gastrostomy decision‐making discussions can arise as a matter of debate amongst clinicians working in the field of neurology. This review aimed to synthesise current evidence on the effects of gastrostomy in Parkinson's disease and parkinsonism, Multiple Sclerosis and Huntington's disease. Methods: Three databases (Web of Science, Ovid Medline and Embase) were searched for research on the impacts of gastrostomy, including survival, complication rates, and nutrition changes, in adults with progressive neurological diseases, excluding Motor Neurone Disease. Quality was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist: Primary Research, and a narrative synthesis was conducted. Results: Twelve (n = 12) studies were eligible for inclusion, with either retrospective cohort (n = 12) or cross‐sectional (n=1) design, examining the effects of percutaneous endoscopic gastrostomy (PEG) (n = 8), radiologically inserted gastrostomy (RIG) (n = 1), or gastrostomy not further defined (n = 4) in adults with Parkinson’s (n = 6), parkinsonism (n = 3), Multiple Sclerosis (n = 3), or Huntington’s Disease (n = 3). There was variability in outcomes and comparators with inconclusive results. Quality was assessed as positive (n = 3) or neutral (n = 9). Survival post‐gastrostomy insertion ranged from 13.8 to 31.3 months, and in some cases, appeared to be improved by the presence of gastrostomy. Gastrostomy insertion in patients with progressive neurological disease appears to increase health service utilisation and is associated with varying rates of major and minor associated complications. Nutrition‐related outcomes were scarcely reported and did not reflect the potential meaningful impact on the population of interest. Conclusion: Gastrostomy appears to improve survival in the population cohort, however, the quality of data on this is limited. The review identified an association between gastrostomy and reduced likelihood of discharge home in the population of interest. Gastrostomy appears to be associated with low levels of major complications in the cohort of interest, and varying levels of minor complications. Patients with Huntington’s Disease appear to be at higher risk of dislodgements and tube site infections, potentially due to increased choreiform movements challenging tube-related use and care. The review highlights the need for further, high quality, research to determine the benefits of gastrostomy on well‐defined nutrition‐related outcomes and survival in this patient cohort, as well as the prevalence of relevant gastrostomy‐related complications. In practice, it is hoped this review will provide support to decision‐making practices regarding gastrostomy insertion in this patient cohort.

Dr. Guido Primiano 1 , Assoc. Prof. Domenico Plantone 2 , Dr. Delia Righi 2 , Dr. Angela Romano 1 , Dr. Luca Leonardi 3 , Dr. Valeria Guglielmino 4 , Dr. Francesca Forcina 3 , Asst. Prof. Marco Ceccanti 5 , Assoc. Prof. Maurizio Inghilleri 5 , Prof. Fiore Manganelli 6 , Asst. Prof. Stefano Tozza 6 , Dr. Maria Ausilia Sciarrone 4 , Dr. Francesca Vitali 4 , Dr. Andrea Sabino 4 , Dr. Carlo Manco 2 , Dr. Angela Stufano 7 , Dr. Maria Laura Stromillo 2 , Prof. Nicola De Stefano 2 , Prof. Paolo Calabresi 4 , Asst. Prof. Marco Luigetti 4 1 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy . 2 University of Siena, Siena, Italy . 3 Sant’Andrea Hospital, Rome, Italy . 4 Università Cattolica del Sacro Cuore, Rome, Italy . 5 Sapienza Università Di Roma, Rome, Italy . 6 University of Naples ‘Federico II’, Naples, Italy . 7 University of Bari Aldo Moro, Bari, Italy Background: Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a rare, progressive, and fatal multisystemic disease caused by pathogenic variants in the TTR gene. Peripherin, a type III intermediate filament protein predominantly expressed in the peripheral nervous system (PNS), has recently emerged as a promising biomarker for axonal damage in peripheral neuropathies. This study aims to investigate serum peripherin levels in symptomatic and presymptomatic ATTRv subjects, alongside serum neurofilament light chain (sNfL) levels, and to examine their correlations with disease progression and severity. Methods: This multicenter, cross-sectional cohort study included 96 individuals with TTR gene variants (49 presymptomatic and 47 symptomatic ATTRv subjects) and 42 healthy controls (HCs). Serum peripherin levels were measured using a highly sensitive homebrew immunoassay developed on the Simoa SR-X platform, whereas sNfL levels were determined using a commercially available Simoa Neurology 2-Plex B assay. Statistical analyses included non-parametric Spearman correlations, Kruskal-Wallis ANOVA, ANCOVA, and binomial logistic regression. Results: Serum peripherin levels were significantly elevated in both presymptomatic (p < 0.001) and symptomatic ATTRv groups (p < 0.001) compared to HCs, with no significant difference between the presymptomatic and symptomatic groups. Peripherin levels did not correlate with age, sNfL levels, or clinical severity (NIS scores), but showed a strong discriminative ability between ATTRv and HCs (AUC = 0.83, sensitivity = 76%, specificity = 76%, p < 0.001). Conclusion: This study demonstrates that serum peripherin represents a promising biomarker for early detection of PNS damage in ATTRv, with elevated levels detectable even in presymptomatic stages.

Dr. Kang-Yang Jih , Prof. Yi-Chung Lee Taipei Veterans General Hospital, Taipei, Taiwan Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with significant but incompletely explained heritability. Short tandem repeat (STR) expansions, established as disease mechanisms in other neurodegenerative conditions, are increasingly recognized as contributors to ALS risk and disease severity modifying factors. This study aims to investigate the role of common STRs in ALS pathogenesis. Methods: We investigated ten STRs ( C9ORF72, ATXN1, ATXN2, ATXN8/ATXN8OS, TBP, HTT, NOTCH2NLC, DMPK, CNBP and FMR1 ) associated with common neurological disease among 730 Taiwanese ALS patients and 1,173 controls by PCR and fragment analysis. Detail clinical information of these patients was collected. We analyzed the effect of STRs on ALS risk, survival and disease progression. Results: STR expansions were identified in 12.7% of all ALS patients (Figure, upper). Pathogenic C9ORF72 expansions were most frequent STR among ALS patients (4.2%). High risk alleles of ATXN2 , ATXN8/ATXN8OS and TBP , defining as repeat number greater than 32, 79 and 43, respectively, are significantly enriched in ALS patients over controls. In addition, ATXN1  expansions were the second most prevalent one and its pathogenicity is associated with a risk allele of UNC13A SNP, rs12608932. STR expansions, particularly in ATXN2 and ATXN8/ATXN8OS , correlated with accelerated functional decline and significantly reduced survival (Figure, lower), suggesting STR expansions are disease modifiers of ALS. Conclusion: STR expansions in neurodegeneration-associated genes are important ALS risk and disease modifiers. The pathogenicity of STRs is likely modulated in an oligogenic basis. Recognizing the roles of STR enhances understanding of ALS genetic architecture and guides future interventions.

Dr. Giulio Gadaleta , Dr. Giulia Maccarrone, Dr. Guido Urbano, Dr. Enrica Rolle, Dr. Eleonora Leopizzi, Dr. Silvia Boschi, Dr. Liliana Vercelli, Assoc. Prof. Tiziana Mongini Neuromuscular Unit, Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by the absence of dystrophin, leading to progressive muscle degeneration with respiratory and cardiac involvement. Despite its monogenic origin, DMD shows inter-individual variability, only partially explained by the primary dystrophin mutation. Disease progression is influenced by additional modifiers, including care-related factors and genetic modifiers that remain incompletely characterized. Methods: Longitudinal neuromuscular, cardiac, and respiratory evaluations were collected, together with genetic analyses results. Results: We report the case of a 23-year-old young adult with DMD, diagnosed prenatally due to a positive maternal family history with classic clinical course, confirming an exon 45 deletion of the DMD gene. Early development showed mild global motor and language delay, with independent ambulation achieved at 24 months, together with osteo-articular dysplasia. Daily deflazacort was initiated at 4 years of age and continuously maintained, with dosage adjusted according to body weight. Independent ambulation was preserved until 23 years of age, markedly later than expected in classical DMD. Longitudinal motor assessments showed an overall slow functional decline, including a well-preserved upper limb performance even after loss of ambulation. From a cardiac standpoint, echocardiography revealed a bicuspid aortic valve associated with hypoplasia of the tricuspid valve and right ventricle after birth, without hemodynamic compromise. Left ventricular systolic function remained preserved over time (ejection fraction 58% at 23 years), under ACE inhibitor (started at 11 yo) and beta-blocker therapy (started at 20 yo). Respiratory involvement progressed slowly, requiring nocturnal non-invasive ventilation only at 23 years, without dysphagia. Given the atypical features and disease course, next-generation sequencing using a targeted panel for skeletal malformative disorders (>300 genes) was performed. This identified a heterozygous loss-of-function likely pathogenic variant in SMAD6 (c.1084C>T; p.Gln362*), segregating with bicuspid aortic valve disease in the patient’s father, and a de novo variant of uncertain significance in SETD5 , potentially accounting for neurodevelopmental and osteo-dysmorphisms. SMAD6 encodes an inhibitory SMAD that negatively regulates bone morphogenetic protein (BMP) signaling, a pathway involved in myogenesis, maintenance of the muscle satellite cell pool, and antagonism of transforming growth factor beta (TGF-β)–mediated fibro-adipogenic activation and extracellular matrix deposition. Nonetheless, BMP signaling exerts context- and dose-dependent effects in dystrophic muscle, as demonstrated in mdx models. Another example, instead, comes from murine LMNA −/− H2K myoblast models, in which SMAD6 overexpression inhibits satellite cell pool expansion, whereas SMAD6 inactivation restores BMP responsiveness without inducing premature or inefficient myogenic differentiation. These data may indicate that SMAD6 plays a central role in regulating the balance between satellite cell maintenance, differentiation, and regeneration. In this patient, SMAD6 heterozygous loss-of-function could therefore contribute to a milder neuromuscular phenotype by favoring timely muscle regeneration, preventing premature satellite cell exhaustion, and limiting TGF-β–mediated fibrosis. Conclusion: This case supports the concept that additional genetic factors may modulate DMD severity. SMAD6 partial loss-of-function emerges as a plausible disease modifier and therapeutic target, although its pleiotropic role—particularly in cardiovascular development—warrants caution. Further studies are needed to validate its modifier effect in preclinical DMD models.

Dr. Sally Spendiff CHEO Research Institute, Ottawa, Canada Background: Congenital myasthenic syndromes (CMS) are rare inherited disorders of the neuromuscular junction (NMJ) caused by mutations in one of more than 35 genes. These defects impair neuromuscular signalling through diverse molecular mechanisms. CMS typically presents with fatigable weakness, and in severe cases, life threatening respiratory crisis. Treatment outcomes vary widely by genetic subtype. Acetylcholinesterase inhibitors (AChEi) are first line treatments for many forms but have limitations, including short half-life, muscarinic side effects, and variable efficacy. They may worsen symptoms in common subtypes such as COLQ - and DOK7 -CMS. Recent advances have identified promising mechanistic directed therapies. MuSK agonist antibodies show strong benefit in DOK7 -CMS mice models by restoring MuSK phosphorylation, NMJ morphology, and motor performance. These findings suggest potential use in additional CMS forms involving defects in AGRIN-LRP4-MuSK signaling or in proteins that interact with the pathway. In parallel, chloride channel (ClC-1) inhibitors, which enhance muscle excitability, have produced functional gains in NMD models and early human studies. Methods: MuSK agonist antibody experiments used differentiated mouse or human myotubes to measure MuSK phosphorylation, acetylcholine receptor (AChR) clustering, and downstream signalling activation. In vivo experiments assed therapeutic benefit in mouse models with Dok7 , Agrn , or ColQ mutations. Outcomes included survival, body weight, motor performance, and NMJ morphology and function. Studies of ClC‑1 chloride channel inhibitors used a combination of electrophysiology, pharmacokinetics, and functional testing. Motor performance was evaluated using grip strength, hindlimb suspension, inverted screen assays, and measures of fatigability. Electrophysiological approaches such as repetitive nerve stimulation were used to assess neuromuscular transmission. Tissues were collected for histological and biochemical analyses, including fibre-type immunolabelling, quantification of fibre size distributions, and measurement of protein expression. Results: Both strategies demonstrated measurable improvements in NMJ function, motor performance, and survival of mutant mice. MuSK agonist antibodies consistently restored AGRIN-LRP4-MuSK signalling, increasing MuSK phosphorylation, and AChR clustering in Dok7 - and Agrn -CMS models. Treatment produced robust gains in body weight, grip strength, and fatigue resistance, with some models showing full rescue of survival. However, therapeutic response was gene-dependent, with no benefit observed ColQ -CMS models. ClC-1 inhibitors also yielded encouraging results, increasing muscle excitability, grip force, and overall motor endurance. Treatment was associated with enlarged muscle fibre size, improved neuromuscular transmission, and partial correction of aberrant fibre-type composition. Conclusion: Together, these results demonstrate opportunities to improve neuromuscular transmission across multiple forms of CMS, highlighting the therapeutic promise of pathway targeted interventions. They also underscore the importance of matching treatment strategy to genetic subtype. As both mechanistic understanding and therapeutic toolkits expand, the future of CMS care appears increasingly precise, personalised, and hopeful.

Dr. Zoltan Zsigmond Major 1,2 , Dr. Cristina Pamfil 3 , Dr. Elisabeta Candrea 4 , Mrs Kinga Andrea Major 5 , Dr. Ioana Crisan 6 1 National Center for Spinal Disorders, Budapest, Hungary. 2 Municipal Clinical Hospital, Neurology Department, Cluj-Napoca, Romania. 3 Cluj County Clinical Emergency Hospital, Rheumatology Department, Cluj-Napoca, Romania. 4 Cluj County Clinical Emergency Hospital, Dermatology Department, Cluj-Napoca, Romania. 5 Nexus Medical Association, Cluj-Napoca, Romania. 6 Municipal Clinical Hospital, Allergology Department, Cluj-Napoca, Romania Background: When a patient is seen with a solid, bilateral, persistent facial and eyelid edema accompanied with erythema, without definite muscle involvement, the is determined to think about rather rare diagnostic directions. Morbihan disease might be an option, at least when only signs are considered, but other diseases might also be unusual, but feasible options. One of these is amyopathic dermatomyositis. Methods: We report a case of chronic persistent solid edema of the eyelids and face, developed gradually since 2018, with a weak response to the various applied treatments. The patient has mild associated morbidities: diabetes mellitus type II, controlled by diet to this point, with a mild axonal sensory polyneuropathy, dorsal and lumbar polysegmental discopathy and was operated for gallbladder lytiasis. Besides swelling and erythema of the eyelids and face, the patient reports time-to-time associates paraesthesia of the lower limbs and muscular pain, without significant electrophysiological changes, and no elevated CK levels. Imagery reveals no particular feature for atrophy or swelling of scheletal muscle, the only pathological change is related to the swelling of the soft tissues of the upper face, although local tissue biopsy reveals lymphocitic infiltrate resembling features of dermatomyositis rather than other pathology. Muscle biopsy was not characteristic. Laboratory reveals mildly increased circulating immune complexes, hypercholesterolemia, and transient positivity in the myositis profile for dermatomyositis, with a mediocre response to the common immune-suppressive drugs, but also with only a partial response to isotretinoin treatment. Results: At this point, taking into account the responses also to the applied treatments, we consider that the above presented features are at least partially supporting the diagnosis of amyopathic dermatomyositis, although Morbihan disease remains a strong second option, and other diseases are also there as possibilities, several evaluations are still undergoing. Conclusion: The case proves to be a diagnostic challenge, to this point without a definite diagnosis, an ongoing struggle towards a final diagnosis and proper treatment options. We are further investigating the case, along with concomitant, diverse treatment options

Dr. Jeffrey Statland 1 , Dr. Nicholas Johnson 2 , Dr. John Vissing 3 , Dr. Ryan Frieler 4 , Dr. Guochen Song 4 , Dr. Jing Marantz 4 , Dr. Tina Duong 5 , Dr. Leslie Nelson 6 , Dr. John Staropoli 4 1 Department of Neurology, The University of Kansas Medical Center, Kansas City, United States. 2 Department of Neuology, Virginia Commonwealth University School of Medicine, Richmond, United States. 3 Department of Neurology, Copenhagen Neuromuscular Center, Copenhagen, Denmark. 4 Scholar Rock, Inc., Cambridge, United States. 5 Departments of Neurology and Clinical Neurosciences, Stanford University, Palo Alto, United States. 6 Department of Physical Therapy, University of Texas Southwestern Medical Center, Dallas, United States Background: Facioscapulohumeral muscular dystrophy (FSHD) is a progressively debilitating disease characterized by progressive, facial muscle weakness that spreads to the shoulders and lower limbs. Patients with later adult-onset FSHD often present with progressive muscle weakness, accompanied by a loss of strength and function. The progressive nature of this disease presents an opportunity for therapeutic intervention with a muscle-targeted treatment to build muscle and potentially improve strength and motor function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits activation of myostatin, a negative regulator of muscle growth, leading to increased muscle mass and improved motor function. In previous clinical studies for spinal muscular atrophy (Phase 2 TOPAZ, NCT03921528 ; Phase 3 SAPPHIRE, NCT05156320 ), the muscle-targeted treatment led to clinically meaningful and statistically significant improvements in motor function and was well tolerated across a broad range of patients who were also receiving a survival motor neuron-targeted treatment (nusinersen or risdiplam). Recent preclinical studies also showed that the murine analog of apitegromab (muSRK-015) significantly increased skeletal muscle mass, muscle force, and endurance in a FLExD murine model of FSHD. Methods: FORGE, a Phase 2, randomized, double-blind, placebo-controlled, multicenter study, will assess the efficacy, pharmacokinetics, pharmacodynamics, safety, and tolerability of apitegromab in patients with FSHD. Results: Approximately 60 ambulatory adult patients (aged 18-60 years) will be recruited to participate in the FORGE study. Patients with genetically confirmed FSHD (FSHD1 or FSHD2), a clinical severity score of 1.5-3.0 (Ricci score, range 0 to 5), and baseline 10MWRT time ≤5 seconds will be eligible for enrollment. Individuals with any medical condition, clinically significant laboratory result, or ECG value that may compromise safety, interfere with study compliance, or confound the interpretation of the results, are ineligible for the study. Exclusion criteria also include a history of hypersensitivity reactions to monoclonal antibodies or recombinant proteins, any acute or comorbid condition interfering with the well-being of the participant within 7 days prior to screening, and previous exposure to apitegromab. Eligible patients will be randomized to receive either apitegromab 10 mg/kg monotherapy or placebo by intravenous infusion every 4 weeks. The FORGE study will include a screening period of up to 4 weeks, a 52-week treatment period (13 doses), and a 20-week safety follow-up period for patients opting to not enter the open-label extension study. The primary endpoint will be percent change from baseline in total lean muscle volume by a full body MRI at week 52 of the study. Conclusion: Supported by the pivotal outcomes from previous clinical and preclinical work, the FORGE study will investigate apitegromab, an investigational muscle-targeted treatment, in the adult FSHD patient population. FORGE is expected to be conducted across 20 sites in North America and Europe.

Dr. Dalisha Dalisha National Hospital Of Neurology and Neurosurgery, London, United Kingdom Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with limited therapeutic options. Participation in clinical trials offers patients access to experimental treatments, close clinical monitoring, and often renewed hope. However, when trials fail to meet endpoints or are terminated early, patients frequently experience an abrupt loss of support, with minimal structured follow up or guidance. This transition can negatively impact well being, yet it remains underexplored in ALS research. Patients returning to routine care after trial completion often lose access to multidisciplinary teams, regular monitoring, and communication with research staff. Trial failure can lead to emotional distress, feelings of abandonment, and declining quality of life. Caregivers experience heightened burden and uncertainty regarding future care. While informed consent addresses risks and potential lack of efficacy, it rarely prepares participants for the emotional and practical consequences of trial discontinuation. The absence of standardized post trial support highlights a gap between research obligations and patient centered care. Ethical research practice requires proactive planning for continuity of care beyond trial endpoints. Methods: Proposing a prospective, pilot study to evaluate the feasibility, acceptability, and potential impact of a structured post-trial support program for ALS clinical trial participants. Adult patients approaching trial completion or experiencing early termination, along with their caregivers, will be invited to participate. The intervention consists of a standardized post trial transition program initiated near trial completion and extending for six months. Core components include: 1. Structured end-of-trial consultations with research and clinical staff to communicate trial outcomes, manage expectations, and outline next steps. 2. Reintegration into multidisciplinary ALS clinic care. 3. Referral to psychological, social work, and palliative care support as indicated. 4. Written and verbal guidance regarding symptom management and potential future research opportunities. 1. Structured end-of-trial consultations with research and clinical staff to communicate trial outcomes, manage expectations, and outline next steps. 2. Reintegration into multidisciplinary ALS clinic care. 3. Referral to psychological, social work, and palliative care support as indicated. 4. Written and verbal guidance regarding symptom management and potential future research opportunities. Planned assessments include patient-reported quality of life, psychological distress, and perceived continuity of care, as well as caregiver burden and satisfaction. Semi structured interviews with patients, caregivers, and staff will explore experiences of trial transition and perceived value of post trial support. Feasibility metrics, including participation rates, referral uptake, and adherence to consultations, will inform recommendations for broader implementation. Results: Expected Outcomes Anticipating that the program will be feasible and acceptable to patients and caregivers. Expected benefits include improved patient-reported quality of life, reduced psychological distress, enhanced perception of continuity of care, and decreased caregiver burden. Qualitative data are expected to demonstrate the importance of clear communication, coordinated care, and structured support following trial completion. Feasibility metrics will provide guidance for integrating post-trial support into future ALS clinical trial designs. Conclusion: Addressing the unmet post trial support needs of ALS patients is critical for ethical research conduct and patient-centered care. Implementing a structured support pathway has the potential to mitigate emotional harm, preserve trust in research, and enhance the overall experience of both patients and caregivers. This approach could serve as a model for integrating patient-centered post-trial care into neurodegenerative disease research.

Prof. Shanshan MAO Children‘s hospital, Zhejiang university school of medicine, HANGZHOU, China Background: While neurofilament light chain is a promising biomarker in spinal muscular atrophy (SMA), its dynamics in presymptomatic patients remain unestablished. This study aimed to analyze the plasma neurofilament light chain (pNfL) as a treatment response biomarker in patients with presymptomatic spinal muscular atrophy (SMA) undergoing nusinersen treatment. Methods: Eight 5q-SMA patients with three SMN2 copies (four presymptomatic patients from newborn screening and four symptomatic patients) were prospectively enrolled from August 2022 to June 2023. All patients received nusinersen treatment and were followed up for 660 days. pNfL levels were measured at baseline and throughout the treatment, analyzing their temporal changes and correlation with motor function outcomes. Results: At baseline, presymptomatic patients exhibited higher pNfL levels than symptomatic patients (388.74 ng/L vs. 113.60 ng/L). During the loading phase, pNfL levels decreased markedly in both groups, with greater reductions in presymptomatic patients (94.64% vs 79.50%). All presymptomatic patients achieved age-appropriate motor milestones. Decreased pNfL levels strongly correlated with motor function improvements, as measured by CHOP INTEND (r = −0.548, p < 0.01) and HINE-2 scores (r = −0.635, p < 0.01). Conclusion: pNfL is a promising biomarker for monitoring treatment response in patients with presymptomatic SMA, highlighting the importance of early diagnosis and treatment through newborn screening.

Dr. Henry Kaminski , Prof. Linda Kusner George Washington University, Washington DC, United States Background: Thymectomy provides durable clinical benefit in myasthenia gravis (MG), yet the systemic immune mechanisms underlying its efficacy remain incompletely understood. Methods: We performed longitudinal whole-blood RNA sequencing and serum proteomic profiling in participants from a randomized clinical trial comparing prednisone alone with prednisone plus thymectomy. Analyses were designed to identify treatment-associated transcriptional signatures linked to clinical severity over time. Results: Global clustering and compound Poisson mixed-effects modeling showed that baseline gene expression had limited predictive value for short-term clinical improvement. In contrast, longitudinal modeling identified robust treatment-by-severity interactions involving 238 genes. Early disease severity was associated with increased interferon/STAT1 signaling, enhanced antigen-loading machinery, NF-κB regulatory networks, and elevated immunometabolic demand. Although baseline features did not predict outcomes, long-term clinical improvement was associated with coordinated modulation of pathways regulating STING activity (SKIL), dendritic cell tolerance and antigen presentation (DCSTAMP, AIRE), cytokine negative feedback (SOCS3), inflammasome-associated regulatory programs (AIM2, IL18R), and B-cell receptor and plasma-cell survival pathways (IGLV5-45, TNFRSF17/BCMA), together with epigenetic regulators of HLA expression (BRD2, HCG27). Conclusion: Thymectomy was associated with sustained attenuation of immune activation, reduced cellular metabolic demand, and remodeling of intracellular transport and cytoskeletal pathways, consistent with transition toward a less inflammatory immune state. These findings demonstrate that dynamic transcriptional trajectories, rather than baseline molecular profiles, capture treatment response and provide mechanistic insight into the durable therapeutic benefit of thymectomy in MG.

Dr. Angela Genge McGill University Health Center Research Institute, Montreal, Canada Background: ACCESS ALS is a new initiative in Canada based upon the success of Dr Genge's site at McGill university and now at the McGill University Health Center Research Institute. Access ALS will develop phase 1 clinical trials sites across Canada based upon the success of the Mcgill efforts. The coordinating center will partner with academic ALS sites across Canada to develop, train and support the staff tasked with executing Phase 1 trials. This model can/will be extended to other neuromuscular diseases to take advantage of the favorable regulatory environment in Canada for innovative Phase 1 drug development. Methods: Access ALS has developed a model coordinating center for the execution of Phase 1 trials in ALS and ultimately other neurological conditions. It includes an operations manager, network coordinator, nurse navigator, pharmacist, contracts specialist, ethics and regulatory manager and phase 1 supervisor. This coordinating center will network with sites across the country to increase the expertise and capabilities across a large geographic region. Results: Access ALS is currently being established at the McGill University Health Center Research Institute and partners with ALS CAPTURE and the CALS network Conclusion: The network will immediately enable a more efficient approach to phase 1 drug development in ALS/MND

Prof. Claudia Sommer University Hospital Würzburg, Würzburg, Germany Background: The prevalence of peripheral neuropathy is greatly increased in elderly people. Various factors may be involved in this finding. Cumulative effects of adversive lifestyle factors and environmental toxins have been implied. Furthermore, senescent Schwann cells are induced by aging and are associated with impaired axonal regeneration and inflammation. These senescent Schwann cells may be a negative prognostic factor in patients with neuropathies, especially in older patients and may be a therapeutic target. Age-related mediators like sirtuins and neprilysin are supposed to form an important link between aging and inflammation. SIRT1 a is a NAD+-dependent deacetylase that participates in various biological processes. Decreased SIRT1 activity may be associated with autoimmune diseases, and neuropathic pain. Neprilysin also decreases with aging, and rare variants in the encoding gene are associated with a late-onset neuropathy, indicating that decreased neprilysin activity may promote the development of chronic nerve damage.

Dr. Davide Pareyson Fondazione IRCCS Istituto Neurologico Carlo Besta,, Milan, Italy Conclusion: Hereditary ataxic neuropathies encompass a clinically and genetically heterogeneous group of disorders predominantly characterized by sensory ataxia, either isolated or combined with motor involvement, cerebellar ataxia, or other neurological findings. This phenotype overlaps with cerebellar ataxias and related disorders and poses significant diagnostic challenges. The discovery of biallelic intronic repeat expansions in RFC1 has revolutionized the field, identifying the most common cause of late-onset ataxia with sensory neuropathy, known as CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia syndrome). Chronic cough and abnormalities of the vestibulo-ocular reflex (VOR) are strong red flags for CANVAS. The phenotypic spectrum of RFC1 -related disease is broader than initially described and includes incomplete and atypical presentations. Moreover, there are CANVAS-like phenotypes not associated with RFC1 variants, including cases associated with heterozygous variant(s) in RNF170 . Several additional inherited conditions may present with sensory ataxia, either as a prominent or initial feature. These include Friedreich’s ataxia and ataxia with vitamin E deficiency (AVED), which combine cerebellar and sensory involvement, as well as mitochondrial disorders related to POLG and TWNK mutations. Recessive ataxias such as DARS2 -related disease may also present with a sensory ataxic phenotype. Furthermore, certain inherited neuropathies, particularly early-onset demyelinating forms such as MPZ -related CMT1B and PRX -related CMT4F, can manifest with prominent sensory ataxia and may be misclassified. Other rare conditions to be considered are PHARC (Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract) and abetalipoproteinemia. The differential diagnosis is broad and includes treatable metabolic disorders, such as Refsum disease, cerebrotendinous xanthomatosis and vitamin deficiencies, as well as immune-mediated sensory neuronopathies, including those associated with Sjögren syndrome or paraneoplastic conditions. This lecture will provide a practical clinical approach to patients presenting with sensory ataxia, emphasizing key clinical features, appropriate use of neurophysiology and imaging, and a rational strategy for genetic testing. The aim is to improve diagnostic accuracy, facilitate early identification of treatable conditions, and better define the expanding spectrum of hereditary ataxic neuropathies.

A. Lewis, Richard PP01.261 Ab Ghapar, Amirul Asyraf OS07.01 Abati, Elena OS08.04 Abbasi, Maria PP01.137 Abdel-Hamid, Hoda Z. PP01.46 Abdelhak, Sihem PP01.69, PP01.70 Abdelkrim, Abdelmadjid PP01.69, PP01.70 Abe, Tatsuya PP01.334, PP01.356 Abedi, Mehrdad PP01.171 Abicht, Angela PP01.66 Abraham, Alon PP01.381 Abrahao, Agessandro PP01.305 Abuzinadah, Ahmad PP01.328 Acar Arslan, Elif PP01.109 Acerra, Gabriella Maria PP01.204 Acsadi, Gyula PP01.67 Addinsall, Alex PP01.389 Adetoro, Nikki PP01.130 ADIGÜZEL, Emre PP01.380 Aggarwal, Ayush PP01.220 Aggarwal, Rohit PP01.103, PP01.262, PP01.90 Agircan, Dilek PP01.181 Aguennouz, Mhammed PP01.120 Aguirre, Maria Adela PP01.153 Ahmadiharchegani, Fatemeh PP01.42 Ahmed, Bouhouche PP01.06, PP01.07 Ahn, Sohyun PP01.227 , PP01.302 Ahn, Tae-Beom PP01.330 Ain, Quratul PP01.362 Ait Allali, Nesaiba OS02.03, PP01.03, PP01.323 Ait-Tihyaty, Maria PP01.206, PP01.211 Ajroud Driss, Senda SS45.02 Akbeyaz, Hakki PP01.109 AKCADAG CAMAN, Tugce PP01.190 Akhavanfar, Mohammad H. PP01.372 Akpınar, Ahmet PP01.77 Al Chalabi, Ammar SS32.02 Al-Khalili Szigyarto, Cristina PP01.73 Al-Khalili, Yasir PP01.287 Al-Muhaizea, Mohammad PP01.343 Al-Rubayie, Karnavaal PP01.367 Ala, Pierpaolo PP01.44 Albano, Noemi OS01.04 Alberti, Claudia OS08.04, PP01.104 Alberti, Paola SS10.02 Albini, Sonia PL01.03 Alboini, Paolo Emilio OS04.03, OS04.05, PP01.214, PP01.231 Aldridge, Jamie PP01.215 Alecu, Iulian PP01.52 Alemañ, Jose PP01.203 Alessi, Federica OS02.05, PP01.67 Alfaidi, Nouf PP01.305 Alfredsson, Lars PP01.205 Ali Pacha, Lamia PP01.241 Allegra, Cosimo OS07.04 Allegri, Isabella OS01.04 Allen, David PP01.213 Allen, Jeffrey PP01.268, PP01.88 Allen, Jeffrey A PP01.267 Allen, Jeffrey A. PP01.279, PP01.282, PP01.284 Allenbach, Yves PL04.03 , PP01.103 Almeida, Jaqueline PP01.43 Alnajjar, Sara PP01.305 Alonso Alonso, Miguel PP01.267 Alonso-Alonso, Miguel PP01.261, PP01.265 Alonso-Jiménez, Alicia PP01.172 Alpaydın Baslo, Sezin PP01.355 Alroughani, Raed PP01.173 Alshareef, Aysha PP01.328 Alshehri, Ali PP01.193 Alsulami, Manal PP01.328 Altamura, Concetta PP01.25 Amato, Anthony OS01.01, TC14.01 Amato, Anthony A. PP01.262 Amayra, Imanol PP01.391 Ambati, Ravi PP01.245 Amornvit, Jakkrit PP01.371 An Haack, Kristina OS03.06 An, Jae-Young PP01.306 Andersen, Henning OS07.03 Andersen, Kasper PP01.389 Anderson, Ashley PP01.218, PP01.219 Andzeva, Elisa PP01.275 Angadi, sanjana PP01.139 Angelelli, Alessia PP01.35 Angelini, Corrado OS03.01 , PP01.107 , PP01.111, PP01.391 Anijs, Thomas PP01.61, PP01.62 Annoni, Karin PP01.214, PP01.231 Anokhina, Katerina PP01.278 Antonini, Giovanni OS01.04, PP01.145, PP01.187, PP01.232 Antozzi, Carlo PP01.175 , PP01.176 , PP01.177 , PP01.178, PP01.189, PP01.235, PP01.236, SS04.01 Aoyagi, Ryohei PP01.191 Appelqvist, Hanna PP01.128 Araújo, Alexandra PQC PP01.343 Araúzo-Bravo, Marcos J PP01.362 Arbogast, Thomas OS06.06 ARDIÇLI, Didem PP01.380 Arena, Ignazio PP01.127 Arena, Ignazio Giuseppe PP01.119 , PP01.120 Arici, Sehnaz PP01.291 Arman, Inbar PP01.199 Armani, Andrea PP01.152 Arnaoutoglou, Marianthi PP01.110 Arndt, Raquel Cristina OS05.02 Arnold, W. David PP01.329 Aronica, Eleanora OS06.03 Aronica, Eleonora PP01.103 Arpaia, Chiara PP01.55 Arslan, Doruk OS07.06 Arsov, Todor PP01.357 Arteaga Rodriguez, Carlos PP01.254 ARTERO, RUBÉN OS01.03 Arunachal, Gautham PP01.138, PP01.150 Arustamyan, Kristine PP01.217 Arvin-Berod, Clémence PP01.272 Arvin-Bérod, Clémence PP01.279 Ascherman, Dana OS01.01 Ashraghi, Mohammad PP01.188, PP01.192 Assis, Carolina OS07.05 Astrea, Guja PP01.11 Atchayaram, Nalini PP01.138 , PP01.139 Atiya, Yael PP01.199 Attarian, Shahram PP01.169, PP01.194, PP01.265, PP01.282 Audhya, Ivana F. PP01.48 Auinger, Peggy PP01.367 Ayanoglu, Cigdem OS01.06 Aydin, Gozde PP01.237 Azcona, Carolina PP01.153 Azuma, Hiroto OS03.04 Azzimonti, Matteo PP01.117 Babu, Merly PP01.65 Bachman, Eric OS04.06 Bae, Jisun PP01.304 Bae, Jong Seok PP01.293 Baek, Seol-Hee PP01.333 Baets, Jonathan PP01.172 Bagg, Matthew PP01.99 Baima, Jader PP01.366 Bakircioglu Duman, Ezgi PP01.188, PP01.192 Bakircioglu-Duman, Ezgi OS09.01 Bal, Mehmet PP01.181 Balasubramaniam, Shanti PP01.65 Balbino, Bianca PP01.382 Baldassari, Simona PP01.09 Baldissera, Martina PP01.316 Baldwin, Joel OS04.04, PP01.79 Baldwin, Tomas PP01.44 Balique-Laplanche, Aurore PP01.132 Ballarini, Nicolas PP01.346, PP01.347 Bamps, Kobe OS08.06, PP01.359 Banerjee, Tanya PP01.290 Bansal, Prashant PP01.59 Baptista, Linda PP01.286 Baranello, Giovanni OS01.06 , PP01.33, PP01.44, PP01.46 , TC09.04 Baratto, Serena PP01.34 Barbaccia, Adele OS01.04 Barbosa, Guilherme PP01.165 Barbov, Ivan PP01.157 BARGIELA, ARIADNA OS01.03 Baric, Ivo PP01.129 Barnett-Tapia, Carolina PP01.178 , PP01.238, PP01.305 Baronchelli, Carla PP01.04, PP01.05 Barone, Carolina OS05.06 Barone, Paolo OS04.03, PP01.155, PP01.204 Barp, Andrea PP01.373 Barrera-Sierra, Sergio PP01.289 Bartels, Bart PP01.17 Barthelemy, Florian PP01.28 Bartolomejovava, Pavla Bortolomejovava PP01.40 Basa, Mihail PP01.13 Baskar, Dipti PP01.139, PP01.150 BASSE FAYE, ANNA MODJI PP01.354 Bauer-Ventura, Iazsmin PP01.90 Baumann, Matthias PP01.325 Beange, Kristen H.E. PP01.372 Bearden, David PP01.259 Beatrice, Francesca OS08.01 Beazley, Bethany PP01.268 Becker, Michael SS22.05 Bedir, Ali Zeki PP01.08 Beer, Kelly PP01.99 Beermann, Mary Lou PP01.37 Beggs, Simon PP01.45 Behin, Anthony PP01.113 Bekoeva, Zemfira PP01.298 Belachew, Shibeshish PP01.368 Belimezi, Maria PP01.182 Bellanti, Roberto OS06.04 Bello, Luca OS01.02, PP01.42 Beltran, Sergi PP01.129 BEN OMRAN, TAWFEG PP01.72 Ben Youssef-Turki, Ilhem SS05.01 Benatar, Michael PP01.170, PP01.199, PP01.80, PP01.81 Benchaabi, Ouissem PP01.321 , PP01.69, PP01.70 Benedetti, Luana PP01.370 Benguerba, Kamal PP01.52 Benkirane, Nada PP01.126 Benmhammed, Noor PP01.369 Bennetts, Bruce PP01.65 Benussi, Alberto PP01.316 Benveniste, Olivier OS01.01 Beretta, Francesca PP01.212, PP01.86 Bergin, Cathleen PP01.218, PP01.219 Bergstrom Johnson, Claire OS06.04 Berling, Edouard PP01.132, PP01.151 Bernardo, Katrina PP01.249 Bernert, Guenther PP01.40 Bernert, Günther PP01.325 Bertella, Enrica OS02.03, PP01.04, PP01.05 Berti, Beatrice PP01.55 Berti, Gianna OS03.05 Bertini, Enrico PP01.11, PP01.343 Bertolasi, Laura OS07.03 Bertolasi, Letizia PP01.104, PP01.105 Bestetti, Ilaria OS08.04 Bettica, Paolo OS02.05, PP01.67 , PP01.74 Bevilacqua, Jorge A. SS30.01 Bevilacqua, Liliana OS04.03, PP01.155, PP01.204 Beydoun, Said OS01.01, PP01.206 Beytia, Maria de los Angeles PP01.58 Bhatia, Rohit PP01.220 Bhavaraju-Sanka, Ratna PP01.176, PP01.269 Biddeci, Roberta PP01.10 Bieuvelet, Séverine PP01.133 Bikmazer, Bilgihan PP01.109 Bilgraer, Raphael PP01.223 Bini, Paola PP01.86 Biran, Yifat PP01.237 Birman Har-Noy, Nurit PP01.373 , PP01.381 Birouk, Nazha PP01.124, PP01.125, PP01.126 Bischoff, Gert PP01.135 Bischoff, Monika PP01.135 Bisecco, Alvino OS04.03 Bisson, Camille OS08.02, PP01.369 Bitoun, Marc SS21.01 BİRBİR, Buse PP01.380 Blaauw, Bert PP01.152 Blanco, Rocio PP01.153 Blank, Bert PP01.364 Blankenbiller, Tricia PP01.108 Blaschek, Astrid OS02.04 Blasini, Romina OS09.04 Bleecker, Jan De PP01.175 Blein, Cécile PP01.191, PP01.194, PP01.272 Bloemers, Jos PP01.179, PP01.186, PP01.195, PP01.201 Blum, Stefan PP01.173, PP01.221, PP01.237, PP01.238 Bobadilla, Edna Julieth PP01.40 Boccanegra, Brigida PP01.29, PP01.30 Boemia, Virginia PP01.352 Boespflug-Tanguy, Odile PP01.67, PP01.74 Boffa, Laura PP01.144, PP01.247, PP01.250, PP01.251, PP01.318 Bogaards, Johannes OS01.05 Bogatyreva, Anna PP01.01 Boggs, Kirsten PP01.65 Boluk, Ebru PP01.291 Bonaccorso, Rosa OS02.02, PP01.19 Bonanno, Silvia OS01.04, OS04.03, PP01.96 Bonar, Kerina PP01.214, PP01.231 Bonci, Tecla PP01.368 Bongiolatti, Stefano PP01.212 Bonofiglio, Federico PP01.283 Bonventre, Joseph V. PP01.46 Boonyapisit, Kanokwan PP01.174 Boonyuen, Wanicha PP01.371 Borghs, Herman PP01.61, PP01.62 Bormann, Daniel PP01.325, PP01.326 Boroojerdi, Babak PP01.179 Bortolani, Sara OS08.03 Boschi, Silvia PP01.47, PP01.84 Bossuyt, Patrick PP01.103 Botrous, Mina PP01.238 Botta, Annalisa PP01.145 Bougamra, Sirine PP01.169 Bouman, Karlijn PP01.14 Bourg-Alibert, Nathalie PL01.03 Bouzaglo, Omer PP01.381 Bovy, Nicolas PP01.369 Boyer, Stéphane PP01.286 Boz, Cavit PP01.173 Braen, Angélique PP01.329 Brais, Bernard PP01.154 Brajuskovic, Goran PP01.143 Brajušković, Goran PP01.358 Branas, Maria PP01.57 Brandsema, John F. PP01.67 Brannagan, Thomas OS01.01 Brannagan, Thomas H. PP01.284 Bratina, Alessio PP01.316 Braun, Jessica PP01.54 Brauner, Susanna OS02.06, OS04.02, OS06.05, OS09.03, PP01.197, PP01.205 Bray, Sarah PP01.170 Breiner, Ari PP01.193 Brennan, Christopher M. PP01.37 Briani, Chiara PP01.297, PP01.370, SS13.02 Brierley, Russell PP01.130 Briggs, Caitlin PP01.159, PP01.206, PP01.211 Brighina, Filippo OS04.03, PP01.370 Bril, Vera OS04.04, PP01.175, PP01.186, PP01.195, PP01.201, PP01.218, PP01.219, PP01.228, PP01.305, PP01.78, PP01.79 Brkusanin, Milos PP01.143, PP01.27, PP01.358 Brockt, Alicia PP01.367 Brogna, Claudia PP01.55 Brokamp, Katharina PP01.180 Brolatti, Noemi OS07.04, PP01.35, PP01.36 Brooks, Gabriel PP01.68 Brown, Thomas PP01.339 Bruex, Hannah PP01.363 Brulc, Erika PP01.153 Bruno, Claudio OS07.04, PP01.11, PP01.34, PP01.35, PP01.36 Brureau, Anthony PL01.03 Brusa, Chiara PP01.33 Bubb, Vivien OS06.01 Bucci, Elisabetta PP01.145 Budding, Kevin PP01.284 Budikayanti, Astri PP01.308 Buffel, Connor PP01.168 Bugatti, Mattia PP01.04, PP01.05 Bukacova, Katerina PP01.40 Buliņa, Inita PP01.98 Burcklen, Michel PP01.175 Burden, Steven PP01.158 Burden, Steven J. PP01.156, PP01.166 Businaro, Pietro OS04.05 Butler, Lesley PP01.222 Butzkueven, Helmut PP01.238 Buzzard, Katherine PP01.173, PP01.237, PP01.238 Bähr, Mathias PP01.363 Bönnemann, Carsten G. OS02.04 Caballero-Avila, Marta PP01.382 Cabraal, Isobel PP01.188, PP01.192 Cacchio', Gabbriella PP01.297 Cadour, Stéphanie PP01.279, PP01.282 Cadri, Silvi PP01.373 Cai, Na PP01.46 Cakar, Arman PP01.118 Calabresi, Paolo OS05.05 Calderon Castro, Andrea del Pilar PP01.40 Calma, Aicee Dawn OS07.01, OS07.02 Calvo, Andrea TC13.03 Camacho, Ana PP01.57 CAMAN, Mahmut Bilal PP01.190 Cambier, Audrey PP01.113 Camdessanché, Jean-Philippe PP01.194 Camelo, Clara PP01.40 Cameron, Donnie PP01.14 Camizaru, Alexander PP01.11 Campbell, Craig PP01.46 Campbell, Nolan PP01.209 Campo, Sofia OS04.03 Camprubi, Sandra OS07.03 Canale, Fabrizio PP01.370 Canales, Blanca PP01.80 Canali, Elena OS01.04 Candrea, Elisabeta PP01.106 Canning, Jake OS09.01 Cano, Robert PP01.329 Cantisani, Teresa PP01.370 Cao, Weihua PP01.228, PP01.78 Capasso, Anna PP01.55 Cappellari, Ornella PP01.29, PP01.30, PP01.31 Carapella, Nicola PP01.04, PP01.100 Cardoso, Igor Baroni PP01.257 Caress, James OS01.01 Caria, Filomena OS02.03, PP01.04, PP01.05, PP01.323, PP01.373 Carment, Loïc PP01.132, PP01.133 Carmona-Martinez, Ricardo PP01.129 Carnazzi, Alessandra PP01.21 , PP01.22, PP01.96 Carpo, Marinella PP01.370 Carrera-García, Laura PP01.341 Carrillo, Nuria PP01.268 Carugati, Roberto OS02.03, PP01.03 Carvalho, Alzira PP01.112, PP01.116, PP01.163, PP01.164, PP01.165, PP01.18, PP01.91, PP01.92, PP01.93, PP01.94, PP01.95 Carvalho, Diana PP01.40 Carvalho, Nara OS07.05 Carver, Aleks PP01.335, PP01.336, PP01.337 Casiraghi, Jacopo Luca PP01.373 Casneuf, Tineke PP01.382 Cassano, Emanuele PP01.370 Castellar-Leones, Sandra Milena OS03.03, PP01.246, PP01.258 Castiglioni, Claudia PP01.58 Castillo, Laura PP01.368 Castro, Ana Laura OS03.03, PP01.246, PP01.258 Castro, Paz PP01.340, PP01.341 Cataldi, Matteo PP01.09 Cataldo, Stefania PP01.317 Catapano, Francesco OS02.02 Catteruccia, Michela PP01.11 Cavalcante França Jr, Marcondes PP01.344 Cavalcante, Paola PP01.96 Cavka, Mislav PP01.129 Cazzaniga, Sara OS02.05 Ceccanti, Marco OS05.05 Ceccherini, Elisa PP01.32 Cella, Ricardo Rojo PP01.177 Cenacchi, Giovanna PP01.107 Cendron, Laura PP01.152 Centonze, Diego PP01.144, PP01.247, PP01.250, PP01.251, PP01.318 Cepele, Alba OS04.05 , PP01.233 Cerchiara, Alessandro Giovanni PP01.29 Cerovac, Natasa PP01.27 Cetin, Hakan OS08.05, PP01.325, PP01.326 Chacon, Aline PP01.43 Chae, Juhee PP01.294 Chahin, Nizar PP01.88, PP01.90 Chakraborty, Eesha PP01.89 Chambers, Darren PP01.45 CHAN, Irene Heung Lan PP01.315 Chan, Sophelia PP01.40 Chan, Sophelia Hoi Shan PP01.345 Chan, Stephen Wing Wai PP01.345 Chang, B. Kalei PP01.270 Chang, David PP01.171 Chang, David J PP01.90 Chang, Hee Jin PP01.330 Chang, Herng-Hua PP01.311 Chang, Kai Chieh PP01.365 Chao, Chi-Chao OS05.03, PP01.311 Chao, Kenneth PP01.249 Chary, Sowmya PP01.142 Chaudhari, Umesh OS04.06 Cheli, Marta OS04.03, PP01.96 Chen, Lei PP01.243 Cheng, Mei-Fang OS05.03 Cheng, Sue PP01.170, PP01.80, PP01.81 Cheng-Zhang, Jia Qi PP01.37 Cherney, David PP01.305 Chernova, Natalia PP01.298 Cherubino, Christabella PP01.339 Chesmore, Kevin PP01.28 Cheung, Mei Wun PP01.345 Cheva, Aggeliki PP01.110 Chiang, Ming-Chang OS05.03 Chiarella, Lorenzo PP01.36 Chien, Yin-Hsiu OS03.06 CHING, Wai Kin PP01.315 Chinoy, Hector PP01.262 Chitimus, Diana PP01.115 Chiyonobu, Tomohiro PP01.348 Chloca, Fernando PP01.41 cho, eun bin PP01.324 Cho, Jeong Hee PP01.167, PP01.20, PP01.23, PP01.24 Cho, Jin Whan PP01.330 Cho, Joong-Yang PP01.277 Choi, Kyomin PP01.330 Choi, Young-Chul PP01.167, PP01.20, PP01.23, PP01.24 Choi, Yunjung PP01.167, PP01.20 , PP01.23, PP01.24 Chollet, Grégory PP01.214, PP01.231 Choo, Seung Ho PP01.324 Choudhary, Gaurav PP01.90 Choudhry, Zia PP01.177, PP01.210 Chourpiliadis, Charilaos OS06.05 Christiansen, Silvia PP01.153 Christopher-Stine, Lisa OS01.01 Chroni, Elisabeth PP01.173, PP01.193, PP01.238 Chu, Binh PP01.329 Chu, Wing Sum PP01.45 Chuang, Tzu-I PP01.311 Chávez, Daniel Cesar PP01.246 Chávez, Daniel César OS03.03 Ciafaloni, Emma PP01.170, PP01.367, PP01.41, PP01.80, PP01.81 Ciaiola, Francesca PP01.318 Cicala, Gianpaolo PP01.55, TC04.01 Cinnante, Claudia Maria PP01.105 Cintas, Pascal PP01.132, PP01.214 Ciscato, Patrizia PP01.104, PP01.105 Ciumas, Mariana PP01.272 Ciurea, Stephan PP01.171 Claeys, Kristl PP01.130 , PP01.359 Claeys, Kristl G. OS08.06, PP01.169, PP01.178, PP01.193, PP01.202, PP01.279 , PP01.61 Claeys, Kristl. G. PP01.62 Clarke, Andrew PP01.264 Clarkson, Kristen A. PP01.81 Claudione, Letizia PP01.30 Clay, Ieuan PP01.156 Clemens, Paula OS01.02, PP01.42 Clemens, Paula R. PP01.51 Cluzeau, Céline OS08.02, PP01.369 Coarelli, Giulia PP01.154 Coats, Julie OS02.04 Coccia, Michela PP01.373 Cocito, Dario PP01.370 Cogell, Ashley PP01.285 Colacicco, Giovanni SS18.01 Cole, Suzanne OS09.06 Colitta, Alessandro PP01.233 Collet Vidiella, Roger PP01.382 Collins, Michael OS01.01 Colombi, Chiara PP01.03 Comi, Giacomo OS08.01, OS08.04 Comi, Giacomo Pietro PP01.100, PP01.104, PP01.105, PP01.117 Conte, Elena PP01.30 Conte, Giorgio PP01.117 Cooper, Ian PP01.99 Coppejans, Rani PP01.166 Coratti, Giorgia PP01.55 Corazzini, Roseli PP01.112, PP01.116, PP01.163, PP01.164, PP01.165, PP01.92, PP01.93, PP01.94, PP01.95 Corbo, Michela Maria PP01.212 Cordani, Ramona PP01.36 Cordiglieri, Chiara OS08.01 Cornblath, David PP01.268 Cornell, Nikki PP01.44 Correa-Arrieta, Cristian OS03.03, PP01.246, PP01.258 Correia, Carolina PP01.164 Corse, Andrea PP01.215 Cortes-Vicente, Elena SS33.03 Cortese, Andrea PL02.02 Corti, Stefania OS03.05, OS08.01 , OS08.04, PP01.100, PP01.104 , PP01.105 , PP01.117 Cortés Vicente, Elena PP01.186 , PP01.201 Cortés-Vicente, Elena PP01.169, PP01.236 Cosentino, Giuseppe PP01.244, PP01.370 Costanza, Massimo PP01.96 Cotti Piccinelli, Stefano OS02.03 Coudyzer, Walter PP01.61, PP01.62 Crisan, Ioana PP01.106 Cristiano, Enrica PP01.31 Croce, Michele Giovanni PP01.100 , PP01.244 Crockett, Lucy PP01.364 Cross, Jennifer PP01.160 Cruse, Belinda PP01.173, PP01.237, PP01.238 Cunha, Keyla OS07.05 Cuoghi Costantini, Riccardo OS01.04 Curtin, Julie PP01.65 Cutter, Gary PP01.238, PP01.89 Cuveele, Eline PP01.38 , PP01.39 , PP01.40 César-Chávez, Daniel PP01.258 D' Angelo, Andrea OS08.01 D'Alvano, Giulia OS04.03 D'Amico, Adele PP01.11 D'Andrea, Francesca PP01.374, PP01.375, PP01.378, PP01.379 D'Angelo, Maria Grazia OS01.04 D'Errico, Eustachio PP01.317 Da Silva Cardoso, Juliana PP01.40 Dadali, Elena PP01.342 Dal-Pra Ducci Cirino, Renata PP01.252, PP01.255, PP01.327 Dalakas, Marinos C. OS07.03 Dalisha, Dalisha PP01.390 Dalla Zanna, Gianmarco PP01.154 Dallorso, Stefania PP01.09 Damasio, Joana PP01.154 Damato, Valentina OS04.05, PP01.212, PP01.86, SS33.01 Damioli, Simona OS02.03, PP01.03, PP01.05 Damsker, Jesse OS01.02 Dang, Utkarsh OS01.02, PP01.42, PP01.73 Dang, Utkarsh J. PP01.51 Daniel Martin, Klaus SS22.06 Danielsson, Olof PP01.128 Daron, Aurore OS08.02 Das, Animesh PP01.220 Dash, Suravi PP01.138 Davis, Mark PP01.65 Day, John W. PP01.52 De Baets, Marc PP01.199 De Bleecker, Jan OS01.01 De Bleecker, Jan L. PP01.176 De Clercq, Lieselot PP01.166 De Cuyper, Tine PP01.62 de Cuyper, Tine PP01.61 De Felice, Sofia PP01.152 de Laat, Elisabeth C.M. PP01.17 de Laat, Ilse PP01.14 De Lorenzo, Alberto PP01.370 De Luca, Annamaria PP01.29 , PP01.30 , PP01.31 De Luca, Marcella OS06.02 De Maria, Martina PP01.352 De Merlier, Martijn PP01.202 De Mori, Roberta PP01.318 de Paepe, Els PP01.289 De Ridder, Willem PP01.172 de Rivera Garrido, Francisco JR PP01.133 De Roeck, Arne PP01.269, PP01.278, PP01.382 De Spirito, Marco OS08.03 De Stefano, Nicola OS03.05, OS05.05 de Toledo Justo, João Guilherme PP01.253 De Valle, Katy PP01.40 de Visser, Marianne PP01.103 De Vivo, Darryl C. PP01.52 De Waele, Liesbeth PP01.38, PP01.39, PP01.40, PP01.46, PP01.53, PP01.63, PP01.64 Decio, Alessandra PP01.30 Deconinck, Nicolas PP01.41, PP01.46, PP01.53, PP01.71 Deepracha, Tharadon PP01.371 Degan, Chiara PP01.73 Dejaeger, Marian PP01.61, PP01.62 Del Bo, Roberto OS08.04, PP01.104 Del Vecchio, Guido PP01.117 Del-Águila-Mejía, Javier PP01.230 DeLasHeras, Virginia PP01.173 Della Bella, Eleonora PP01.370 Della Marina, Adela OS02.01 Della Toffola, Jacopo PP01.316 Delmont, Emilien PP01.272 Delmonte, Valeria PP01.317 Delstanche, Stephanie PP01.116 Delstanche, Stéphanie PP01.369 Demeret, Sophie PP01.214 Demmel, Walter SS22.07 Demsar, Nina PP01.40 Dengler, Nora Florenz SS22.04 Denkberg, Galit PP01.199 Denlinger, Katherine OS03.06 Desai, Soaham PP01.173 Desaphy, Jean-François PP01.25 Desguerre, Isabelle PP01.52 DeVeaux, Michelle OS04.06 DeWaele, Liesbeth PP01.71 Dhall, Aishwarya PP01.361 Dhanabal, Mohanraj PP01.37 Di Bari, Alessandra SS18.01 Di Feo, Maria Francesca OS01.04 Di Iorgi, Natascia PP01.35 Di Marco, Carmine OS08.03 Di Martino, Giuseppe OS04.03 Di Muzio, Antonio PP01.55 Di Stefano, Vincenzo OS04.03, PP01.214, PP01.370 DIAGNE, NGOR PP01.354 Diamanti, Luca PP01.244 Diaz Manera, Jordi PP01.73 Diaz-Ruiz, Jorge Arturo OS03.03 , PP01.246, PP01.258 Diefes, Alexander PP01.88 DiFeo, Mariafrancesca PP01.11 Difonzo, Gianni PP01.317 Dimachkie, Mazen OS01.01, PP01.211 , PP01.88, TC06.02 Dimachkie, Mazen M PP01.133 Dimachkie, Mazen M. PP01.283 Dimova, Kalina PP01.53 Dinoi, Giorgia PP01.30 Dionne, Annie PP01.261 DIOP SENE, MARIEME SODA PP01.354 Dittmayer, Carsten PP01.180 Dixit, Vineet PP01.310 Dixon, Stacy OS01.01 Dmitrienko, Alex OS01.01 do V.P. Rodrigues, Paula Raquel PP01.327 do Vale Pascoal Rodrigues, Paula Raquel PP01.252, PP01.255 Dobeddu, Pietro PL02.03 Dobelmann, Vera PP01.129 Dobrescu, Amelia PP01.11 Dohring, Orlando PP01.346, PP01.347 Dohrn, Maike PP01.243 Doksani, Paolo OS02.01 , OS08.05 , PP01.180 Dolanska, Anezka PP01.40 DOLEK, Turgay PP01.190 Domanska, Barbara PP01.229 Donadio, Vincenzo TC12.03 Doneddu, Pietro E. PP01.282 Doneddu, Pietro Emiliano PP01.283 , PP01.284 , PP01.285 , PP01.370 Dong, Yin PP01.166 Dos Santos Souza, Cleide PP01.329 dos Santos, Thalita Aparecida PP01.252 Dosi, Claudia PP01.40 Douglas, Lyndal PP01.65 Doverty, Althea PP01.99 Dowery, Reem PP01.199 Dowling, James J. OS02.04 Doykov, Ivan PP01.44 Drago, Selene PP01.119, PP01.127 Drago, Selene Francesca Anna PP01.120 Drakou, Eleni PP01.129 Dreezen, Jente PP01.39 Dreyer, Meret PP01.363 Drory, Vivian PP01.381, TC07.01 Drudge, Chris PP01.346, PP01.347 Drummond, Kerri PP01.41 Druzhinina, Eugenia PP01.296 Drużdż, Artur OS04.04, PP01.201 Dube, Bright PP01.222 Dubey, Divyanshu SS36.03 Dubois, Charline PP01.369 Dubuisson, Nicolas OS06.04 Ducci, Renata Dal-Pra OS05.02, PP01.257 Duchemin-Pelletier, Eve PP01.388 Duchesne, Elise PP01.136 Dufva, Ann Eriksson PP01.197 Dugas, Marc-Olivier PP01.136 Dulak, Józef PP01.26 Duncombe, Paul PP01.262 Duong, Monica PP01.346, PP01.347 Duong, Tina PP01.82 Dupont, Melissa PP01.285 Dupont, Patrick OS08.06, PP01.359, PP01.61, PP01.62 Durmus, Hacer PP01.118 Durr, Alexandra PP01.154 Dusemund, Carla OS02.01, OS08.05 Dutta, Bhaskar PP01.132 Dyck, P James SS23.02 Dyck, P. James PP01.270 Dyck, P. James B. Dyck TC12.02 Dysgaard, Tina PP01.268 D’Hooghe, Lena OS09.06 Ebong, Ima PP01.132 Echaniz-Laguna, Andoni PP01.194, PP01.272 Echeverry, Eduardo OS03.03, PP01.246, PP01.258 Edens, Coughi PP01.90 Edmundson, Christyn PP01.218, PP01.219 Edwards, Robert PP01.177, PP01.189 Eftimov, Filip OS01.05, PP01.103, PP01.268 Eggenspieler, Damien OS08.02 , PP01.369 Eggers, Christian PP01.269, PP01.325 Eisenblätter, Luca PP01.363 Ejarque, Vanessa PP01.341 Ekinci, Aysen Suzen PP01.291 Ekstrom, Anne-Berit PP01.40 Elavarasi, Arunmozhimaran PP01.220 Elgsås, Tonje PP01.40 Ellor, Susan PP01.284 Elsouda, Dina PP01.366 Engebrecht, Charlotte PP01.367 Engelstad, JaNean PP01.270 Engvall, Martin PP01.128 Erasmus, Corrie PP01.14, PP01.40 Erasmus, Corrie. E. PP01.17 Erbaş, Yasemin PP01.52 Erdem-Ozdamar, Sevim OS07.06 Erdler, Marcus PP01.325, PP01.56 Erez, Shir PP01.199 Eriksson-Dufva, Ann OS04.02 Erra, Carmen OS04.05, PP01.155, PP01.214 Eskesen, Nicolas PP01.389 ESPINONSA-ESPINOSA, JORGE OS01.03 Esposito, Gabriella OS03.05 Esposito, Martina PP01.152 Espíndola, Gisele PP01.116 Etemadifar, Masoud PP01.173 Eura, Nobuyuki PP01.102 , PP01.123 Europa, Tarin PP01.259 Evangelista, Teresinha TC12.01 Evers, Sanne OS01.05, PP01.103 Evoli, Amelia TS10.03 Ewenczyk, Claire PP01.154 Eymard, Bruno PP01.241 Fadli, Nurul PP01.308 Faedo, Elena PP01.34 Faelens, Ruben PP01.208 Fajardo, Val PP01.54 Falso, Siliva PP01.86 Falso, Silvia OS04.03, OS04.05, PP01.231 Falzone, Yuri OS04.03, PP01.370 Fan, Dongsheng SS32.01 Fang, Fang OS04.02, OS06.05, PP01.197, 611 Fang, Yuan OS01.02 Farhat, Emna SS05.01 Faria, Nathalia PP01.327 Farmakidis, Constantine PP01.175 Farrar, Michelle OS07.02, PP01.65 Farrar, Michelle A PP01.343 Farrugia, Emily PP01.313 , PP01.314 Farwell, Wildon PP01.75 Feder, David PP01.163, PP01.164, PP01.165, PP01.92, PP01.93, PP01.94, PP01.95 Feitoza, Pablo PP01.116 Ferguson, Francesca PP01.188 , PP01.192 Fernandez, David OS01.01 Fernandez, Joaquin Alejandro PP01.57 Fernández-Torrón, Roberto PP01.147 Ferraiuolo, Laura PP01.329 Ferrari Aggradi, Carola SS18.01 Ferrari, Elisabetta PP01.03 Ferri, Carolina PP01.32 Ferullo, Lucia OS02.03, PP01.04, PP01.05, PP01.323 Feticu, Marian PP01.115 Filosto, Massimiliano OS01.04, OS02.03, OS03.05, PP01.03, PP01.04, PP01.05, PP01.100, PP01.323, PP01.370, PP01.373, SS08.01 Finanger, Erika L. PP01.67 Finelli, Palma OS08.04 Finkel, Richard S PP01.343 Finkel, Richard S. PP01.52 Finsterer, Josef PP01.121 , PP01.122 Fiogbé, Elie PP01.136 Fionda, Laura OS04.03, OS04.05, PP01.187, PP01.201 , PP01.214, PP01.86 Fiorillo, Chiara PP01.09 , PP01.10 , PP01.11 , PP01.34 Firholz, Monika PP01.40 Fitzgibbon, Marie PP01.175, PP01.177, PP01.189, PP01.208 , PP01.209 , PP01.210 , PP01.235, PP01.236 Flaender, Mélanie PP01.388 Flanigan, Kevin PP01.129, PP01.68, PP01.71 Florczyk-Soluch, Urszula PP01.26 Florea, Laura PP01.115 Florio, Lucia OS04.05 Floudiotis, Niki PP01.259 Folz, Mary PP01.360 Fontana, Pedro PP01.164 Fontanelli, Lorenzo PP01.32 Foong, Yi Chao PP01.173, PP01.238 Foray, Marine PP01.388 Forcina, Francesca OS05.05, PP01.232, PP01.370, PP01.86 Fortes, Clarisse PP01.43 Foschi, Matteo PP01.173 Fossati, Gianluca PP01.30 Fox, Ashley PP01.329 Fraddosio, Angela PP01.317 Fraga, Luiza PP01.327 Francavilla, Teresa PP01.317 Franchi, Ester PP01.03, PP01.323 Franco da Graça, Felipe PP01.344 Frangiamore, Rita OS04.03, PP01.231 Fratini, Paula PP01.91 Freimer, Miriam OS01.01, PP01.179, PP01.229 Freytag, Bianca PP01.388 Frezatti, Rodrigo PP01.18 Frezza, Erica PP01.144 , PP01.145 , PP01.247, PP01.250, PP01.251, PP01.318 Frieler, Ryan PP01.82 Fu, Lijun OS03.06 Fujino, Masahiro PP01.02, PP01.76 Fujita, Syugo PP01.356 Fukumoto, Yuta PP01.240 Fukushima, Naoshi OS09.03 Fulop, Krisztina PP01.312 Furmanak, Thomas PP01.171, PP01.90 Furness, Kate PP01.314 Fustes, Otto Jesus Hernandez OS05.02, PP01.257 Gable, Karissa PP01.283, PP01.285, PP01.88 Gable, Karissa L. PP01.284, PP01.372 Gadaleta, Giulio PP01.47 , PP01.84 Gaegan, Chloe PP01.40 Gaffney, Daniel PP01.137 Gafson, Arie PP01.269, PP01.278 Gagliardi, Delia OS08.01, OS08.04, PP01.104, PP01.105 Gagnon, Cynthia PP01.136 Gaignard, Pauline PP01.113 Gaio, Nikolas PP01.31 Gaki, Eleni PP01.343 Galatolo, Daniele PP01.11 Gallus, Gian Nicola OS03.05 Gana, Simone PP01.244 Gandhi, Kavita PP01.177, PP01.209, PP01.210, PP01.235, PP01.236 Garai, Nemanja PP01.358 Garassini, Marina SS43.03 Garay-Albízuri, Patricia PP01.147 Garbey, Marc SS24.03 Garcia Dominguez, Carlota OS03.06 Garcia, Beatriz OS07.03 García, Irune PP01.391 García-López, Sofía PP01.341 GARCÍA-MARTÍN, ALBERTO OS01.03 Garg, Ajay PP01.220 Garibaldi, Matteo PP01.187, PP01.232, PP01.86 Garletti, Giorgia PP01.03 Garofali, Francesca OS02.03, PP01.03 Garrido, Cristina PP01.40 Garrido-Hernández, Tania PP01.230 Gastaldi, Matteo OS04.05, PP01.231 Gauthier, Remiche PP01.130 Gavanji, Roya PP01.346, PP01.347 Gavrilaki, Maria PP01.110 GAYE, ARAME PP01.354 Gaëlle-Dosne, Anne PP01.223 Geckinli, Bilge Bilgen PP01.109 Gedikbası, Asuman PP01.118 Geiger, Christopher OS01.01 Gelinas, Deborah PP01.218, PP01.219 Gemelli, Chiara OS05.06 Gemma, Marco OS04.03 Genge, Angela SS26.03 Gentile, Luca PP01.370 Gentyala, Rahul OS02.04 George, Kelly OS03.06 Georgiadou, Elissavet PP01.185 Gerischer, Lea OS02.01, PP01.133 Gerovska, Daniela PP01.362 Geuens, Sam PP01.38, PP01.39, PP01.63, PP01.64 Gevorgyan, Edgar PP01.217 Ghati, Chetan PP01.138 Ghizoni Teive, Hélio PP01.254 Giacobbe, Juliette PP01.01 Giacopuzzi Grigioli, Eleonora OS04.03 Giagnorio, Eleonora PP01.21 Giampá, Sara PP01.253 Gibertini, Sara PP01.21, PP01.22, PP01.25, PP01.96 Gicquel, Evelyne PL01.03 Gil Garzon, Monica Rebeca PP01.45 Gilberti, Giulia PP01.03, PP01.323 Gilhus, Nils Erik PP01.206, PP01.222, SS20.02 Gillebert, Céline PP01.38, PP01.39, PP01.40 Gillenstrand, Jonas PP01.40 Gilmour, Kimberly PP01.44 Giouroukos, Sotiris PP01.185 Giovanelli, Giorgia OS02.03, PP01.03, PP01.04, PP01.05 Giramé-Rizzo, Lídia PP01.203 Girgenrath, Mahasweta PP01.37 Gistelinck, Fien PP01.178 Giunta, Giada PP01.96 Gkougka, Dionysia PP01.207 Glaubitz, Stefanie PP01.363 Gleeson, Frank PP01.75 Glāzere, Ieva PP01.274 , PP01.98 Godoy, Lara PP01.253 Goedee, Stephan PP01.289 , SS23.01 Goedeker, Natalie PP01.74 Goel, Abeer PP01.290, PP01.310 Goglia, Mariangela PP01.144, PP01.145, PP01.247, PP01.250 , PP01.251 , PP01.318 Gokhale, Sankalp PP01.159 Gold, Valeriu PP01.325 Gomez-Figueroa, Enrique PP01.173 Gonorazky, Hernan PP01.68 Gontika, Maria PP01.207 Gonzalez, Patrick PP01.68 Gonzalez-Perez, Paloma OS01.01 Gooch, Katherine L. PP01.48 Goodwin, Robert OS03.05 Goosens, Veerle OS08.06, PP01.359, PP01.61, PP01.62 Gordon, Robert PP01.177 Goret, Marie OS06.06 Gorin, Clarissa PP01.132 Gorni, Ksenija PP01.343 Gosk-Tomek, Magdalena PP01.325 Govaarts, Rosanne PP01.63, PP01.64 Govaarts, Rossane PP01.40 Goyal, Namita OS01.01 Goyal, Neelam OS01.01 Gozke, Eren PP01.77 Graham, Ryan B. PP01.372 Grandis, Marina OS01.04, OS03.05, OS04.03, OS05.06, PP01.34 Grandone, Anna PP01.379 Grazia, Devigili SS44.01 Graziosi, Bruno PP01.112, PP01.163 , PP01.164 , PP01.165 Greco, Giulia PP01.144, PP01.145, PP01.247, PP01.250, PP01.251, PP01.318 Greenslade, Annie PP01.364 Griedl, Theresa Antonia PP01.325 Grigoryan, Mariam PP01.217 Grimm, Alexander PP01.248, PP01.260 , SS22.02, SS22.03 Grinzinger, Susanne PP01.325 Griveau, Louise PP01.388 Groepenhoff, Floor OS01.05 Groothuis, Jan PP01.14 Groothuis, Jan T. PP01.17 Grote, Daniela PP01.135 Gruber, Felix PP01.325, PP01.326 Grudniak, Mariusz PP01.175 Grumati, Paolo PP01.152 Gruosso, Francesco PP01.144, PP01.247 , PP01.250, PP01.251, PP01.318 Gräßl, Michael PP01.325 Gröhl, Janek PP01.363 Gueye, Mouhamed PP01.339 Guglielmi, Marco PP01.317 Guglielmino, Valeria OS05.05 Guglieri, Michaela PP01.71 Guglieri, Michela OS01.02, PP01.40, PP01.42, PP01.51, PP01.67, PP01.73 Guha, Shashwat PP01.45 Guida, Melania OS04.03, OS04.05, PP01.231, PP01.233 Guillen, Elisa PP01.57 Guite, Kaitey PP01.51 Gulati, Sheffali PP01.41 Guliani, Gaurav K PP01.132 Gunawardane, Shivi PP01.287 Gundogan, Sevgin PP01.291 Guntrum, Debra PP01.367 Gupta, Anu PP01.220 Guptill, Jeff PP01.223 Guptill, Jeffrey PP01.169 Guptill, Jeffrey T. PP01.193 Gurgel Giannetti, Juliana OS07.05 Gurgel-Giannetti, Juliana PP01.344 GURSOY, Melik PP01.190 Gutierrez, Haydee PP01.329 Guye, Sabrina PP01.222 Guémy, Clément PP01.151, PP01.351 Gwathmey, Kelly OS01.01 Gómez Andrés, David PP01.74 Gómez-Andrés, David PP01.340, PP01.53 Ha, Sue young PP01.149 Haack, Tobias PP01.248 Haarmann, Axel PP01.216 Haberlova, Jana PP01.40 Habetswallner, Francesco OS04.05, PP01.155, PP01.370 Habib, Ali OS04.06, PP01.170 , PP01.171 , PP01.186, PP01.215 Habib, Ali A. OS04.04, PP01.169 , PP01.195, PP01.201, PP01.79 Hachisuka, Akiko PP01.334 Haddad, Hafedh PP01.284 Hagenacker, Tim PP01.216 Hagerty, Laura OS01.02 Haghikia, Aiden OS04.01 Hahn, Andreas OS03.06 Hahn, Katrin TC08.01 Hahn, Max PP01.389 Hahn, Sihoun OS03.06 Hajdú, Nándor PP01.141 Hajok, Kalina PP01.26 Hakim, Manfaluthy PP01.308 Hallal, Sihem PP01.69 hallal, Sihem PP01.70 Haltner, Anja PP01.346, PP01.347 Hamedani, Mehrnaz OS05.06 Hamilton, Alexander PP01.389 Hamilton, Tara PP01.301 Hamir, Muhammed PP01.364 Hamstra, Sophie PP01.54 Han, Kyungdo PP01.324 Han, Mitchell PP01.31 Hansen, Henrik PP01.389 Harbo, Thomas PP01.268, PP01.282 Harel, Ofer PP01.199 Harmelink, Matthew PP01.68 Harsono, Adrian Ridski PP01.308 Hartung, Hans-Peter PP01.265 Hashimoto, Atsuki OS02.04 Hasuike, Yuhei PP01.85 Hathout, Yetrib OS01.02, PP01.73 Haugh, Joy PP01.46 Hawley, Brien PP01.283 Hayashi, Shinichiro OS03.04, PP01.140 Hayat, Ghazala PP01.177 Hayat, Ghazala S. PP01.189 Hazotte, Aurélie PP01.286 Heatwole, Chad PP01.367 Hebestreit, Katja PP01.137 Heckmann, Jeannine PP01.173, PP01.238, PP01.259 Hedberg-Oldfors, Carola PP01.08 , PP01.349 Heerlein, Kristin PP01.218, PP01.219, PP01.223 Hegelmaier, Tobias OS04.01 , PP01.216 Heindl, Felix PP01.154 Heinzel, Johannes SS22.02, SS22.03 Heinzmann, Anna PP01.154 Heitzman, Daragh OS01.01 Hejas, Reka PP01.312 Helmlinger, Gabriel PP01.59 Henderson, Robert OS01.01, PP01.108 Heng, Hazel PP01.313 Henriquez, Alicia PP01.68 Henshaw, Joshua PP01.364 Hentschel, Andreas PP01.129, PP01.180, PP01.243 Henzi, Bettina PP01.40 Heo, Namjin OS05.04 Herczegfalvi, Agnes PP01.129 Herdick, Meret OS02.01, OS08.05 Hermes, Alexandra SS22.03 Hernandez Fustes, Otto PP01.252 , PP01.253 , PP01.254 , PP01.255 Hernandez Fustes, Otto Jesus PP01.327 Hernandez, Ana Luisa PP01.92 Hewamadduma, Channa PP01.179 , PP01.279, PP01.368 Heywood, Wendy PP01.44 Hickey, Luke PP01.159, PP01.206, PP01.211, PP01.268 Hideki Kawamura Junior, Edson PP01.252 Hiebeler, Miriam PP01.56, PP01.66 Higashimoto, Yuji PP01.320, PP01.322 Hill-Smith, Emilie PP01.40 HIRANO, MAKITO PP01.322 Hirano, Makito PP01.240, PP01.320 Hjartarson, Helgi OS02.06 Ho, Gladys PP01.65 Ho, Kelly PP01.166 Hobson-Webb, Lisa OS01.01 Hockey, Briana PP01.54 Hoffman, Eric OS01.02 , PP01.42 Hoffman, Eric P. PP01.51 Hoffman, Sarah PP01.223 Hoffmann, Sarah OS02.01, OS08.05, PP01.175, PP01.180, PP01.193 Hofman, Erik PP01.382 Hogan, Jonathan PP01.171 Holla, Elisa PP01.129 Holliday, Nicholas OS09.06 Hong, Seokchan PP01.97 Horber, Veronka PP01.248 Horeau, Mathieu PP01.60 Horlings, Corinne PP01.325 Horvath, Rita PP01.129, PP01.243 Hoshino, Genki PP01.240 Hotter, Anna PP01.325 Hou, Can OS06.05 Houwen - van Opstal, Saskia PP01.14 Houwen-Van Opstal, Saskia PP01.40 Howard Jr, James F OS04.06 Howard Jr, James F. PP01.176, PP01.178, PP01.193 , PP01.223 Howard Jr., James F. PP01.170, PP01.80, PP01.81 Howard, James PP01.179, PP01.215, PP01.228, PP01.78 Howe, B. Matthew PP01.270 Hsieh, Sung-Tsang OS05.03, PP01.311 Hsueh, Hsueh-Wen OS05.03, PP01.311 Hsueh, Sung-Ju PP01.365 Hu, Yihan OS06.05 Huang, Wan-Yi PP01.176, PP01.193 Huang, Yan PP01.383 Hughes, Tom PP01.218, PP01.219 Huijbers, Maartje PP01.158 Hummelgen, Eduardo PP01.253 Huntemann, Niklas PP01.216 Hurley, Erin PP01.329 Hurth, Helene PP01.260, SS22.03 Hussain, Yessar OS01.01, OS04.06, PP01.169 Hussain, Yessar M. PP01.278, PP01.282 Hustinx, Manon PP01.116, PP01.369 Huynh-Ba, Olivier OS03.06 Huysmans, Lotte OS08.06, PP01.359 Hwang, Eunbyol PP01.271 Héjas, Réka PP01.141 Höftberger, Romana OS08.05 Hübner, Miriam OS09.04 Hüpper, Anna PP01.325 Iadarola, Antonella PP01.36 Iaffaldano, Antonio PP01.317 Iannibelli, Eliana PP01.21, PP01.22 , PP01.96 Idoux, Romane PP01.129 Iguchi, Naohiko PP01.102 Ikada, Miki PP01.386 Ilagan, Janine PP01.137 Ilderton, Charlotte PP01.40 Ilic, Nikola PP01.13 Im, Sun PP01.304 Imai, Tomihiro PP01.356 Imbrici, Paola PP01.29 Inagaki, Sho PP01.191 Indrawati, Luh Ari PP01.308 Inghilleri, Maurizio OS05.05, PP01.370 Ingre, Caroline OS06.05 Inkhao, Peerakan PP01.371 Inoue, Masato PP01.386 Iolascon, Giovanni PP01.374, PP01.375, PP01.376, PP01.377, PP01.378, PP01.379 Iorio, Raffaele OS04.03, OS04.05, PP01.133, PP01.214, PP01.218 , PP01.219 , PP01.86, SS12.03 Iovino, Aniello PP01.204 Iovino, Veronica OS04.05, PP01.233 Iruzubieta, Pablo PP01.147, PP01.154 Irving, Adam PP01.237 Irving, Kathryn PP01.40 Irwin, Charlotte PP01.367 Ishigaki, Keiko PP01.40 Ishiguro, Kumiko PP01.40 Ishizuchi, Kei PP01.198 ISONO, CHIHARU PP01.322 Isono, Chiharu PP01.320 Istas, Geoffrey PP01.382 Iterbeke, Louise PP01.359 Ito, Genta PP01.386 Ito, Yasuo PP01.356 Ivanova, Kristīne PP01.98 Iwabe, Cristina PP01.344 Iyisenyurek, Seyme PP01.109 Izumi, Yuishin PP01.320 Iñarra Velasco, María José PP01.147 İNAL ÖZÜN, Özgü PP01.380 J Hopkin, Robert OS03.06 Jaber, Abbass PL01.03 Jackson, Louis PP01.210 Jacob, Saiju OS04.06 Jaffe, Linda PP01.307 Jahr, Kristen PP01.364 Jaiswal, Jyoti OS01.02 Jakobsen, Johannes OS07.03 Jakovčevic, Antonia PP01.129 Jakubczak, Ewa PP01.26 Jakubiec, Alexander PP01.368 Jalali, Neda OS04.06 James, Lucy OS02.04 Januario, Nelio OS07.05 Januzi, Donjetë PP01.362 Jaque, Carlos PP01.58 Jayaseelan, Dipa PP01.130 Jeon, Hara PP01.242 Jerez, Fátima PP01.340 Jevtic, Svetlana PP01.228, PP01.78 Jih, Kang-Yang OS03.02 Jimenez, Rosa H. PP01.169, PP01.193 Jimenez, Rosa Hermina PP01.176, PP01.178 Jiménez, Belén Valenzuela PP01.208 Jin, Lee-Way PP01.239 Jo, Geun Yeol PP01.200 Joe, Sangwon PP01.167 Jofré, Javiera PP01.58 Johnson, Nicholas PP01.82, SS18.01, SS18.02 Johnson, Victoria SS22.02 Jones, Kristi J PP01.65 Jones, Maxwell PP01.346, PP01.347 Jonson, Per-Harald PP01.21 JOUBAILY, ZEINA PP01.354 Jovanovic, Vladimir PP01.143 Joy, Shiny PP01.220 Ju, Hyunjin PP01.148 Juang, Jyh-Ming Jimmy OS05.03 Judit Molnar, Maria PP01.41 Juel, Vern C. PP01.178 Julazadeh, Hana PP01.329 Junek, Rosie PP01.65 Jung, Hee-Jae PP01.97 Jung, Ye Joon PP01.226 Jungbluth, Heinz PP01.17, TC09.02 Juntas, Raúl PP01.203 Juntas-Morales, Raul PP01.214 Juraver, Adrien PP01.368 Järvinen, Elina PP01.133 Júnior, Euldes PP01.116 Kabli, Bouchra PP01.125 Kably, Bouchra PP01.124 Kaffe, Korina PP01.110 Kaibin Kuan, Kelvi PP01.292 Kalcev, Goce PP01.157 Kaltsa, Argiro PP01.183 Kalvāne-Brokāne, Sintija PP01.98 Kaminski, Henry PP01.199, SS24.03 , SS37.02 , SS40.02 Kamoi Kay, Claudia Suemi PP01.327 Kamperman, Renske OS01.05, PP01.103 Kamsteeg, Erik-Jan PP01.129, PP01.154 Kan, Hermien E. PP01.63, PP01.64 Kanagaiah, Preshetha PP01.367 Kang, Heung-Won PP01.97 Kang, Hong-Yo PP01.387 Kang, Min PP01.171 Kang, Sa-Yoon PP01.224 , PP01.225 Kao, Yi-Hui PP01.311 Kapetanovic Garcia, Solange PP01.231 Kapoor, Mahima PP01.238 Karali, Sukru PP01.229 Karam, Chafic PP01.282, PP01.88 , PP01.89 KARATAŞ, Ceren Şevval PP01.380 Karcagi, Veronika PP01.129 Kariyawasam, Didu PP01.65 Karkkainen, Elena PP01.335 , PP01.336 , PP01.337 Karlsson, Markus PP01.360 Karmous, Wisam PP01.210, PP01.235, PP01.236 Karydi, Eirini-Anastasia PP01.207 Kaspar, Allan PP01.329 Kaspar, Brian PP01.329 Katsalouli, Marina PP01.183, PP01.184, PP01.185 Katz, Jon PP01.268 Katz, Sonja OS02.01 Katzberg, Hans PP01.268, PP01.282, PP01.305 Kavanagh, Alex PP01.45 Kawasaki, Hitoshi PP01.356 Kawka, Aleksandra OS03.05 Kay, Claudia Suemi Kamoi OS05.02, PP01.257 Kecelioglu Binnetoglu, Kiymet PP01.109 Kediha, Mohamed Islam PP01.241 Keerthipriya, Muddassu PP01.139 Keerthipriya, Muddasu Suhasini PP01.150 Kenis, Vladimir PP01.342 Kennelly, Laura PP01.280 Kerasidis, Anastassia PP01.287 Keritam, Omar PP01.325 , PP01.326 Kermode, Allan PP01.173 Kerr, Douglas PP01.142 , PP01.59, PP01.71 Keyzor, Ian PP01.366 Khachatryan, Lili PP01.281 Khan, Farid PP01.173 Khan, Waleed PP01.88 Khosla, Tanvir PP01.288 Khuram, Hassan PP01.287 Kief, Katharina PP01.363 Kieseier, Bernd PP01.78 Kihara, Yuki PP01.40 Kilinc, Muhammed OS07.06 Kim, Ahwon PP01.149 Kim, Bongseong PP01.324 Kim, Byoung Joon OS05.04, PP01.330 Kim, Byung-Jo PP01.332, PP01.333 Kim, Dayoung PP01.330 Kim, Ho Cheol PP01.97 Kim, Hyun Gi PP01.273 Kim, Hyunjin OS06.03 , PP01.97 Kim, Jee-Eun PP01.276 Kim, Jin-Ah PP01.331 Kim, Jinhyeong OS06.03 Kim, Jong-Il PP01.331 Kim, Junho OS06.03 Kim, MinGi PP01.273 Kim, Sang Beom PP01.167, PP01.20, PP01.23, PP01.24, PP01.309 Kim, Sang-Beom PP01.350 Kim, Seung Woo PP01.196, PP01.226 Kim, Sooyoung PP01.330 Kim, Sunyoung PP01.299 Kim, Won PP01.97 Kim, Woo-Kyung PP01.167, PP01.20, PP01.23, PP01.24 Kim, Young Chul PP01.97 Kimiskidis, Vasilios PP01.110 Kimura, Yosuke PP01.348 Kinga Sárvári, Anitta PP01.389 Kiriyama, Takao PP01.102, PP01.123 Kirk, Edwin PP01.65 Kirschner, Janbernd PP01.40, PP01.52 Kishnani, Priya OS03.06 Kiss, Christian PP01.325 Klabsook, Ratiporn PP01.174 Klein, Andrea PP01.40 Kleinveld, Vera PP01.325 Kleopa, Kleopas SS10.03 Kletzl, Heidemarie PP01.343 Klopčič, Matic PP01.83 Kluczka, Eugénie PP01.366 Kneer, Katharina PP01.260, SS22.03 Knipp, Florian PP01.325 Knopp, Rachel PP01.295 Ko, Vivian PP01.329 Kobayashi, Shunsuke PP01.386 Kok, Jannigje PP01.329 Kokkinou, Eleftheria PP01.183 , PP01.184 , PP01.185 Koks, Sulev OS06.01 Kolb, Stephen J. PP01.329 Kolbenschlag, Jonas SS22.02, SS22.03 Komaki, Hirofumi PP01.40 Komori, Tetsuo PP01.334 Koneczny, Inga OS08.05 Korngut, Lawrence OS01.01 Korobko, Denis PP01.176 Kosac, Ana PP01.27 Kostera-Pruszczyk, Anna PP01.01, PP01.176 Kotambail, Ananthapadmanabha PP01.150 Koutsioumpa, Charalampia PP01.88 Kovacevic, Gordana PP01.13 Kovalchuk, Maria PP01.281 , PP01.296 Kravitz, David PP01.381 Krenn, Martin OS08.05, PP01.325, PP01.326 Kretz, Alexandra PP01.362 Krittanupong, Supaporn PP01.371 Kroeksattayaporn, Apinya PP01.174 Krutovs, Vladimirs PP01.98 Krämer, Heidrun H. PP01.216 Krümmer, Norma PP01.216 Kteyan, Armine PP01.217 Kubo, Hiroshi OS09.03 Kueh, Kelly PP01.173 Kumutpongpanich, Theerawat PP01.174 Kunsztler, Luca PP01.55 Kuntz, Nancy L. OS02.04 , PP01.01, PP01.156 Kurt, Can Ebru OS07.06 Kusner, Linda SS37.02, SS40.02 Kusunoki, Susumu PP01.240 Kutch, Michael PP01.189, PP01.235, PP01.236 Kuthiala, Manni PP01.343 KUTLU, Gulnihal PP01.190 Kuwahara, Motoi PP01.240 Kvalsund, Michelle PP01.259 Kvarnung, Malin PP01.12 Kwon, Patrick PP01.269 Kwon, Soonwook PP01.324 Kölbel, Heike PP01.243 Küpper, Hanna PP01.248 Küsters, Benno PP01.129 Kıyan, Esen PP01.118 La Rosa, Elena OS07.04 Labella, Beatrice OS02.03, PP01.05, PP01.113 Lacueille, Clémentine PP01.272 Ladisa, Alberto PP01.30 Laforet, Pascal PP01.115, PP01.351, TC11.01 Laforêt, Pascal PP01.132 , PP01.133 , PP01.151 Laghetti, Paola PP01.25 Lagrange, Emmeline PP01.132, PP01.214 Lalla, Marianna PP01.160, PP01.206, PP01.211 Lambert, Phil PP01.75 Lan, Lan PP01.01 Land, Natalie PP01.339 Landrieu, Blandine PP01.133 Lange, Dale J. OS04.04 Langenscheidt, Dieter PP01.325 Lanzi, Gaetana PP01.04, PP01.05 laporte, jocelyn OS06.06 Larimore, Kevin PP01.137, PP01.364 Lasorella, Piergiorgio PP01.352 Lassner, Franz SS22.05 Lauer, Henrik SS22.02 Lauletta, Antonio PP01.187, PP01.232, PP01.86 Laura, Fionda PP01.232 Lauria Pinter, Giuseppe PP01.370 Lauria, Giuseppe TC08.02 Laurie, Steven PP01.129 Lauro, Rita OS07.04 Laverty, Chamindra PP01.71 Lavrov, Andreea PP01.222 Lavrov, Arseniy PP01.78 Law, Eric PP01.65 Le Lam, Thao Nguyen PP01.369 Le Masson, Gwendal PP01.272 Leandri, Massimo OS05.06 Lee, Ada PP01.108 Lee, Do-Yeon PP01.149, PP01.331 Lee, Eun Kyoung PP01.330 Lee, Eun-Jae PP01.97 Lee, Han PP01.239 Lee, Hyung-Soo PP01.353 Lee, Jeehun PP01.71 Lee, Jeong Ho OS06.03 LEE, Jhee PP01.319 Lee, Jin Yong PP01.309 Lee, Jung Hwang PP01.271 Lee, Seungkeun PP01.276 Lee, Sun PP01.215 LEE, William Kah Howe PP01.87 Lee, Yi-Chung OS03.02 Lefeuvre, Claire PP01.151 Lefever, Kristen PP01.221 Lehnerer, Sophie OS02.01, PP01.133 Leila, Tamaoui PP01.06 Leite, M Isabel PP01.192 Leite, M. Isabel PP01.170, PP01.179, PP01.188, PP01.80, PP01.81 Lenti, Roberta PP01.30 Leonardi, Luca OS05.05, PP01.187, PP01.232, PP01.370, PP01.86 Leonardis, Lea PP01.83 Leone, Daniela PP01.55 Leopizzi, Eleonora PP01.47, PP01.84 Lerario, Alberto PP01.104, PP01.105 Lerman, Andrew PP01.278 Lesport, Quentin SS24.03 Leu, Jocelyn H. PP01.208, PP01.209 Leung, Rebecca PP01.221 Levine, Todd OS04.06 Lewis, Richard PP01.268 León, Ana María PP01.341 Li, Jenny PP01.53 Li, Lingyun PP01.215, PP01.218, PP01.219 Li, Mingming OS09.03 Li, Qing PP01.80 Li, Tianhong PP01.239 Li, Xiang PP01.37 Li, Yuebing PP01.210 Lian, Wenlong PP01.37 Liang, Christina OS01.01 Liantonio, Antonella PP01.29 Licandro, Simonetta Andrea PP01.30 Lignos, Dimitris PP01.183, PP01.184 Ligouri, Rocco TC05.02 Liguori, Sara PP01.374 , PP01.375 , PP01.376 , PP01.377 , PP01.378 , PP01.379 Lilleker, James OS01.01 Lim, Jamie PP01.158 Lim, Young-Min PP01.97 Lima Nogueira Tolentino, Alessandra PP01.116 Lin, Boya PP01.218, PP01.219 Lin, Cheng-Chen PP01.311 Lin, Jie PP01.261 Lin, Yen-Hung OS05.03 Lindgren, Ulrika PP01.128 Lindroos, Jenny PP01.222 Litchy, William PP01.270, TC05.03 Little, Courtney PP01.90 Liu, Hai OS01.06 Liu, Haoming PP01.37 Liu, Jingyi PP01.218, PP01.219 Liu, Li PP01.169, PP01.176 Liu, Ling PP01.137 Liu, Nanjun PP01.53 Liu, Weijian PP01.41 Liu, Ya-Fen PP01.387 Liu, Zhan PP01.385 Lizio, Andrea PP01.373 Llarch, Paula PP01.382 Llauradó, Arnau PP01.203 Lledó-Garcia, Rocio OS09.06 Lloyd, Thomas OS01.01 Lo Iacono, Aurora OS04.05, PP01.233 Lo, Daryl Yin Keong PP01.292 Lochmuller, Hanns PL04.01 Lochmüller, Hanns PP01.129 Lochmülller, Hanns PP01.156 , PP01.166 Lodato, Simona OS08.01 Logullo, Francesco PP01.297 Long, Davalos PP01.88 Long, Nick PP01.37, PP01.53 Longone, Patrizia PP01.318 Longoni, Natalia OS07.04 Lopergolo, Diego OS03.05 Lopez, Cristina PP01.214, PP01.231 Lopez, Juan David OS03.03, PP01.246, PP01.258 Lorentzos, Michelle PP01.65 Lorenzoni, Paulo Jose PP01.252, PP01.255, PP01.327 Lorenzoni, Paulo José OS05.02 , PP01.257 Lotti, Antonio PP01.86 Lovas, Gabor PP01.238 Lozi, Claudia PP01.370 Lu, Huifang PP01.90 Lu, Jessica PP01.65 Lu, Yi PP01.261, PP01.265, PP01.267 Lucchetta, Marta PP01.370 Lucchiari, Sabrina OS08.04 Luigetti, Marco OS05.05, PP01.370 Luiza Romanelli Tavares, Vanessa PP01.344 Lukash, Oleg PP01.178 Lundberg, Ingrid E. PP01.262 Luo, Jiangyuan PP01.191 Luo, Sushan PP01.193 Lure-Berregi, María PP01.147 Luzuriaga-Carpio, Diana OS03.03, PP01.246, PP01.258 Lyden, Kate PP01.156 LYECE, YARGUI PP01.338 Lykopoulou, Evangelia PP01.185 Lymperatos, Kosmas PP01.183, PP01.184 Lynch, Karen PP01.283, PP01.285 Lynch, Karen M. PP01.267, PP01.372 Lépée-Aragón, Clara PP01.391 Löscher, Wolfgang PP01.325 Lünemann, Jan D. OS02.01 Macaione, Vincenzo PP01.120 Maccarrone, Amanda PP01.36 Maccarrone, Giulia PP01.47 Macedo-Silva, André PP01.92 Machado, Pedro OS01.01 Mackay, Lori PP01.221 MacNally, Meghan PP01.53 MacPherson, Rebecca PP01.54 Madić, Sanja PP01.358 Madruga-Garrido, Marcos OS01.06 Maes, Frederik OS08.06, PP01.359 Maestri Tassoni, Michelangelo OS04.05, PP01.233 Maestri, Michelangelo PP01.214 Maggi, Lorenzo OS01.04, OS04.03, PP01.156, PP01.21, PP01.22, PP01.25, PP01.96, TC11.03 Maghnie, Mohamad PP01.35 Magistrado-Coxen, Pamela PP01.41 Magri, Francesca OS03.05, OS08.04, PP01.104, PP01.117 Mahajerin, Arash PP01.215 Mahal, Simone PP01.325, PP01.40 Maharramov, Eshgin OS07.06 Mahesh, karthik Vinay PP01.310 Mahoney, Paul PP01.179, PP01.186, PP01.195, PP01.201 Mahuwala, Zabeen PP01.186, PP01.195, PP01.208, PP01.79 Mahuwala, Zabeen K. PP01.201 Maiorano, Simone SS18.01 Maisenbacher, Mathias PP01.131 Major, Kinga Andrea PP01.106 Major, Zoltan Zsigmond PP01.106 Makuch, Mateusz OS06.04 Makunina, Eleonora PP01.298 Malaichamy, Sivasankar PP01.129 Malandrini, Alessandro OS03.05 Malaspina, Andrea PL03.02 Malatesta, Lindsay PP01.132 Malfatti, Edoardo PP01.11, SS08.03 , TC09.03 Malm, Eva PP01.135, PP01.66 Mammen, Andrew L. PP01.262 Mancardi, Margherita PP01.10 Manco, Carlo OS05.05 Mancuso, Michelangelo SS06.03 Manera, Umberto SS25.02 Manfrini, Marianna PP01.343 Manganelli, Fiore OS05.05, PP01.370, SS17.01 Manganotti, Paolo PP01.316 Maniaci, Marisa OS07.04 Maniaol, Angelina PP01.179 Mannila, Maria PP01.12 Mantegazza, Renato OS04.06 , PP01.169, PP01.195, PP01.201, PP01.79 Mantero, Vittorio OS04.03 Mantuano, Paola PP01.29, PP01.30 Manzur, Adnan PP01.33 Manzur, Adnar PP01.11 MAO, Shanshan PP01.161 , PP01.162 Marando, Demetrio PP01.232, PP01.86 Marantz, Jing PP01.82 Maravic, Melissa PP01.339 Marchese, Davide OS08.03 Marchi, Margheria SS44.02 Marchioni, Enrico PP01.86 Marciano E Ortolano, Anita PP01.352 Marcotte, Robert T. PP01.156 Marcuzzo, Stefania PP01.21, PP01.96 Marfia, Girolama Alessandra PP01.370 Margollicci, Giuseppina OS02.03 Maric, Nina PP01.13 Marigliano, Davide OS04.03 Marina, Anna OS07.05 Marinelli, Manuel PP01.31 Marini Bettolo, Chiara PP01.335, PP01.336, PP01.337 Marini, Sofia OS04.05, PP01.86 Mariën, Lore PP01.166 Markandeya, Yogananda PP01.138 Markov, Martin PP01.284 Maroni, Sofia SS18.01 Marques, Wilson PP01.18 Martinovic, Jelena PP01.27 Martins, Bruno PP01.218, PP01.219, PP01.48 Martorell, Loreto PP01.147 Martín-Aguilar, Lorena PP01.382 Martínez, Óscar PP01.391 Martínez-Salmerón, María del Mar PP01.230 Marx, Almuth PP01.346, PP01.347 MARZOUK, BASMA PP01.124 MARZOUK, Basma PP01.126 Marzouk, Basma PP01.125 Masciocchi, Stefano PP01.86 Maselli, Ricardo PP01.239 Masingue, Marion PP01.113 Mason, Stefanie PP01.46 Massa, Roberto OS03.05, PP01.144, PP01.145, PP01.247, PP01.250, PP01.251, PP01.318 Massacesi, Luca PP01.212 Masschaele, Delphine PP01.169, PP01.193 Masson, Riccardo PP01.40 Massucco, Sara OS05.06, PP01.34 Masud, Ameneh PP01.41 Matalonga, Leslie PP01.129 Mataluni, Giorgia PP01.370 Materia, Roberto OS07.04 Mathews, Katherine PP01.108, PP01.46 Matijašević Joković, Suzana PP01.358 Matrone, Federica OS04.05 Matsubara, Tomoyasu PP01.320 Matsumura, Tsuyoshi PP01.85 Matsuoka, Taro PP01.348 Matsuura, Amane PP01.348 Matà, Sabrina PP01.370 Mauermann, Michelle PP01.270, SS13.02 Maurino, Jorge PP01.57 Mauriño, Jorge PP01.340, PP01.341 Mavor, Matthew P. PP01.372 Mazor, Roei D. PP01.199 Mazurkiewicz-Beldzinska, Maria PP01.41 Mazurkiewicz-Bełdzińska, Maria PP01.343 Mazzeo, Anna OS06.02, PP01.370 Mazzà, Claudia PP01.368 Maçaneiro, Bruna PP01.327 McAdam, Laura PP01.40 McAlonis-Downes, Melissa PP01.329 McCarthy, Grace PP01.346, PP01.347 McCombe, Pamela PP01.173 McConnon, Aine PP01.173 McDonald, Craig PP01.41, PP01.68 MCFARLANE, Robert PP01.87 MCKINTY, Ailie PP01.87 McLaughlin, Laurie PP01.221, PP01.237, PP01.238 McMillan, Hugh PP01.40, PP01.71 Meagher, Karoline A OS04.06 Medeiros Mota dos Reis, Tertuliana PP01.344 Mehrabyan, Anahit PP01.134 , PP01.217 Meilleur, Katy PP01.59 Meisel, Andreas OS02.01, OS04.06, OS08.05, PP01.169, PP01.176, PP01.178, PP01.180 Melnik, Evgeniya PP01.342 Melton, Andrew PP01.364 Mendoza, Meg PP01.305 Menezes, Flavia PP01.01 Meng, Stefan HO01.01 Menichella, Daniela PL02.01 Menon, Parvathi OS07.01, OS07.02 Menon, Sarath SS29.02 Mercelis, Rudy PP01.172 Mercuri, Eugenio OS02.05 , PP01.41 , PP01.46, PP01.68, PP01.74 Mercuri, Eugenio M. PP01.52 Mercuri, Eugenio Maria PP01.40, PP01.55 Mertens, Johan PP01.62 Messer, Jordan PP01.59 Messina, Sonia OS06.02 , OS07.04 , PP01.55 Metay, Corinne PP01.113 Meyer, Stefanie PP01.363 Meyer, Thomas TC13.02 Meznaric, Marija PP01.111 Mi-Young, Mi-Young OS05.04 Miceli, Carrie PP01.28 Michael, Eva PP01.08 Michaud, Maud PP01.132 Michelassi, Francesco OS03.05 Michiura, Toru PP01.240 Miguet, Lauren PP01.202 Mihara, Masahito PP01.02 Miladi, Najoua SS05.01 Milanez, Lucina OS07.05 Milic Rasic, Vedrana PP01.27 Mills, Kevin PP01.44 Min, Ju-Hong PP01.324 Minetti, Carlo PP01.36 Minks, Eduard PP01.175 Minn, Yang-Ki PP01.20, PP01.23, PP01.24, PP01.309 Minn, Yangki PP01.227, PP01.302 Miotto, Matteo OS08.01 Miranda, Rubén PP01.63 Mironovs, Staņislavs PP01.274 Misheva, Mariya OS06.04 Missaglia, Sara OS03.01 Mitchell, Ryan PP01.75 Mitsui, Yoshiyuki PP01.240 Miyagoe-Suzuki, Yuko PP01.386 Miyamoto, Yosuke PP01.348 Mladenovic, Jelena PP01.27 Moat, Dionne PP01.336, PP01.337 Modi, Manish PP01.290 Modi, Tanish PP01.300 Moggio, Maurizio OS01.04 Mohassel, Payam OS01.01 Molitierno, Nicola OS08.04, PP01.104, PP01.105 Mondou, Elsa OS07.03 Monforte, Mauro OS08.03 Mongini, Tiziana PP01.47, PP01.84 Mongini, Tiziana Enrica OS01.04 Monickaraj, Judith PP01.367 Monif, Mastura PP01.238 Montolio, Marisol PP01.57 Moon, Sookin PP01.148 Moraes, Ana PP01.91 Morando, Simone PP01.36 Moreno, Cristiane PP01.40 Moret, Federica PP01.370 Moretti, Antimo PP01.374, PP01.375, PP01.376, PP01.377, PP01.378, PP01.379 Morgan, Jennifer PP01.19 Morgenroth, Lauren OS01.02 Mori, Eiichiro PP01.123 Morimoto, Masafumi PP01.348 Morino, Stefania PP01.187, PP01.232 morino, stefania PP01.86 Moroni, Isabella PP01.21, PP01.22, PP01.25 Morrison, Alexander PP01.88 Moschou, Maria PP01.110 Mou, Yongchao PP01.37 Mouly, Vincent PP01.31 Moura, Ana Carolina OS07.05 Mousser, Souheila PP01.69 Moustafellou, Anna PP01.183, PP01.184, PP01.185 Mouzis, Nikolaos PP01.183, PP01.184 Moynihan, Meghan PP01.222 Mozaffar, Tahseen PP01.108, PP01.90 Muaremoska Kanzoska, Ljelja PP01.357 Mucha, Olga PP01.26 Muhmann, David PP01.243 Muni Lofra, Robert PP01.335, PP01.336, PP01.337 Munot, Pinki PP01.11, PP01.33 Muntean Firanescu, Cristina PP01.12 Muntoni, Francesco OS02.02, PP01.15, PP01.19, PP01.33, PP01.40, PP01.41, PP01.44 , PP01.45 , PP01.52, SS28.01 Muppidi, Srikanth PP01.228, PP01.78, PP01.88 Murai, Hiroyuki OS04.06, PP01.210 Murayama, Shigeo PP01.320 Musumeci, Olimpia PP01.119, PP01.120, PP01.127 , SS39.03 Muñoz, Juan Pablo OS03.03, PP01.246, PP01.258 Myo, Arkar PP01.87 Myszka, Małgorzata PP01.26 Männlin, Stephanie SS22.02 Müller, Petra PP01.325 Müller-Felber, Wolfgang OS02.04 Nadaj-Pakleza, Aleksandra PP01.132 Naddaf, Elie OS01.01, PP01.90 Nag, Heidi Elisabeth PP01.40 Nagai, Yoshitaka PP01.240, PP01.320, PP01.322 Nagano, Mamoru PP01.320 Nagaraju, Kanneboyina OS01.02 Nagy, Sara PP01.154 Naito, Hiroyuki OS04.04 Najem, Catherine PP01.170 Nakahara, Jin PP01.198 Nakamura, Harumasa PP01.85 Nakamura, Hiroto PP01.240 Nakamura, Shuhei PP01.123 Nalepa, Anna PP01.26 Nalini, Atchayaram PP01.150, SS31.02 Namura, Hitoshi PP01.240 Nanaura, Hitoki PP01.102, PP01.123 Napoli, Laura PP01.104, PP01.105 Narayanaswami, Pushpa PP01.159 Nardes dos Santos, Flávia PP01.344 Nardes, Flávia PP01.43 Narrayanaswami, Pushpa TS10.02 Nascimento Osorio, Andrés PP01.41 Nascimento, Andres PP01.46 Nascimento, Andrés PP01.341 Nashi, Saraswati PP01.139, PP01.150 Nathani, Dev PP01.245 Nathorst-Böös, Kristofer OS02.06 Natoli, Silvia OS04.05 Naylor, Maria PP01.59 , PP01.71 Nazha, Birouk PP01.06 , PP01.07 NDOYE SALL, NDEYE FATOU PP01.354 Nectoux, Juliette PP01.113 Needham, Merilee OS01.01 Needham, Merrilee PP01.99 Neil, David OS01.06 Nel, Melissa PP01.259 Nelson, Leslie PP01.339 , PP01.343, PP01.82 Nelson, Stanley PP01.28 Nennesmo, Inger PP01.128 Neyens, Martine PP01.208 Ng, Joanne PP01.45 Nicolas, Guillaume PP01.132, PP01.151, PP01.351 Nicolini De Gaetano, Lucia PP01.22, PP01.96 Nicolis, Filippo PP01.03 Nicolosi, Silvia PP01.100 Nigro, Vincenzo PL01.02 Nikitin, Sergei PP01.342 Niks, Erik OS01.06, PP01.40 Niks, Erik H. PP01.01, PP01.64 Nilsson, Emil PP01.128 Nilsson, Malin PP01.349 Nishimatsu, Shin-ichiro PP01.02, PP01.76 Nishimori, Yukako PP01.102, PP01.123 Nishino, Ichizo OS03.04, PP01.123, PP01.140, PP01.85, TC07.02 Niu, Dau-Ming PP01.114 Nobile-Orazio, Eduardo PP01.268 , PP01.269 , PP01.282, PP01.370 Nobili, Lino PP01.09, PP01.10, PP01.36 Noel, Wim PP01.177, PP01.210, PP01.235 , PP01.236 Noer, Julie B PP01.362 Nogara, Leonardo PP01.152 Noguchi, Satoru OS03.04, PP01.140 Noioso, Ciro Maria PP01.204 Nollet, Fran OS07.03 Norcia, Giulia PP01.55 Norris, Sarah PP01.65 Notturno, Francesca PP01.370 Nouioua, Sonia PP01.321, PP01.69 , PP01.70 Noukens, Jan PP01.01 Noushad, Muhammed Ameen PP01.213 Novelli, Giuseppe PP01.145 Nowacek, Dustin PP01.215 Nowak, Richard J. PP01.170, PP01.175, PP01.80, PP01.81 Nuccetelli, Marzia PP01.144, PP01.145, PP01.250 Nucifora, Elsa PP01.153 Nunez, Daniel PP01.171 Nunez, Manuel PP01.267 Nuredini, Andi OS01.04 Nyougui, Elisabeth OS09.04 Nümann, Astrid PP01.154 O'Toole, Orna PP01.280, PP01.301 Obadović, Ksenija PP01.358 Obadović, Vanja PP01.358 Obrochta Moss, Kristin PP01.137 Obrochta-Moss, Kristin PP01.364 Octaviana, Fitri PP01.308 Oezturk, Menekse OS02.01 Ogrodnik, Mikolaj SS46.01 Oh, Eungseok PP01.330 Oh, Jeeyoung PP01.330 Oh, Seong-il PP01.330 Oh, Sun-Young PP01.294 Ohagen, Patrik PP01.214, PP01.231 Ohashi, Tomohito PP01.102, PP01.123 Ohsawa, Yutaka PP01.02 , PP01.76 Okada, Kensuke PP01.198 Okuba, Kei PP01.356 Oldfors, Anders PP01.08, PP01.128, PP01.349 Oldfors, Carola PP01.128 Oldham, Andrew PP01.366 Oliveira, Thiago PP01.116 Oliveri, Emanuele PP01.05 Olivieri, Emanuele OS02.03 Olulana, Oluwaseyi PP01.287 Opsomer, Matthias OS08.06 , PP01.61 , PP01.62 Orban, Nikolett PP01.312 Ortez, Carlos PP01.57 Ortiz-Corredor, Fernando OS03.03, PP01.246, PP01.258 Osredkar, Damjan OS08.02, PP01.40 Ostojic, Slavica PP01.13 Ostrovskiy, Denis PP01.132 Ottelli, Elisa PP01.03 Ottoboni, Linda OS08.01 Ouaja, Rabye PP01.286 Ouchkat, Fatima PP01.124, PP01.125 OUISSEM, BENCHAABI PP01.338 Oury, Julien PP01.166 Oved, Kfir PP01.199 Oyama, Genko PP01.356 Ozonoff, Alexander PP01.89 Ozturk, Gulten PP01.109 Ozyurt Kose, Selen OS09.05 O’Neil, Daniel PP01.129 Packnett, Elizabeth PP01.222 Pacucci, Eleonora PP01.317 Padovani, Alessandro OS02.03, PP01.03, PP01.04, PP01.05, PP01.323 Page, Jess PP01.335, PP01.336, PP01.337 Pagliarani, Serena OS08.04 Paik, Julie SS41.02 Pajot, François PP01.168 Paker, Asif PP01.261, PP01.265 , PP01.267 Pal, Endre PP01.312 Palace, Jacqueline PP01.156 Palombo, Flavia OS03.05 Paltiel, A. David PP01.89 Pamfil, Cristina PP01.106 Pandit, Awadh Kishor PP01.220 Pane, Marika OS01.06, PP01.55 Panicucci, Chiara PP01.11, PP01.34 , PP01.35 , PP01.36 Panos-Basterra, Paula PP01.113 Paoletta, Marco PP01.374, PP01.375, PP01.376, PP01.377, PP01.378, PP01.379 Paolicelli, Damiano PP01.317 Paolucci, Sophia PP01.55 Papadaki, Iliana PP01.183 Papadaki, Ilianna PP01.184 Papanikolaou, Aikaterini PP01.183 Parasrampuria, Ridhi PP01.53 Paravisi, Elena PP01.61, PP01.62 Pareyson, Davide SS21.02 , TC11.02 Parihar, Jasmine PP01.220 Parinello, Guillaume OS08.02, PP01.369 Parisi, Mosè OS08.04, PP01.104, PP01.105 Park, Geun-Young PP01.304 Park, Hyung Jun PP01.167, PP01.20, PP01.23 , PP01.24 Park, Jeongju PP01.196 Park, Jin-Mo PP01.146 Park, Jin-Sung PP01.146 , PP01.175, PP01.97 Park, Jin-Woo PP01.333 Park, Jinse PP01.330 Park, Jinwoo PP01.332 , SS34.03 Parlindungan, Faisal PP01.308 Parman, Yesim PP01.118 Parodi, Andrea PP01.74 Parravicini, Stefano PP01.40 Pascual-Goñi, Elba PP01.382 Pascuzzi, Robert OS04.04, PP01.186, PP01.79 Pascuzzi, Robert M. PP01.195, PP01.201 Patel, Reena PP01.284 Patel, Vihar PP01.239 Patki, Kiran PP01.53 Paul, David PP01.108 Pavani, Rodrigo OS04.06 Pavey, Nathan OS07.01, OS07.02 Pavlou, Miranta PP01.183, PP01.184 Pawaskar, Dipti OS04.06 Pechmann, Astrid PP01.40 Pedemonte, Marina OS07.04, PP01.35, PP01.36 Pedersen, Estrid PP01.389 Pedroso, José PP01.116 Peer, Cody J. PP01.81 Peeters, Herman PP01.61 Peeters, Ronald OS08.06, PP01.359 Pegoraro, Elena OS01.02, OS01.04, PP01.42 Pellacani, Enzo PP01.112, PP01.163, PP01.164, PP01.165, PP01.18, PP01.91 , PP01.92 , PP01.93 , PP01.94 , PP01.95 Pellerin, David PP01.154 Pensrisirikul, Benjamat PP01.371 Pepe, Georgis PP01.110 Perez de Arenaza, Diego PP01.153 Perez Ruixo, Juan-Jose PP01.208 Peric, Stojan PP01.143, PP01.159, PP01.268, PP01.279, PP01.282 Peris-Moreno, Dulce OS01.03 Perlee, Lorah OS04.06 Perlman, Seth J. PP01.46 Perna, Alessia PP01.145 Persson, Emma PP01.279 Persson, Emma K PP01.289 Persson, Emma K. PP01.282 Pesic-Heuvrard, Natacha PP01.133 Pesovic, Jovan PP01.143, PP01.27 Petat, Eva PL01.03 Petersson, Malin OS04.02, PP01.205 Petitta, Ilaria PP01.144 Petri, Susanne OS07.03 Petrie, Dennis PP01.237 Petrucci, Antonio PP01.145, PP01.247, PP01.86 Petschke, Kurt PP01.89 Petterson, Malin PP01.197 Pezzini, Camilla OS09.02, PP01.60 Peña Padilla, Christian PP01.129 Pešović, Jovan PP01.358 Pfaff, Abigail OS06.01 Pham, Tan P. PP01.366 Phan, Han PP01.46 Philips, Glenn PP01.215 Phillips, Glenn PP01.218, PP01.219 Pianto, Samuele PP01.03 Piasecka–Stryczyńska, Karolina OS07.03 Piccione, Ezequiel OS01.01 Piccolo, Gwenaelle OS06.06 Pichiecchio, Anna PP01.100 Piehl, Fredrik OS04.02, OS06.05, OS09.03, PP01.197, PP01.205 Pierno, Sabata PP01.30 Piga, Daniela OS08.04, PP01.117 Pikus, Liubov PP01.298 Pini, Veronica OS02.02 , PP01.15, PP01.19 Pinto, Ashwin PP01.213 Pinto, Marcus PP01.295, PP01.300, SS27.02 Pinto, Marcus Vinicius TC03.03 Pinzur, Lena PP01.199 Pirreca, Shelley PP01.65 Piscosquito, Giuseppe PP01.204, PP01.370 Plantone, Domenico OS05.05 Plecko, Barbara PP01.325 Podhorna, Jana PP01.194 Pogosean, Artor PP01.234 Polavarapu, Kiran PP01.129 , PP01.139, PP01.150 Poleur, Margaux OS08.02, PP01.369 Poli, Loris OS02.03, PP01.04, PP01.05, PP01.323, PP01.370 Pons, Roser PP01.185 Poon, Ming Chung PP01.345 Porco, Dania M.D. PP01.53 Porrello, Emanuela PP01.19 Poulidou, Vasiliki PP01.110 Poupiot, Jérôme PL01.03 Povedano, Monica SS31.01 Povedano, Mónica PP01.340 Power, Robert PP01.137 Poza, Juan José PP01.147 Press, Rayomand PP01.12 Preusse, Corinna PP01.180 Previtali, Stefano OS01.04, PP01.71 Previtali, Stefano Carlo OS02.02, OS04.03, PP01.15, PP01.19 Prigent, Hélène PP01.132, PP01.151 Primiano, Guido OS05.05 , PP01.130 Prior, Robert OS06.04 Privolizzi, Riccardo PP01.45 Proud, Crystal PP01.68 Proud, Crystal M. PP01.52 Prufer, Alexandra PP01.43 Prunetti, Paolo PP01.244 Psarra, Aggeliki PP01.207 Psichari, Iliana PP01.183 Psichari, Ilianna PP01.184 Pugliese, Alessia OS04.05 Puig, Cristina PP01.341 Pulley, Michael T PP01.132 Pumberger, Matthias PP01.180 Punga, Anna Rostedt PP01.234 Pupillo, Elisabetta SS29.01 Putko, Brendan PP01.300 Puzzi, Mattia PP01.03 Pyko, Andrei OS06.05 Pál, Endre PP01.141 Péréon, Yann PP01.132 Qi, Cynthia PP01.215, PP01.218, PP01.219 Qi, Yulan PP01.364 Qin, Yating PP01.362 Qiu, Yi-Hua PP01.384 Quagliotto, Magda PP01.316 Quarta, Raffaella PP01.30, PP01.31 Quasthoff, Stefan PP01.325 Querol, Luis PP01.261, PP01.267, PP01.268, PP01.279, PP01.282, PP01.284, PP01.382 Quick, Stephen PP01.313 Quijano-Roy, Susana PP01.52 Quinn, Colin OS01.01 Quinn, John OS06.01 Quintiens, Jilmen PP01.61, PP01.62 Raaphorst, Joost OS01.05, PP01.103 Rabinowicz, Shira PP01.33 Radenkovic, Lana PP01.143 Radenković, Lana PP01.358 Radovanovic, Nemanja PP01.143 Radovanović, Nemanja PP01.358 Ragole, Thomas PP01.132 Rainey, Amy PP01.108 Raja, Shruti M PP01.132 Rajabally, Yusuf A. PP01.268 Rajasingham, Thulashitha PP01.108 Raju, Dheeraj PP01.52 Rakocevic-Stojanovic, Vidosava PP01.143 Ramadža, Danijela Petković PP01.129 Ramchandren, Sindhu PP01.175, PP01.177, PP01.189, PP01.208, PP01.209, PP01.210, PP01.235, PP01.236 Ramdane Cherif, Ferroudja PP01.69, PP01.70 Ramdane-Cherif, Farroudja PP01.321 Ramdas, Sithara PP01.01 , TC04.03 Ramirez-Montaño, Diana OS03.03, PP01.246, PP01.258 Ramos Masa, Maria PP01.223 Ramprasad, V L PP01.139 Randhawa, Simrat PP01.159 Ranieri, Enzo PP01.65 Ranum, Laura P. W. PP01.320 Rappold, Mika PP01.325 Rath, Jakob PP01.325, PP01.326 Ravaglia, Sabrina OS01.04, PP01.100, PP01.244 Ravera, Beatrice OS08.03 Ray, Soma PP01.142, PP01.59, PP01.71 Rayner, Chris PP01.137 Raza, Syed PP01.168 Rebel, Marcos PP01.43 Recchia, Fabio Anastasio PP01.32 Reddel, Stephen PP01.173, PP01.228 , PP01.237, PP01.238, PP01.78 Reddel, Stephen W. PP01.178 Reddy, Divya PP01.53 Reef, Sharon PP01.199 Rehaume, Linda PP01.160 REID, Alice PP01.87 Reilly, Mary SS19.01 Rejdak, Konrad OS07.03 Remmerie, Anneleen PP01.269, PP01.278 Renaud, Mathilde PP01.154 Renegarajan, Sophie PP01.28 Repetto, Agnese PP01.35 Reshef, Ran PP01.171 Restrepo, Juan Luis PP01.203 Retailleau, Emilie PP01.351 Reviers, Evy SS45.01 Reyes, Óscar PP01.368 Reyna, Sandra P. PP01.52 Rezania, Fatemeh OS09.01 , PP01.303 Ribera Armengol, Mar OS09.06 Ribolla, Fulvia PP01.84 Ricci, Edoardo PP01.316 Ricci, Enzo OS08.03 Ricci, Federica Silvia PP01.40 Ricci, Giulia OS01.04 Ricciardi, Dario OS04.03, PP01.155, PP01.370 Richard, Isabelle PL01.03 Richman, David PP01.171, PP01.239 RIEDEL, NATALIA OS01.03 Rigamonti, Andrea OS04.03 Righi, Delia OS05.05 Rigler, Nicole PP01.101 Riley, Nicholas PP01.346 , PP01.347 Rinaldi, Simon OS06.04, PP01.282, PP01.284 Rini, Nicasio OS04.03, PP01.231 Riolo, Giorgia PP01.96 Ripolone, Michela PP01.104, PP01.105 Risi, Barbara OS02.03 , OS03.05, PP01.03 , PP01.04 , PP01.05 , PP01.100, PP01.323, PP01.370 Riso, Vittorio PP01.145 Riyanto, Dinda Larastika PP01.308 Rizzo, Federica OS08.01 Robb, Stephanie PP01.33 Roberts, Lauren PP01.314 Roberts, Leslie OS09.01, PP01.303 Roberts, Mark PP01.366 Rocchi, Camilla PP01.247, PP01.251, PP01.318 Rocchiccioli, Silvia PP01.32 Roddate, Marija PP01.274, PP01.98 Rodolico, Carmelo OS01.04, OS04.05, OS06.02, PP01.119, PP01.120, PP01.127, PP01.231 Rodrigues da Silva, Ádria PP01.255 Rodrigues, Gonçalo M.C. PP01.189 Rodrigues, Paula Raquel do Vale Pascoal OS05.02, PP01.257 Rodrigues, Thaina Louise PP01.112 , PP01.164 Rodrigues, Thainá Louise PP01.163, PP01.18 Rodriguez, Alicia PP01.107 Rodriguez, Sebastian PP01.262 Rodríguez, Alicia Aurora PP01.391 Rodríguez-Camacho, Marta PP01.230 Roelants, Caroline PP01.388 Rohonczi, Mirtill PP01.312 Rolle, Enrica PP01.47, PP01.84 Romano, Angela OS05.05 Romano, Carmela PP01.86 Ronchi, Dario OS08.04 , PP01.104, PP01.117 Roos, Andreas PP01.129, PP01.180, PP01.243 Roostalu, Urmas PP01.389 Rosen, Orli OS01.06 Rosenberger, Andreas Dybesland PP01.40 Rosenfeld, Marie PP01.53 Rosero, Spencer PP01.367 Rosewich, Hendrik PP01.248 Rosignoli, Paula Silvia PP01.327 Rosow, Laura OS01.01 Ross, Lauren OS09.01, PP01.303 Ross, Ryan PP01.222 Rossi, Salvatore PP01.145 Rossi, Simone PP01.86 Rossini, Elena OS04.03, OS04.05, PP01.187 , PP01.231, PP01.232, PP01.86 Rosso, Tiziana PP01.370 Rostedt Punga, Anna TC05.01 Rouyer, Alice PP01.151 Roveta, Edoardo OS05.06 Roy, Bhaskar OS01.01, PP01.234, PP01.279, PP01.88, PP01.89 Rozsa, Csilla PP01.238 Ruas, Erica PP01.43 Ruck, Tobias OS01.01, PP01.129 Rudnicki, Michael PP01.75 Rueckert, Jens-Carsten PP01.180 Ruffin, Nicolas OS09.03 Ruggero, Susanna PP01.297 Ruggieri, Alessandra PP01.21, PP01.22, PP01.25, PP01.96 Ruggieri, Martino PP01.36 Ruggiero, Lucia OS01.04, OS03.05, PP01.352 Rugginini, Bianca PP01.244 Rugiero, Marcelo PP01.153 Ruiter, Annabel M OS02.01 Ruiz-Ospina, Edicson OS03.03, PP01.246 , PP01.258 Russell, Jacqu PP01.65 Russo, Anna PP01.352 Russo, Massimo OS06.02 Russo, Rosario PP01.352 Ruszin-Perecz, Brigitta PP01.141 Rzepiński, Łukasz PP01.178, PP01.193 Röttger, Richard OS09.04 Sabbatini, Daniele OS01.02, PP01.42 Sabino, Andrea OS05.05 Sacca, Francesco PP01.211 Sacconi, Sabrina OS04.04, PP01.132, PP01.195, PP01.201, PP01.214, PP01.231, PP01.79, TC07.03 Sadjadi, Reza PP01.88 Saeki, Satoru PP01.334 Safri, Ahmad Yanuar PP01.308 Sahagian, Gregory PP01.169 Said, Ibrahim OS07.04 Saigoh, Kazumasa PP01.240, PP01.322 Saito, Fumiaki PP01.386 Saito, Kayoko PP01.52 Saito, Yoshihiko PP01.85 Saito, Yuko PP01.320 Sakata, Hanami PP01.240 Sakurai, Hidetoshi PP01.386 Salerno, Franco PP01.22, PP01.96 Saltarella, Ilaria PP01.25 Salvadó, Maria PP01.203 Salvalaggio, Alessandro PP01.297, PP01.370 Salvi, Erika PP01.22 Sam, Geuens PP01.40 Sambruni, Irene PP01.22 Samuelsson, Kristin PP01.12 SAMUKAWA, MAKOTO PP01.322 Samukawa, Makoto PP01.240 , PP01.320 Sandri, Marco OS09.02 , PP01.152, PP01.60, SS46.03 Sandroni, Paola SS34.02 Sanga, Panna PP01.175 Sangrut, Phuettha PP01.371 Sansone, Valeria OS01.06, PP01.74 , SS18.01 Sansone, Valeria Ada PP01.373 Sansone, Valeria Ada Maria PP01.55 Santilli, Ashley PP01.101 Santorelli, Filippo PP01.154 Santorelli, Filippo Maria OS03.05 Santos Benetti, Webert Alex PP01.252 Santos Silva, Claudia OS07.02 Santos, Schwend PP01.364 Sarajlija, Adrijan PP01.13 Sareidaki, Doxa-Eleni PP01.183, PP01.184, PP01.185 Sarkozy, Anna PP01.11, PP01.33 Sarparanta, Jaakko PP01.21 SARR, MAMADOU MOUSTAPHA PP01.354 Sartori, Roberta OS09.02, PP01.60 Savarese, Marco OS03.05, PP01.21, TC14.02 Savic Pavicevic, Dusanka PP01.27 Savic, Natasa PP01.179, PP01.214 , PP01.229 Savic-Pavicevic, Dusanka PP01.143 Savić Pavićević, Dušanka PP01.358 Saxon, David PP01.287 Scannell Bryan, Molly PP01.285 Schaarschmidt, Marco OS09.04 Schara, Ulrike PP01.243 Schara-Schmidt, Ulrike PP01.129, PP01.40, TC09.01 Scheiner, Christophe A PP01.132 Schelfhout, Matthias PP01.63 , PP01.64 Schenone, Angelo OS05.06, PP01.370 Schenone, Cristina OS05.06 Schepers, Josef OS09.04 Schipani, Elke PP01.270 Schirinzi, Erika PP01.370 Schlader-Ratzinger, Michaela PP01.170 Schmidhammer, R SS22.08 Schmidt, Jens OS01.01 Schneider-Gold, Christiane PP01.216 Schoser, Benedikt PL01.01 Schouten, Meyke PP01.129 Schroeter, Michael OS02.01 Schuelke, Markus PP01.180 Schuhmann, Martin PP01.260 Schuller, Jan C. PP01.285, PP01.372 Schumann, Martin SS22.03 Schutze, Katherine PP01.99 Schwab, Matthias PP01.362 Schwabe, Paula PP01.363 Schwaede, Abigail N. PP01.01 Schwerin-Nagl, Anette PP01.325 Schänzer, Anne PP01.129 Schömig, Friederik PP01.180 Sciacco, Monica OS08.04, PP01.104 Sciarrone, Maria Ausilia OS05.05 Scola, Rosana Herminia OS05.02, PP01.252, PP01.257, PP01.327 Scola, Rosana Hermínia PP01.255 Scoto, Mariacristina PP01.33, PP01.44 Secil, Yaprak PP01.291 SECK, LALA BOUNA PP01.354 Seferian, Andrea OS02.04 Segall, Hailey PP01.134 Seghers, Ineke PP01.193 Sehinovych, Ihor PP01.41 Seiderer, Linda OS09.01 Seier, Mara PP01.256 Sejersen, Thomas OS02.06, PP01.40 Sellami, Noura PP01.132, PP01.133 Seluzhytsky, Alex PP01.285, PP01.372 Semciw, Adam PP01.313 Sen, Annabel PP01.28 SENGHOR, HENRIETTE PP01.354 Seo, Jung-Hwa PP01.266 Seok, Jin Myoung PP01.330 Servais, Aude PP01.151 Servais, Laurent OS08.02, PP01.343, PP01.369, PP01.52 , PP01.53 , SS05.03 , 659 Seshadri, Madhav PP01.171 Seth, Arjun OS01.01, PP01.169, PP01.278, PP01.283, PP01.285 Sethuraman, Natarajan PP01.53 Sevilla, Teresa PP01.175 Sframeli, Maria OS07.04 Shah, Hemant PP01.305 Shah, Jaimin OS01.01 Shaibani, Aziz OS01.01, OS04.06 Shane, Olivia PP01.48 SHARMA, MEHAR PP01.361 Shaughnessy, Laura PP01.222 Sheehan, Jennie TC04.02 Sheffield, James PP01.268 Shehatha, Ruby PP01.99 Sheikh Saker, Tahani PP01.381 Shelly, Shahar OS05.01 , PP01.159 , PP01.160 , TS10.01 Shen, Yan PP01.128 Sherman, Steven OS04.06 Shieh, Perry OS01.01, PP01.68 , PP01.71 Shieh, Perry B. OS02.04, PP01.52 Shimazaki, Rui PP01.123, PP01.140 Shimizu, Hironori PP01.102 Shimizu-Motohashi, Yuko PP01.40 Shin, Dong Wook PP01.324 Shin, Ha Young PP01.173, PP01.226, PP01.273 Shin, Kyong Jin PP01.200 , PP01.330 Shin, Sarah PP01.65 Shiota, Tomo PP01.102, PP01.123 Shock, Anthony OS09.06 Shouman, Kamal PP01.300 Shree, Ritu PP01.290 Shupe, Christina PP01.367 Sian, Veronica PP01.21 Siciliano, Gabriele OS01.04, PP01.32, PP01.370, TC14.03 Siddiqui, Uzma PP01.159, PP01.206, PP01.211 Sidhu, Ishnoor PP01.137 Signore, Giovanni PP01.32 Signori, Alessio PP01.370 SIHAM, HALLAL PP01.338 Sikorski, Patricia SS43.01 Silva, Ana Marina PP01.112, PP01.116, PP01.163, PP01.164, PP01.18, PP01.92, PP01.93, PP01.94, PP01.95 Silva, Erika Christina PP01.255 Silvestri, Gabriella PP01.145 Silvestri, Nicholas PP01.168, PP01.215 Simmons, Zachary OS01.01 Simms, Laura PP01.335, PP01.336, PP01.337 Singh, Rajesh kumar PP01.220 Singhvi-Hanns, Laura OS09.06 Sinha, Uma PP01.108 Sipos, Andrea PP01.141 , PP01.312 Sirbu, Carmen Adella PP01.115 Sirina, Julija OS09.06 Sivakumar, Kumaraswamy OS01.01, PP01.175 Skopek, Jiri OS07.03 Skripuletz, Thomas PP01.269 Slader, Cassandra PP01.214, PP01.231 Slowik, Agnieszka PP01.159 Sluzevich, Jason PP01.90 Smilowski, Marek PP01.159, PP01.175, PP01.206 , PP01.211 Smith, Barbara K. OS02.04 Smith, Gordon PP01.215 Smith, Tanya PP01.99 Smithuis, Frank OS01.05 So, Jungmin PP01.353 Soekhradj, Jayant A. PP01.63, PP01.64 Sohn, Eunhee PP01.330 Solidoro, Paolo PP01.84 Solé, Guilhem PP01.194, PP01.231 Somma, Teresa PP01.352 Sommer, Claudia PP01.267 , SS10.01 , SS46.02 Song, Guochen PP01.82 Song, Hee-Jung PP01.309 Songsliph, Nicha PP01.45 SONIA, NOUIOUA PP01.338 Soontrapa, Pannathat PP01.174 Sorgente, Annamaria PP01.03 Sorrenti, Benedetta OS04.03 Souttou, Amal OS04.06 SOYLU, Çağlar PP01.380 Soysal, Aysun PP01.355 Spagni, Gregorio PP01.212, PP01.86 Spallone, Vincenza SS27.03 Spalloni, Alida PP01.318 Spelman, Tim PP01.173 Spendiff, Sally PP01.129, PP01.166, SS42.03 Spies, Judith TC08.03 Spin, Paul PP01.346, PP01.347 Spinner, Robert PP01.270, SS23.03 Spitali, Pietro PP01.73 Sproule, Douglas PP01.108 Squillaci, Angelica OS06.02 Srikanth, Nikethana PP01.346, PP01.347 Srivastava, Achal kumar PP01.220 St. Andre, Michael PP01.37 Stadheim, Terrance A. PP01.37 Stahl, Jan-Hendrik PP01.260, SS22.03 Stahl, Mark PP01.329 Stamatakis, Iasonas-George PP01.183, PP01.184, PP01.185 Starling, Ana Lucia OS07.05 Staropoli, John PP01.82 Stascheit, Frauke OS02.01 Staskus, Lexa PP01.137 Statland, Jeffrey PP01.82 Stavropoulou- De Lorenzo, Sotiria PP01.207 Steeland, Sophie PP01.223 Steffan, Davide PP01.152 Stein, Maike OS02.01 Steiner, Leonie PP01.40 Steinkühler, Christian PP01.30 Stenzel, Werner PP01.180 Sternberg, Damien PP01.241 Stettner, Mark PP01.282, PP01.284 Stinghel Pellacani, Enzo PP01.116 Stobbe, Alica PP01.363 Stocker, Grace PP01.129 Stoddart, Leigh OS09.06 Stojkovic, Tanya PP01.113, SS21.01 Stokke, Simen PP01.40 Strano, Camilla PP01.370 Strataki, Eleni PP01.182 Straub, Volker PP01.108, PP01.40 Street, Jonathan PP01.368 Streicher, Nicholas PP01.287 Striano, Pasquale PP01.36 Strijbos, Paul OS08.02 Stromillo, Maria Laura OS05.05 Stroppi, Marco PP01.117 Strupp, Michael PP01.154 Study Group, MGBase PP01.173 Stufano, Angela OS05.05 Stögmann, Eva PP01.325 Su, Mao-Yuan OS05.03 Su, Wendy PP01.228 Suboh, Amani OS02.01, OS08.05 Suel, Laurence PL01.03 Suemi Kamoi Kay, Cláudia PP01.252, PP01.255 Sugata, Mayu PP01.102 Sugie, Kazuma OS03.04, PP01.102, PP01.123 , PP01.140 Suh, Bum Chun PP01.167, PP01.20, PP01.23, PP01.24, PP01.309, PP01.350 Suh, Jee Hyun PP01.49 , PP01.50 Suk, Jungim PP01.16 Suman, Adrian Florentin PP01.32 Summers, Dave PP01.343 Sun, Fang PP01.169 Sun, Yuyao PP01.283, PP01.285 Suna, Inga PP01.275 Sunada, Yoshihide PP01.02, PP01.76 Sunebo, Sofie PP01.128 Sung, Jung-Joon OS06.03, PP01.149, PP01.331 Sunnegardh, Oskar OS02.06 suri, vaishali PP01.361 Suárez, Bernardita PP01.58 Swijsen, Ann PP01.158 SY, MAMADOU PP01.354 Synofzik, Matthis PP01.154 Szabo, Lena OS08.02 Szabolcs, Szatmari PP01.115 Szczałuba, Krzysztof OS03.05 Szmulewicz, David OS09.01, PP01.303 Sáiz, Pilar OS07.03 Sánchez-Tejerina, Daniel PP01.203 Tae, Woo-Suk PP01.333 Takacs, Sara PP01.132 Takada, Rei PP01.348 Takahashi, Masanori P. PP01.191 Takatoshi, Sato PP01.40 Takeshita, Erit PP01.40 Takizawa, Hotake PP01.85 Taliani, Rebecca PP01.212 Talloen, Willem PP01.156 Tamaoui, Leila PP01.124, PP01.124 , PP01.125 , PP01.126 Tan, Elizabeth Ming Jing PP01.292 Tan, Ersin OS07.06 Tan, Pauline PP01.37 Tan, Zhibin PP01.292 Tanaka, Akito PP01.102 Tanaka, Hiroaki PP01.102 Tang, Fengming PP01.80, PP01.81 Tannemaat, Martijn R OS02.01 Tanner, Stephanie PP01.336 Tanriverdi, Zeynep PP01.291 Tarancón, Thais OS04.04 Tarancón, Thaïs PP01.186, PP01.195, PP01.201, PP01.231 , PP01.79 Tard, Céline PP01.132 Tasca, Giorgio OS08.03 Taskin, Seyhan PP01.181 Tavian, Daniela OS03.01 Teng, Sophie PP01.239, PP01.288 Teng, Yee Sean PP01.292 Teran, Nataša PP01.83 Teranishi, Hirofumi PP01.191 , PP01.194 Terrancle, Angeles PP01.340, PP01.57 Tetorou, Konstantina PP01.45 Tetunashvili, Kristine PP01.56 Thaisetthawatkul, Pariwat PP01.131, PP01.256 Thams, Sebastian PP01.12 Thenral, S G PP01.139 Thiele, Simone PP01.135, PP01.56, PP01.66 Thomas-Ahner, Jennifer M. PP01.46 Thompson, Ben OS06.03 Thompson, Rachel PP01.129 Thomsen, Gretchen PP01.329 Tierro, Benedetta PP01.297 Tiet, May PP01.243 Tikhomirova, Evgeniya Anatolyevna PP01.296 Tizzano, Eduardo PP01.52 Tobin, Rebecca PP01.73 Tolentino, Alessandra PP01.112, PP01.163, PP01.164, PP01.92, PP01.93, PP01.94, PP01.95 Tomaselli, Pedro PP01.18 Tonholo, Thiago PP01.116 Tonin, Paola PP01.107 Topakian, Raffi PP01.325 Topaloglu, Haluk OS01.06 Torchia, Eleonora OS08.03 Torella, Annalaura PL01.02 Toriello, Antonella PP01.204 Toscano, Antonio OS06.02, PP01.119, PP01.120, PP01.127 Tozawa, Takenori PP01.348 Tozza, Stefano OS05.05 Tozzi, Marco PP01.389 Trakman, Gina PP01.314 Traum, Avram Z. PP01.46 Trauschütz, Andreas PP01.154 Traverso, Monica PP01.09, PP01.10, PP01.11, PP01.34 Tripathi, Manjari PP01.220 Troger, Johannes PP01.325 Trojan, Daria A. OS07.03 Trucco, Federica OS07.04, PP01.11, PP01.34, PP01.35, PP01.36 Truini, Andrea SS44.03 Truman, Matt PP01.159 Tsai, I-Ching PP01.210 Tsargush, Vadim PP01.342 Tsimakidi, Chrysanthi PP01.207 Tsolakidis, Savas SS22.08 Tsonaka, Roula PP01.73 Tsuda, Koichi PP01.191 Tsuji, Yukiko OS07.01, OS07.02 Tuccillo, Francesco PP01.155 Tucht, Calvin PP01.129 Tufano, Laura OS04.05, PP01.145, PP01.187, PP01.232, PP01.86 Tulimiero, Lisamaura PP01.30 Tummala, Raj PP01.171, PP01.90 Tung, Angel Wing Lam PP01.345 Tupler, Rossella OS01.04 Turkdogan, Dilsad PP01.109 Turkoz, Ibrahim PP01.175, PP01.189, PP01.209, PP01.210, PP01.235, PP01.236 Turner, Catherine PP01.40 Tuttle, Edward PP01.48 Tuzova, Elizaveta PP01.281 Tzartos, John PP01.173 Tzavella, Dimitra PP01.182 Tzeng, Shiou-Ru OS05.03 TÜRKER, Duygu PP01.380 Ueda, Reoto OS03.04 Ulane, Christina PP01.171 Unver, Olcay PP01.109 Uppara Kowthalam, Madhurima OS03.06 Urbano, Guido PP01.47, PP01.84 Urbano, Isabella PP01.03 Usbergo, Cristian PP01.119, PP01.120, PP01.127 Utsugisawa, Kimiaki OS04.04, PP01.170, PP01.176, PP01.179, PP01.201, PP01.228, PP01.78, PP01.80, PP01.81 Uzawa, Akiyuki PP01.178, PP01.194 Vakrakou, Aigli G PP01.182 Valente, Enza Maria PP01.244 Valentino, Maria Lucia OS01.04, OS03.05 Valenza, Alice SS18.01 Vallefuoco, Francesca PP01.352 Vallve Maine, Camila PP01.45 van Alfen, Nens PP01.17 van Bragt, Tonke PP01.01 van de Camp, Sanne A.J.H. PP01.17 Van de Steen, Olivier PP01.279, PP01.284, PP01.289 Van de Walle, Inge PP01.284 van de Warrenburg, Bart PP01.154 van den Ameele3, Jelle PP01.243 van den Anker, Johannes OS01.02 van den Bos, Mehdi A.J OS07.01 Van den Bos, Mehdi A.J. OS07.02 van der Burgt, Yuri PP01.73 van der Kooi, Anneke OS01.05, PP01.103 van der Pol, Ludo PP01.289 van der Pol, W. Ludo PP01.17, PP01.282 Van der Walt, Anneke PP01.173 , PP01.237 van der Walt, Anneke PP01.238 van der Woning, Bas PP01.262 van Doorn, Jeroen L.M. PP01.17 van Doorn, Pieter PP01.269 Van Hoorick, Benjamin PP01.156, PP01.168 Van Huynegem, Karolien PP01.158 van Leeuwen, Esther PP01.103 van Lenthe, Harry PP01.61, PP01.62 Van Lieshout, Marloes PP01.40 van Prooije, Teije PP01.154 van Schaik, Ivo OS01.05, PP01.103 Van Schil, Paul PP01.172 Van Vleet, Jeremy PP01.364 Vandenborne, Krista OS02.05 Vangeneugden, Tony PP01.223 Vanhauwaert, Roeland PP01.156, PP01.158, PP01.166 Vankerckhoven, Bernhardt PP01.166 Vanoli, Fiammetta OS04.03, OS04.04 , PP01.214 Varga, David PP01.312 Varga, Dávid PP01.141 Varma, Anika PP01.367 Vartianen, Jenny PP01.45 Vashishta, Prashanth PP01.138 Vasquez, Edison OS03.03, PP01.246, PP01.258 Vattemi, Gaetano OS01.04, PP01.107 Veerapandiyan, Aravindhan PP01.68 Vegezzi, Elisa PP01.244, PP01.370 Velardo, Daniele OS01.04, OS08.04, PP01.100, PP01.104, PP01.105 Velazquez, Peter OS01.06 Veltsista, Dimitra PP01.238 Vencovský, Jiri PP01.262 Venditti, Romina PP01.55 Veneruso, Marco PP01.36 Vengalil, Seena PP01.138, PP01.150 vengalil, seena PP01.139 Ventre, Erwann PP01.388 Vera, Valentina PP01.187, PP01.232 , PP01.86 Vercelli, Liliana PP01.47, PP01.84 Verebi, Camille PP01.113 Verhamme, Camiel PP01.103 Verhamme, Fien M. PP01.176, PP01.178 Verovnik, Barbara PP01.40 Verschuuren, Jan PP01.158, SS40.01 Verschuuren, Jan J. G. M. PP01.176 Verza, Massimiliano Ugo OS04.05 Vettori, Katia PP01.325 Vibha, Deepti PP01.220 Vicart, Savine PP01.130 Vicino, Alex PP01.96 Vietri, Giovanni PP01.144, PP01.247, PP01.250, PP01.251, PP01.318 Villa, Marianna PP01.55 Villano, Daniella PP01.40 Villar-Quiles, Rocío-Nur PP01.130 Villella, Chiara PP01.104 Vinay Mahesh, Karthik PP01.290 Vincenten, Sanne PP01.14 Vinciguerra, Claudia OS04.03 , PP01.155 , PP01.204, PP01.214 Vinçonneau, Gilles PP01.229 Visconti, Virginia Veronica PP01.145 Visentin, Andrea PP01.297 Vissing, John OS04.04, OS04.06, PP01.108, PP01.133, PP01.159, PP01.170, PP01.186, PP01.195, PP01.201, PP01.228, PP01.78 , PP01.79 , PP01.80 , PP01.81 , PP01.82 , TC06.01 Visuttijai, Kittichate PP01.08 Vitali, Francesca OS05.05 Vlodavets, Dmitry PP01.343 Voermans, Nicol PP01.129, PP01.14 Voermans, Nicol C. PP01.17 Voet, Nicoline B.M. PP01.17 Vogrig, Alberto PP01.86 Volkov, Jenell PP01.171, PP01.90 Voltolini, Luca PP01.212 Voorn, Eric Lukas PP01.136 Vorobeva, Sofya PP01.296 Vovk, Andrej PP01.40 Vrščaj, Eva OS08.02 Vu Hong, Ai PL01.03 Vu, Tuan OS04.04, OS04.06, PP01.159, PP01.160, PP01.175, PP01.176, PP01.186, PP01.193, PP01.201, PP01.209, PP01.215, PP01.79 Vucic, Steve OS07.01, OS07.02 Vucinic, Dragana PP01.27 Vujcic, Miodrag PP01.282, PP01.289 VY, Vishnu PP01.220 Vélez-Gómez, Beatriz PP01.230 Wa Somwe, Somwe PP01.259 Waddington, Simon PP01.45 Wadman, Renske I. PP01.17 Walsh, Sarah PP01.346, PP01.347 Walter, Dr. Maggie C. PP01.56 Walter, Farah J. PP01.135, PP01.56 Walter, Maggie PP01.66 Walter, Maggie C. PP01.135 WAN, Lok Man PP01.315 Wang, Dazhe PP01.71 Wang, Jin PP01.363 Wang, Leo OS01.01 Wang, Te-Wei OS05.03 Wang, Yong Lin PP01.238 Wanschitz, Julia PP01.325 Warren, Francis PP01.343 Wasilewicz, Luc PP01.54 Waters, Kate PP01.33 Waters, Patrick OS09.01 Waśniowska, Urszula PP01.26 Weber, Markus TC13.01 Webster, Richard PP01.166 Wee, Yong Kiat PP01.65 Wei, Kuo-Ting PP01.387 Weigl, Lukas OS08.05 Weihl, Conrad OS01.01 Weinstein, Jennifer PP01.367 Weis, Joachim PP01.243 Weisburd, Ben OS02.02 Weisman, Mia PP01.88 Weiss, Michael D. PP01.179 Weiss, Ryan PP01.329 Wendel, Caterina PP01.66 Wendel, Caterina M. PP01.135 Wenninger, Stephan PP01.135, SS39.02 Werneck, Lucas Cesar PP01.257 White, Yvonne PP01.171 Whyms, Dermot OS07.03 Widholm, Per PP01.360 Wiendl, Heinz PP01.176, PP01.228, PP01.78 Wierenga, Lara M. PP01.63 Wiesenhofer, Anna PP01.325 Wilfong, Erin Marie PP01.90 Wilkins, H. Jeffrey OS01.01 Willcocks, Rebecca OS02.05 Willems, Natasha OS09.01 Willen, Joanna PP01.38, PP01.39 Willi, Roman PP01.228 Willis, Tracey PP01.74 Winkel, Antony PP01.173, PP01.263 , PP01.264 Winter, Natalie SS22.02, SS22.03 Winter, Nathalie PP01.260 Winthrop, Kevin L. PP01.177 Wiratman, Winnugroho PP01.308 Withana, Ayana PP01.45 Witt, Evan PP01.137 Witte, Otto W PP01.362 Wittebols, Kim PP01.38, PP01.39 Witters, Peter OS03.06 Wittlinger, Julia SS22.02, SS22.03 Wolfe, Gil PP01.199, PP01.215, PP01.218, PP01.219, SS40.03 Wolff, David PP01.52 Wolfsgruber, Marlene OS08.05 Wong, Sui H. PP01.178 Woodcock, Ian PP01.40, PP01.71 Worner, Murray OS09.01, PP01.303 Wotton, Tiffany PP01.65 Wu, Jing OS02.06, OS04.02, OS06.05 , PP01.197 , PP01.205 Wu, Ning PP01.239, PP01.288 Wu, Wanqing OS02.06, OS04.02 , PP01.197 Wu, Yao-Yu PP01.311 Wu, Yujie PP01.215 Wurm, Raphael PP01.325, PP01.326 Xi, Jianying PP01.178 Xiang, Cheryl PP01.218, PP01.219 Xiong, Ge PP01.239 , PP01.288 Xiong, Li PP01.267 Yamada, Nanami PP01.102 Yamagishi, Yuko PP01.240 Yamanaka, Ai OS03.04 , PP01.102, PP01.123 Yamaoka, Minako PP01.102, PP01.123 Yang, Chia-Feng PP01.114 Yang, Hongbo PP01.215 Yang, Huan PP01.175 Yang, Min PP01.218, PP01.219, PP01.48 Ye, Dongni PP01.215 Yee, Patrick PP01.40 Yeghiazaryan, Nune PP01.217 Yeh, Jiann-Horng OS04.04 Yeh, Ti-Yen PP01.311 Yilmaz, Zeynep PP01.109 Yin, Xiaoyan PP01.59 Yiu, Eppie PP01.40 Yoo, Dallah PP01.330 Yoon, Byeol-A PP01.266 Yoon, Seo Yeon PP01.49 Yoon, Won Tae PP01.350 Yoshida, Hideki PP01.348 Yoshikawa, Keisuke PP01.240 Yoshioka, Wakako PP01.85 Youn, Jinyoung PP01.330 Young, Joanne PP01.388 Yu, Ara PP01.364 Yu, Shuli PP01.142 Yuan, Julie Yue PP01.15 Yuan, Yue Julie PP01.19 Yungher, Benjamin PP01.132 YÜKSEL, Deniz PP01.380 Zabudskaya, Kseniya PP01.342 Zaidman, Craig PP01.68 Zambrano-Vera, Dario OS03.03, PP01.246, PP01.258 Zanolini, Alice SS18.01 Zanoteli, Edmar PP01.343, PP01.40, PP01.92, SS11.02 Zanotti, Simona PP01.104, PP01.105 Zhai, Yaya PP01.156 Zhang, WenWen PP01.238 Zhang, Xin PP01.237 Zhao, Chongbo PP01.178, PP01.193 Zhao, Xin PP01.168 Zhao, Yang PP01.160 Zheng, Yunlong PP01.191 Zhong, Wayne PP01.234 Zhou, Haiyan PP01.44 Zhou, Huiyu PP01.364 Zhou, Junguo PP01.329 Zhou, Tianyue OS03.06 Zhu, Chao PP01.238 Zhu, Yaowei PP01.175, PP01.208, PP01.209 Zimba, Stanley PP01.259 Zimprich, Fritz OS08.05, PP01.325, PP01.326 Zinaï, Saad PP01.132, PP01.133 Zinman, Lorne PP01.305 Zoppi, Dario OS01.04, OS03.05, PP01.352 Zouvelou, Vasiliki PP01.182, PP01.185 Zozulya-Weidenfeller, Alla PP01.130 Zschuentzsch, Jana OS02.01, OS09.04 Zschüntzsch, Jana PP01.130, PP01.195 , PP01.363, PP01.79 Zuccarino, Riccardo PP01.373 Zulehner, Gudrun PP01.325, PP01.326 Zupan, Amadea PP01.83 Álvarez, Carmen PP01.341 Álvarez-Velasco, Rodrigo PP01.178 Ávila-Smirnov, Daniela PP01.58 Özbezen Kızıltan, Ebru PP01.355 Özdemir, Sadıka PP01.355 Özkaynar, Pinar OS01.05 , PP01.103 Öztosun, Gülşen SS24.03 ÖZTÜRK, Merve PP01.380 Čopič, Alenka PP01.21 Ķauķe, Gundega PP01.274, PP01.98 Ķēniņa, Viktorija PP01.274, PP01.98 Łoboda, Agnieszka PP01.26 Šikic, Katarina PP01.129 Šuput, Dušan PP01.40 Žigman, Tamara PP01.129

Prof. Seungkeun Lee, Prof. Jee-Eun Kim Soonchunhyang University Bucheon Hospital, Seoul, Korea, Republic of Background: Nonsystemic vasculitic neuropathy (NSVN) is regarded as a single-organ vasculitis limited to the peripheral nervous system (PNS), yet emerging evidence suggests that neurological involvement may represent a spectrum rather than discrete entities. Methods: We present a case in which initially isolated vasculitic neuropathy evolved to involve the skin and central nervous system(CNS), supporting the concept of a PNS-CNS vasculitis spectrum as a distinct neurological phenotype of vasculitis. Results: A 63-year-old woman presented with subacute left posterior calf–sole pain and left foot drop three months prior to admission. One month later, similar pain developed in the right posterior calf and foot, followed by right hand tingling and weakness. Neurological examination revealed left ankle dorsiflexion and eversion weakness and right finger abduction weakness, sensory loss in the right ulnar nerve territory, and diffusely hypoactive deep tendon reflexes. Nerve conduction studies demonstrated asymmetric sensorimotor polyneuropathy consistent with mononeuritis multiplex. Extensive laboratory evaluation for vasculitis, paraneoplastic, and autoimmune etiologies, spine MRI, abdomen & chest CT and cerebrospinal fluid analysis, were unremarkable. She was diagnosed with nonsystemic vasculitic neuropathy and treated with oral prednisolone, resulting in gradual improvement. However, during tapering, she developed severe ischemic toe pain with color change and ulceration, along with acute dysarthria. Brain MRI revealed an acute right corona radiata infarction, while CT angiography showed no steno-occlusive disease. Relapsing vasculitic neuropathy with skin and central nervous system involvement was suspected, and treatment with high-dose corticosteroids and azathioprine led to sustained improvement without relapse. Conclusion: Rather than representing discrete entities such as NSVN or primary CNS vasculitis, this presentation suggests a continuous PNS-CNS vasculitis spectrum, representing a neurological phenotype of vasculitis characterized by preferential small-vessel involvement of neural tissues, with or without cutaneous manifestations. Single-organ vasculitis may reflect an early or incomplete expression within a broader vasculitic continuum rather than a static disease entity.

Prof. Pariwat Thaisetthawatkul , Assoc. Prof. Mara Seier Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States Background: Charcot-Marie-Tooth type 1C (CMT 1C) is a rare, dominantly inherited neuropathy caused by mutation in the lipopolysaccharide-induced tumor necrosis factor (LITAF) gene. The frequency has been estimated to be about 0.5% of all CMT1 cases. Here we report a genetically confirmed case of CMC-1C with mild sensory symptoms and signs without motor weakness or gait disturbance. Methods: A case report Results: A 69-year-old male, with underlying Parkinson disease responding to carbidopa-levodopa treatment and diabetes mellitus, started having numbness, coldness and neuropathic pain in both feet for 5 years prior to evaluation. The sensory symptoms later progressed to both hands. There were no cranial nerve symptoms, limb weakness, falls or loss of balance. Family history revealed CMT of unknown type in his sister and mother. Neurological exam revealed clinical signs of Parkinsonism including tremor, bradykinesia and rigidity but normal cranial nerve functions, no motor weakness, normal deep tendon reflexes, absent vibration sense from toes to knees but normal pin and proprioceptive senses, normal cerebellar functions and ability to walk by himself with mild stooping posture. Electrodiagnostic test revealed findings of chronic demyelinating neuropathy with uniform, marked slowing with conduction blocks and dispersion between distal and proximal limb recording in motor conduction studies. Laboratory investigation revealed normal CSF analysis and unremarkable blood tests. Genetic testing showed pathogenic heterozygous c. 334G>A mutation of LITAF gene diagnostic of CMT1C. Conclusion: We report a case of CMT1C, a rare form of CMT1, that presents without motor weakness, and mild clinical signs with predominantly sensory symptoms without or with minimal gait disturbance consistent with previous reports. The symptoms and signs in CMT1C were reported to be generally milder than those of CMT1A. Electrodiagnostic findings in CMT1C shows uniform, marked slowing in demyelination ranges and may include conduction blocks and dispersion in motor conduction studies.

Dr. Giovanni Vietri 1,2,3 , Dr. Francesco Gruosso 4,2,5 , Dr. Mariangela Goglia 1,2 , Dr. Erica Frezza 1,2 , Dr. Giulia Greco 1,2 , Dr. Camilla Rocchi 1,2 , Prof. Diego Centonze 1,3 , Dr. Laura Boffa 1,2 , Dr. Francesca Ciaiola 6 , Dr. Alida Spalloni 6 , Dr. Roberta De Mori 7 , Prof. Roberto Massa 1,2,3 , Prof. Patrizia Longone 6 1 Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 2 Neuromuscular Diseases Unit, Tor Vergata University Hospital, Rome, Italy. 3 Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy. 4 Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy. 5 Unit of Neurology, IRCCS Neuromed, Rome, Italy. 6 Molecular Neurobiology Unit, Experimental Neurology, Fondazione Santa Lucia, Rome, Italy. 7 Stem Cell Facility, Fondazione Santa Lucia, Rome, Italy Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystemic disorder in which disturbances of proteostasis and cellular homeostasis are not strictly confined to motor neurons. Increasing evidence points to dysfunction of the autophagy–lysosome pathway (ALP), encompassing macro-autophagy and chaperone-mediated autophagy, as a key pathogenic pathway across sporadic and genetic ALS. In this context, accessible patient-derived cellular models may enable patient-specific profiling and quantitative approaches to patient stratification. We investigated whether primary dermal fibroblasts from ALS patients reflect ALP-related cellular and molecular alterations observed in the human disease. Methods: We performed a monocentric observational pilot study at a tertiary ALS center. ALS patients (mild-to-moderate disease stages) and matched healthy controls were enrolled after informed consent, with exclusion of major metabolic comorbidities. Skin punch biopsies were obtained and primary fibroblast cultures were established under standardized conditions. Proliferation rate was assessed counting at 0, 24, 48, and 96 hours. ALP-related markers were evaluated using immunoblotting using antibodies against autophagy-related markers, normalized to β-actin and quantified by computerized densitometry. Qualitative protein distribution was assessed through immunofluorescence for autophagy markers, acquiring confocal images at 63× (Zeiss LSM800). Statistical analyses were conducted in Prism; group comparisons used unpaired t-tests with significance at p ≤0.05. Results: Nine biopsies were collected: five ALS fibroblast lines managed to produce a complete colony, four cultures showed a reduced proliferation rate and clonal production. The ALS cohort included sporadic and genetic forms with heterogenous genotype. Compared with matched healthy controls, ALS fibroblasts showed an early and persistent slower growth rate, with significantly reduced cell numbers at 24 hours (p ≤0.01) and 96 hours (p ≤0.05). Preliminary western blot and immunofluorescence data confirmed an altered autophagy pathway, consistent with altered lysosomal trafficking and impaired vesicle turnover. Conclusion: Patient-derived dermal fibroblasts in ALS display convergent abnormalities across proliferation, autophagic pathways, and lysosomal organization, supporting an early peripheral ALP defect compatible with a multisystemic model of ALS. Despite the small sample size and reduced culture survival, the agreement across independent assays and the observed inter-patient variability suggest that fibroblast-based multi-marker assays may capture biologically meaningful heterogeneity useful for patient stratification and, in future larger cohorts, could be linked to clinical severity and progression rate and integrated with established and emerging fluid biomarkers.

Dr. David Gómez-Andrés 1 , Dr. Paz Castro 2 , Dr. Jorge Mauriño 2 , Mrs Angeles Terrancle 2 , Mrs Fátima Jerez 2 , Dr. Mónica Povedano 3 1 Pediatric Neurology, Vall d´Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 2 Medical Departament, Roche Farma, Madrid, Spain. 3 Department of Neurology, Hospital Universitari de Bellvitge, Institut d´Investigació Biomèdica de Bellvitge-IDIBELL, Barcelona, Spain Background: The therapeutic landscape of spinal muscular atrophy (SMA) has changed in recent years with the introduction of new therapies. Despite these advances and the availability of validated scales, current assessment tools often fail to capture the full spectrum of symptoms and signs that significantly affect patients’ daily lives and health-related quality of life. In addition, they may lack the sensitivity needed to detect subtle but clinically meaningful improvements from the patient’s perspective. Therefore, there is a clear need to study the quality of life of this population in a broader context, covering all ages and individual characteristics, to obtain a more comprehensive understanding of the disease burden from the patient and the caregiver perspective. Methods: To evaluate the perception of patients regarding their quality of Life, decision-making, and care, as reported by both them and their caregivers, to capture data that reflects the unique characteristics of the healthcare system and sociocultural environment. Results: We present the design of a cross-sectional, non-interventional study. Approximately 100 patients are planned to be enrolled across Spain. Patients aged ≥ 2 years with a confirmed diagnosis of SMA will be included. The study will be based on a single data collection point, coinciding with a medical follow-up visit. A battery of validated clinical outcomes assessments (COAs) will be administered to the patient or their caregiver. These assessments are designed to evaluate several key domains specific to SMA patients across different age groups: 2 to 5 years, 6 to 15 years, and 16 years and up. Quality of Life (using the INQoL or PedsQoL); level of participation in shared decision-making (using SDM-Q-9, SURE DCS, DRS, and CPS); quality of chronic care (using PACIC); and psychological and emotional factors, identification of symptoms, and treatment satisfaction, among others. The primary outcome will be the mean total quality of life score. Correlation factors between the COAs and clinical/demographic variables will be determined. Furthermore, factors associated with quality of life (INQoL/PedsQoL) will be analyzed using correlation and linear regression analyses with other COAs, specifically grouping them into psychological factors, uncertainty/concerns, and care/decision experience. Conclusion: The collected data is expected to provide a more comprehensive and nuanced view of the SMA patient population in Spain across all ages and their individual characteristics. Ultimately, the findings are anticipated to contribute to identifying areas for improvement, guiding clinical practice towards more patient-centered care, and allowing for the enhancement of meaningful outcomes in the context of emerging treatments.

Dr. Tanvir Khosla 1 , Assoc. Prof. Ge Xiong 1 , Dr. Ning Wu 2 , Asst. Prof. Sophie Teng 1 1 University of California, Sacramento, United States. 2 Kaiser Permanente, Roseville, United States Background: Lewis-Sumner Syndrome (LSS), also known as multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, is a rare asymmetric demyelinating polyneuropathy that falls within the spectrum of chronic inflammatory demyelinating polyneuropathy (CIDP). LSS is characterized by segmental demyelination and remyelination due to immune attacks on the myelin sheath by autoantibodies and inflammatory cells. The pathology is similar to classic CIDP but more localized, leading to multifocal conduction blocks. Unlike classic CIDP, LSS primarily affects the upper limbs and follows multifocal distribution, mimicking mononeuropathy multiplex. It may be misdiagnosed as compression neuropathy, multifocal motor neuropathy, vasculitic neuropathy, even hereditary neuropathies. Methods: We have compiled a list of 6 patients that have been diagnosed with LSS from 2018 to 2025 at Sacramento Metropolitan area. We summarized the clinical features, neurological examination, lab tests, EMG/NCS study findings as well as imaging abnormalities. All cases have varying clinical presentations with different time courses to achieve the right diagnosis and various treatment responses. Results: All the patients in this case series presented with asymmetric sensorimotor deficits. Weakness and paresthesia occur in patchy nerve distributions, most commonly affecting the median and ulnar nerves. Reflexes are diminished or absent in all extremities for 4 cases. Out of 6 patients, 3 had lower extremity onset and 3 with upper extremity onset of symptoms. One presented with all distal extremities at the onset. Six cases were slow onset but one had acute onset. The time from onset to confirmed diagnosis ranged from 5 months to 7 years. One case was misdiagnosed as motor neuron disease, one case was first considered to have cervical radiculopathy, one case was initially diagnosed with multiple compression neuropathies. The acute onset case was initially diagnosed as Guillain Barre syndrome (GBS). This case continued progressing over 8 weeks with 2 relapses in 4 months. EMG and nerve conduction studies are crucial for diagnosis. Key findings include multifocal conduction block, prolonged distal motor latency, and temporal dispersion, suggesting primary demyelination neuropathy. Sensory and motor responses are affected asymmetrically. Neuromuscular ultrasound could offer clues of focal fascicles abnormalities at non compression sites that may help improve diagnosis yield. All cases had been treated with intravenous immunoglobulin (IVIg) treatment. Four cases have steady improvements after IVIg treatment. One patient responded to IVIg for 2 years then deteriorated without clear triggering factors. He did not respond to combined steroids and IVIg then started Rituximab. One patient had severe allergic reactions to Ig with Dressler syndrome, and refused steroids/plasmapheresis. He was treated with azathioprine for more than 5 years and slowly progressed. Now this case has been on efgartigimod. The acute onset case responded to steroids and plasmapheresis during exacerbations and has been improving with IVIg. Conclusion: Lewis-Sumner Syndrome is a rare but treatable immune-mediated neuropathy with distinct clinical and electrophysiological features. Early recognition and targeted immunotherapy, particularly IVIg, can significantly improve outcomes. Further strategies have been considered in this case series with the addition of high-resolution neuromuscular ultrasound to assist in diagnosis.

Dr. Laura Fionda 1,2 , Dr. Elena Cortés Vicente 3 , Dr. Artur Drużdż 4 , Dr. Ali A. Habib 5 , Dr. Zabeen K. Mahuwala 6 , Prof. Renato Mantegazza 7 , Dr. Robert M. Pascuzzi 8 , Prof. Sabrina Sacconi 9 , Dr. Kimiaki Utsugisawa 10 , Prof. John Vissing 11 , Dr. Tuan Vu 12 , Dr. Paul Mahoney 13 , Dr. Jos Bloemers 14 , Dr. Thaïs Tarancón 15 , Dr. Vera Bril 16 1 Department of Neurology, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. 2 Neuromuscular and Rare Disease Centre, Sant'Andrea Hospital, Rome, Italy. 3 Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 4 Department of Neurology, Municipal Hospital, Poznań, Poland. 5 MDA ALS & Neuromuscular Center, Department of Neurology, University of California, Irvine, Orange, CA, United States. 6 Department of Neuromuscular Medicine, Epilepsy and Clinical Neurophysiology, University of Kentucky, Lexington, KY, United States. 7 Emeritus and Past Director, Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy. 8 Neurology Department, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, United States. 9 Université Côte d'Azur, Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France. 10 Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. 11 Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 12 Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, United States. 13 UCB, Slough, United Kingdom. 14 UCB, Brussels, Belgium. 15 UCB, Madrid, Spain. 16 Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada Background: Generalised myasthenia gravis (gMG) is characterised by fluctuating muscle weakness, with treatment responses varying across different muscle groups. In the randomised, double-blind, Phase 3 MycarinG study ( NCT03971422 ), one 6-week cycle of rozanolixizumab significantly improved Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores versus placebo in patients with gMG. Patients could subsequently enrol in open-label extensions MG0004 ( NCT04124965 ), then MG0007 ( NCT04650854 ), or MG0007 directly. Here, we investigate the effect of repeated rozanolixizumab treatment cycles on individual item scores within the MG-ADL and QMG total scores, using final pooled data from the extension studies. Methods: In MG0004, patients received chronic once-weekly rozanolixizumab infusions for ≤52 weeks. In MG0007, after one initial 6-week cycle (rozanolixizumab 7 mg/kg or 10 mg/kg), subsequent cycles were administered upon symptom worsening (investigator’s discretion). Final efficacy data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 for patients with ≥2 symptom-driven cycles (efficacy pool). In this post hoc analysis, MG-ADL and QMG item-level scores were assessed at baseline and Day 43 across 13 cycles, in addition to change from baseline (CFB) to Day 43, using means weighted by sample size. Results: 129 patients had ≥2 symptom-driven cycles. A reduction in weighted-mean score from baseline was observed at Day 43 for MG-ADL and QMG items ( Table 1 ). For MG-ADL items, weighted-mean (SD) CFB to Day 43 scores ( Table 1 ) were: −0.5 (0.8) for double vision, −0.6 (0.9) for eyelid droop, −0.5 (0.7) for talking and chewing and −0.4 (0.6) for swallowing. For QMG items, weighted-mean (SD) CFB scores ( Table 1 ) were −0.5 (1.0) for double vision, −0.7 (1.1) for ptosis, −0.4 (0.7) for facial muscles, right arm outstretched and left arm outstretched, −0.3 (0.6) for right leg outstretched, −0.4 (0.6) for left leg outstretched and −0.5 (0.9) for speech after counting aloud from 1 to 50. Conclusion: Long-term rozanolixizumab treatment cycles led to improvements from baseline across ocular, bulbar, respiratory and limb weakness/gross motor items in MG-specific outcomes, demonstrating consistent benefit across a broad range of signs and symptoms. Funding: UCB.

Ms. Evy Reviers EUpALS, Leuven, Belgium Background: The European Organisation for Professionals and People with ALS (EUpALS) unites 30 national ALS Assiociations from 22 European countries to collaborate better together. As a non-profit European umbrella organisation, we take the interests of European people with ALS (pALS) to heart. In particular, we facilitate access to ALS clinical trials and provide information about it. Methods: EUpALS stimulates ALS clinical research by engaging in partnerships with industry and academic consortia, to bring in and safegarding the patient perspective. Results: Gathered information is disseminated via the EUpALS website, social media, and quaterly Newsletters. In addition, we organise Round Tables satellite to scientific meetings, and are partner in a number of EU Horizon projects. Conclusion: Several examples of the aforementioned EUpALS activities will be presented and discussed during this session.

Dr. Melik GURSOY, Dr. Turgay DOLEK, Dr. Tugce AKCADAG CAMAN, Dr. Mahmut Bilal CAMAN, Prof. Gulnihal KUTLU Mugla SK University, School of Medicine, Department of Neurology, Mugla, Turkey Background: Myasthenia gravis (MG) is a heterogeneous autoimmune neuromuscular disorder requiring long-term follow-up and individualized treatment strategies. This study aimed to evaluate the demographic, clinical, electrophysiological, and serological characteristics of MG patients followed in a tertiary neurology center. Methods: Fifty-eight patients with MG who were regularly followed between 2018-2024 were retrospectively analyzed. Data regarding age at diagnosis, sex, disease subtype, antibody status, electrophysiological findings, thymectomy history, and treatments administered during follow-up were recorded. Results: The majority of patients were male, particularly among those diagnosed after the age of 40, while female predominance was observed in younger-onset cases. Generalized MG was the most common disease subtype. Acetylcholine receptor antibody positivity was high, whereas anti-MuSK positivity was rare. Most patients required combined immunomodulatory treatments, including corticosteroids, immunosuppressive agents, and intravenous immunoglobulin during follow-up. Conclusion: MG patients followed at our center predominantly presented with generalized disease and high seropositivity rates. The frequent need for combination immunotherapy reflects the clinical burden of MG in a tertiary-care setting.

Dr. Alicia Alonso-Jiménez 1,2 , Dr. Willem De Ridder 1,2 , Prof. Paul Van Schil 1 , Prof. Jonathan Baets 1,2 , Prof. Rudy Mercelis 1 1 University Hospital of Antwerp, Edegem, Belgium. 2 Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium Background: It is well known that scientific literature has a significant gender gap, as gender differences were not considered until very recently. Women were often excluded from studies, and even when included, the results are rarely analyzed separately by gender. This study aims to investigate gender-specific differences in patients with Myasthenia Gravis (MG) by segregating data from our cohort of patients in Antwerp (Belgium). Methods: We analyzed the data of our previously published cohort of 163 patients with MG visited in the Antwerp University Hospital between 2019 and 2021, segregating the information by gender to observe any significant differences. Results: The analysis revealed several notable gender-specific differences. Women experienced a delay in diagnosis of over one year more frequently than men. They also had dysarthria as presenting symptom more often than men. The MGFA scores at maximum severity were higher in women, who also reported more limitations due to the disease and required more treatments to control it. While some differences could be attributed to the younger onset of the disease in women, certain differences were independently influenced by gender Conclusion: Women experience more limitations due to MG than men and may face a more severe disease course. These differences should be taken into account when determining follow-up and treatment strategies. Additionally, these findings highlight the importance of segregating data by gender in scientific studies to better understand gender-specific differences in disease presentation and management.

Dr. Zhan Liu Nantong University, Nantong, China Background: Neuroin ammation has been involved in pathogenesis of Parkinson's disease (PD), a chronic neurodegenerativedisease characterized neuropathologically by progressive dopaminergic neuronal loss in the substantia nigra(SN). We recently have shown that helper T (Th)17 cells facilitate dopaminergic neuronal loss in vitro. Herein,we demonstrated that interleukin (IL)-17A, a proin ammatory cytokine produced mainly by Th17 cells, con-tributed to PD pathogenesis depending on microglia. Methods: Mouse and rat models for PD were prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or striatal injection of 1-methyl-4-phenylpyridinium (MPP+), respectively. Results: Both in MPTP-treated mice and MPP+-treated rats, blood–brain barrier (BBB) was disrupted and IL-17A level increased in the SN but not in cortex. E ector T (Te ) cells that were adoptively transferred via tail veins in ltrated into the brain of PD mice but not into that of normal mice. The Te cell transfer aggravated nigrostriatal dopaminergic neurodegeneration, microglial activation and motor impairment. Contrarily, IL-17A de ciency alleviated BBB disruption, dopaminergic neurodegeneration, microglial activation and motor impairment. Anti-IL-17A-neutralizing antibody that was injected into lateral cerebral ventricle in PD rats ameliorated the manifestations mentioned above. IL-17A activated microglia but did not directly a ect dopaminergic neuronal survival in vitro. IL-17A exacerbated dopaminergic neuronal loss only in the presence of microglia, and silencing IL-17A receptor gene in microglia abolished the IL-17A e ect. IL-17A-treated microglial medium that contained higher concentration of tumor necrosis factor (TNF)-α facilitated dopaminergic neuronal death. Further, TNF-α-neutralizing antibody attenuated MPP+-induced neurotoxicity Conclusion: The ndings suggest that IL-17A accelerates neurodegeneration in PD depending on microglial activation and at least partly TNF-α release.

Dr. Christian Eggers 1 , Dr. Ratna Bhavaraju-Sanka 2 , Dr. Patrick Kwon 3 , Prof. Eduardo Nobile-Orazio 4 , Prof. Thomas Skripuletz 5 , Dr. Arne De Roeck 6 , Dr. Arie Gafson 6 , Dr. Anneleen Remmerie 6 , Prof. Pieter van Doorn 7 1 Kepler University Hospital, Linz, Austria. 2 UT Health San Antonio, San Antonio, United States. 3 NYU Grossman School of Medicine, New York, United States. 4 University of Milan, Milan, Italy. 5 Hannover Medical School, Hanover, Germany. 6 argenx, Ghent, Belgium. 7 Erasmus University Medical Center, Rotterdam, Netherlands Background: The pivotal ADHERE study ( NCT04281472 ) and open-label extension ADHERE+ ( NCT04280718 ) assessed efficacy and safety of efgartigimod PH20 subcutaneous (SC) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods: Enrolled participants with active CIDP (standard treatments withdrawn during run-in) received open-label, weekly efgartigimod PH20 SC 1000 mg (stage-A). Responders were randomized (1:1) to weekly efgartigimod PH20 SC or placebo (stage-B). Participants with clinical deterioration in stage-B, ongoing in stage-B at 88 th relapse, or who completed ADHERE could enter open-label ADHERE+. The Inflammatory Neuropathy Cause and Treatment (INCAT) score is the standard measure of arm and leg disability in CIDP (maximum score=10; minimal clinically important difference: decrease of ≥1 point). Minimal symptom burden in CIDP currently remains undefined. This post hoc analysis aims to contribute to the characterization of minimal symptom burden by reporting the percentage of stage-A responders reaching an INCAT ≤1 (no or minimal disability) by ADHERE stage-B last assessment and during ADHERE+. Results: At ADHERE stage-A baseline, stage-A responders had an INCAT score of 4.6 (standard deviation, 1.6; n=220); no participants had an INCAT ≤1 at ADHERE run-in baseline (n=191) or stage-A baseline (n=220). At stage-A last assessment, 28/221 (12.7%) stage-A responders had an INCAT ≤1 (13 were subsequently randomized to placebo). At stage-B last assessment, 20/111 (18.0%) efgartigimod-treated and 7/109 (6.4%) placebo-treated stage-A responders had an INCAT ≤1. The percentage of participants at ADHERE+ Week 12, 24, and 36 with an INCAT ≤1 increased to 20.3% (38/187), 26.0% (46/177), and 24.4% (42/172), respectively. 68/196 (34.7%) stage-A responders reached INCAT ≤1 at any point in ADHERE+. Conclusion: Over one-third of stage-A responders achieved an INCAT ≤1 at any time in ADHERE+. Nearly 1 in 5 efgartigimod-treated stage-A responders reached INCAT ≤1 at ADHERE stage-B last assessment, showing minimal symptom burden (i.e., no disability [INCAT=0], walking without support [INCAT=1]).

Dr. Alicia Aurora Rodríguez 1 , Dr. Irune García 1 , Miss Clara Lépée-Aragón 1 , Dr. Corrado Angelini 2 , Dr. Óscar Martínez 1 , Dr. Imanol Amayra 1 1 University of Deusto, Bilbao, Spain. 2 University of Padua, Padua, Italy Background: Limb–girdle muscular dystrophy (LGMD) is a group of rare genetic disorders causing progressive weakness and muscle atrophy in the proximal limbs. They are classified into autosomal dominant and recessive forms. About 10% of these dystrophies are dominant and 90% are recessive. Research on LGMD is limited, particularly for low-prevalence subtypes such as the dominant form limb–girdle muscular dystrophy D2 (LGMD-D2), which shows variable age of onset and occurs in both familiar and sporadic cases. First identified in an Italo-Spanish family, LGMD-D2 is characterized by generalized muscle atrophy and can lead to disability and dependence on others. There is currently no curative treatment, and existing therapies are symptomatic, with the disease negatively affecting life expectancy and quality of life. This study represents the first investigation into the quality of life of individuals affected by a dominant form of limb–girdle muscular dystrophy, specifically LGMD-D2. Methods: A cross-sectional study was conducted. The study further seeks to examine patient-reported outcomes in functional performance and quality of life of patients, as well as differences between LGMD-D2 and recessive forms of LGMD. The tools employed included a sociodemographic questionnaire, the Gait-Scale-Gowers-Chair scale (GSGC), and the INQoL instrument. The sample comprised six adults diagnosed with LGMD-D2 and three patients with recessive LGMD. Participants were recruited through patient associations and a hospital in Padua. The study was approved by the Commission for Responsible Ethics (Ref: ETK-39/18-19). Results: Individuals affected by LGMD-D2 experience multiple symptoms that result in disability and, consequently, dependence on assistance. The findings of the present study indicate that LGMD-D2 has a more pronounced impact on activities of daily living, fatigue, muscle pain, and independence compared with other LGMD subtypes. The results also suggest that age may influence quality of life, and that muscle weakness represents a particularly disabling feature of this variant. Conclusion: People affected by LGMD-D2 have multiple symptoms that lead to disability and dependence, which ultimately lead to dependence on their environment. The present study shows that they seem to have a greater impact on the activities of daily living, independence, the emotional sphere, and body image perception than other LGMD pathologies or other NMDs, considering the limitations of the comparisons, which were only at a descriptive level. It also appears that the impact is greater if the affected person is older, and that muscle weakness is a very disabling symptom in this variant. In the context of ongoing research aimed at developing new treatments in LGMD, it is crucial to identify the aspects most significantly affected by the disease.

Dr. Wildon Farwell , Dr. Phil Lambert, Dr. Ryan Mitchell, Dr. Michael Rudnicki, Mr. Frank Gleeson Satellos Bioscience Inc., Toronto, Canada Background: Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to progressive muscle degeneration, loss of ambulation, and premature mortality. SAT-3247 is an oral small molecule that enhances muscle regeneration by modulating muscle stem cell (satellite cell) polarity and asymmetric division via regulation of adapter associated kinase 1 (AAK1). The objective of LT-001 is to assess long-term safety and efficacy of orally administered SAT-3247 in adult participants with DMD that previously completed SAT-3247-CL-101, a Phase 1 study of SAT-3247. Methods: This open-label study will assess long-term safety, tolerability and potential efficacy of extended dosing of 60 mg of orally administered SAT-3247 in a 5-days on/2-days off (i.e. weekday dosing) regimen. Participants will receive SAT-3247 for 11 months, for a total of 12 months of treatment including the duration of the SAT-3247-CL-101 study. Safety endpoints will include incidence, temporal profile, and severity of treatment emergent adverse events (TEAEs). Efficacy endpoints will include changes from baseline in intramuscular fat fraction in muscle quantitative magnetic resonance (qMR) in biceps brachii, changes from baseline in muscle force measurements as measured by dynamometry, and changes from baseline in the Performance of Upper Limb (PUL2.0) assessment following SAT-3247 treatment. Additionally, exploratory analyses of various biomarkers are being conducted. Results: Summary results after 6 months of dosing will be presented. Conclusion: Summary conclusions after 6 months of dosing will be presented

Dr. Sung-Ju Hsueh 1 , Dr. Kai Chieh Chang 2 1 National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan. 2 National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan Background: Studies had shown that both peripheral neuropathy (PN) and central nervous system (CNS) disorders, such as Parkinson’s disease (PD), could results in the loss of muscle mass and strength in patients. These changes could be measured using bioelectrical impendance analysis (BIA) and hand grip as markers, respectively. However, comparison of muscle mass changes and strength among patients with different diseases were seldom reported. We investigate whether different etiologies may result in different pattern of muscle mass and strength changes in patients with neurological disorders. Methods: Patients with PN and PD were enrolled from a general neurology clinic, in which we routinely recorded grip strength using a hand dynamometer and performed body composition analysis using an Accuniq BC380 multi-frequency BIA device (Selvas Healthcare, Daejeon, Republic of Korea) at the patients’ first encounter. Clinically, PD was diagnosed based on the Movement Disorder Society diagnosis criteria, while PN was diagnosed based on neurological examinations by neurologists and electrophysiological studies with results compatible with peripheral nervous system dysfunction. Appendicular skeletal muscle mass (ASM) was measured using BIA and was further adjusted with height according to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus (height-adjusted muscle mass, HAMM) to better represent the patients’ state of muscle health. Patients not able to stand without support, with significant deformities, with history of cerebrovascular diseases or traumatic brain injury resulting in significant functional impairment, or declined to be evaluated were excluded. After the clinical examinations, the patients received medical treatment and exercise instructions based on the etiology and the attending neurologist’s clinical judgements. Follow-up evaluations were performed if deemed to be necessary by the neurologist. Results: 18 patients with PN and 12 patients with PD were included for analysis. No significant difference in age and gender distribution was noted among the two groups. Six of the PN patients had diabetic neuropathy. 6 patients with PN and 2 patients with PD fulfill the criteria for decreased muscle mass based on the AWGS 2019 consensus according to the HAMM measured by BIA. Significant correlation with grasp strength was observed between the patients’ age (p=0.012) and HAMM (p=0.036), while there was no significant correlation between the patients’ age and HAMM. No significant difference of HAMM and grip strength were observed between PN and PD patients, and between patients with diabetic neuropathy and non-diabetic PN. Among the 10 PN and 11 PD patients who were under medical treatment and received follow-up evaluations more than 5 months after the initial evaluation, the average monthly changes of HAMM were not significant different between the two groups of patients. Conclusion: Patients with either PN or PD could have changes in muscle strength measured by grip strength related to loss of ASM, and the pattern of changes are similar. Since both the loss of muscle mass and decreased strength may result in disability in either PN or CNS disorders, routine evaluation of these parameters in patients with various neurological disorders should be considered to better understand the factors that may contribute to the disability of patients.

Dr. Edouard Berling 1 , Dr. Aude Servais 2,3 , Prof. Hélène Prigent 4 , Dr. Clément Guémy 1 , Dr. Alice Rouyer 1 , Dr. Claire Lefeuvre 1 , Prof. Guillaume Nicolas 1 , Prof. Pascal Laforêt 1 1 Service de Neurologie, AP-HP, Hôpital Raymond Poincaré, Centre de référence Nord-Est-Ile-de-France, Garches, France. 2 ERKNet Department of Kidney and Metabolic Diseases, Transplantation and Clinical Immunology, Necker Hospital, AP-HP, Centre of Reference for the French Nationwide MARHEANetwork (CNR-MARHEA), Paris, France. 3 Inserm U1163, Imagine Institute, Paris, France. 4 Physiology Department, Hopital Raymond Poincaré GHU APHP Université Paris Saclay, Garches, France Background: Cystinosis is a rare lysosomal storage disorder characterized by progressive multiorgan cystine accumulation. With improved survival into adulthood owing to cysteamine therapy and kidney transplantation, late-onset extrarenal complications have become increasingly apparent. Myopathy is a recognized but underdiagnosed manifestation, often evolving insidiously and potentially leading to severe respiratory and swallowing complications. Sensitive tools for early detection and longitudinal monitoring of cystinosis-associated myopathy remain poorly defined. Methods: We conducted a prospective, longitudinal observational study in adults with genetically confirmed cystinosis recruited from French national reference centers between 2020 and 2025. Participants underwent comprehensive neuromuscular, respiratory, and swallowing assessments at baseline and after 12 months. Muscle involvement was evaluated using clinical examination, Medical Research Council sum score (MRCss), functional motor tests, and upper-limb strength and dexterity measures. Patients were classified as having clinically overt muscle weakness (MRCss <58/60) or no overt weakness. Among those without overt weakness, occult muscle involvement was defined by reduced vital capacity (<80% predicted) and/or swallowing impairment. Longitudinal changes in motor and functional outcomes were analyzed. Results: Twenty-four adults (median age 36 years) were included. Clinically overt muscle weakness was present in 10 patients (41.7%). Respiratory insufficiency, dysphagia, and sleep apnea were frequent, particularly in patients with overt weakness, but were also observed in those without apparent weakness. Functional motor performance was more impaired in patients with overt weakness, notably affecting distal strength, hand dexterity, and global motor function. Among patients without overt weakness, 57.1% exhibited occult muscle involvement, characterized primarily by respiratory or swallowing abnormalities. In this subgroup, dominant-hand grip and key pinch strength were frequently reduced despite preserved gait and global motor function. Over 12 months, most strength and functional measures remained stable, with only minor declines observed in selected timed motor tasks. Conclusion: Muscle involvement in adult cystinosis is common and frequently under-recognized, including in patients without clinically overt weakness. Subtle distal strength deficits, particularly in the dominant hand, may signal occult myopathy and associated respiratory or swallowing complications. Short-term progression appears limited, highlighting a window for early detection and preventive intervention. Simple upper-limb strength assessments may represent practical screening tools to guide referral and longitudinal monitoring in this rare population.

Dr. Mariangela Goglia 1 , Dr. Erica Frezza 1,2 , Dr. Giulia Greco 1 , Dr. Francesco Gruosso 1,2 , Dr. Giovanni Vietri 1,2 , Dr. Laura Boffa 1 , Dr. Marzia Nuccetelli 3 , Prof. Diego Centonze 4,2 , Prof. Roberto Massa 1,2 1 Neuromuscular Diseases Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy. 2 Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy. 3 Division of Clinical Biochemistry and Clinical Molecular Biology, University of Rome Tor Vergata, Rome, Italy. 4 Department of Systems Medicine, Tor Vergata University, Rome, Italy Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular disorder characterized by the progressive degeneration of upper and lower motor neurons. Recent studies have reported increased levels of blood phosphorylated tau181 (p-tau181) in patients with ALS compared to controls. According to the literature lower motor neuron (LMN) damage may represent a potential peripheral source of p-tau181 elevation. This hypothesis was supported by analyses of clinical and electromyographic measures of LMN impairment, as well as by neuropathological studies. These findings have raised concerns regarding the specificity of blood p-tau181 as a biomarker. More recently, skeletal muscle tissue has been proposed as an alternative peripheral source of p-tau. Despite these recent findings, our understanding of p-tau181 in ALS remains limited, and it is still unclear whether it could serve as a potential biomarker of lower motor neuron damage or offer insights into disease progression and prognosis. Methods: The aim of this study was to evaluate blood p-tau181 levels in patients with ALS in relation to clinical parameters and disease progression rate. In this study we recruited patients diagnosed with ALS and a healthy control group. Patients underwent the ALS functional rating scale-revised (ALSFRS-R), MRC sum score and Penn upper motor neuron score (PUMNS). Disease progression rate was calculated as (48 – ALSFRS-R)/disease duration (months) and patients were stratified into fast and slow progressors. Plasma p-tau181 was detected both in patients and control group by CLEIA assay (Lumipulse). Results: Eighteen patients (11 males and 7 females, 14 with spinal and 4 with bulbar onset) and 18 healthy controls were recruited. Median age was 65.8 years (IQR 13.8). Median disease duration was 12 months (IQR 11.5). Median ALS-FRS-R score was 40 (IQR 6.0). Eleven out of eighteen patients were slow progressors. Median p-tau181 level was 3.99 pg/mL (IQR 3.75) in ALS patients and 1.08 pg/mL in the control group (IQR 0.7). P-tau181 levels were significantly increased in ALS patients compared to the control group (p < 0.001). We found no correlations between ALS clinical parameters and p-tau181 levels. A negative correlation between p-tau181 and disease progression rate was observed (rho -0.5; p = 0.03). Moreover, slow progressors had higher p-tau181 values than fast progressors (p = 0.01). Conclusion: According to recent studies, plasma p-tau181 levels were significantly higher in ALS patients compared with healthy controls. No associations were observed between p-tau181 levels and clinical measures. In contrast, p-tau181 showed a significant inverse correlation with disease progression rate, with higher levels observed in slow progressors compared to fast progressors. These results suggest that p-tau181 might be linked to slower functional decline, potentially reflecting predominant lower motor neuron involvement, a pattern frequently associated with slower disease progression. At the same time, its behaviour could reflect both the extent of lower motor neuron damage and the degree of denervation, suggesting that plasma p-tau181 may follow different trajectories depending on the stage of disease. Larger cohorts and longitudinal studies are required to clarify whether plasma p-tau181 could reflect or influence the rate of functional decline in ALS.

Assoc. Prof. Ali Habib 1 , Assoc. Prof. Christina Ulane 2 , Assoc. Prof. Min Kang 3 , Prof. David Richman 4 , Prof. Stephan Ciurea 1 , Prof. Ran Reshef 2 , Asst. Prof. Madhav Seshadri 3 , Prof. Mehrdad Abedi 4 , Dr. Jonathan Hogan 5 , Dr. Yvonne White 5 , Dr. Jenell Volkov 5 , Dr. Daniel Nunez 5 , Mr. Thomas Furmanak 5 , Dr. Raj Tummala 5 , Dr. David Chang 5 1 UCI, Irvine, United States. 2 Columbia University, New York, United States. 3 UCSF, San Fransisco, United States. 4 UC Davis, Davis, United States. 5 Cabaletta Bio, Philadelphia, United States Background: Generalized Myasthenia Gravis (gMG) is a B-cell-mediated disease; most patients have detectable autoantibodies targeting the neuromuscular junction. Available therapies require chronic administration, increasing the risk of side effects, and many patients remain refractory despite treatment with several agents. Rese-cel (formerly CABA-201) is an investigational, fully human, autologous 4-1BB CD19-CAR T cell therapy, designed to deeply and transiently deplete CD19+B-cells following a single, weight-based infusion, potentially enabling an “immune reset” with durable responses. RESET-MG ™ ( NCT06359041 ) is a Phase 1/2 trial evaluating the safety and efficacy of rese-cel in 2 independent cohorts of anti-AChR-antibody-positive and anti-AChR-antibody-negative gMG. Methods: Eligible patients are 18-70 years old with MGFA Classification II-IV gMG and MG-ADL ≥6 despite ≥2 prior/current treatments. A single rese-cel infusion of 1x10 6 cells/kg is administered following standard preconditioning with fludarabine and cyclophosphamide. All non-glucocorticoid immunomodulatory agents are discontinued by preconditioning; glucocorticoids and acetylcholinesterase inhibitors are tapered post-infusion. Adverse events, gMG medications and gMG activity were assessed. CAR T cells and B cells were profiled in peripheral blood pre- and post-infusion by digital PCR and flow cytometry, respectively. Results: As of 11 September 2025, four patients (2 per cohort) have received rese-cel and completed at least 1 month follow-up (Table 1) in the RESET-MG trial. Rese-cel was well-tolerated with no dose-limiting toxicity or serious infection. One patient had a Grade 2 cytokine release syndrome (CRS), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was observed The 2 evaluable patients achieved improvements in MG disease activity off of all gMG medications: AChR-neg1 experienced an improvement in MG-ADL 17 to 0 (achieving minimal symptom expression) and QMG from 22 to 5 at 20 weeks post-infusion; AChR-neg2 experienced an improvement in MG-ADL from 14 to 7 and QMG from 21 to 11 at 8-weeks post-infusion. The 3rd patient was not evaluable due to use of a prohibited cytotoxic medication that may have inhibited CAR T activity; the 4th patient has insufficient follow up. PK and PD profiles were available for 3 adult patients. Rese-cel expanded in all patients and peaked 7 days (median; IQR: 5-10) following infusion at 8 cells/µL (median; IQR: 4-97). Peripheral B cell counts reached a minimum at 7 days (median; IQR: 6.8-7.4) post-infusion with an average depletion duration of 48 days (median; range: 14-81), calculated from the 2 patients who exhibited B cell repopulation at the time of the data cut. Repopulating B cells were mostly transitional naïve, supporting B cell compartment reset. Conclusion: These initial data suggest that rese-cel is well-tolerated and can lead to immune reset in gMG, allowing patients to achieve meaningful clinical responses off of gMG therapies. Both cohorts are fully enrolled, and additional data will be presented at ICNMD.

Assoc. Prof. Marianthi Arnaoutoglou 1 , Dr. Korina Kaffe 2 , Dr. Vasiliki Poulidou 2 , Dr. Maria Moschou 1 , Dr. Maria Gavrilaki 2 , Assoc. Prof. Aggeliki Cheva 3 , Mrs Georgis Pepe 4 , Prof. Vasilios Kimiskidis 2 1 Department of Clinical Neurophysiology , AHEPA University Hospital Aristotle University of Thessaloniki, Thessaloniki, Greece. 2 1st Department of Neurology , AHEPA University Hospital Aristotle University of Thessaloniki, Thessaloniki, Greece. 3 Department of Pathology, Aristotle University of Thessaloniki, Thessaloniki, Greece. 4 Genekor, Athens, Greece Background: Desminopathy is a rare subtype of myofibrillar myopathy caused by pathogenic variants in the DES gene encoding desmin, a muscle-specific intermediate filament critical for cytoskeletal integrity. While desminopathies traditionally present in adulthood with skeletal and cardiac muscle symptoms, early-onset cases with multisystemic features are increasingly reported. Gastrointestinal and respiratory involvement are less common but may represent underrecognized features. Diagnosis is challenging, especially in sporadic cases without family history, making molecular diagnostics such as WES essential tools. Methods: This is a case report presentation of a 17-year-old female presented with progressive generalized muscle weakness, low BMI, and chronic gastrointestinal symptoms, including persistent diarrhea and loss of appetite. Symptoms began subtly in early adolescence, with increasing fatigue and reduced exercise tolerance. Over time, she developed significant respiratory weakness, manifesting as dyspnoea on exertion and poor nocturnal ventilation. She experienced an acute clinical deterioration following a self-limited viral illness, with marked decline in mobility and respiratory capacity. There was no relevant family history of neuromuscular or cardiac disorders. Growth and neurodevelopment had been normal in early childhood. An extensive aboratory investigations was conducted including CK levels, Muscle biops and WES. Clinical investigation included extensive evaluation of cardiovascular function ( including cardiac MRI), evaluation of respiratory function (spirometry and sleep study) and bowel and stomach endoscopy. The differential diagnosis included: LGMD , Mitochondrial myopathies Congenital myopathies , Chronic inflammatory myopathies, GI dysmotility due to autoimmune or metabolic causes Results: Definitive diagnosis was made by WES , which identified a heterozygous de novo pathogenic variant in DES : NM_001927.4 :c.1217G>C, p.(Arg406Pro). Parental testing confirmed the variant was not inherited. Biopsy confirmed the severe and catastrophic myopathy. The patient’s condition stabilized after initial deterioration but remained significantly limited in mobility and respiratory endurance. She continued nocturnal ventilation and received ongoing multidisciplinary care. No cardiac involvement was evident at the time but will be monitored periodically due to the known cardiomyopathic risk in desminopathies. Conclusion: Desminopathies are rare neuromuscular disorders caused by mutations in DES , which encodes desmin, an intermediate filament protein involved in muscle fiber integrity and organelle positioning. While the classic presentation involves limb-girdle weakness and cardiomyopathy in adulthood, this case highlights the early-onset, multisystem variant of desminopathy with predominant skeletal, GI, and respiratory involvement — in the absence of cardiac symptoms or family history. The patient’s c.1217G>C (p.Arg406Pro) previously reported in association with early and severe myopathy phenotypes. The de novo nature of the mutation underscores the importance of considering DES mutations even in patients without familial patterns. Respiratory muscle weakness is well-documented in desminopathy but often underrecognized. The exacerbation following viral illness further supports observations that systemic infections can unmask or accelerate muscle decompensation in genetically susceptible individuals. Gastrointestinal involvement, though less common, has been reported and may result from smooth muscle or autonomic dysfunction. Our patient’s diarrhea and appetite loss were not explained by structural abnormalities on imaging, suggesting a functional component linked to the underlying myopathy. This case adds to the growing literature on desminopathy as a phenotypically variable disorder with non-classical presentations , especially in children and adolescents.

Dr. Kei Ishizuchi , Dr. Kensuke Okada, Prof. Jin Nakahara Department of Neurology, Keio University School of Medicine, Tokyo, Japan Background: In 2022, the Japanese regulatory authority approved the terminal complement C5 inhibitor ravulizumab (RAV) for the treatment of anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG). Its indication was however limited to patients whose symptoms were difficult to control with intravenous immunoglobulin therapy or plasmapheresis. In April 2025, the label was expanded and RAV became available as an add-on to the standard-of-care treatments including oral corticosteroids (e.g. prednisolone [PSL]) and/or non-steroidal immunosuppressant therapies (NSISTs). This study was conducted to evaluate the real-world efficacy of RAV in a high-volume center in Tokyo, Japan. Methods: A retrospective medical chart review was conducted. The data cut-off (DCO) date was January 10 th , 2026. Patients who no longer visited the hospital within 8 weeks of the DCO date were excluded. Patients previously enrolled in RAV or eculizumab clinical trials, patients with actively-treated thymoma, and patients harboring C5 polymorphism (c.2654G>A) were excluded from the study. Results: A total of 25 RAV-treated gMG cases (13 males and 12 females) were identified. 10 cases had previous curative treatment history of thymoma. The average onset age was 47.7±16.1 years old and the average disease duration was 13.0±12.6 years. All patients were currently treated with prednisolone (the average daily dose was 9.5±3.5mg), with 20 patients utilizing concomitant NSISTs (17 tacrolimus and 3 cyclosporine). The average MG-ADL score at baseline was 9.3±4.3, whereas it was 5.7±3.8 under RAV at the last follow-up (the average follow-up duration was 22.8 weeks [range 2-138 weeks]). No meningococcal infection was reported. Conclusion: Improvements of MG-ADL scores by the add-on RAV in the present cohort were consistent with the previously reported clinical trial results (i.e. the mean MG-ADL score improved by 3.1 on week 26; Vu et al, NEJM Evid (2022)). The above data will be updated, and further analysis will be discussed during the presentation.

Dr. Edoardo Roveta 1,2 , Dr. Mehrnaz Hamedani 3 , Dr. Sara Massucco 3 , Dr. Chiara Gemelli 4 , Dr. Cristina Schenone 3 , Dr. Marina Grandis 4 , Dr. Carolina Barone 3 , Dr. Massimo Leandri 3 , Dr. Angelo Schenone 4 1 University of Genoa, DINOGMI, Genoa, Italy. 2 Fondazione David Chiossone Impresa Sociale, Genoa, Italy. 3 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Genoa, Italy. 4 Department of Neurology, IRCCS Polyclinic Hospital San Martino, Genoa, Italy Background: Charcot–Marie–Tooth (CMT) disease is a hereditary peripheral neuropathy characterized by progressive distal muscle weakness, sensory impairment and balance dysfunction, leading to gait instability and increased fall risk. Quantitative measures are needed to detect subtle balance deficits beyond standard clinical assessments. This study aims to evaluate the reliability and responsiveness of a static and dynamic stabilometric platform (SP) in individuals with CMT. Methods: The full study plans to enroll 40 patients with genetically confirmed CMT and 60 healthy controls (HC), aged between 18 and 80 years. At this preliminary stage, data are available from 24 patients and 30 HC. Eligibility criteria included the absence of significant comorbidities, no recent orthopedic surgery and a pain score below 3 on the Visual Analogue Scale (VAS<3). All participants underwent balance assessment using the SP under static conditions (Eyes Open, Eyes Closed) and dynamic conditions (Eyes Open Toes Up Small Perturbation, Eyes Open Backward Stimulation). During dynamic trials, surface electromyography was used to assess activation timing of the tibialis anterior and soleus muscles. Patients with CMT also performed standardized clinical assessments, including the Berg Balance Scale (BBS), Modified Barthel Index (MBI), Tinetti Scale (TS), 10-Meter (10MWT) and 6-Minute Walking Tests (6MWT). Patients were randomized to traditional physiotherapy or platform-based rehabilitation, both consisting of 30 daily sessions of 1 hour. Results: No significant test–retest differences were found in HC, confirming platform reliability. In patients, significant post-treatment improvements were observed in Sway Area and Sway Path during static EO and EC trials (p = 0.01). Correlation analysis revealed significant associations between Sway Area and activation times of the tibialis anterior (r = 0.65, p = 0.03) and soleus (r = 0.72, p = 0.01). Post-treatment changes in balance parameters were also significant when measured using the following clinical scales: BBS t0: 46.70 ± 2.22, t1: 51.70 ± 1.32 (p< 0.023), 10MWT time domain t0: 9.30 ± 2.65, t1: 8.17 ± 2.17 (p<0.005), TS t0: 22.50 ± 3.20, t1: 25.00 ± 1.94 (p<0.005), 6MWT t0: 362.00 ± 114.12, t1: 401.00 ± 102.61 (p<0.004). Conclusion: Due to the current sample size, no comparison between platform-based and traditional rehabilitation was performed, and results reflect the overall rehabilitation effect in CMT patients. Combining traditional assessments with quantitative metrics improves sensitivity to small functional changes. More comprehensive results will be reported upon study completion.

Dr. Jing Wu 1,2,3 , Dr. Malin Petterson 2,3,4 , Miss Wanqing Wu 2,3 , Dr. Ann Eriksson Dufva 2,3,4 , Prof. Fang Fang 1 , Prof. Fredrik Piehl 2,3,4 , Assoc. Prof. Susanna Brauner 2,3,4 1 Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden. 2 Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Institutet, Solna, Sweden. 3 Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden. 4 Department of Neurology, Karolinska University Hospital, Solna, Sweden Background: Thymic hyperplasia is common in early-onset myasthenia gravis (EOMG; onset <50 years) but much less common in late-onset MG (LOMG; onset ≥50 years). The Nordic MG guidelines recommend thymectomy for patients aged 50-65 years. However, reliable imaging and biomarkers for thymic hyperplasia are not available. Thus, we aimed to identify clinical factors that predict hyperplasia in non-thymomatous patients and to determine whether patients with hyperplasia derive greater benefit from thymectomy in terms of long-term clinical outcomes. Methods: We identified 416 thymectomized non-thymomatous MG patients in the Swedish MG Register (MGreg), which collected information on clinical characteristics, biological measurements, treatment, and disease activities as part of clinical routine practice. Clinical factors comprised sex, age of disease onset, anti-acetylcholine receptor (AChR) antibody, and disease duration. Information on environmental and lifestyle factors (including education, BMI, physical activity, alcohol consumption, and smoking status) of 208 patients was collected by linking Genes and Environment in the Myasthenia Gravis Study. Rescue treatment was assessed between hyperslasia and normal pathology at 2 and 5 years after diagnosis. Logistic regression was used to estimate the odds ratio (OR) of hyperplasia in relation to clinical and lifestyle factors with 95% confidence intervals (CI). Results: The majority of the participants were female (n=292; 70.2%), and the mean age at disease onset and thymectomy were 31.7 (SD: 15.5) and 35.6 (SD: 15.4) years, respectively. Patients with hyperplasia were predominantly female, younger, had lower BMI, and were more likely to be anti-AchR positive compared to those lacking thymic hyperplasia. In the clinical factor model, age at onset and disease duration were associated with a lower odds of hyperplasia (OR 0.91, 95%CI 0.89, 0.93 and OR 0.92, 95%CI 0.83, 1.01, respectively). While female sex (OR 2.24, 95%CI 0.97, 5.17) and anti-AchR positivity (OR 2.71, 95%CI 1.18, 6.20) were associated with higher odds of hyperplasia. Intriguingly, higher BMI (OR 0.78, 95%CI 0.67, 0.91), regular physical activity (OR 0.22, 95%CI 0.05, 0.90), and low alcohol consumption (OR 0.23, 95%CI 0.06, 0.88) were associated with lower risk of hyperplasia. Former (OR 2.48, 95%CI 0.43, 14.19) and current smokers (OR 2.15, 95%CI 0.46, 9.97) showed a tendency towards a higher risk of hyperplasia. In terms of clinical outcomes, only 7.7% and 14.2% patients with hyperplasia ever received rescue treatment within 2- and 5-year follow-up compared to patients with normal histology (19.8% and 24%), respectively. Further, patients with hyperplasia tended to receive rescue treatment later than patients with normal pathology (12.5±14.4 vs 21.8±16.9 months). Conclusion: This study identified potential predictive clinical and lifestyle factors for thymic hyperplasia. Patients aged >50 years more rarely undergo thymectomy in Sweden. Thus, these results are working in progress to be validated in a Finnish cohort where thymectomy frequencies in LOMG are higher. A better outcome of MG after thymectomy is linked to thymic hyperplasia, and therefore, these clinical predictors of hyperplasia should be actively used when selecting patients for thymectomy.

Miss Francesca Ferguson 1 , Miss Isobel Cabraal 1 , Dr. Ezgi Bakircioglu Duman 1 , Dr. Mohammad Ashraghi 1,2 , Assoc. Prof. M. Isabel Leite 1,3 1 University of Oxford, Oxford, United Kingdom. 2 Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom. 3 Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom Background: While myasthenia gravis (MG) is known to be associated with thymic malignancies, data regarding its association with extrathymic malignancies are sparse. Limited reports describe associations between MG and extrathymic malignancies, including secondary malignancies following thymic malignancy, with prolonged traditional immunosuppressive treatment proposed as a contributing factor. Here, we investigate the type and timing of thymic and extrathymic malignancies in patients with MG receiving traditional immunosuppression using data from the UK Myasthenia Gravis Database (UKMyDb). Methods: This retrospective observational study included all adults (≥18 years) with MG treated at Oxford University Hospitals and enrolled in UKMyDB, a combined retrospective-prospective registry containing demographic and clinical data. Patients receiving targeted therapies (zilucoplan, rituximab, efgartigimod) or regular intravenous immunoglobulin or plasma exchange were excluded. Timing of malignancy diagnosis relative to MG onset was described across demographic groups. Statistical analysis was performed using R (version 4.5.2). Results: 416 patients were included (211 male [50.7%], 205 female [49.3%]), with a median age of 65.0 years (IQR 25.3). Thymic malignancy was identified in 25/416 patients (6.0%), and 36/416 patients (8.7%) had an extrathymic malignancy. Among extrathymic malignancies, skin (n = 8) and prostate (n = 7) were most frequent; breast, colorectal, genitourinary (excluding prostate), and haematological malignancies each occurred in n = 3, followed by gynaecological (n = 2), other malignancies (n = 2), and central nervous system malignancies (n = 1). Four patients had more than one malignancy type, including colorectal and skin (n = 1), genitourinary (excluding prostate) with other (n = 1) or skin (n = 1), and prostate and skin (n = 1). The majority of thymic malignancies (17, 68.0%) were diagnosed within one year before or after the onset of MG. Of extrathymic malignancies, only 4 (10.5%) were diagnosed within this ±1-year interval, with no clear association between malignancy type and proximity to MG onset. For several extrathymic malignancy types, including skin, prostate, breast, and haematological malignancies, the majority of diagnoses occurred after MG onset (60.0%, 57.1%, 60.0%, and 66.7%, respectively); however, numbers were small and findings should be interpreted cautiously. Two patients with thymic malignancy also had a reported extrathymic malignancy, both were women with breast malignancy diagnosed more than 10 years after MG onset. The lower frequency of extrathymic malignancies in the thymic malignancy cohort may reflect younger age at MG onset (median 58.6 years [IQR 17.9] vs 77.1 years [IQR 11.3]). Conclusion: In this cohort, no clear temporal association was observed between MG onset and the occurrence of extrathymic malignancies, providing no strong evidence to support a paraneoplastic relationship outside of thymic malignancy, although interpretation of these findings is limited by small case numbers. The identification of two cases of breast cancer following thymic malignancy highlights the potential risks associated with radiotherapy and radiation exposure during long-term surveillance. This analysis includes patients exposed to conventional immunosuppressive therapies; further work will assess whether treatment dose or duration is associated with extrathymic malignancy risk, and will explore the low incidence of extrathymic malignancy within the thymic malignancy cohort.

Dr. Francesco Gruosso 1,2,3 , Dr. Mariangela Goglia 1,2 , Dr. Erica Frezza 1,2,3 , Dr. Giulia Greco 1,2 , Dr. Giovanni Vietri 1,2,3 , Dr. Laura Boffa 1,2 , Prof. Diego Centonze 1,3 , Dr. Camilla Rocchi 1,2 , Dr. Antonio Petrucci 4 , Prof. Roberto Massa 1,2,3 1 Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 2 Neuromuscular Diseases Unit, Tor Vergata University Hospital, Rome, Italy. 3 Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy. 4 Center for Neuromuscular and Neurological Rare Diseases, San Camillo Forlanini Hospital, Rome, Italy Background: Charcot-Marie-Tooth disease (CMT) is a spectrum disorder with variable progression and severity, but reliable biomarkers for predicting severity are lacking. This study aimed to widely evaluate whether combining neurophysiological measures, plasma biomarkers, and standardized clinical scales may identify independent predictors of severity across CMT subtypes and distinguish phenotype-specific patterns of disease progression. Methods: Forty-six genetically confirmed CMT patients (PMP22, NEFL, GDAP1, MFN2, GJB1, HSBP1, LRSAM1, MPZ, KIF1A) performed standardized assessment at two Italian referral centres: clinical scales (CMTNSv2, NIS, ONLS, MRC) and quality-of-life measures (SF-36, MAM-16); neurophysiological evaluation, including conventional tests(CMAP, SNAP, MNCV) and advanced quantitative techniques: Motor Unit Number Index (MUNIX) in the abductor digiti minimi muscle, reflecting motor unit loss quantitatively; Motor Unit Size Index (MUSIX), assessing denervation-reinnervation dynamics. Plasma biomarkers (neurofilament light chain [NfL], phosphorylated-tau181 [p-tau181]) were measured in 22 patients via advanced immunoassays. Stratification by electrophysiological phenotype enabled phenotype-specific analysis (axonal 56.5%, demyelinating 43.5%), with multivariable regression models identifying independent severity predictors within and across phenotypes. Results: MUNIX was considerably reduced in the whole cohort compared to normal reference values (57.7±34.2 vs ∼158±40 units, p <0.001), demonstrating a marked motor unit denervation characteristic of CMT pathophysiology. Notably, axonal phenotype showed significantly higher MUNIX (69.7±33.2) than demyelinating forms (40.2±28.4, p =0.005). Furthermore, MUNIX negatively correlated with clinical disability parameters, for instance, CMTNSv2 total severity (r=-0.467, p =0.002), suggesting how MUNIX may be an objective, quantitative marker of motor reserve. MUSIX (mean 103.6±48.4 μV) was elevated 52.4% above normal values, reflecting compensatory motor unit remodelling through collateral sprouting. NfL was elevated in 17.4% of patients and p-tau181 in 22.7%, but neither correlated significantly with clinical severity measures (NfL-CMTNSv2: ρ=-0.156, p =0.481; p-tau181-CMTNSv2: ρ=-0.102, p =0.713). This finding suggests these biomarkers may reflect acute denervation events rather than cumulative chronic disease burden, as in other disorders, such as amyotrophic lateral sclerosis (ALS). Multivariable regression showed MUNIX and disease duration as independent severity predictors (R²=0.650, p =0.011). Phenotype-stratified models found strong prediction in demyelinating forms (R²=0.862, p =0.037), in contrast to axonal ones (R²=0.530, p =0.450). Conclusion: MUNIX emerges as the most robust, objective neurophysiological predictor of clinical severity in CMT disease, greater than plasma biomarkers and electrophysiological patterns alone when evaluated in univariate analysis. Phenotype-specific assessment is essential for precision monitoring and stratification: demyelinating forms benefit from MUNIX-based severity prediction with remarkably robust models (R²=0.862) more than axonal phenotypes, which require complementary biomarker strategies, as traditional neurophysiological measures and cross-sectional plasma markers incompletely capture severity drivers in these heterogeneous forms. Plasma biomarkers (NfL, p-tau181), although elevated in a minority of cases, may reflect acute denervation cascades rather than chronic disease burden, and their longitudinal utility warrants prospective validation. This integrated phenotype-stratified multimodal assessment, combining quantitative motor unit analysis, genetic and electrophysiological stratification, plasma biomarkers, and clinical standardized scales, provides a comprehensive framework for individualized outcome assessment and monitoring in genetically diverse CMT. Future longitudinal studies and clinical trials should employ phenotype-stratified models to enhance patient selection, outcome prediction, and treatment response monitoring in CMT.

Assoc. Prof. Raffaele Iorio Università Cattolica del Sacro Cuore, Rome, Italy. Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy Background: Myasthenia gravis (MG) is an autoantibody-mediated disorder in which autoreactive B cells play a central pathogenic role by producing antibodies against acetylcholine receptors (AChR) or muscle-specific kinase (MuSK), causing fluctuating muscle weakness. B cell depletion is indeed a rational therapeutic strategy. Rituximab, an anti-CD20 monoclonal antibody, depletes mature B cells but spares plasmablasts and long-lived plasma cells that may continue producing pathogenic autoantibodies. Inebilizumab targets CD19, a marker retained across a broader B-lineage spectrum including plasmablasts and plasma cells, enabling more comprehensive depletion. Three randomized controlled trials have evaluated these approaches in generalized MG, with divergent results. Methods: Three randomized, double-blind, placebo-controlled trials were analyzed. BeatMG (Nowak et al., 2022) was a phase 2 futility-design trial of rituximab in 52 AChR-Ab+ gMG patients on prednisone, with steroid-sparing as the primary outcome over 52 weeks. RINOMAX (Piehl et al., 2022) evaluated a single 500 mg rituximab infusion in 47 treatment-naïve patients with new-onset gMG, targeting minimal disease manifestations at 16 weeks. MINT (Nowak et al., 2025) was a phase 3 trial of inebilizumab in 238 AChR-Ab+ or MuSK-Ab+ gMG participants, with change in MG-ADL score at week 26 as the primary endpoint. Results: BeatMG reached its futility endpoint (p = 0.03), with steroid-sparing rates of 60% for rituximab versus 56% for placebo, suggesting that a clinically meaningful benefit was unlikely despite an acceptable safety profile. Conversely, RINOMAX showed that early rituximab use led to minimal disease manifestations in 71% versus 29% with placebo (probability ratio 2.48; 95% CI 1.20–5.11; P = .007), with fewer rescue treatments. In the MINT trial, inebilizumab significantly improved MG-ADL scores (adjusted difference −1.9; 95% CI −2.9 to −1.0; P < 0.001) and QMG scores (adjusted difference −2.5; 95% CI −3.8 to −1.2; P < 0.001) versus placebo, with sustained benefits at 52 weeks in AChR-Ab+ patients and a favorable safety profile. Conclusion: The efficacy of B cell depletion in MG appears influenced by disease stage, molecular target, and study design. Notable heterogeneity across trials—in patient populations (established versus new-onset disease), antibody subtypes (AChR-Ab+ only versus AChR-Ab+ and MuSK-Ab+), dosing regimens, endpoints, and sample sizes—limits direct comparisons and warrants caution. Rituximab did not demonstrate steroid-sparing superiority in established AChR-Ab+ disease but showed benefit when given early in treatment-naïve patients (RINOMAX), although the small RINOMAX sample calls for confirmatory studies. Inebilizumab, through broader CD19-mediated depletion encompassing plasmablasts and plasma cells, demonstrated significant efficacy across both antibody subtypes in the larger MINT trial, though long-term safety and durability data are needed. Collectively, these findings support the therapeutic potential of B cell depletion in MG and suggest that CD19-directed therapy may address some limitations of anti-CD20 approaches, while further research is needed to define optimal patient selection and treatment timing.

Prof. Jan Verschuuren Leiden University Medical Centre, Leiden, Netherlands Background: Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare autoimmune disease caused by antibodies to presynaptic voltage-gated calcium channels. It is characterized by proximal muscle weakness, most predominantly in the legs, and loss of tendon reflexes and autonomic dysfunction. The incidence is less than 1 per million. LEMS has a strong HLA association in the predominantly female, early-onset group. Aside from this idiopathic form, in about half of the patients the disease is associated by small cell lung cancer, more often in the older population. LEMS is very likely to be underdiagnosed, as the most predominant symptom of proximal leg weakness is not very specific and can be explained by other disorders, especially at an older age. LEMS is a treatable condition. Effective symptomatic and immunosuppressive treatments are available. The diagnosis of LEMS is relatively easy, if the patient is tested for serum VGCC antibodies or electromyography with repetitive nerve stimulation is performed. Conclusion: Current treatment and the newly evolving therapies for autoimmune neuromuscular synapse disorders will be discussed.

Dr. Stephan Goedee Universitair Medisch Centrum Utrecht, Utrecht, Netherlands Background: Diagnosis of peripheral neuropathies has long been based on combination of clinical evaluation and electrodiagnosis; neuromuscular imaging has been shown to be a versatile and important complementary tool that is increasingly implemented in an increasing number of neuromuscular disorders, including neuropathies. Methods: This session wil cover the complementary role of neuromuscular imaging in the diagnosis of peripheral neuropathies, focusing on ultrasound and MRI; this includes practical examples, consideration of relevant pitfalls and implementation in routine clinical practice. Results: Clinical assessment is an important determinant of adequate selection of ancillary testing and correct interpretation of its results, including US and MRI imaging in diagnosis of peripheral neuropathies. Each techniques has its own intrinsic strengths and limitations, and shared overlap of abnormalities found in distinct causes of peripheral neuropathies -e.g. hereditary demyelinating, chronic dysimmune and paraprotaenemic-. Conclusion: Attendees will be able to recognize distinctive patterns of US and MRI, and consider interpretation in relevant clinical context, as complementary tool in the diagnosis of peripheral neuropathies.

Dr. karthik Vinay Mahesh, Dr. Vineet Dixit , Dr. Abeer Goel Post graduate institute of medical education and research, chandigarh, India Background: Trigeminal neuralgia (TGN) is commonly attributed to neurovascular compression, but neurovascular contact is also frequently seen in asymptomatic individuals. This suggests that additional vascular factors, such as vessel wall pathology and systemic vascular risk, may influence symptom generation. Vessel wall imaging (VWI) provides a novel approach to evaluate arterial wall characteristics beyond luminal anatomy. Methods: This was a prospective case–control study including 100 patients with TGN and 17 age- and sex-matched controls with asymptomatic neurovascular conflict of the trigeminal nerve. All participants underwent high-resolution MRI with 3D CISS, TOF angiography, and vessel wall imaging. Neurovascular compression was graded (0–3) based on nerve–vessel relationship. Basilar artery parameters including lumen diameter, wall thickness, lumen-to-wall ratio, and tortuosity index were assessed. Clinical pain severity was evaluated using the Penn Facial Pain Scale. Vascular risk factors and ASCVD scores were recorded. Statistical comparisons were performed between compressive cases and controls. Results: Among TGN patients, 77% demonstrated neurovascular compression. Cases were significantly older than controls (p = 0.046). Vessel wall thickness, lumen-to-wall ratio, and trigeminal nerve segment length did not differ significantly between compressive cases and controls. Pain severity did not show a significant correlation with compression grade (Spearman rho = 0.11, p = 0.27). Although compressive cases showed higher prevalence of vascular risk factors and higher mean ASCVD scores, these differences were not statistically significant. Conclusion: Neurovascular compression is common in trigeminal neuralgia; however, macroscopic vessel wall and nerve morphometric parameters alone do not fully explain clinical severity. The findings suggest a multifactorial pathophysiology in which microstructural neural changes and dynamic vascular factors may play a greater role than static imaging features. Vessel wall imaging is feasible in TGN and may provide complementary insights, warranting further large-scale studies

Dr. Lorenzo Fontanelli 1 , Ms. Carolina Ferri 2 , Mr. Adrian Florentin Suman 3 , Dr. Elisa Ceccherini 3 , Prof. Fabio Anastasio Recchia 1 , Prof. Gabriele Siciliano 2 , Prof. Giovanni Signore 2 , Dr. Silvia Rocchiccioli 3 1 Health Science Interdisciplinary Center - Scuola Superiore Sant'Anna, Pisa, Italy. 2 University of Pisa, Pisa, Italy. 3 Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Pisa, Italy Background: Duchenne muscular dystrophy (DMD) is caused by the absence of functional dystrophin - a protein encoded by the DMD gene - leading to increased membrane fragility and subsequent muscle degeneration. However, the specific effects of dystrophin deficiency on lipid composition in human cardiac cells remain largely unexplored. The aim of this study was to evaluate differences in the lipidomic landscape of human cardiac organoids modeling DMD. Methods: Cardiac organoids were generated from a human induced pluripotent stem cell (hiPSC) line carrying a nonsense mutation (c.4375_4379del, exon 45) in the DMD gene using a direct, stepwise differentiation protocol. Simultaneously, hiPSC-derived cardiac organoids were developed from a control cell line. Five biological replicates were obtained for each condition. Lipids extraction was performed using a modified version of the Folch method. Lipid extracts were subjected to a targeted lipidomic analysis performed by HPLC-MS/MS. Statistical significance was determined using a false discovery rate threshold of <0.05. Results: We found that nine phosphatidylcholine species and eight sphingomyelin species were significantly upregulated in the DMD condition compared to controls. Conversely, SM (38:1) and bis(monoacylglycerol)phosphates (BMPs), specifically BMP (16:1-18:1) and BMP (18:1-18:1), were significantly downregulated in DMD samples. Moreover, compared with controls, DMD samples exhibited a reduction in polyunsaturated fatty acids and an increase in monounsaturated fatty acids, accompanied by a shift toward shorter fatty acid chain lengths. Conclusion: Cardiac organoids replicate key in vivo features of DMD, such as increased levels of PC (34:1). The observed alterations in fatty acid chain length and the degree of unsaturation are consistent with the enhanced membrane permeability reported in vivo. Moreover, since polyunsaturated fatty acids are more susceptible to oxidative stress, the increase in monounsaturated fatty acids at the expense of polyunsaturated ones may reflect an adaptive response to an elevated oxidative environment. Finally, the reduction in BMP levels may indicate lysosomal dysfunction. Collectively, these results indicate that cardiac organoids accurately capture DMD-associated lipid remodeling and offer a powerful human-based platform for elucidating disease mechanisms and testing therapeutic approaches to restore membrane integrity and lipid homeostasis.

Dr. Carolina Azcona , Dr. Marcelo Rugiero, Dr. Erika Brulc, Dr. Maria Adela Aguirre, Dr. Rocio Blanco, Dr. Diego Perez de Arenaza, Dr. Silvia Christiansen, Dr. Elsa Nucifora Hospital Italiano, Ciudad Autonoma de Buenos Aires, Argentina Background: Amyloid myopathy is a rare and likely underdiagnosed manifestation of systemic light-chain (AL) amyloidosis, in which renal and cardiac involvement are more commonly recognized. When skeletal muscle involvement predominates early in the disease course, the condition may be misclassified as an acquired or, less frequently, a genetic myopathy, leading to delayed recognition of the underlying plasma cell dyscrasia. Although early diagnosis and timely initiation of therapy are associated with improved outcomes in AL amyloidosis by limiting irreversible organ damage, data regarding functional skeletal muscle recovery following effective systemic treatment remain scarce. Methods: We report a 63-year-old woman with systemic AL amyloidosis and progressive muscle weakness. Relevant clinical data were retrospectively reviewed Results: The patient presented with a 2-year history of progressive, symmetric proximal weakness involving all four limbs and axial muscles, later progressing to distal, bulbar, and respiratory involvement. Due to the severity of weakness, she became wheelchair-dependent and required assistance with activities of daily living. Serum muscle enzymes were elevated (creatine kinase 990 U/L; aldolase 15 U/L). Muscle magnetic resonance imaging revealed muscle edema involving the sartorius, hamstrings, adductor magnus, and tibialis anterior muscles, along with moderate fatty replacement of the gluteal muscles, sartorius, hamstrings, and adductor magnus, with symmetric involvement of both anterior and posterior compartments of the lower limbs. An inflammatory myopathy was initially suspected by rheumatology; however, there was no response to immunosuppressive therapy, myositis-specific antibodies were negative, and the initial muscle biopsy was non-diagnostic. Whole-exome sequencing revealed no clinically relevant variants, making a genetic myopathy less likely as well. The patient subsequently developed symptoms of heart failure. Cardiac evaluation showed a pseudo-infarction pattern on electrocardiogram, restrictive physiology, and cardiac magnetic resonance imaging findings consistent with amyloid cardiomyopathy. Bone scintigraphy with technetium-labeled pyrophosphate excluded transthyretin amyloidosis. Laboratory studies identified a monoclonal gammopathy with markedly elevated free kappa light chains (3532.09 mg/L) and suppressed lambda light chains (6.62 mg/dL). Bone marrow biopsy confirmed plasma cell dyscrasia, with flow cytometry demonstrating a clonal kappa-restricted plasma cell population. Reevaluation of the muscle biopsy demonstrated Congo red–positive deposits with apple-green birefringence under polarized light within epimysial and perimysial vessels, consistent with amyloid myopathy. Amyloid deposition was also identified in salivary glands. A diagnosis of systemic AL amyloidosis with muscle and cardiac involvement, Mayo stage IV, was established. Treatment with cyclophosphamide, bortezomib, dexamethasone, and daratumumab resulted in a marked hematological response accompanied by significant improvement in muscle strength and functional capacity. Conclusion: This case highlights amyloid myopathy as a rare but clinically relevant manifestation of systemic AL amyloidosis that may represent the dominant initial presentation of the disease, leading to diagnostic delay and misclassification as other myopathies. Importantly, it demonstrates that effective treatment of the underlying plasma cell disorder can result not only in hematological response but also in substantial recovery of muscle strength and functional capacity. Maintaining a high index of suspicion and routinely considering amyloid myopathy, particularly in late-onset myopathies, may enable earlier diagnosis and improve outcomes in this potentially lethal yet treatable condition.

Nora Florenz Dengler Background: In recent years, a paradigm shift has occurred in the understanding of (formerly) neuralgic (shoulder) amyotrophy. It is no longer limited to shoulder nerves that are affected, and the clinical presentation can be highly heterogeneous, complicating diagnosis. In addition to genetic causes, immunological pathomechanisms (such as viral infections) are increasingly coming into focus. For some time now, nerve torsion has also been associated with neuralgic amyotrophy. Pain management and corticosteroid therapy are considered the primary treatment. Several case series on surgical treatment have been published. However, to date, there are no uniform diagnostic criteria or treatment recommendations. Methods: Landmark publications on the topic will be shown, with a focus on surgical therapy series.Results: Following the publication of an initial review article in the German Medical Journal by Holle et al. in 2024, numerous outcome series after surgical treatment have been published (Pöschl et al. 2024, Granata et al. 2024, Campbell et al. 2025, Bang et al. 2024, Shi et al. 2024, Solaja et al. 2023). This presentation will compare and contrast different surgical treatment strategies and compare the available outcomes. Conclusion: To date, there is no structured analysis based on comparable outcome criteria. The extent to which a multicenter study design can contribute to knowledge gain will be discussed.

Assoc. Prof. Seol-Hee Baek 1 , Dr. Woo-Suk Tae 2 , Assoc. Prof. Jin-Woo Park 3 , Prof. Byung-Jo Kim 3,2 1 Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea, Republic of. 2 Brain Convergence Research Center, Korea University Medical Center, Seoul, Korea, Republic of. 3 Department of Neurology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea, Republic of Background: Cerebrospinal fluid (CSF) plays a critical role in maintaining brain homeostasis through mechanical protection, metabolic support, and clearance of metabolic waste. The glymphatic system, a recently identified pathway that facilitates CSF–interstitial fluid exchange, is considered a major brain waste clearance mechanism and has been implicated in the pathogenesis of neurodegenerative diseases. In the brain, the choroid plexus (CP) is a key structure responsible for CSF production and homeostasis. Thus, alterations in the CP may be associated with disrupted CSF dynamics and impaired glymphatic function. Accordingly, this study aimed to investigate whether the CP is altered in patients with amyotrophic lateral sclerosis (ALS) compared with normal controls (NCs). Methods: We analyzed 25 patients with ALS and 43 age- and sex-matched NCs. Collected demographic and clinical data included age, sex, disease duration, ALS functional rating scale-revised (ALSFRS-R) score, and ΔALSFRS-R. The ΔALSFRS-R was calculated using the following equation: (48–ALSFRS-R score)/disease duration (months). Three-dimensional T1-weighted MRI was acquired using a 3-T scanner, and CP segmentation was performed with FreeSurfer. Generalized linear models with covariate was performed to compare CP volume between ALS and NCs. Age-adjusted partial correlation analyses were conducted to assess associations between CP volume fraction and clinical variables. CP volume fraction was calculated as the sum of right and left CP volume divided by total intracranial volume (TIV). Results: Age and sex did not differ between groups (p=0.340, and p=0.803, respectively). After adjustment for age, right and left CP volumes were significantly larger in the ALS group than in the NC group (p=0.004, and p=0.046, respectively), whereas TIV did not differ between the groups (p=0.919). In addition, CP volume fraction was higher in the ALS group than in the NC group (0.092% vs. 0.070%; p=0.004). CP volume fraction was positively correlated with age (r=0.442; p=0.027). Age-adjusted partial correlation analyses revealed that CP volume fraction was positively correlated with disease duration (r=0.482; p=0.017) and negatively correlated with ΔALSFRS-R (r=-0.444; p=0.034). However, no significant correlation was observed with the ALSFRS-R score (r=-0.053; p=0.812). Conclusion: This study revealed CP volume enlargement in patients with ALS compared to NCs, and CV volume fraction was negatively correlated with ΔALSFRS-R. These findings may reflect an association between impaired glymphatic function and disease progression in ALS. Further studies with larger cohorts are needed to validate these findings.

Dr. Sara Liguori 1 , Dr. Francesca D'Andrea 1 , Dr. Marco Paoletta 2 , Assoc. Prof. Antimo Moretti 1 , Prof. Giovanni Iolascon 1 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy. 2 Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy Background: Neuromuscular diseases (NMDs) comprise a heterogeneous group of disorders characterized by progressive impairment of muscle strength, motor control, and functional mobility. Pain is a highly prevalent and frequently under-recognized symptom in patients with NMDs. Beyond its direct impact on physical function and psychosocial well-being, pain has been shown to interfere with sensorimotor processing, proprioceptive acuity, and postural strategies, contributing to balance deficits and an increased risk of falls. The aim of this study was to further investigate the association between pain and postural stability in adults with NMD through an objective stabilometric assessment. Methods: In this cross-sectional study, we included patients aged >18 years with a confirmed diagnosis of NMD. The assessment protocol comprised the collection of anthropometric data, pain evaluation using the Brief Pain Inventory (BPI), and balance assessment performed with a ProKin stabilometric platform. Postural stability tests were conducted under eyes-open (EO) and eyes-closed (EC) conditions to better challenge proprioceptive control mechanisms. From these tests, sway area (mm²) was derived, defined as the area encompassing all center of pressure (CoP) displacement points during postural oscillations. The NMD population was stratified according to the absence of pain (group 0) or presence of pain (group 1). The association between pain status and sway area under EO and EC conditions was analyzed using the chi-square test and odds ratio (OR). Results: A total of 39 patients with NMD were included, with a mean age of 45.8 ± 16.4 years and a mean BMI of 25.0 ± 4.26 kg/m². Eleven patients reported no pain on BPI assessment, whereas 28 reported the presence of pain. Sway area parameters under EO and EC conditions were stratified according to reference cut-off values reported in the literature. In group 0, 3 patients showed altered sway area under EO conditions and 4 under EC conditions, whereas in group 1, 8 patients showed alterations under EO conditions and 16 under EC conditions. Statistical analysis revealed that patients with pain exhibited a significantly higher prevalence of abnormal sway under EC conditions compared with those without pain (72.2% vs 27.8%, p = 0.015). Furthermore, patients with pain had a 5.2-fold increased risk of pathological sway area under EC conditions compared with group 0 (95% CI: 1.3–20.5). Conclusion: In this cohort of patients with NMD, the presence of pain was associated with an increased sway area with eyes-closed, indicating impaired balance compared with patients without pain. These findings suggest that pain may play a relevant role in proprioceptive dysfunction and balance impairment in patients with NMD.

Prof. Mary Reilly Division of Neurology in UCL Queen Square Institute of Neurology, London, United Kingdom Background: The inherited neuropathies include those neuropathies in which the neuropathy is the sole abnormality and those where the neuropathy is part of a more complex condition. The former group are known as Charcot Marie Tooth disease (CMT) and also includes the related conditions, hereditary neuropathy with liability to pressure palsy (HNPP), hereditary sensory neuropathy (HSN) and hereditary motor neuropathies (HMN). There have been huge advances in identifying causative genes for CMT in the last two decades especially with the use of whole exome sequencing and this has been further helped by the addition of short read whole genome sequencing (SR WGS) in the last decade. We published a study in 2024 of over 1500 patients with CMT using next generation sequencing including SR WGS, in which we achieved a diagnostic rate of 77%. Although this is a marked improvement in the diagnostic rate, we still have nearly a quarter of patients who do not receive a genetic diagnosis. Most of our unsolved cohort are patients with motor predominant axonal neuropathies often labelled as CMT2 or HMN. This talk will explore the possible reasons that these patients remain unsolved and the approaches we are taking to try to solve them. This includes the increasing use of new technologies like long read sequencing but also the recognition of the broadening of phenotypes associated with specific genes. Multidisciplinary meetings where clinicians, geneticists, clinical scientists and research scientists meet to discuss individual patients are becoming an increasingly important tool in solving the unsolved cohort.

Dr. Stefan Meng Radiology, Hanusch Hospital, Vienna, Austria. Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria Background: This part of the nerve ultrasound workshop focuses on landmark-based localization and tracking of clinically important nerves at the head, neck, and trunk. Pitfalls and technical implications will be discussed. Methods: As ultrasound is based on the combination of knowledge and manual skills, this workshop will be hands-on. Results: Ideally, the participants take home practical skills and experience for nerve ultrasound. Conclusion: Ultrasound is an important imaging modality in the diagnosis of neuropathies. Physicians should be aware of the strengths and weaknesses.

Assoc. Prof. Michelangelo Mancuso University of Pisa, Pisa, Italy Background: Mitochondrial myopathies are a heterogeneous group of disorders caused by defects in oxidative phosphorylation leading to impaired energy production. Despite advances in genetic diagnosis, effective disease-modifying therapies remain limited. This lecture will provide an overview of current management strategies, emphasizing symptomatic treatments and emerging standards of care aimed at improving quality of life. The second part will focus on recent therapeutic developments targeting the underlying pathophysiology. These include pharmacological approaches to enhance mitochondrial biogenesis and function, such as small molecules and metabolic modulators, as well as antioxidant strategies to mitigate oxidative stress. Advances in nucleoside therapy for mitochondrial DNA depletion syndromes and the growing role of precision medicine will also be discussed. Finally, the lecture will explore the challenges related to clinical trial design, heterogeneity of phenotypes, and outcome measures will be addressed, alongside the importance of international collaboration. Overall, this presentation aims to provide a comprehensive and forward-looking perspective on the evolving therapeutic landscape in mitochondrial myopathies, bridging current clinical practice with cutting-edge research and offering insights into the path toward effective disease-modifying treatments.

Asst. Prof. Jee Hyun Suh 1 , Asst. Prof. Seo Yeon Yoon 2 1 Seoul National University Bundang Hospital, Seongnam-si, Korea, Republic of. 2 Yonsei University College of Medicine, Seoul, Korea, Republic of Background: Speech sound disorders (SSD), including articulation and phonological impairments, are prevalent in childhood and adversely affect early literacy and academic achievement. In South Korea, SSD represents a substantial proportion of pediatric communication disorders. Although telerehabilitation offers a promising solution to regional disparities in access to care, existing standardized assessments such as the Urimal Test of Articulation and Phonology (UTAP) rely on time-intensive manual scoring and face limitations in digital implementation. To address these challenges, a novel digital articulation assessment instrument, Hi-DongDong, was developed using a three-round Delphi process with multidisciplinary experts. This study aimed to evaluate the reliability and concurrent validity of Hi-DongDong in children aged 2–13 years. Methods: This prospective multicenter study was conducted across five institutions. Children aged 2–13 years were recruited from outpatient clinics and community childcare facilities. Speech samples were recorded in a single session and assessed using Hi-DongDong and either UTAP-1 or UTAP-2 (randomized 2:1). Anonymized recordings were independently evaluated by three experienced speech-language pathologists. Inter-rater reliability was assessed using intraclass correlation coefficients (ICC). Concurrent validity and inter-instrument reliability were examined using ICCs, Pearson correlation coefficients, Wilcoxon signed-rank tests, and Bland–Altman analyses. Results: A total of 931 children were recruited, with analyses conducted on participants with valid paired datasets. Inter-rater reliability was excellent for all variables across instruments (ICC ≥ 0.98, p<0.001). Hi-DongDong demonstrated good-to-excellent agreement with UTAP-1 and UTAP-2 for consonant- and word-level measures, particularly Total PCC and Total PCC-R. Concurrent validity showed very strong positive correlations across all outcomes (all r=1, p<0.001). Bland–Altman analyses indicated minimal mean bias for utterance-level consonant accuracy indices, while systematic differences were observed for PMLU and PVC. Conclusion: Hi-DongDong is a reliable and valid digital articulation assessment tool, demonstrating strong agreement with established standardized instruments and supporting its clinical utility for efficient, telerehabilitation-ready evaluation of pediatric SSD.

Mr. Luc Wasilewicz 1 , Dr. Jessica Braun 2 , Dr. Sophie Hamstra 1 , Ms. Briana Hockey 1 , Dr. Rebecca MacPherson 1 , Dr. Val Fajardo 1 1 Brock University, St.Catharines, Canada. 2 University of Copenhagen, Copenhagen, Denmark Background: Duchenne Muscular Dystrophy (DMD) is an X-linked, genetically inheritable disease, characterized by muscle wasting and cardiorespiratory failure. To study DMD, it is important to use accurate animal models and research settings that are as closely translatable to the human population as possible, including housing temperature. Thermoneutrality is the temperature range that is most physiologically relevant to conduct research as there are no compensatory responses by the animal to alter core temperature, with this range being 28-30ºC for mice. While the mdx mouse has been widely used in the study of DMD, studies to date have housed mice at “room temperature” (22-24ºC). Although appropriate for humans, this range represents a mild cold stress in mice and imposes additional metabolic demands that may alter disease pathology and potentially conflict with the interpretation of results. Previously, we demonstrated that when DBA/2J (D2) mdx mice were housed at thermoneutrality, their muscle-wasting pathology worsened. This was demonstrated by reductions in the resistance to muscle fatigue of the extensor digitorum longus (EDL) muscle and increased cardiac impairments (i.e., reduced left ventricular internal diameter, end-diastolic volume, and cardiac output). From a mechanistic standpoint, we demonstrated that glycogen synthase kinase 3β (GSK3β) activity is higher, based on decreased inhibitory phosphorylation levels, in mice housed at thermoneutrality than at room temperature, which could contribute to the worsened pathology observed in mdx mice housed at thermoneutrality. We have previously demonstrated that GSK3β inhibition via a 4-week NP12 treatment can improve muscle strength and overall health in D2 mdx mice housed at room temperature. However, whether inhibiting GSK3β will produce similar benefits when D2 mdx mice are housed at thermoneutrality remains unknown. Thus, we sought to determine the effects of a 4-week NP12 treatment on skeletal and cardiac muscle in D2 mdx mice housed at thermoneutrality. Methods: 20 DBA/2J mdx mice (age 5 weeks) were randomly divided into a vehicle or NP12 group (n = 10 per group). All mice were provided a vehicle (poloxamer) or NP12 solution (10 mg/kg/day) via oral gavage 5x/week for 4 weeks. Analyses; In vivo : metabolic caging, body composition scans, insulin-tolerance-test, and high-frequency ultrasound. Ex vivo : EDL muscle fatigue contractility. Biochemical : creatine kinase assay, western blotting, and histological muscle fibre-type staining. Results: Metabolic caging revealed no differences in O 2 consumption, respiratory exchange ratio, cage activity or food intake between groups. There were no differences in body composition (i.e., body mass, fat mass, lean mass), serum creatine kinase, and total GSK3β between groups. An insulin-tolerance-test demonstrated that NP12-treated mice had increased insulin sensitivity and a high-frequency ultrasound demonstrated improved cardiac function (i.e., increases in stroke volume, cardiac output, end-diastolic volume). NP12-treated mice had improved EDL fatigue resistance alongside a higher percentage of type IIA and I oxidative fibres. Conclusion: Overall, our results demonstrate that NP12 treatment is able to improve indices of skeletal and cardiac muscle health, as well as whole-body insulin sensitivity in thermoneutrally-housed D2 mdx mice. These results help pave a path towards targeting GSK3 for DMD in the clinical setting.

Prof. Mohamed Islam Kediha 1,2 , Dr. Damien Sternberg 3 , Prof. Bruno Eymard 4 , Prof. Lamia Ali Pacha 1,2 1 Mustapha university hospital, Algiers, Algeria. 2 Benyoucef Benkhedda medical school, Algiers, Algeria. 3 Pitié Salpetrière hospital, Paris, France. 4 Rothschild foundation, Paris, France Background: Congenital myasthenic syndromes (CMS) are disorders that exhibit a wide range of phenotypic and genotypic diversity. To date, at least 35 genes have been identified, with the majority being autosomal recessive, which relates to the level of consanguinity and endogamy, still prevalent in Algeria. This research involves analysing a group of Algerian families from both phenotypic and genetic perspectives. This series represents the first cohort study of CMS in Algeria and in north Africa. Methods: We analyzed the clinical and paraclinical phenotypes of our families based on data from neurological examinations, general somatic examinations (particularly pleuropulmonary), EMG tests to detect decrement and double response of motor potential, and genetic studies of these families. These patients were scored using the Garches myasthenic score and the QMG (Quantitative myasthenai gravis) score before and after treatment. Results: We have gathered data from 33 families (71.7%) and detected various mutations (including 5 novel ones) across different identified genes (COLQ, COL13A1, CHRNE, CHRNA1, CHRND, GMPPB, and RYR1). Two families have been diagnosed with Escobar syndrome, while 11 families are currently under investigation. The most common mutations occur in the CHRNE gene, with the '1293insG' mutation, primarily found in North Africa, being the predominant one identified. The phenotype is classified as moderate and generally shows a good response to pyridostigmine treatment. The initial step should involve identifying the founder mutation in all cases of congenital myasthenic syndromes (CMS) in North Africa.The pharmacological approach is well-established, tailored to each specific gene and the underlying pathophysiological mechanisms of the post-synaptic genes, including receptor deficiencies or kinetic anomalies.Several novel treatments have also been explored such as Salbutamol, Fluoxetine, and corticosteroids. Additionally, palliative care delivered within a multidisciplinary framework is a crucial aspect of the treatment plan. Conclusion: Our series is the largest ever studied in Africa on CMS. We have identified several genes and new mutations, providing a genetic map of these conditions in Algeria and North Africa. We have also tested certain repurposed and innovative therapies, which have led to considerable functional improvement in some patients.

Dr. Katherine Mathews 1 , Dr. Tahseen Mozaffar 2 , Dr. Volker Straub 3 , Dr. Robert Henderson 4 , Dr. Douglas Sproule 5 , Dr. Ada Lee 5 , Ms. Amy Rainey 5 , Dr. David Paul 5 , Ms. Tricia Blankenbiller 5 , Dr. Uma Sinha 5 , Ms. Thulashitha Rajasingham 5 , Dr. John Vissing 6 1 University of Iowa, Iowa City, United States. 2 University of California Irvine, Irvine, United States. 3 Newcastle University, Newcastle upon Tyne, United Kingdom. 4 University of Queensland, Brisbane, Australia. 5 ML Bio Solutions Inc., a BridgeBio company, Palo Alto, United States. 6 University of Copenhagen, Copenhagen, Denmark Background: Limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) is an autosomal recessive disorder caused by pathogenic variants in the FKRP gene that impair alpha-dystroglycan (αDG) glycosylation, leading to progressive muscle weakness and cardiopulmonary decline. No approved therapies currently exist. BBP-418 is an oral, small molecule designed to restore αDG glycosylation and stabilize muscle integrity. Methods: FORTIFY ( NCT05775848 ) is an ongoing randomized, double-blind, placebo-controlled, Phase 3 study evaluating the efficacy and safety of BBP-418 in individuals with LGMD2I/R9. The prespecified 1-year interim analysis assessed biochemical, functional, and safety endpoints. The primary endpoint was change from baseline in glycosylated αDG at 3 months, with key secondary endpoints including serum creatine kinase (CK), 100-meter timed test (100MTT), and forced vital capacity (FVC) at 12 months. Results: At the interim analysis, BBP-418 treatment showed a 1.8-fold increase in glycosylated αDG from baseline at 3 months (p<0.0001), which was sustained through 12 months (p<0.0001) versus placebo. Serum CK decreased by 82% on average from baseline in the BBP-418 dosed participants at 12 months (p<0.0001 vs placebo). Statistically significant and clinically meaningful improvements were observed in 100MTT velocity (+0.14 m/s from baseline in BBP-treated participants; difference of 0.27 m/s in BBP-treated participants vs. placebo, p<0.0001) and FVC (+3% predicted from baseline in BBP-treated participants; difference of 5% predicted in BBP-treated participants vs. placebo, p=0.0071). BBP-418 was well tolerated with no new safety findings. Additional data from the interim analysis will be presented at the time of the meeting, with a focus on the Patient-Reported Outcomes Measurement Information System (PROMIS) tool. Conclusion: The interim analysis results from the ongoing 3-year FORTIFY Phase 3 trial demonstrated that BBP-418 provides significant improvements in αDG glycosylation, decreases in CK levels and functional benefits with a favorable safety profile. These data support BBP-418 as the potential first disease-modifying therapy for LGMD2I/R9.

Asst. Prof. Ouissem Benchaabi , Prof. Sonia Nouioua, Asst. Prof. Farroudja Ramdane-Cherif EHS Cherchell, TIPAZA, Algeria Background: SYNE1-related disorders are a group of genetic conditions,with a broad phenotypic spectrum, most commonly presenting as adult-onset Autosomal Recessive Cerebellar Ataxia (ARCA1) or SYNE1-ataxia with possible motor neuron disease, cognitive deficits (Cerebellar Cognitive Affective Syndrome), muscle weakness, and severe neonatal hypotonia with joint contractures in rare cases(SYNE1-deficient arthrogryposis multiplex congenita). To date, a pure juvenile-onset ALS phenotype has not been clearly established as part of the SYNE1-related disease spectrum. Methods: We performed detailed clinical, neurophysiological and genetic analysis, by neuromuscular panel next generation sequencing, in two sisters with juvenil amyotrophic lateral sclerosis (JALS) followed by variant interpretation according to current pathogenicity criteria to describe a novel clinical phenotype associated with SYNE1 mutations by reporting a juvenil-onset amyotrophic lateral sclerosis and intellectual disability without cerebellar signs over time Results: We report a consanguineous family with two sisters, aged 16 and 13 years, presenting with juvenile-onset motor neuron disease fulfilling clinical and electrophysiological criteria for ALS. In both patients, disease onset occurred at approximately four years of age, with progressive distal and proximal muscle weakness evolving over time and associated with combined upper and lower motor neuron signs, leading to severe functional impairment. In addition to motor involvement, both sisters exhibited early-onset intellectual disability. One patient presented with congenital hearing loss. Notably, no cerebellar manifestations were observed during the follow-up. Next-generation sequencing-based genetic analysis, including a neuromuscular panel of genes, identified a pathogenic variant in the SYNE1 gene: a homozygous nonsense variant, c.20227C>T (p.Gln6743Ter). Juvenile-onset amyotrophic lateral sclerosis (JALS) is a rare motor neuron disorder defined by symptom onset before the age of 25 years. Very early-onset forms, occurring before the age of 10 years, are particularly uncommon and are most often associated with autosomal recessive genetic etiologies. JALS is characterized by the progressive degeneration of upper and lower motor neurons and may be associated with additional neurological or neurodevelopmental manifestations. $ù=ùPMhe SYNE1 gene (OMIM *608441) k;pà)omencodes nesprin-1, a large nuclear envelope protein involved in nuclear positioning and cytoskeletal organization. Pathogenic variants in SYNE1 are classically associated with autosomal recessive cerebellar ataxia type 1 (ARCA1), but an expanding phenotypic spectrum has been described, including spastic paraplegia, motor neuron disease with overlapping features, intellectual disability, and multisystem neurodegeneration. To date, a pure juvenile-onset ALS phenotype has not been clearly established as part of the SYNE1-related disease spectrum. In this context, reporting novel clinical presentations is essential to improve genotype–phenotype correlations and refine genetic diagnostic strategies in early-onset motor neuron diseases. Conclusion: This report expands the clinical spectrum of SYNE1-related disorders by identifying juvenile-onset ALS as a novel associated phenotype. Our findings support the inclusion of SYNE1 in next-generation sequencing panels gene for ALS, particularly in juvenile cases and in the presence of associated neurodevelopmental features. Further studies are needed to better define phenotype genotype correlations in SYNE1-related motor neuron diseases.

Assoc. Prof. Antony Winkel Sunshine Coast Health, Sunshine Coast, Australia. Griffith University, Sunshine Coast, Australia Background: Entrapment neuropathy is a common cause of neuropathic pain, although outside of the tarsal tunnel syndrome, foot entrapment syndromes are uncommon. Methods: Here, we present the case of a 50-year-old lady with no risk factors for nerve entrapment or neuropathy, who presented with entrapment of the lateral dorsal sural nerve, causing refractory neuropathic foot pain until surgical intervention provided symptomatic relief. Results: A 50-year-old lady, who was otherwise well with no significant medical or family history, presented with a 3-year history of right foot pain, radiating into the lateral dorsal foot. There was no inciting trauma or injury. Assessment at another institution failed to identify an aetiology, and she was treated with escalating doses of gabapentinoids after normal nerve conduction studies. Despite this, her symptoms were ongoing and debilitating and she sought further review. On review at our institution, her symptoms were identified to be concordant with the lateral dorsal cutaneous sural nerve territory. Additional nerve conduction studies using a modified published technique demonstrated a mild relatively prolonged sensory peak latency on the symptomatic side. Focal neuromuscular ultrasound was not available at the time, but MRI of the area showed T2 hyperintensity of the lateral dorsal cutaneous sural nerve branch. Surgical exploration revealed a fibrous band and thickened nerve at the entrapment site, and this was released and surgical neurectomy performed. At last follow up 2 years since surgery, the patient is on low-dose gabapentin (300mg/day) and apart from residual non-debilitating sensory disturbance is pain-free. Conclusion: This case reinforces the importance of tailoring neurophysiological assessment to the symptomatic issue. Non neuromuscular physicians should not be reassured by 'normal' routine nerve conduction studies unless the neurophysiologist has explicitly considered the possible symptomatic structures.

Prof. Francesco Muntoni Paediatric Neurology and the Director of the Dubowitz Neuromuscular Centre, at the UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children, and Director of the Genetic Therapy Accelerator at the UCL Institute of Neurology, London, United Kingdom Background: In the last decade there have been consistent advances in different approaches aimed at restoring dystrophin production in skeletal and cardiac muscle in patients with Duchenne muscular dystrophy (DMD). RNA therapies paved the way, with a number of first generation splice-switching antisense oligonucleotides (ASOs), several having received conditional FDA approval, targeting specific “skippable” mutations. We are now in the era of second generation ASOs, with several pivotal trials underway that are likely to become the next standard of care. The path of adeno-associated virus (AAV) gene therapy has also demonstrated success of the first generation vectors; and many competitors are currently building on the experience of the first studies to try to develop more potent therapies. Parallel but different efforts have also been devoted to a growing list of interventions which deal with other aspects of muscle pathology clearly delineating a path of multiple combinatorial therapies that will represent the standards of care in the year to come. In my presentation I will provide an overview of what could be the hypothetical therapeutic landscape in DMD, and also which are bottlenecks that will need to be overcome to have the maximal impact for the life of people living with DMD

Dr. Hsueh-Wen Hsueh 1,2,3 , Mr. Yao-Yu Wu 4 , Mr. Tzu-I Chuang 4 , Ms. Cheng-Chen Lin 5 , Dr. Ti-Yen Yeh 5 , Ms. Yi-Hui Kao 5 , Prof. Herng-Hua Chang 6 , Prof. Chi-Chao Chao 7 , Prof. Sung-Tsang Hsieh 1,8 1 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. 2 Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan, Taipei, Taiwan. 3 Department of Neurology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. 4 School of Medicine, National Taiwan University, Taipei, Taiwan. 5 Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. 6 Department of Engineering Science and Ocean Engineering, National Taiwan University, Taipei, Taiwan. 7 Department of Neurology, National Taiwan University Hospitalt, Taipei, Taiwan. 8 Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwant, Taipei, Taiwan Background: Diabetic neuropathy is common and imposes a substantial disease burden on the general population, in particular, affecting small-diameter sensory nerves, small fiber neuropathy (SFN). The degeneration of intraepidermal nerve fiber (IENF) on the skin impairs the protection of painful insult, which leads to a high risk of wound and amputation. Traditionally, the assessment of skin innervation by counting IENFs normalized to the length of the epidermis, IENF density (IENFd), has been the standard. However, the quantification is labor-intensive and time-consuming, and thus hampers the diagnosis of SFN. Advance in machine learning-based image analysis had the potential to facilitate the entire process of quantification without sacrificing the accuracy and reliability. This study aimed to (1) develop and validate new IENF biomarkers with the aid of machine learning algorithms for the diagnosis of SFN in diabetes, and (2) compare its diagnostic performance and clinical significance with the standard of IENFd. Methods: This study recruited patients with diabetic neuropathy and the control subjects for comparison. Area-based morphometry of IENF (IENFa) parameters were developed using machine learning system for automatic quantification, including three algorithms: Weka-based automatic annotation, edge detection, and custom-convolution methods. The IENFa parameters were further refined according to the area or perimeter of the epidermis as IENFa/A and IENFa/P respectively. The diagnostic performance was assessed according to Receiver Operating Characteristic (ROC) analysis. The clinical implications of the various IENFa parameters were examined by exploring the correlation to metabolic profiles and the electrophysiological studies. Results: The cohorts, diabetic neuropathy (n=48) and control subjects (n=63), were comparable in the age and gender [age: 59.3 ± 12.5 vs. 56.8 ± 13.0; male gender: 31 (65%) vs. 40 (63%)]. IENFa parameters of different algorithms were inversely correlated with the age and only the IENFd and IENFa/A were sex-dependent in the control group. All IENFa parameters showed equivalent performance according to (1) the correlation with IENFd and (2) the diagnosis of IENFd-based SFN using the area-under-curve (AUC) of ROC analysis, i.e., AUC: 0.91-0.95, P > 0.05. Furthermore, the IENFa biomarkers were significantly correlated to the sural sensory nerve action potential (SNAP) amplitudes, indicating the parallel involvement of small fiber (IENF) and large fiber (SNAP amplitudes) in diabetic neuropathy. Conclusion: The IENFa using the automatic annotation is time-saving and showed comparable performance to IENFd in the diagnosis of SFN in diabetes. Furthermore, this IENFa also reflect the parallel involvement of large fiber nerves of diabetic neuropathy, showing its efficiency and reliability. Given IENFa-based measure reflects the total area of all IENFs, the results also imply global axonal atrophy in diabetic neuropathy.

Ms. Eline Cuveele 1,2 , Dr. Geuens Sam 1,2 , Dr. Céline Gillebert 2 , Dr. Katy De Valle 3 , Dr. Kathryn Irving 3 , Dr. Daniella Villano 3 , Dr. Ian Woodcock 3 , Dr. Eppie Yiu 3 , Dr. Guenther Bernert 4 , Dr. Simone Mahal 5 , Dr. Clara Camelo 6 , Dr. Cristiane Moreno 6 , Dr. Edmar Zanoteli 6 , Dr. Emilie Hill-Smith 7,8 , Dr. Hugh McMillan 7,8 , Dr. Laura McAdam 9 , Dr. Sophelia Chan 10 , Dr. Patrick Yee 10 , Dr. Edna Julieth Bobadilla 11 , Dr. Andrea del Pilar Calderon Castro 12 , Dr. Pavla Bortolomejovava Bartolomejovava 13 , Dr. Katerina Bukacova 13 , Dr. Anezka Dolanska 13 , Dr. Jana Haberlova 13 , Dr. Monika Firholz 14 , Dr. Ulrike Schara-Schmidt 14 , Dr. Janbernd Kirschner 15 , Dr. Astrid Pechmann 15 , Dr. Eugenio Maria Mercuri 16 , Dr. Riccardo Masson 17 , Dr. Stefano Parravicini 17 , Dr. Claudia Dosi 17 , Dr. Federica Silvia Ricci 18 , Dr. Hirofumi Komaki 19 , Dr. Yuko Shimizu-Motohashi 19 , Dr. Erit Takeshita 19 , Dr. Keiko Ishigaki 20 , Dr. Kumiko Ishiguro 20 , Dr. Yuki Kihara 20 , Dr. Sato Takatoshi 20 , Dr. Andreas Dybesland Rosenberger 21 , Dr. Tonje Elgsås 22 , Dr. Heidi Elisabeth Nag 22 , Dr. Simen Stokke 22 , Dr. Diana Carvalho 23 , Dr. Juliana Da Silva Cardoso 24 , Dr. Cristina Garrido 24 , Dr. Dušan Šuput 25 , Dr. Damjan Osredkar 25 , Dr. Nina Demsar 25 , Dr. Andrej Vovk 25 , Dr. Barbara Verovnik 25 , Dr. Thomas Sejersen 26 , Dr. Anne-Berit Ekstrom 27 , Dr. Jonas Gillenstrand 28 , Dr. Bettina Henzi 29 , Dr. Andrea Klein 29 , Dr. Leonie Steiner 29 , Dr. Rossane Govaarts 30 , Dr. Erik Niks 30 , Dr. Saskia Houwen-Van Opstal 31 , Dr. Corrie Erasmus 31 , Dr. Marloes Van Lieshout 31 , Dr. Francesco Muntoni 32 , Dr. Chloe Gaegan 33 , Dr. Michela Guglieri 33 , Dr. Charlotte Ilderton 33 , Dr. Volker Straub 33 , Dr. Catherine Turner 33 , Dr. Liesbeth De Waele 1,2 1 University Hospitals Leuven, Leuven, Belgium. 2 KU Leuven, Leuven, Belgium. 3 The Royal Children's Hospital, Melbourne, Australia. 4 University Hospital Vienna, Vienna, Austria. 5 Klinik Favoriten Vienna, Vienna, Austria. 6 Universidade de São Paulo, São Paulo, Brazil. 7 Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada. 8 University of Ottawa, Ottawa, Canada. 9 Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, University of Toronto, Toronto, Canada. 10 Hong Kong Children’s Hospital and The University of Hong Kong, Hong Kong, Hong Kong. 11 Hospital Pediatrico de la Misericordia, Bogota, Colombia. 12 Hospital Universitario Nacional de Colombia, Bogota, Colombia. 13 Motol and Homolka University Hospital, Charles University,, Motol, Czechia. 14 University Children’s Hospital Essen, Essen, Germany. 15 University Hospital Freiburg, Freiburg, Germany. 16 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Centro Clinico Nemo, Rome, Italy. 17 Fondazione IRCCS Instituto Neurologico Carlo Besta, Milan, Italy. 18 University of Turin, Turin, Italy. 19 National Center of Neurology and Psychiatry Tokyo, Tokyo, Japan. 20 Tokyo Women’s Medical University, Tokyo, Japan. 21 University Hospital of North Norway, Norwegian Centre for Rare Diseases, Tromsø, Norway. 22 Norwegian Centre for Rare Diseases - Unit Frambu, Tromsø, Norway. 23 Unidade Local de Saúde de Trás-os-Montes e Alto Douro (ULSTMAD, Trás‑os‑Montes e Alto Douro, Portugal. 24 Centro Materno- Infantil de Norte, Unidade Local de Saúde de Santo António (CMIN, ULSSA), Porto, Portugal. 25 University of Ljubljana, Ljubljana, Slovenia. 26 Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. 27 Region Pediatric Rehabilitation Center, Queen Silvia Children’s Hospital, Gothenburg; University of Gothenburg, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden. 28 University of Gothenburg;Habilitation & Health, Region Västra Götaland, Gamlestaden, Gothenburg, Sweden. 29 Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 30 Leiden University Medical Center,, Leiden, Netherlands. 31 Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands. 32 UCL Great Ormond Street Institute of Child Health, University College London & Great Ormond Street Hospital Trust, London, United Kingdom. 33 John Walton Muscular Dystrophy Research Centre, Newcastle Hospitals NHS Foundation Trust and Newcastle University, Newcastle, United Kingdom Background: Duchenne muscular dystrophy (DMD) is increasingly understood as a multisystem condition that affects not only muscle but also brain development. Many boys with DMD experience cognitive difficulties, including problems with learning and attention, as well as challenges in social interaction, emotion regulation, behavior, eating and sleeping. Although these symptoms vary widely across individuals, they place a burden on children and families and may significantly contribute to reduced quality of life. Existing research remains fragmented, often cross-sectional, based on small samples and largely derived from Western, high-income countries, limiting our understanding of how genetic, treatment-related and environmental factors jointly influence neurodevelopment in DMD. Methods: To address these limitations, the DuMAND Network (Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties) was established as an international collaboration among clinicians and researchers in child neurology, psychology and psychiatry. A central component of the initiative is the DuMAND Checklist, a caregiver-administered instrument designed to measure a broad spectrum of neurobehavioral domains, divided into five categories: (1) cognition and learning , (2) emotion regulation , (3) social responsiveness , (4) externalizing behavior and (5) eating and sleeping . The DuMAND Checklist supports early recognition and structured monitoring of challenges within these DuMAND-categories, and offers a first step toward a more standardized approach to neurobehavioral assessment in clinical practice. Results: The DuMAND Network currently includes partners from more than 17 countries across five continents and works toward two complementary aims. First, the network advances research efforts to examine cultural differences in behavior, explore genotype-phenotype relationships (including dystrophin isoform involvement) and investigate the influence of treatments such as corticosteroids on cognitive and behavioral outcomes. Integrating clinical, behavioral, and genetic data will facilitate the development of culturally sensitive, longitudinal insights and help guide future brain‑related outcome measures and targeted interventions in DMD. Second, by evaluating and validating the DuMAND Checklist globally, the network aims to enhance clinical care and contribute to greater consistency in the evaluation of neurobehavioral symptoms in DMD. Through shared expertise and collaborative learning, the DuMAND Network aims to strengthen clinical neurobehavioral management and support for boys with DMD. Conclusion: Preparatory work has shown that the DuMAND Checklist can be feasibly implemented across diverse clinical contexts. An international validation study is planned for 2026, inviting centers with varying expertise and resources to participate. To conclude, the DuMAND Network addresses existing evidence gaps by providing a standardized international framework to advance research, clinical evaluation and ultimately management of neurobehavioral challenges in patients with DMD.

Dr. Marek Smilowski 1 , Prof. Nils Erik Gilhus 2 , Dr. Maria Ait-Tihyaty 3 , Dr. Caitlin Briggs 3 , Dr. Uzma Siddiqui 3 , Mr. Luke Hickey 3 , Dr. Marianna Lalla 3 , Dr. Said Beydoun 4 1 Neurologia Śląska Centrum Medyczne, Katowice, Poland. 2 Haukeland University Hospital, Bergen, Norway. 3 Dianthus Therapeutics, New York, United States. 4 University of Southern California, Los Angeles, United States Background: The classical complement pathway plays a significant role in generalized myasthenia gravis (gMG) pathology. Claseprubart is a potent monoclonal antibody that selectively targets the classical pathway by inhibiting active C1s (aC1s). Remission is a key goal in gMG and achieving minimal symptom expression (MSE) with claseprubart is a key treatment objective. Methods: MaGic ( NCT06282159 ), is a global Phase 2, randomized, double-blind, placebo-controlled trial. Patients treated with claseprubart (300mg, Q2W) were evaluated for MSE (MG-ADL ≤1 or QMG ≤3) compared with placebo. p-values were one-sided and nominal significance was assessed at an alpha= 0.1. Outcomes include proportion of patients achieving MSE at Week 13 and anytime during the study, earliest timepoint of MSE achievement, and durability defined as sustained MSE for at least 6 weeks. Results: At Week 13, 37% of claseprubart treated patients achieved MG-ADL-MSE versus 14% with placebo (OR 3.81; p=0.0550). 43% achieved MG-ADL-MSE at least once during the study versus 14% of placebo (OR: 4.72; p=0.0231). This effect was observed as early as Week 1 (median time to response was Week 3). Sustained remission-like states (for at least 6 weeks) were seen in all patients who achieved MSE. Similar results were observed using QMG minimum symptom expression threshold. Conclusion: Claseprubart patients were more than four times more likely to achieve MSE than placebo patients and MSE was observed as early as Week 1. Patients who achieved MSE maintained responses for at least 6 weeks. These results highlight the therapeutic potential of aC1s inhibition in AChR+ gMG.

Prof. Claudia Sommer University Hospital Würzburg, Würzburg, Germany Background: Painful neuropathies represent a major clinical challenge, often leading to chronic, debilitating pain that is difficult to treat. Neuropathic pain by definition arises from injury or dysfunction of the somatosensory nervous system and is characterized by abnormal neuronal excitability, peripheral and central sensitization, and neuroimmune interactions. The pathophysiology is complex. For example, changes in voltage-gated sodium and calcium channels can enhance ectopic neuronal firing, while microglial activation in the spinal cord can amplify pain signaling through the release of cytokines and neurotrophic factors. Mechanistic insights have opened the door to novel therapeutic targets and more mechanism-based treatment strategies. Emerging treatments focus on modulating specific molecular pathways involved in neuronal hyperexcitability and neuroinflammation, such as selective sodium-channel blockers (e.g., targeting Nav1.7), sigma-1 receptor antagonists, and agents that interfere with glial activation or cytokine signaling. In addition, the dorsal root ganglion itself has gained attention as a promising therapeutic target, with neuromodulation techniques such as DRG stimulation and spinal cord stimulation showing potential benefits in refractory neuropathic pain.

Dr. Marcus Erdler 1 , Dr. Miriam Hiebeler 2 , Ms. Farah J. Walter 2 , Dr. Kristine Tetunashvili 3 , Dr. Simone Thiele 2 , Prof. Dr. Maggie C. Walter 2 1 Klinik Donaustadt, Dept. of Neurology, Vienna, Austria. 2 Friedrich-Baur-Institute, Dept. of Neurology, Klinikum LMU Munich, Munich, Germany. 3 Klinik Donaustadt, Dept. of Neurology, Wien, Austria Background: Vamorolone is a dissociative corticosteroid approved by the FDA (patients ≥2 years) and EMA (patients ≥4 years) for treating Duchenne muscular dystrophy (DMD). We here present the first real-world experience of vamorolone use in adults. Methods: This retrospective, real-world, early point-in-time analysis evaluated characteristics and utilization patterns of 25 adult DMD patients treated with vamorolone in one German and one Austrian centre (13 and 12 patients, respectively). Results: The median age was 23 years (range 19-34). Mean age at diagnosis was 5,5 years, while mean symptom onset was at age 3,6 years in our cohort. All patients were non-ambulatory, since a median age of 11,6 years (range 8-19). Mean BMI was 21,4, ranging from 9 to 32. Six patients were corticosteroid (CS) naïve, 16 had prior prednisone and three prior deflazacort treatment. Of the 19 previously CS-treated subjects, eight patients directly switched from other CS; 11 were restarting treatment after previously discontinuing treatment 2-16 years prior to vamorolone, and six patients started first-line. Vamorolone was initiated to preserve upper limb motor function or due to prior CS side effects (e.g. osteoporosis, obesity, Cushing’s syndrome). Twelve patients received vamorolone at capped dose of 240 mg/day (all ≥40 kg); 13 received a lower dose of 2 mg/kg/day (if <40 kg) or capped at 80 mg/day (if ≥40 kg), following DMD guidelines for non-ambulatory patients who often remain on reduced CS dose due to prior adverse effects. In four of the latter, the dose was increased to 120 mg/day (all ≥40 kg) after 6+ month due to weight or PUL improvement. PUL was done in the Munich cohort, 4/13 patients showed PUL improvement, 4/13 stabilization, 5/13 were only recently initiated and have no follow-up data yet. All patients with prior CS-related side effects (obesity, Cushing’s syndrome, behavioural problems) showed reduced or no symptoms on vamorolone. At the last follow-up, no weight gain or new adverse events were reported. Conclusion: This first real-world analysis demonstrates clinical efficacy of vamorolone regarding stabilization or even mild improvement in adult DMD patients who were CS-naïve, had discontinued previous CS treatment, or switched from other CS. This data further highlights the importance of continued corticosteroid treatment beyond loss of ambulation. Conclusion: This first real-world analysis demonstrates clinical efficacy of vamorolone regarding stabilization or even mild improvement in adult DMD patients who were CS-naïve, had discontinued previous CS treatment, or switched from other CS. This data further highlights the importance of continued corticosteroid treatment beyond loss of ambulation.

Dr. Jana Zschüntzsch 1 , Dr. Ali A. Habib 2 , Dr. Zabeen Mahuwala 3 , Prof. Renato Mantegazza 4 , Prof. Robert M. Pascuzzi 5 , Prof. Sabrina Sacconi 6 , Prof. John Vissing 7 , Dr. Jos Bloemers 8 , Dr. Paul Mahoney 9 , Dr. Thaïs Tarancón 10 , Dr. Vera Bril 11 1 Department of Neurology, University Medical Center Göttingen, Göttingen, Germany. 2 MDA ALS & Neuromuscular Center, Department of Neurology, University of California, Irvine, Orange, United States. 3 Department of Neuromuscular Medicine, Epilepsy and Clinical Neurophysiology, University of Kentucky, Lexington, United States. 4 Emeritus and Past Director, Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy. 5 Neurology Department, Indiana University School of Medicine, Indiana University Health, Indianapolis, United States. 6 Université Côte d'Azur, Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France. 7 Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 8 UCB, Brussels, Belgium. 9 UCB, Slough, United Kingdom. 10 UCB, Madrid, Spain. 11 Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University of Toronto, Toronto, Canada Background: Generalised myasthenia gravis (MG) is a chronic autoimmune disease that can significantly affect patients’ quality of life (QoL). In the randomised, double-blind, Phase 3 MycarinG study ( NCT03971422 ), one 6-week cycle of rozanolixizumab (7 mg/kg or 10 mg/kg) improved MG-QoL 15-item revised (MG-QoL15r) total scores compared with placebo in patients with generalised MG. Here, we evaluate the effect of long-term, cyclic rozanolixizumab treatment on QoL using MG-QoL15r item-level scores. Methods: Following MycarinG, patients could enrol in open-label extensions MG0004 ( NCT04124965 ) and MG0007 ( NCT04650854 ). In MG0004, patients received once-weekly rozanolixizumab for ≤52 weeks. MG0007 comprised an initial 6-week rozanolixizumab cycle, with further cycles administered upon symptom worsening. Final efficacy data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 for patients with ≥2 symptom-driven rozanolixizumab cycles. Change from baseline (CFB) to Day 43 in MG-QoL15r item-level scores across Cycles 1–13 was assessed post hoc using means weighted by sample size. Results: Overall, 129 patients received ≥2 symptom-driven cycles. Across 13 cycles (N=890 patient-cycles), weighted-mean scores improved between baseline and the end of each 6-week rozanolixizumab cycle for all MG-QoL15r items. Weighted-mean (standard deviation) CFB in item-level scores was: −0.4 (0.7) for “trouble using my eyes”, “trouble eating”, “bothered by limitations in performing work” and “difficulty speaking” (N=889 patient-cycles); −0.3 (0.7) for “limited social activity” and “limited ability to enjoy hobbies/fun activities”; −0.3 (0.6) for “frustrated by my MG”, “trouble meeting the needs of family”, “have to make plans around my MG”, “lost some personal independence”, “trouble walking”, “trouble getting around public places” and “overwhelmed by my MG”; −0.2 (0.5) for “depressed about my MG” and “trouble performing personal grooming”. Conclusion: Long-term rozanolixizumab treatment cycles led to improvements in all MG-QoL15r item-level scores, demonstrating consistent efficacy across the range of impacts on health-related QoL that MG symptoms have. Funding: UCB.

Prof. Stephen Reddel 1 , Prof. Vera Bril 2 , Prof. James Howard 3 , Prof. Srikanth Muppidi 4 , Prof. Kimiaki Utsugisawa 5 , Prof. John Vissing 6 , Dr. Weihua Cao 7 , Dr. Svetlana Jevtic 8 , Dr. Wendy Su 7 , Dr. Roman Willi 8 , Prof. Heinz Wiendl 9 1 University of Sydney, Departments of Neurology and Molecular Medicine, Sydney, Australia. 2 Toronto General Hospital, Toronto, Canada. 3 Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, United States. 4 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, United States. 5 Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. 6 Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 7 Novartis Pharmaceuticals Corporation, East Hanover, United States. 8 Novartis Pharma AG, Basel, Switzerland. 9 Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, Germany Background: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder caused by autoantibodies against neuromuscular junction (NMJ) components, leading to debilitating muscle weakness and other clinical manifestations. Inhibition of Bruton’s tyrosine kinase (BTK), resulting in reduced activation of B cells and innate immune cells, offers a potential mechanism to modulate the immune response and reduce the autoimmune attack on the NMJ. Remibrutinib is a novel, highly selective and potent, covalent, oral BTK inhibitor with a promising pharmacological and safety profile. Here, we present the design of the Phase 3 RELIEVE study that aims to evaluate the efficacy and safety of remibrutinib in people living with gMG who are on stable, standard-of-care (SOC) treatment. Methods: RELIEVE is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study. The study will enroll patients aged 18 to 75 years diagnosed with gMG (Myasthenia Gravis Foundation of America disease class II–IV) who are either acetylcholine receptor positive (AChR+), muscle-specific tyrosine kinase positive (MuSK+), or double-seronegative (AChR− and MuSK−), with a Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≥6 (>50% non-ocular), and who are on stable SOC treatment. Eligible participants will be randomized 1:1 to receive either remibrutinib or placebo during the 6-month double-blind core treatment period, followed by an open-label extension with remibrutinib treatment for up to 60 months. The primary endpoint is the change from baseline to Month 6 in MG-ADL total score. Key secondary endpoints include assessments of Quantitative MG (QMG), Minimal Symptom Expression (MSE), and MG Composite (MGC), among others. Results: The ongoing study will enroll approximately 180 eligible participants. Further details of the study design will be presented at the congress. Conclusion: The pivotal Phase 3 RELIEVE study will investigate the efficacy and safety of remibrutinib versus placebo in adult patients with gMG across serotypes.

Prof. Paulo José Lorenzoni , Prof. Renata Dal-Pra Ducci, Dr. Paula Raquel do Vale Pascoal Rodrigues, Prof. Otto Jesus Hernandez Fustes, Miss Raquel Cristina Arndt, Dr. Claudia Suemi Kamoi Kay, Prof. Rosana Herminia Scola Universidade Federal do Paraná, Curitiba, Brazil Background: Myasthenia gravis (MG) is frequently associated with pathological alterations of the thymus, including thymoma and thymic hyperplasia. Thymidylate synthase (TYMS) is a key enzyme involved in DNA synthesis, and its expression is influenced by polymorphic variations within the thymidylate synthase enhancer region (TSER). These polymorphisms include variable numbers of tandem repeats (VNTRs), most commonly two (2R, TSER 2) or three (3R, TSER 3) 28-base pair repeats (rs45445694). TYMS polymorphisms have been implicated in malignancy risk and immune dysregulation; however, their potential role in thymic pathology in MG remains poorly understood. It is therefore plausible that TSER polymorphisms affecting TYMS expression may influence susceptibility to thymic abnormalities in MG. Methods: This study aimed to determine the frequency of TYMS polymorphisms in patients with MG and to evaluate their association with thymic pathology in a real-world outpatient cohort from Southern Brazil. Additionally, the prevalence of TYMS genotypes was estimated for Brazilian MG patients. Genotyping was performed to identify the VNTR polymorphism in the TSER region of the TYMS gene (rs45445694: 2R and 3R alleles). Associations between TYMS polymorphisms and thymic pathology were assessed using univariate logistic regression, with patients presenting a normal (involuted) thymus serving as the reference group. Results: The study included 73 patients with MG, of whom 36 underwent thymectomy. Histopathological analysis revealed a normal (involuted) thymus in 15 patients (41.7%), thymoma in 12 patients (33.3%), and follicular hyperplasia in 9 patients (25%). Genotype frequency of 2R/2R, 2R/3R and 3R/3R in the total cohort were 23.28%, 42.46% and 34.24%, respectively. Total genotype distributions were consistent with Hardy–Weinberg equilibrium in the total cohort and in the reference group with normal thymus. No significant differences were observed in allele frequencies of the 2R and 3R variants between patients with thymoma or thymic hyperplasia and those with normal thymus. The 3R allele was not associated with thymoma (OR = 0.51, 95% CI 0.17–1.55; p = 0.28) or thymic hyperplasia (OR = 0.54, 95% CI 0.16–1.83; p = 0.43). No statistically significant associations were identified between TYMS genotypes and thymic pathology. Although a trend towards reduced risk of thymic hyperplasia was observed for the 2R/3R genotype (OR = 0.095, 95% CI 0.01–1.06), this did not reach statistical significance (p = 0.08). Conclusion: This study characterises the prevalence of TYMS 2R and 3R polymorphisms in Brazilian patients with MG. Allelic frequencies were consistent with Hardy–Weinberg expectations but differed from those reported in other Brazilian populations. No association was identified between TYMS polymorphisms and the risk of thymoma or thymic hyperplasia in MG.

Prof. Dusanka Savic-Pavicevic 1 , Asst. Prof. Jovan Pesovic 1 , Dr. Lana Radenkovic 1 , Asst. Prof. Milos Brkusanin 1 , Prof. Goran Brajuskovic 1 , Dr. Vladimir Jovanovic 2 , Prof. Vidosava Rakocevic-Stojanovic 3,4 , Asst. Prof. Stojan Peric 3,4 , Mr. Nemanja Radovanovic 1 1 University of Belgrade-Faculty of Biology, Center for Human Molecular Genetics, Belgrade, Serbia. 2 Human Biology and Primate Evolution, Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Berlin, Germany. 3 University of Belgrade-Faculty of Medicine, Belgrade, Serbia. 4 Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia Background: Myotonic dystrophy type 1 (DM1) is caused by an unstable expansion of CTG repeats in the 3' untranslated region of the DMPK gene within a range from 50 to 6000 repeats. Ongoing somatic repeat instability is expansion-biased, contributes to individual patient variability, confounds genotype-phenotype correlation and is assumed to underlie the progressive nature of DM1. Here, we aimed to examine somatic expansion dynamics and their relation to the progression of skeletal muscle weakness. Methods: We performed a longitudinal study on 39 adult DM1 patients with pure CTG repeats, followed up for 7.6±1.3 years (range 5-9 years). Patients were blood-genotyped at baseline and follow-up using single-cell small-pool PCR. We used baseline 10th percentile allele length as the best estimate of progenitor allele length (ePAL), modal allele length (MAL) as a measure of somatic expansions, and MAL increment as a measure of longitudinal increase in somatic expansion. Muscle strength was manually assessed using the MRC scale with a maximal score of 20 points. Patients were classified as progressive based on a decrease of ≥2 points during follow-up. Statistical analysis included linear mixed-effect (LME) models and logistic regression. Results: According to an LME model, the MAL increased over time with larger ePAL (p=1.22e–15), older baseline age (p=2.83e–4) and elapsed time (p=6.55e–13), with a slight decrease due to the interaction between ePAL and elapsed time (p=0.037). A representative cohort individual with a mean ePAL of 425 repeats and a mean baseline age of 40 years was characterized by an average annual rate of MAL increase of approximately 20 repeats. The model explained 79.1% of the variance in MAL increase (marginal R²=0.791) with an additional 15.5% when accounting for baseline individual differences (conditional R²=0.946). To examine the annual rate of MAL increase in progressive versus non-progressive patients, we incorporated the interaction between elapsed time and progression status in the above described LME model while accounting for baseline MRC score. We observed a higher annual rate of MAL increase in the progressive group compared to the non-progressive (21.8 vs. 13.8 repeats) (p=0.030). To explore the risk of MRC score-defined muscle weakness progression, we performed logistic regression using progression status as the outcome variable and MAL increment and elapsed time as the predictors. When adjusting for baseline age, each 10-repeat gain in MAL increment corresponded to a 15% increase in the odds of progression (p=0.019), while each additional year corresponded to an increase in odds by a factor of 2.39 (p=0.020). Conclusion: Our results demonstrate that the rate of somatic expansions is higher in blood cells of patients experiencing a more rapid decline in muscle strength and emphasize the usefulness of MAL increment as a biomarker for disease progression. Collectively, our findings suggest that therapeutic interventions aimed at stabilizing ongoing somatic expansions could significantly alter the natural history of DM1 by slowing the functional skeletal muscle decline. This research was supported by the Science Fund of the Republic of Serbia, #7754217, READ-DM1.

Dr. Isabelle Richard , Mrs Eva Petat, Mrs Laurence Suel, Mrs Nathalie Bourg-Alibert, Dr. Sonia Albini, Dr. Abbass Jaber, Mr. Jérôme Poupiot, Dr. Anthony Brureau, Dr. Evelyne Gicquel, Dr. Ai Vu Hong Genethon, Evry-Courcouronnes, France Background: Muscular dystrophies (MDs) are debilitating genetic disorders marked by progressive muscle degeneration, with no curative treatments currently available. Adeno-associated virus (AAV)–mediated gene therapy has shown clinical promise for monogenic MDs, yet its broader application remains limited by the need for very high systemic doses, dose-related toxicities, exclusion of patients with pre-existing neutralizing antibodies, and substantial manufacturing burden. Recent advances in AAV engineering, including rational capsid design, directed evolution, and high‑throughput screening, are driving the development of vectors with improved tropism, enhanced transduction efficiency, and superior safety profiles for therapeutic applications. Methods: A myotropic AAV capsid, LICA1, was developed to target skeletal muscle across species via binding to the conserved receptor integrin αVβ6. We further developed an AI-guided engineering strategy that generates improved αVβ6-binding of this caspid. In this process capsid sequence-structure pairs were concurrently optimized for thermostability using physics-based modeling, sequence plausibility using large protein language models, and sequence-structure compatibility using deep-learning–based protein design. Top AI-designed variants, together with AAV9 and LICA1 controls, were evaluated in a low-N barcoded library in human muscle models in vitro and in mouse biodistribution studies in vivo. Results: We previously developed LICA1, showing that cross-species myotropism can be achieved by redirecting AAV tropism toward the conserved receptor integrin αVβ6. We further improved this capsid through an AI-guided strategy by jointly optimizing sequence-structure through thermostability modelling, use of protein language model and sequence design. Among top AI-designed variants, the lead capsid, LICA3, achieves logarithmic improvements in skeletal and cardiac muscle transduction, surpassing state-of-the-art myotropic capsids, together with strong liver-detargeting and improved manufacturability. These myotropic capsids were tested in several models of muscular dystrophies by systemic administration at a low dose. In these experiments, while LICA1 was demonstrating superior gene transfer than AAV9, LICA3 significantly outperformed LICA1, achieving near-complete myofiber transduction, including in highly affected diaphragm, markedly reducing fibrosis and normalizing serum MYOM3 levels to near-wild-type levels, and fully restoring muscle function. Conclusion: These results demonstrate that AI-guided design can overcome long-standing barriers in vector engineering, providing a scalable framework for the development of safe, high-potency gene therapies. Collectively, these results also establish LICA3 as a highly potent, clinically promising gene therapy vector for muscle diseases. Improvement of capsid properties is one element to consider for ensuring higher safety and efficacy of gene therapy. Another important element is the choice of promoters and regulator elements to achieve expression at the right place, right time and right level.

Mrs Emily Farrugia 1,2 , Dr. Hazel Heng 1,2 , Dr. Stephen Quick 1,2 , Prof. Adam Semciw 2,1 1 Northern Health, Melbourne, Australia. 2 La Trobe University, Melbourne, Australia Background: The Victorian Virtual Emergency Department (VVED) is the largest virtual emergency service in Victoria, free for all Victorians requiring urgent but non-critical care as an alternative to in-person care. It remains a novel pathway to managing patients at home who may require more timely medical and support across metropolitan, rural and remote areas across the state. Virtual models of healthcare are rapidly expanding, yet their reach for patients with neuromuscular diseases requiring time-sensitive care, irrespective of funding, age, location or cultural differences, remains unclear. Studies published to date have explored preferences for virtual care and/or remote patient monitoring in comparison to in-person care, as well as barriers and enablers to the mode of these assessments. However, no published studies have examined virtual care use for patients with neuromuscular diseases in the emergency care setting, and evidence within the Australian context is particularly limited. Understanding how patients with neuromuscular diseases use virtual health services is a critical first step to identifying gaps in service delivery, access and scope for advancing multidisciplinary support. This study aimed to explore the uptake, acuity and timing of all presentations to the VVED by patients with neuromuscular diseases and identify relevant referral reasons and usage patterns. A secondary aim was to compare physical emergency department re-presentation rates and outcomes across different VVED referral pathways and identify patient subgroups with higher re-presentation rates. Methods: A retrospective audit of service data from July 2022 to June 2025, analysing usage patterns and outcomes for patients with neuromuscular diseases including presentations, geographical distribution, admission rates to a physical emergency department and acuity following virtual consultation as well as demographic characteristics using descriptive statistics and pre-defined VVED metrics. Demographic statistics will include age, gender and primary language spoken at home. Re-presentation rates will be calculated as proportions with 95% confidence intervals. Kaplan-Meier survival analysis and Cox proportional hazards regression will examine time to re-presentation. Results: Between July 2022 and December 2025, n=2,115 presentations with neuromuscular diseases, including Parkinson’s Disease and Multiple Sclerosis, were identified. Analysis is underway to determine the proportion of patients managed virtually without the need for physical emergency department attendance, presenting complaints, and factors associated with the need to transfer to physical emergency department care. Conclusion: As healthcare systems increasingly adopt virtual-first models, ensuring these innovations meet the needs of patients with neuromuscular diseases is critical. This study will provide foundational evidence to guide the development of tailored virtual pathways for the neuromuscular disease community, with potential for integration into existing multidisciplinary care models.

Topic Group 8 - Patient Related Issues: Palliative Care Invited Speaker Program – Not peer reviewed

Prof. Corrado Angelini 1 , Prof. Daniela Tavian 2 , Dr. Sara Missaglia 2 1 University of Padova, Padova, Italy. 2 Catholic Univertsity, Milan, Italy Background: NLSD with Ichthyosis (NLSDI) is due to the CGI activator variant ( chromosome 3 ).NLSDI or Chanarin Dorfman syndrome (CDS), is a rare AR disorder encountered in pa tients of Mediterranean and Middle Eastern origin. Patients come to medical attention for ichthyosis. Neutral Lipid Storage with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by impaired Adipose Triglyceride Lipase (ATGL) activity, leading to neutral lipid accumulation in various tissues. Methods: We did genetic epidemiological research of NLSDI/NLSDM molecularly proven cases from 1975 to 2025, investigated their genetic epidemiology, country of origin, and private mutations in 176 patients. Results: There are two types of Neutral Lipid Storage Disease:NLSDM is a rare lipid metabolism disorder caused by impaired Adipose Triglyceride Lipase (ATGL) activity, leading to neutral lipid accumulation in various tissues. It typically manifests with progressive skeletal myopathy, with an onset of age around 35 years. An NLSDI type with Ichthyosis and liver involvement is due to the CGI activator and usually has an earlier age of involvement. We investigated the Genetic epidemiology of these two disorders and the country of origin or mutation hotspot. Patients come to medical attention for ichthyosis. We found in Mediterranean countries, 124 NLSDI cases: 10 in Italy,3 in Greece, and 48 in Turkey. Two siblings had CNS involvement, myopathy, neurosensory hearin g loss, cataracts, nystagmus, strabismus, and mental impairment; their molecular analysis revealed the presence of the N209* mutation. Patients with ichthyosis or Jordan's anomaly are referred to the clinic for CK elevation, and muscle biopsies are consi stent with lipid storage. In Palestine,5 cases were detected (common mutation c.960+5G>A ), 9 in Israel,4 in Algeria,26 in Tunisia,3 in France,7 in Spain,4 in Egypt, and 3 in Morocco. To date, 176 CDS patients have been reported worldwide. In India, 19 mutations were found.NLSDI patients have onset in the first/second decade. Usually, children,or people are admitted for congenital ichthyosis, Jordan's anomaly, liver steatosis; CNS changes are then detected. Conclusion: In few NLSDI cases detected for congenital ichthyosis, Jordan's anomaly, liver steatosis; CNS changes are then detected. Myopathology is consistent with lipid storage. The myopathy can be treated with an MCT diet, and retinoids such as acitretin can be useful in skin treatment, even in the presence of liver damage.

Dr. Ester Franchi 1 , Dr. Barbara Risi 1,2 , Dr. Nesaiba Ait Allali 1 , Dr. Giulia Gilberti 1 , Dr. Lucia Ferullo 1 , Dr. Filomena Caria 1 , Dr. Loris Poli 3 , Prof. Alessandro Padovani 3,4 , Prof. Massimiliano Filosto 1,3,4 1 NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy. 2 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 3 Unit of Neurology, ERN EURO-NMD Center ASST Spedali Civili, Brescia, Italy. 4 Department of Clinical and Experimental Sciences, University of, Brescia, Italy Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that frequently affects bulbar motor control, leading to impairments in speech and voice. Acoustic voice analysis may represent a non-invasive approach for monitoring functional changes; however, longitudinal data across different ALS phenotypes remain limited. The objective of the study is to longitudinally characterize acoustic voice parameters in patients with spinal-onset ALS and to explore their descriptive co-variation with motor-functional status, respiratory measures, quality of life, and clinical phenotype (mixed vs. flail-arm). Methods: Five adults with spinal-onset ALS were enrolled (three with mixed phenotype and two with flail-arm phenotype) and evaluated at baseline and after 3, 6, 9, and 12 months. Acoustic parameters were extracted using Praat software (version 6.2.22), including jitter, shimmer, maximum phonation time (MPT), fundamental frequency (F0), and degree of voice breaks (DVB). Motor and functional status (ALSFRS-R, Barthel Index), respiratory function (forced vital capacity [FVC], peak expiratory flow [PEF]), and quality of life (ALSAQ-40, QOL-DYS) were assessed. Analyses were limited to descriptive statistics. Results: At baseline, shimmer values were markedly elevated in both phenotypes (median [Q1–Q3]: 16.3% [12.3–17.3] in mixed; 16.8% [14.5–17.2] in flail-arm), while median jitter ranged from 1.01% (0.29–1.25) in mixed to 1.39% (0.91–1.88) in flail-arm patients. MPT was shorter in flail-arm patients (median 6.4 s [4.7–8.13]) compared with mixed-phenotype patients (9.9 s [5.6–28.6]). Over follow-up, mixed-phenotype patients showed a reduction in shimmer values (median [Q1–Q3]: 2.9% [2.7–13.7] at 12 months) and variable MPT, whereas flail-arm patients exhibited persistently shorter MPT and higher DVB. Lower ALSFRS-R total scores (median [Q1–Q3]: 20 [16–24] at 12 months in flail-arm patients) tended to co-occur with greater vocal instability. FVC percentage values remained moderately reduced over time without consistent parallel changes in acoustic measures. From baseline (T0) to T4, worsening in QOL-DYS scores was observed, accompanied by a parallel increase in shimmer. Conclusion: In this preliminary study, acoustic voice parameters displayed phenotype-specific longitudinal patterns and showed parallel descriptive changes with motor-functional impairment and communication-related quality of life. No consistent descriptive association was observed with respiratory decline. Further longitudinal studies in larger cohorts are warranted to clarify phenotype-related voice changes in ALS over time.

Dr. Divyanshu Dubey Mayo Clinic, Rochester, United States Background: Immune-mediated neuromuscular disorders comprise a heterogeneous group of peripheral nervous system disorders in which autoantibodies play key diagnostic and mechanistic roles. While established antibodies have refined disease classification, a substantial proportion of patients remain seronegative, limiting diagnostic precision and targeted therapy. Methods: We employ a multimodal discovery platform integrating tissue-based indirect immunofluorescence assays, phage immunoprecipitation sequencing (PhIP-Seq), immunoprecipitation coupled with mass spectrometry, and protein microarray. Serum and CSF samples from well-phenotyped patients with suspected autoimmune neuropathies are systematically evaluated through a biomarker discovery pipeline, followed by antigen identification and orthogonal confirmation. Results: This approach has enabled the identification and validation of novel antibody targets associated with distinct clinical phenotypes. Some of the new characterized antibodies demonstrate specific staining patterns, reproducible antigen binding, and clinicopathologic correlations. Conclusion: Advanced antibody discovery platforms are expanding the spectrum of immune neuropathies and improving diagnostic yield. Identification of novel autoantibodies enhances disease classification, informs prognosis, and may guide therapeutic decision-making, underscoring the importance of continued translational efforts in neuroimmunology.

Dr. Alessandra Lima Nogueira Tolentino 1 , Dr. Ana Marina Silva 1 , Dr. Gisele Espíndola 2 , Dr. Euldes Júnior 3 , Dr. Pablo Feitoza 4 , Dr. Thiago Tonholo 5 , Dr. Thiago Oliveira 6 , Dr. Stephanie Delstanche 7 , Dr. Manon Hustinx 7 , Dr. Roseli Corazzini 1 , Prof. José Pedroso 5 , Prof. Alzira Carvalho 1 , Prof. Enzo Stinghel Pellacani 8 1 Faculdade de Medicina do ABC, São Paulo, Brazil. 2 Hospital Universitário Polydoro Ernani de São Thiago - UFSC, Santa Catarina, Brazil. 3 Ambulatório de Doenças Raras, Minas Gerais, Brazil. 4 Universidade Federal do Amazonas, Amazonas, Brazil. 5 Universidade Federal de São Paulo, São Paulo, Brazil. 6 Universidade Federal de Pernambuco, Pernambuco, Brazil. 7 Centre Hospitalier Régional de la Citadelle, Liège, Belgium. 8 ABC Medical School, São Paulo, Brazil Background Introduction:  Pathogenic variants in POLG, encoding the catalytic subunit of mitochondrial DNA polymerase gamma, produce a clinically heterogeneous spectrum of mitochondrial disorders ranging from infantile-onset Alpers-Huttenlocher syndrome to adult-onset progressive external ophthalmoplegia (PEO). Establishing genotype-phenotype correlations is critical for diagnostic precision and accurate prognostic counseling in this complex group of disorders. Objective: To delineate the genotype-phenotype correlations in a cohort of 17 predominantly Brazilian patients harboring pathogenic POLG variants, with emphasis on clinical phenotyping, natural history, and survival outcomes stratified by genotype. Methods: A retrospective cohort study was performed utilizing comprehensive medical record abstraction. Comparative analyses focused on the two most prevalent variants: p.Ala467Thr (n=7) and p.Thr251Ile (n=4). Statistical methods included Fisher-Freeman-Halton exact test for categorical variables and Kaplan-Meier survival curves with Log-Rank testing for time-to-event analysis. Results: Mean age at symptom onset was 34 years (SD ± 14.4), with male predominance (58.8%). Diagnostic latency averaged 15.6 years from symptom onset. Molecular analysis identified homozygous p.Ala467Thr (n=7) and homozygous p.Thr251Ile (n=4) as the most prevalent variants, with additional homozygous variants p.Val400Met and p.Trp748Ser each identified in single patients. Three patients harbored compound heterozygous variants, and one carried a single heterozygous p.Lys947Arg variant. The cardinal clinical features comprised ptosis (94.1%), ophthalmoparesis (88.2%), and sensory neuronopathy (70.6%). Epilepsy occurred in 41.2% overall, with enrichment in the p.Ala467Thr group (57.1%). The phenotypic spectrum additionally encompassed early-onset Parkinsonism, cerebellar ataxia, dystonia, chorea, and stroke-like episodes. Genotype-phenotype analysis demonstrated a significant association between p.Ala467Thr and SANDO (sensory ataxic neuropathy, dysarthria, and ophthalmoparesis) phenotype (100%; p < 0.001). Survival analysis identified p.Thr251Ile as a high-risk genotype, with 75.0% mortality (p = 0.024, Fisher’s test), significantly reduced survival probability (p = 0.040, Log-Rank test), and mean survival of 21.2 years from symptom onset. Conclusion: This genotype-phenotype correlation study establishes p.Ala467Thr as strongly associated with the SANDO phenotype, while p.Thr251Ile confers significantly elevated mortality risk with shortened survival. The marked allelic heterogeneity and phenotypic pleiotropy observed across other variants necessitate comprehensive neuromuscular phenotyping and high clinical suspicion. The protracted diagnostic latency (mean 15.6 years) underscores the critical need for early diagnostic algorithms incorporating clinical red flags, neurophysiological studies, and molecular testing to facilitate timely therapeutic intervention and genetic counseling in POLG-related mitochondrial disorders.

Dr. Mikolaj Ogrodnik Ludwig Boltzmann Institute for Traumatology, Vienna, Austria Background: Cellular senescence is a state of stable cell cycle arrest accompanied by characteristic morphological and molecular alterations. The accumulation of senescent cells (SCs) in various tissues, including the nervous system and skeletal muscle, has been shown to promote inflammation and impair tissue function. Numerous studies have demonstrated a causal relationship between SC accumulation and age-related tissue dysfunction, with the introduction of SCs accelerating aging phenotypes and their clearance attenuating them. In aging muscle, an increased burden of SCs correlates with a decline in muscle performance. This presentation will summarize recent advances in the reliable identification and study of cellular senescence in animal tissues, as outlined in the Guidelines for Minimal Information on Cellular Senescence Experimentation in vivo (MICSE). Furthermore, I will discuss key research directions and findings concerning the role of cellular senescence in the neuromuscular system. Finally, I will present some of our most recent results on cellular senescence in other tissues, highlighting their potential implications for future research on the neuromuscular system and aging.

Dr. Sara Liguori 1 , Dr. Francesca D'Andrea 1 , Dr. Marco Paoletta 2 , Assoc. Prof. Antimo Moretti 1 , Prof. Giovanni Iolascon 1 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy. 2 Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with an estimated incidence of approximately 1 in 3,000 individuals.¹ It is caused by mutations in the NF1 gene located on chromosome 17q11, which encodes the neurofibromin protein. Clinically, NF1 is characterised by the development of benign tumours affecting the central and peripheral nervous systems, including the brain and spinal cord, as well as other organs, the skin, and the skeletal system.² From a clinical perspective, NF1 presents with marked phenotypic heterogeneity, with manifestations varying according to the organs and tissues involved. This variability may result in a wide range of functional impairments that can affect motor performance, autonomy, and overall independence in daily activities. The aim of the present study was to characterise a cohort of paediatric patients with NF1 in terms of muscle strength, gait performance, fatigue, level of autonomy, manual dexterity, balance, and health-related quality of life, as assessed from both the patients’ and parents’ perspectives. Methods: In this observational study, we included patients with a diagnosis of NF1 aged between 3 and 18 years. Anthropometric data, including body weight, height, and body mass index (BMI), were collected. Handgrip strength was evaluated by a portable dynamometer (HGS). Ambulatory capacity was examined using the Functional Ambulation Categories (FAC). Fatigue was assessed with the Fatigue Severity Scale, manual dexterity with the Nine Hole Peg Test, and balance with the Pediatric Balance Scale (PBS). Health-related quality of life was evaluated from both the patient’s and the parent’s perspectives using the Pediatric Quality of Life Inventory (PedsQL) 4.0. Results: Twenty-seven patients with NF1 (16 males, 11 females) were recruited, with a mean age of 12.85 ± 3.03 years and a mean BMI of 22.15 ± 3.74 kg/m². Handgrip strength assessment showed that 21 of 26 patients (80%) had reduced strength compared to normative values for age and sex. Manual dexterity was impaired in 15 of 25 patients (60%) relative to reference values. Gait assessment indicated that 26 patients were classified in FAC category 5 (indipendent), while 1 patient was in category 3 (dependent on supervision). Fatigue, measured by the Fatigue Severity Scale (FSS), had a mean score of 21.7 ± 12.72 (total score 63). Balance, assessed with the Pediatric Balance Scale (PBS), was generally preserved (mean 54.65 ± 2.31). Health-related quality of life, as reported by parents, had a mean score of 25.78 ± 17.06, while patient-reported quality of life had a mean of 20.56 ± 13.4, substantially lower than the European normative mean of 80.3 ± 4.3. Conclusion: In this cohort of paediatric patients with NF1, reduced muscle strength, impaired manual dexterity, and increased fatigue were observed, which may contribute to the perception of lower health-related quality of life. Notably, patients reported a poorer quality of life compared to their parents’ assessments, highlighting potential discrepancies between reported outcomes.

Dr. Laura Kennelly , Dr. Orna O'Toole Cork University Hospital, Cork, Ireland Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) most commonly affects older adults and typically responds to intravenous immunoglobulin (IVIG). Fulminant presentations mimicking Guillain–Barré syndrome (GBS) are rare. We report a young patient with severe, antibody-negative, treatment-refractory CIDP who achieved sustained recovery following combined cyclophosphamide and rituximab therapy. Methods: We report the clinical presentation, investigations, treatment course, and outcome of a 36-year-old man presenting with rapidly progressive distal paraesthesia and limb weakness following a mild gastroenteritis. Serial neurological examinations, cerebrospinal fluid analysis, nerve conduction studies, spinal MRI, antibody testing, nerve biopsy, and genetic testing were performed. Therapeutic responses to IVIG, plasma exchange, corticosteroids, rituximab, and cyclophosphamide were documented. Results: The patient initially presented with mild distal weakness, areflexia, and preserved sensation and coordination but deteriorated despite IVIG to quadriplegia with bulbar and respiratory involvement, requiring intensive care admission, plasma exchange, and tracheostomy. Cerebrospinal fluid demonstrated marked albuminocytologic dissociation (protein 1800 mg/L). Nerve conduction studies showed a severe demyelinating sensorimotor polyneuropathy with absent lower-limb motor responses. MRI of the spine was normal. Ganglioside and nodo-paranodal antibodies were repeatedly negative, and nerve biopsy confirmed demyelination without vasculitis or amyloid. Following minimal response to pulsed corticosteroids and relapse despite rituximab, pulsed cyclophosphamide was introduced, resulting in sustained clinical improvement. The patient progressed from quadriplegia to independent ambulation and return to work within four months, with electrophysiological evidence of remyelination. Conclusion: This case illustrates a rare, severe, antibody-negative CIDP refractory to standard immunotherapies. Combined cyclophosphamide and rituximab achieved disease stabilisation and marked functional recovery, supporting its consideration as rescue therapy in selected cases of fulminant CIDP.

Dr. Henry Kaminski 1 , Dr. Gülşen Öztosun 1 , Dr. Quentin Lesport 2 , Dr. Marc Garbey 2 1 George Washington University, Washington DC, United States. 2 Care Constitution, Houston TX, United States Background: Myasthenia gravis (MG) is a fluctuating autoimmune neuromuscular disorder that presents unique challenges for both in-person and remote assessment. Clinical evaluation relies heavily on the neurological examination, which is inherently subjective and may fail to capture subtle weakness or fatigability. These limitations motivate the development of quantitative digital tools capable of augmenting traditional examination methods. Methods: Initial development involved 52 patients with MG across six centers, generating 104 examination videos analyzed using a quantitative telemedicine platform designed to augment traditional neurological assessments. Computer vision algorithms were used to quantify ptosis, ocular motility, and limb drift, while signal processing and natural language processing methods analyzed speech-derived respiratory measures and vocalization patterns. A reproducibility analysis metric was developed to compare AI-driven quantification with expert clinician assessments. Using this system, an additional cohort of approximately 100 patients and controls has subsequently been evaluated. Results: Initial studies demonstrated that remotely acquired video and speech data capture multiple clinically relevant features of MG, including ptosis dynamics, facial muscle weakness, dysarthria, and fatigue during sustained tasks. These digital biomarkers correlated with clinical severity measures and distinguished patients from controls. Reliability analyses revealed that variation in examiner instructions and differences in video quality significantly affected measurement reproducibility. Ongoing investigations have also identified distinctive vocal signal patterns—present even in the absence of clinically detectable dysarthria—that consistently differentiate patients with MG from controls. Conclusion: In contrast to the categorical classifications (e.g., mild, moderate, severe) typically used in standard clinical assessments, digital examination frameworks enable continuous and quantitative measurement of neuromuscular function. These approaches have the potential to enhance assessment precision, reduce variability in neurological examination, and identify disease-related metrics not detectable during routine clinical evaluation. This scalable methodology may facilitate integration of digital biomarkers into MG clinical care and therapeutic trials.

Dr. Hyun Gi Kim 1 , Ms. MinGi Kim 2 , Prof. Ha Young Shin 2 1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 2 Department of Neurology, Yonsei University College of Medicine, Seoul, Korea, Republic of Background: Autoimmune nodopathy (AN), associated with antibodies against paranodal and nodal proteins, represents a distinct subgroup of immune-mediated neuropathies characterized by unique clinical features and treatment responses. Among these, anti–neurofascin-155 (NF-155) antibody–positive AN is well recognized to predominantly involve the IgG4 isotype. IgG4 class switching is driven by specific immunoregulatory pathways, particularly involving T follicular helper (Tfh) cells, regulatory cytokines, and B-cell survival factors. However, the cytokine milieu associated with IgG4 class switching in NF-155 antibody–positive AN remains poorly defined. Clarifying cytokine profiles related to IgG4 differentiation may provide insights into disease mechanisms and identify potential therapeutic targets distinguishing NF-155 antibody–positive AN from seronegative chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: We conducted a cross-sectional serum cytokine analysis including patients with NF-155 antibody–positive AN (n = 10), patients with seronegative CIDP (n = 21), and healthy controls (n = 7). Serum samples were collected and stored at −80 °C. Cytokines implicated in IgG4 class switching were quantified. Analytes included IL-4, IL-5, IL-10, IL-13, IL-21, IFN-γ, APRIL, BAFF, GITR, GITRL, and TGF-β1, TGF-β2, and TGF-β3. IL-4, IL-5, IL-10, IL-13, IL-21, IFN-γ, APRIL, BAFF, and GITR were analyzed using the Human Premixed Multi-Analyte Kit (R&D Systems). GITRL was measured using the Human Immuno-Oncology Checkpoint Protein Panel 1 (Merck Millipore), and TGF-β isoforms were quantified using the TGF-β 1,2,3 Magnetic Bead Kit (Merck Millipore). All assays were performed on the MAGPIX (Luminex) platform according to the manufacturers’ instructions. Cytokine concentrations were compared among groups to identify differential immunological profiles associated with NF-155 antibody–positive AN. Results: Serum GITRL levels differed significantly among healthy controls, seronegative CIDP patients, and NF-155 antibody–positive AN patients (Kruskal–Wallis H = 9.13, p = 0.010). Median GITRL concentrations were highest in the NF-155 antibody–positive group [28.75 pg/mL (IQR 21.88–48.0)], compared with seronegative CIDP patients [16.5 pg/mL (IQR 13.0–20.5)] and healthy controls [14.5 pg/mL (IQR 13.5–16.25)]. Post-hoc pairwise comparisons with Bonferroni correction demonstrated significantly higher GITRL levels in NF-155 antibody–positive patients compared with healthy controls (adjusted p = 0.006). Differences between seronegative CIDP patients and healthy controls were not statistically significant. Although GITRL levels tended to be higher in NF-155 antibody–positive patients than in seronegative CIDP patients, this difference did not reach statistical significance after correction (adjusted p = 0.064). No significant group differences were observed for other analyzed cytokines, including IL-4, IL-5, IL-10, IL-13, IL-21, IFN-γ, APRIL, BAFF, GITR, or TGF-β isoforms. Conclusion: In patients with NF-155 antibody–positive autoimmune nodopathy, serum GITRL levels were selectively elevated. These findings suggest a potential role for the GITR–GITRL pathway in the immunopathogenesis of IgG4-dominant NF-155–associated disease. Larger studies are warranted to validate these observations and to elucidate the mechanistic relevance of GITRL signaling in NF-155 antibody–positive autoimmune nodopathy.

Prof. Marco Sandri 1,2 , Dr. Camilla Pezzini 1 , Assoc. Prof. Roberta Sartori 1 1 University of Padova, Padova, Italy. 2 Veneto Institute of Molecular Medicine, Padova, Italy Background: Muscle wasting is a debilitating process that occurs in many diseases, and its onset detrimentally affects patients drug treatment, quality of life and clinical outcome. The decrease of muscle mass is consequent to a net loss of cytoplasm due to an increased turnover of contractile proteins and organelles. Among the different proteolytic systems, ubiquitin-proteasome is the main one that removes sarcomeric proteins while autophagy-lysosome controls organelles turnover. Enhancement of protein breakdown requires transcriptional dependent programs that induce the expression of a subset of genes, the atrophy-genes or atrogenes, which encode for rate limiting enzymes not only of the degradation systems (ubiquitin proteasome, autophagy-lysosome) but also of the Integrated Stress Response (IRS) related to the unfolded protein response and translation regulation. The atrophy-genes also control other cellular processes such as mitochondrial bioenergetics and dynamics, calcium homeostasis, chromatin structure and DNA damage response. Several transcription factors such as FoxOs, NFkB, STAT3, Smad2/3 have been described to regulate atrogenes expression and muscle loss during catabolic conditions and their inhibition has been proposed as therapeutic option to preserve muscle mass and strength. Despite several attempts to develop therapeutic approaches, muscle wasting is still orphan of any specific drug/treatment mainly because our understanding of the insights of this process are still largely unknown. By combining cutting edge technologies, mouse models, patients’ biopsies and organoids we dissected the mechanisms that alter the gene signature to induce an anti-neurotrophic, pro-catabolic and pro-inflammatory environment inside muscle tissue in a gender and disease specific manner. The identification of this catabolic gene network enables us to test a novel patient- and disease-specific RNA-based therapeutic approach to preserve muscle mass and prevent muscle loss. Methods: We have performed a multiomic approach, in which snRNA seq and ATAC seq (Multiome) have be simultaneously analyzed, to determine the transcriptional and chromatin signatures of the different cell types in muscles both from rodent models and muscle biopsies of patients. Sections of the same muscles have been also processed for spatial transcriptomic. By cross-referencing the data-sets we have identified the TFs network and the changes of cellular landscape and cytokines-receptors. We have developed myotropic AAV9 vectors expressing shRNAs ad as well as vivo-Morpholinos ASO against the most critical pro-catabolic factors/TFs and tested both in murine models and in patient's derived neuromuscular organoids (NMOs). Results: We have used tumor bearing mice and cancer patients as first catabolic condition. Our findings depicted an unexpected scenario in which almost all the cell types activated a catabolic signature and synergized to promote a pro-catabolic environment. Data analyses identified that FoxOs binding sites were enriched in the open promoter regions of differentially expressed genes in cachectic muscles. We also found that the muscle-specific ubiquitin ligase MuRF1 was upregulated in all the muscle cells. The simultaneous inhibition of FoxO1, 3 and MuRF1 resulted in anabolic and pro-neurotrophic action in mice and human NMOs. Conclusion: These findings pave the way for an innovative RNA multi-target therapy that matches with the concept of precision medicine and could be applied to many muscle wasting diseases.

Asst. Prof. Marcus Pinto Mayo Clinic, Rochester, United States Background: Diabetic Lumbosacral radiculoplexus neuropathy (DLRPN) is a rapidly progressive, painful lower-limb neuropathy. This disease usually begins focally and unilaterally with pain but evolves into widespread often bilateral neuropathy with weakness. Although it is usually monophasic, patients have prolonged morbidity from pain and weakness, may have relapses and many patients become wheelchair-dependent. DLRPN is usually a motor-predominant disease but there is unequivocal evidence of autonomic and sensory involvement. Cutaneous nerves from patients with DLRPN show pathologic evidence of ischemic injury (multifocal fiber loss, perineurial thickening neovascularization, and injury neuroma) and microvasculitis (mural and perivascular inflammation and fragmentation of smooth muscle layers of microvessels). Methods: This lecture examines the clinical and pathological characteristics of DLRPN, evaluates current management and outcomes, and highlights the significant unmet needs in patient care. Results: The pathophysiology of DLRPN remains under investigation, but pathological studies have demonstrated evidence of ischemic injury, microvasculitis, and an upregulation of inflammatory mediators within the nerves. Risk factors associated with an increased risk of development include a history of autoimmune disorders, stroke, and a higher BMI. Potential triggers—which may occur in up to two-thirds of cases—include infections, vaccinations, surgery, and rapid glycemic control. Ultimately, altered metabolism and immune dysfunction appear to be the most influential factors in the development of this immune-mediated neuropathy. In Olmsted County, MN, the incidence of DLRPN is 2.7/100,000 persons per year, fulfilling the definition of a rare disease. Despite its rarity, it is the most common immune-mediated neuropathy in that population. While the disorder is typically considered monophasic, most patients are left with significant disability, and approximately 20% experience a progressive disease course. Consequently, DLRPN is an inflammatory neuropathy characterized by high morbidity and immense unmet medical needs. Recent observations have shown a frequent association between DLRPN and the use of GLP1-RA drugs. A case-control study demonstrated that GLP1-RA use increases the risk of DLRPN by 51%. While the exact mechanisms are not yet clear, the profound metabolic shift induced by these drugs appears to be a primary trigger. Research also indicates that nerve pathology features are very similar between patients with treatment-induced neuropathy of diabetes (TIND) and those with DLRPN. This suggests that DLRPN can be treatment-induced and exists as part of the broader TIND spectrum. Currently, DLRPN is classified as a variant of nonsystemic vasculitic neuropathy. However, there remains no international consensus regarding its clinical management, and there are currently no FDA or EMA-approved therapies available. Conclusion: DLRPN is a rare but highly debilitating immune-mediated neuropathy, identified as the most common of its kind in Olmsted County. Its pathophysiology involves ischemic injury and microvasculitis, often triggered by rapid metabolic shifts from glycemic control or GLP1-RA use. This places TI-DLRPN within the TIND spectrum, characterized by severe morbidity and long-term disability. Despite its classification as a nonsystemic vasculitic neuropathy, the lack of FDAor EMA-approved therapies and clinical consensus highlights an urgent need for targeted research and standardized treatment strategies.

Dr. Hee-Jae Jung 1,2 , Ms. Heung-Won Kang 3 , Dr. Ho Cheol Kim 4 , Dr. Seokchan Hong 5 , Dr. Young Chul Kim 6 , Dr. Won Kim 7 , Dr. Eun-Jae Lee 1 , Dr. Young-Min Lim 1 , Dr. Jin-Sung Park 8 , Dr. Hyunjin Kim 1 1 Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 2 Department of Neurology, Seoul, Korea, Republic of. 3 Department of Neurology, Seoul Medical Center, Seoul, Korea, Republic of. 4 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 5 Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 6 Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 7 Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of. 8 Department of Neurology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea, Republic of Background: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune muscle diseases, and their overlapping clinical phenotypes often complicate subtype differentiation. Muscle magnetic resonance imaging (MRI) is increasingly recognized as a valuable non-invasive diagnostic tool, yet direct comparative analyses across major IIM subtypes remain limited. We aimed to characterize and contrast thigh MRI patterns among anti-synthetase syndrome (ASyS), dermatomyositis (DM), inclusion body myositis (IBM), and immune-mediated necrotizing myopathy (IMNM). Methods: This prospective single-center cohort included 47 patients with IIM (12 ASyS, 15 DM, 11 IBM, 9 IMNM). Thigh MRI (T1-weighted, STIR, and contrast-enhanced T1) was systematically evaluated. Muscle edema was semi-quantitatively graded across the gluteal, hamstring, quadriceps, and adductor compartments (0–3 per compartment; total edema score 0–12). Fatty infiltration was recorded dichotomously, and fascial and subcutaneous involvement, including contrast enhancement patterns, were assessed. Group comparisons were performed using non-parametric statistical tests. Results: Distinct MRI signatures were observed across IIM subtypes. ASyS and DM demonstrated significantly greater edema, particularly in the quadriceps and gluteal compartments, compared to IMNM (quadriceps: ASyS vs. IMNM, 2.0 vs. 0.0, p=0.033; DM vs. IMNM, 2.0 vs. 0.0, p=0.023, gluteal: ASyS vs. IMNM, 3.5 vs. 1.0, p=0.003; DM vs. IMNM, 2.0 vs. 1.0, p=0.007). In contrast, IBM showed markedly higher rates of quadriceps fatty infiltration (90.9%) compared with IMNM (22.2%, p=0.008) and ASyS (41.7%, p=0.027). Fascial involvement further differentiated subtypes: hamstring fascial hyperintensity was most frequent in ASyS (75.0%), followed by DM (33.3%), whereas it was uncommon in IMNM (11.1%, p=0.008) and absent in IBM (0%, p DM >> IMNM/IBM) served as an additional discriminator beyond muscle edema and fatty infiltration. Conclusion: Thigh MRI demonstrates distinct, subtype-specific patterns of muscle and soft tissue involvement in IIMs. Severe anterior and gluteal muscle edema with hamstring fascial hyperintensity characterizes both ASyS and DM, while fascial enhancement further differentiates ASyS from DM. In contrast, prominent quadriceps fatty infiltration is a hallmark of IBM. Together, these radiological profiles represent clinically useful, non-invasive markers that may aid differential diagnosis in routine practice.

Dr. Sara Liguori 1 , Dr. Francesca D'Andrea 1 , Dr. Marco Paoletta 2 , Assoc. Prof. Antimo Moretti 1 , Prof. Giovanni Iolascon 1 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy. 2 Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy Background: Neuromuscular diseases (NMDs) represent a heterogeneous group of musculoskeletal system disorders primarily affecting the anterior horn cells of the spinal cord, peripheral nerves, neuromuscular junctions, or skeletal muscles. Although most NMDs are rare, with an estimated prevalence of 1–10 cases per 100,000 individuals, collectively they impact a substantial number of patients. Clinically, NMDs are characterized by progressive reductions in muscle strength, mobility, and bone mineral density (BMD), often associated with fatigue, loss of ambulation, and impaired functional performance. Novel therapies, including gene-based and symptomatic treatments, have mitigated severe manifestations and slowed disease progression. Despite these advances, emerging complications—such as increased fall risk, fragility fractures, scoliosis, and contractures—have become more prominent, prompting interest in optimizing bone health in NMD patients. This study aimed to evaluate the effectiveness of current interventions for bone health management in this population, considering both pharmacological and nutritional strategies. Methods: A systematic review was conducted by searching PubMed, Embase, and Scopus for studies published until 22 May 2024. The search focused on studies assessing the effects of anti-osteoporotic drugs and/or vitamin D or calcium supplementation on BMD in NMD patients. The methodological quality of the included studies was assessed using the PEDro scale for randomized controlled trials (RCTs) and the JBI‑QES (Joanna Briggs Institute – Qualitative Evidence Synthesis) tool for non‑randomized experimental studies. The protocol was registered on PROSPERO. Results: Of 363 articles retrieved, 28 met inclusion criteria: 6 interventional studies, 14 observational studies, 5 case reports, and 3 case series. Overall, 687 NMD patients aged 0–70 years were included. Duchenne muscular dystrophy was the most prevalent diagnosis (66.6%), followed by spinal muscular atrophy (SMA). The most reported interventions were vitamin D supplementation (68.9%) and calcium (55.1%). Among anti-osteoporotic agents, zoledronate was most commonly employed (37.9%), followed by pamidronate (20.6%) and alendronate (17.2%). Regarding efficacy in improving BMD, vitamin D and calcium supplementation alone were insufficient to prevent progressive bone loss. Zoledronate and alendronate demonstrated consistent positive effects in most studies, while Pamidronate showed partial efficacy, though methodological limitations affected interpretation. Risedronate and neridronate did not demonstrate consistent benefits. Limited evidence suggested denosumab effectively improved BMD in small patient samples, whereas teriparatide maintained stable BMD values. Conclusion: This analysis highlights a lack of data on bone health management in NMD, particularly regarding specific age groups and rarer subtypes. These gaps emphasize the necessity of a targeted, evidence-based approach to prevent and treat bone loss. Early therapeutic interventions, guided by the biological rationale of anti-osteoporotic agents, represent a critical strategy to optimize bone health in NMD, in order to preserve functional capacity, skeletal integrity, and quality of life. Future research should focus on longitudinal outcomes, comparative efficacy of agents and individualized strategies to preserve bone health and quality of life in NMD population.

Mr. Alexander Ozonoff 1 , Prof. Gary Cutter 2 , Ms. Eesha Chakraborty 1 , Mr. Kurt Petschke 3 , Prof. A. David Paltiel 3 , Dr. Bhaskar Roy 1 , Dr. Chafic Karam 4 1 Yale University School of Medicine, New Haven, CT, United States. 2 University of Alabama, School of Public Health, New Haven, CT, United States. 3 Yale School of Public Health, New Haven, CT, United States. 4 University of Pennsylvania, Perelman School of Medicine, Pennsylvania, United States Background: Inclusion body myositis (IBM) is a rare, gradually progressive muscle disease with preferential involvement of quadriceps and long finger flexors, eventually leading to impaired ambulation and hand function. Some patients may also have dysphagia. The potential beneficial role of exercise in IBM has been implicated, but the impact of exercise in IBM, including the safety of exercise in IBM, is not well established. Methods: We used the Yale IBM registry (IBMR) to examine the role of exercise on functional decline in IBM, based on the IBM functional rating scale score (IBM-FRS). We included patients with at least 2 longitudinal reports of IBM-FRS nine months apart, based on the IBM personalized index calculator (IBM-PIC) in the Yale IBM registry, which is a reliable remote measure of IBM-FRS. Results: We included 401 patients (68.4 ± 8.4 years, Female 139 (34.7%)) with longitudinal data, with a baseline mean IBM-FRS score of 26.9 ± 6.8. All subjects showed a decline in IBM-FRS over time. There were no major differences in disease progression based on gender or age. The habit of exercise was associated with a slower rate of decline (p-value < 0.01), with a graded benefit for more active patients (p-value <0.001). Patients actively engaged in physical therapy and walking showed slower deterioration than those with no exercise (p-values of 0.003 and 0.04, respectively). Analyses of within-person changes emphasized the role of continuity of exercise. Conclusion: These findings, based on patients’ self-reports, are supportive of the safety of exercise in IBM. There is also a potential benefit of remaining physically active in IBM. A longer clinical trials with a structured exercise regimen to delineate the true impact of exercise on IBM disease progression is warranted.

Dr. Maria Naylor , Dr. Xiaoyan Yin, Dr. Katy Meilleur, Dr. Jordan Messer, Dr. Gabriel Helmlinger, Dr. Prashant Bansal, Dr. Soma Ray, Dr. Douglas Kerr Dyne Therapeutics, Waltham, United States Background: Duchenne muscular dystrophy (DMD) is a progressive, X-linked neuromuscular disorder caused by pathogenic variants of the DMD gene resulting in the absence of functional dystrophin protein. DMD is a multi-system disease that manifests in progressive muscle degeneration, loss of ambulation, cardiopulmonary complications, neuropsychiatric symptoms, and premature death. Despite recent therapeutic advances, a significant unmet medical need remains for treatments that achieve durable dystrophin restoration and sustained functional benefit. Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages TfR1 to deliver an exon 51 skipping PMO to muscle, with the goal of producing near full-length, functional dystrophin. Previously disclosed data from the ongoing Phase 1/2 DELIVER trial ( NCT05524883 ) have shown a favorable safety and tolerability profile. At the registrational dose of 20 mg/kg Q4W, z-rostudirsen demonstrated a statistically significant increase in dystrophin expression and trends in early and sustained functional improvement across clinical endpoints, supporting advancement to a Phase 3 study. Methods: To evaluate the efficacy, safety, and tolerability of z-rostudirsen 20 mg/kg Q4W in a placebo-controlled, confirmatory study. Results: The Phase 3 FORZETTO study will enroll ∼90 ambulatory participants aged 4-18 years with DMD caused by mutations amenable to exon 51 skipping. Participants will be randomized 1:1 to receive 20 mg/kg Q4W z-rostudirsen or placebo for 72 weeks, followed by a 96-week open-label Long-Term Extension (LTE). Endpoints include multiple measures of muscle function and PROs. Conclusion: The Phase 3 FORZETTO study will further evaluate the clinical benefit and safety of z-rostudirsen in participants with DMD amenable to exon 51 skipping, with endpoints that measure functional improvement.

Asst. Prof. Leila Tamaoui 1,2 , Asst. Prof. Basma MARZOUK 1,2 , Dr. Nada Benkirane 3 , Prof. Nazha Birouk 1,2 1 Clinical Neurophysiology Department, Hôpital des Spécialités of Rabat, Ibn Sina University Hospital, Rabat, Morocco. 2 Medical school of Mohammed V University, Rabat, Morocco. 3 private clinical practie of Neurology, Tangier, Morocco Background: Glycogen storage diseases (GSDs) are rare inherited metabolic myopathies characterized by marked clinical heterogeneity and frequent diagnostic delay. Data from North African populations remain limited. We aim to describe the clinical, electrophysiological, and genetic features of a Moroccan series of patients with GSDs, highlighting phenotypic variability and atypical presentations. Methods: We report a retrospective series of nine patients from six unrelated families diagnosed with GSDs. Seven patients are followed at the Clinical Neurophysiology Department, Rabat, between January 2023 and 2025. Clinical evaluation, serum creatine kinase (CK) levels, electromyography (ENMG), respiratory and cardiac assessments, enzymatic testing, and genetic analyses were reviewed. Results: Three distinct GSD subtypes were identified. Pompe disease (GSD II): Four patients had late-onset Pompe disease (LOPD), and one adolescent girl (13 years) had juvenile-onset disease. Clinical presentations ranged from isolated exertional fatigue to severe proximal weakness with early respiratory failure. Two patients required non-invasive ventilation, and one young female required invasive ventilation. One index case developed rapidly progressive respiratory failure and died before treatment initiation. Familial screening enabled early diagnosis in a paucisymptomatic sibling, allowing prompt initiation of enzyme replacement therapy (ERT). Enzymatic and genetic confirmation was obtained in all cases. Tarui disease (GSD VII): The index case (37 years) presented with childhood-onset exercise intolerance followed by permanent proximal muscle weakness in adulthood. Marked intrafamilial variability was observed, with a older sister initially presenting isolated hemolytic anemia and developing pelvic girdle weakness at 69 years. McArdle disease (GSD V): A 77-year-old male and his daughter presented with typical exercise intolerance and a clear “second-wind” phenomenon. Whole-exome sequencing identified a novel homozygous PYGM mutation. Conclusion: This series highlights the broad phenotypic spectrum of GSDs, ranging from isolated exercise intolerance to life-threatening respiratory involvement. Diagnostic delay remains frequent, particularly in childhood-onset exertional syndromes. LOPD was the most common diagnosis, supporting systematic dried blood spot testing in suspected cases. The Tarui disease family illustrates atypical progression and striking intrafamilial variability. Consanguinity, observed in several families, likely contributed to disease occurrence and emphasizes the importance of genetic counseling and targeted family screening. Early recognition and respiratory monitoring are critical in LOPD. This series underscores the phenotypic pleiotropy of GSD VII and the diagnostic value of the “second-wind” phenomenon in GSD V. Improved access to genetic testing and ERT is essential to optimize outcomes

Dr. Douglas Kerr , Dr. Soma Ray, Dr. Shuli Yu, Dr. Sowmya Chary Dyne Therapeutics, Waltham, United States Background: Myotonic dystrophy type 1 (DM1) is a spliceopathy that results in multi-system clinical manifestations. Zeleciment basivarsen (z-basivarsen, also known as DYNE-101) is an investigational therapeutic that consists of a TfR1-binding Fab conjugated to an ASO designed to target mutant nuclear DMPK RNA in both muscle and CNS with the goal of correcting the underlying spliceopathy. Data from the ongoing Phase 1/2 ACHIEVE trial showed that z-basivarsen had a favorable safety profile. At the selected dose of 6.8 mg/kg Q8W, z-basivarsen led to substantial knockdown of DMPK RNA levels and improvement in splicing, functional improvement across diverse clinical measures, and improvement in patient reported outcomes, including CNS-related measures. Methods: ACHIEVE informed the initial safety and efficacy of z-basivarsen, which will continue to be evaluated in HARMONIA, a global Phase 3, placebo-controlled, randomized, double-blind study designed to assess the efficacy, safety, and tolerability of 6.8 mg/kg Q8W z-basivarsen administered intravenously in participants with DM1. Results: HARMONIA plans to enroll ∼150 participants aged ≥16 years, expanding upon ACHIEVE by including a broader DM1 population. Participants will be randomized 1:1 to receive either z-basivarsen 6.8 mg/kg Q8W or placebo during the 48-week placebo-controlled period, after which they will be eligible to enter an LTE portion. The primary objective is to evaluate the effect of z-basivarsen compared with placebo on improvement in muscle function as measured by the change from baseline in 5 Times Sit-to-Stand (5xSTS). 5xSTS is a validated and reliable measure of lower-extremity strength and functional mobility. It measures the ability to perform activities of daily living and has been shown to be an independent predictor of fall risk, of particular importance in DM1 due to the intrinsically high risk of falls and subsequent injury. Thus, 5xSTS is a clinically relevant endpoint to capture functional improvement in DM1. Key secondary objectives include measures of myotonia, muscle strength and function, as well as patient and clinician-reported outcomes. Moreover, given DM1’s significant CNS component, the study will evaluate potential effects on CNS-related disease burden, including both cognitive and non-cognitive symptoms (e.g., fatigue, sleep), using a combination of actigraphy, clinical, and patient-reported outcomes measures. Conclusion: HARMONIA is designed to rigorously evaluate the multi-systemic impact of spliceopathy correction using functional endpoints related to activities of daily living.

Dr. Daniela Gerovska 1 , Dr. Julie B Noer 2 , Dr. Yating Qin 2 , Dr. Quratul Ain 3 , Dr. Donjetë Januzi 3 , Prof. Matthias Schwab 3 , Dr. Otto W Witte 3 , Dr. Marcos J Araúzo-Bravo 1,4 , Dr. Alexandra Kretz 3 1 Biogipuzkoa Health Research Institute, San Sebastian, Spain. 2 University of Copenhagen, Copenhagen, Denmark. 3 Jena University Hospital, Jena, Germany. 4 Basque Foundation for Science, IKERBASQUE, Bilbao, Spain Background: ALS is a progressive neurodegenerative disorder characterized by motor neuron loss and pronounced genome instability. Mutations in genes such as SOD1 contribute to defects in DNA damage response and repair, highlighting chromosomal vulnerability as a central feature of ALS pathophysiology. Extrachromosomal circular DNAs (eccDNAs) are circular DNA molecules derived from chromosomal sequences that can arise from genome instability, yet their abundance and genic composition in ALS-affected tissues remain largely unexplored. We investigated the number and genic type of eccDNAs in the spinal cord of a genotoxic stress–related murine ALS model expressing human SOD1 G93A . Methods: Cervical spinal cord tissue from nine symptomatic hSOD1 G93A mice and ten non-transgenic controls was processed for eccDNA isolation using rolling circle amplification combined with linear DNA digestion. Purified eccDNAs were sequenced using high-throughput short-read technology, and mapped eccDNAs were analyzed with the DifCir computational approach, which quantifies the production of eccDNAs per gene (DPpGCs). EccDNA abundance, length distribution, and genic origin were compared between ALS and control tissues. To assess functional relevance, eccDNA-producing genes were integrated with proteomic profiles from the same spinal cord samples and cross-referenced with ALS risk genes from genome-wide association studies (GWAS). Results: Analysis revealed a six-fold increase in the number of genomically distinct eccDNAs in ALS spinal cord relative to controls, demonstrating enhanced circular DNA formation under disease-associated genotoxic stress. Beyond this quantitative increase, ALS tissue exhibited a disease-specific shift in eccDNA composition. We identified 225 upregulated DPpGCs (up-DPpGCs), defined as genes generating more eccDNAs from distinct genomic regions in ALS than in controls. Notably, the top six up-DPpGCs showed at least 89% recurrence across samples, indicating high reproducibility of the genic eccDNA signature. Among the 225 upregulated eccDNA-producing genes in ALS spinal cord, 83 (37%) correspond to neural coding genes previously identified as recurrent DNA double-strand break loci, indicating that eccDNAs arise disproportionately from genome-fragile regions in the hSOD1 G93A model. Integration with proteomic data identified 42 corresponding differentially expressed proteins (DEPs), 19 of which were associated with ALS risk in GWAS. Functional annotation revealed that up-DPpGCs and their protein counterparts predominantly contribute to neuron-specific functions. Gene set enrichment analysis indicated significant overrepresentation of the adenylate cyclase–modulating G protein pathway, suggesting that changes in genic eccDNA production intersect with neuronal signaling networks relevant to ALS pathogenesis. Conclusion: Our findings demonstrate both a substantial increase in eccDNA number and a distinct alteration in genic composition in the spinal cord of an ALS murine model. The identified up-DPpGCs correspond with proteomic changes and known ALS risk genes, providing an integrated view of genome instability and its molecular consequences. This study establishes eccDNAs as a previously underappreciated molecular feature of ALS and highlights their potential as biomarkers of genome stress, offering a new dimension for understanding neurodegenerative mechanisms and exploring therapeutic avenues. Reference: Gerovska et al. A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1 G93A  model of ALS. Cell Biosci. 2023 ;13(1):170. doi: 10.1186/s13578-023-01116-1.

Mr. Nicholas Riley 1 , Mr. Nicolas Ballarini 2 , Ms. Almuth Marx 3 , Mr. Orlando Dohring 4 , Ms. Grace McCarthy 5 , Ms. Anja Haltner 6 , Ms. Sarah Walsh 6 , Mr. Chris Drudge 6 , Mr. Maxwell Jones 6 , Ms. Roya Gavanji 6 , Ms. Nikethana Srikanth 6 , Ms. Monica Duong 6 , Mr. Paul Spin 6 1 Novartis, Basel, Switzerland. 2 Novartis, East Hanover, United States. 3 Novartis, Nuremberg, Germany. 4 Novartis, London, United Kingdom. 5 Novartis, Dublin, Ireland. 6 EVERSANA, Burlington, Canada Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder leading to muscle atrophy and loss of motor function. The treatment landscape for SMA has evolved significantly with the use of disease-modifying therapies (DMTs). Intrathecal onasemnogene abeparvovec (OAV101 IT) is a one-time gene replacement therapy for SMA that recently received Food and Drug Administration (FDA) approval and is under regulatory review in other countries. Comparative efficacy or safety of OAV101 IT in patients with SMA versus existing chronically administered SMA therapies, such as risdiplam and nusinersen, have not been assessed in any head-to-head clinical trials. Indirect treatment comparisons (ITCs) are therefore critical for estimating relative efficacy and safety. Objective : To estimate the relative efficacy and safety of OAV101 IT versus risdiplam and nusinersen in SMA DMT-naïve patients using anchored matching-adjusted indirect comparisons (MAICs) to fulfill evidence requirements in addressing the assessment scope requested as part of the Joint Clinical Assessment (JCA) submission in the European Union and support other market access activities for OAV101 IT. Methods: Randomized controlled trials of SMA DMT-naïve patients were identified via a systematic literature review. Pivotal trials were selected based on an in-depth feasibility assessment identifying overlap with OAV101 IT trial populations, using criteria such as age at screening, symptomatic and ambulatory status, and naivety to DMTs. Indirect comparisons were performed using individual patient data from STEER ( NCT05089656 ; OAV101 IT), which enrolled a DMT-naïve patient population, and published summary level data from SUNFISH part 2 ( NCT02908685 ; risdiplam) and CHERISH ( NCT02292537 ; nusinersen). Relative efficacy and safety were primarily evaluated using change from baseline (CFB) in Hammersmith Functional Motor Scale–Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and proportion of patients with treatment-emergent adverse events (TEAEs) and serious TEAEs (STEAEs). Results: For OAV101 IT versus risdiplam, MAIC results showed a numerical improvement in HFMSE favouring OAV101 IT (mean difference [MD]: 1.93; 95% confidence interval [CI]: -0.25, 4.10); p=0.0825). MAIC results for CFB in RULM favoured risdiplam (MD: -1.46; 95% CI: -3.38, 0.46; p=0.1367). Safety comparisons of OAV101 IT versus risdiplam indicated numerical favorability in proportions of patients with at least one TEAE (risk ratio [RR]: 1.11; 95% CI: 0.93, 1.33; p=0.2610) and at least one STEAE (RR: 0.73; 95% CI: 0.25, 2.12; p=0.5614). For OAV101 IT versus nusinersen, MAIC results showed comparable improvements in HFMSE (MD: -0.13; 95% CI: -2.93, 2.66; p=0.9252) and RULM (MD: -1.15; 95% CI: -3.32, 1.01; p=0.2975), both favoring nusinersen. Safety comparisons of OAV101 IT versus nusinersen indicated numerical favorability in proportions of patients with at least one TEAE (RR: 1.12; 95% CI: 0.96, 1.30; p=0.1518) and at least one STEAE (RR: 1.26; 95% CI: 0.43, 3.74; p=0.6709). Conclusion: In the absence of direct head-to-head trials for SMA DMTs, these analyses demonstrate that treatment with OAV101 IT results in similar motor milestone improvement and OAV101 IT has a similar safety profile relative to risdiplam and nusinersen in the SMA DMT-naïve patient population. These findings support OAV101 IT as a viable first-line gene-replacement therapy, expanding treatment options for patients with SMA.

Prof. Geun-Young Park , Dr. Jisun Bae, Prof. Sun Im Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Korea, Republic of Background: Ischemic neuropathy is an uncommon cause of peripheral nerve injury, resulting from compromised blood flow or oxygen delivery to the vasa nervorum. We report a rare case of ischemic multiple mononeuropathies of the right lower limb that developed after percutaneous coronary intervention (PCI). Methods: A 57-year-old male presented to the emergency department of our hospital in May 2023 with dizziness. Electrocardiography (ECG) performed in the emergency department showed ST-elevation myocardial infarction (STEMI). Immediate PCI was performed via the right femoral artery, and a temporary pacemaker was inserted through the right femoral vein. Following the procedure, the patient was hemodynamically stable; however, he subsequently reported pain and weakness in the right lower limb during ambulation. Contrast-enhanced computed tomography (CT) of the tibia, contrast-enhanced three-dimensional CT angiography and venography, and lumbar spine magnetic resonance imaging (MRI) were performed, and the patient was referred to us for electrodiagnostic examination. CT revealed complete occlusion of the right popliteal, proximal posterior tibial, anterior tibial, and peroneal arteries. The patient reported generalized pain, swelling, and weakness in the right lower limb. Muscle strength was evaluated using the Medical Research Council (MRC) scale (0–5). Strength in the right lower limb was as follows: hip flexors and knee extensors, grade 5; ankle dorsiflexors, grade 3; first toe extensors, grade 2; ankle plantar flexors, grade 3. Light touch sensation was reduced over the posterior aspect of the right calf. Purplish discoloration and bullae were observed on the distal portions of the second to fourth toes and the dorsum of the right foot. Results: Initial electromyography (EMG) was performed 4 weeks after symptom onset. EMG was performed. The findings on NCS are consistent with multiple mononeuropathies of the right lower limb, confined to the distal segment below the knee. These lesions are presumed to be associated with ischemia resulting from complete occlusion of the popliteal, anterior tibial, posterior tibial, and peroneal arteries due to a post-PCI embolic event, which is thought to have induced multiple neuropathies involving the distal nerves of the lower limb. Follow-up NCS and EMG were performed in the outpatient clinic in September 2025. Motor strength in the right lower limb showed recovery: grade 5 in the hip flexors and knee extensors, grade 4 in the ankle dorsiflexors, grade 3 in the first toe extensor, and grade 5 in the ankle plantar flexors (MRC scale). On the follow-up study, improvement across multiple nerves was observed, with increased amplitudes in the right peroneal, sural, superficial peroneal, and saphenous nerves compared with the initial examination. On needle EMG, previously observed abnormal spontaneous activities were no longer present. Polyphasic, large-amplitude MUAPs were seen in the right PL, TP, EHL, and GCM, with reduced recruitment and a reduced interference pattern noted in the PL, TP, and EHL. Conclusion: Ischemic neuropathy caused by acute arterial occlusion following PCI is a rare complication. Early recognition of post-PCI arterial thrombosis is crucial for initiating immediate revascularization therapy. Prompt recognition and timely management are key to preventing motor deficits and optimizing functional recovery.

Dr. Linda Jaffe Queens Neurosciences Institute, Honolulu, Hawaii, United States Background: Belts and tight-fitting clothing, obesity, and pregnancy are all common causes of compression of the Lateral Femoral Cutaneous Nerve (LFCN) also known as Meralgia Paraesthetica (MP.) But the LFCN can be vulnerable to other sources of traction as it passes beneath the inguinal ligament. We sought to consider if MP, much to our surprise, could be caused by weight loss. Methods: A review of the literature and commonly used references such as UpToDate was completed to search for the possibility that mechanical factors involved with loss of weight might contribute to MP. This effort was undertaken when a 63 year old non-Diabetic man presented to our clinic with the classic features of LFCN syndrome without any of the commonly associated risk factors and rather than weight gain, he had lost 30 pounds during the pandemic. Results: The most commonly identified risk factors for MP are obesity, Diabetes Mellitus, and older age, pregnancy, increased abdominal girth such as in ascites. Mechanical traction on the nerve due to prolonged leaning against a table or bench, carrying heavy objects supported by the groin, various exercises have also been associated. Postoperative MP is also cited as cause of the compressive neuropathy. But weight loss is not described. Conclusion: Meralgia Paraesthetica is a mononeuropathy of the LFCN and like other neuropathies, injury can be due to various causes with the ultimate result being local ischemia. We report on a case of such injury occurring due to mechanical effects from weight loss rather than weight gain. (This poster was presented at WCN Rome 2021 during the virtual meeting.)

Ms. Eliana Iannibelli 1 , Dr. Alessandra Carnazzi 1 , Ms. Irene Sambruni 2 , Dr. Erika Salvi 2 , Ms. Lucia Nicolini De Gaetano 1 , Mr. Franco Salerno 1 , Dr. Isabella Moroni 3 , Dr. Lorenzo Maggi 1 , Dr. Alessandra Ruggieri 1 , Dr. Sara Gibertini 1 1 Neuroimmunology and Neuromuscular Diseases Unit – Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 2 Data Science Center and Computational multi-Omics of Neurological Disorders (MIND) Lab – Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 3 Department of Pediatric Neurosciences – Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy Background: PLIN4 ‑related distal myopathy is a rare autosomal dominant disorder caused by a PLIN4 expansion resulting in protein aggregation. Perilipin 4 accumulates at the sarcolemma and in sarcoplasmic vacuoles, disrupting myofiber organization and contractility. Protein aggregation and defective aggrephagy, traditionally associated with neurodegeneration, are widely recognized as key contributors to several inherited and sporadic muscle disorders. To elucidate underlying molecular pathways, we analysed the miRNome of PLIN4 ‑associated myopathy and compared it with other vacuolated myopathies with protein aggregates, including Pompe disease (PD), Inclusion Body Myositis (IBM), and Oculopharyngeal Muscular Dystrophy (OPMD). miRNAs have recognized as key post‑transcriptional regulators, and this makes them promising tools for dissecting molecular pathways and for identifying future diagnostic biomarkers. Methods: Primary myoblasts were derived from human muscle biopsies. Libraries were generated from total RNA using standard protocols and sequenced on a high‑throughput platform. Raw reads were quality-checked using FastQC v0.12.1 and trimmed with Trim Galore v0.6.10. The reads were aligned to miRBase (Release 22.1) using Bowtie v1.3.1 and quantified using Samtools (v1.22.1). Lowly expressed miRNAs were filtered out, and differential expression analysis was performed with DESeq2 (v1.44.0, R version 4.4.1). Comparisons were performed between PLIN4 -related myopathy (N=7) and PD (N=5), IBM (N=4), OPMD (N=5), as well as non-vacuolated myopathies (N=5). Only significant miRNAs (padj < 0.05) were considered for target identification using the R package multiMiR (v1.26.0) by querying validated miRNA–target interaction databases. Interactions supported by at least two databases were retained and used for over-representation analysis with the online tool WebGestalt. Results: Over-representation analysis was performed separately for each set of differentially expressed miRNAs identified in each comparison group. Principal Component Analysis (PCA), shows a clear clustering separation between vacuolated and non-vacuolated myopathies, supporting the presence of disease‑specific regulatory signatures. Intriguingly, the analysis highlighted a strong separation of PLIN4 -related myopathy from IBM and non-vacuolated myopathy samples with twenty miRNAs differentially expressed. However, only three were differentially expressed compared to OPMD. Remarkably, the common miRNA up-regulated across all three comparisons was miR-532-5p. The comparison with IBM and non-vacuolated samples, found miR-199b-5p as downregulated. No differentially expressed miRNAs were detected when comparing to PD. These results highlight a disease-specific miRNA profile in PLIN4 -related myopathy in primary myoblasts. Conclusion: Our findings demonstrate that unbiased miRNA profiling is a valuable tool for uncovering reliable molecular biomarkers and disease‑related regulatory pathways in rare muscle disorders. The PLIN4 ‑related myopathy specific miRNA signature, in the primary myoblasts, still requires deeper analysis regarding involved pathways and their biological significance. The obtained results will be combined with miRNA profiling of muscle tissues, which is currently in progress. Further analysis will include functional validations in vitro to assess their biological relevance and regulatory impact. In parallel, their diagnostic potential will be evaluated in patients’ sera to determine their suitability as minimally invasive biomarkers.

Dr. Mazen Dimachkie 1 , Asst. Prof. Francesco Sacca 2 , Dr. Maria Ait-Tihyaty 3 , Dr. Caitlin Briggs 3 , Dr. Uzma Siddiqui 3 , Mr. Luke Hickey 3 , Dr. Marianna Lalla 3 , Dr. Marek Smilowski 4 1 University of Kansas Medical Center, Kansas City, United States. 2 Azienda Ospedaliera Universitaria (AOU) Federico II, Naples, Italy. 3 Dianthus Therapeutics, New York, United States. 4 Neurologia Śląska Centrum Medyczne, Katowice, Poland Background: The classical complement pathway plays a significant role in acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) pathology. Claseprubart is an investigational, clinical-stage, potent monoclonal antibody engineered to selectively target the classical complement pathway, by selectively inhibiting activated C1s protein. The clinical benefit of claseprubart in gMG may be best supported by improvement across multiple validated scales to capture multi-dimensional improvement beyond single-scale analyses. Methods: AChR+ gMG patients treated with 300 mg claseprubart subcutaneously once every 2 weeks in the MaGic study ( NCT06282159 ) – a global Phase 2, randomized, double-blind, placebo-controlled trial – were analyzed for responses based on multiple assessments compared to placebo. p-values are one-sided, with nominal significance assessed at an alpha of 0.1. A responder was defined as achieving an improvement in MG-ADL ≥3 and QMG ≥4. Endpoints include proportion of dual MG-ADL and QMG responders at Week 13, time to response, and proportion of responders sustaining response for at least 6 weeks. Results: 63% of claseprubart patients had dual response improvement in MG-ADL ≥3 and QMG ≥4, versus 14% for placebo (OR 29.00; p=0.0006). Dual responders were seen as early as Week 1. The median time to response was Week 3. All claseprubart patients with dual response at Week 13 had maintained response for at least 6 weeks. Conclusion: Claseprubart-treated patients were more likely to achieve multi-dimensional response than placebo. Responses emerged early and were sustained, confirming rapid, robust, and durable benefit from claseprubart across functional and quantitative measures from both patient and clinician perspectives.

Dr. Paola Laghetti 1 , Assoc. Prof. Concetta Altamura 1 , Dr. Ilaria Saltarella 1 , Dr. Isabella Moroni 2 , Dr. Alessandra Ruggieri 3 , Dr. Sara Gibertini 3 , Dr. Lorenzo Maggi 3 , Prof. Jean-François Desaphy 1 1 Section of Pharmacology, Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari “Aldo Moro”, Bari, Italy. 2 Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 3 Neuroimmunology and Neuromuscular Disease Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy Background: PLIN4-related myopathy is a rare vacuolar myopathy characterized by distal muscle weakness, caused by a pathological expansion of a 33-aminoacids sequence within the amphipathic helix of Perilipin 4 (PLIN4). This mutation leads to protein misfolding and aggregation in the subsarcolemmal region of myofibers, resulting in vacuole formation due to activation and impairment of the aggrephagy pathway. These alterations thereby disrupt the skeletal muscle fiber structure and its contractile function. In addition to myopathic symptoms, clinical myotonia has also been observed in a subset of patients affected by PLIN4-related myopathy. Myotonic syndromes are typically associated with mutations in the CLCN1 and SCN4A genes, encoding for the ClC-1 and Nav1.4 ion channels, respectively. Therefore, this study aimed to investigate the role of these ion channels in the pathogenesis of myotonia in patients with PLIN4 mutation, assessing their gene and protein expression. Methods: Muscle biopsies from an Italian family affected by PLIN4-related myopathy and from patients without myopathy used as controls were used for proteins and RNA extraction. Gene expression of ion channels involved in myotonic syndromes (CLCN1 and SCN4A) and selectively expressed in denervated muscle cells (SCN5A) was assessed by SYBR Green quantitative PCR. Protein expression of ClC-1 and Nav1.4 was evaluated by Western blot analysis. Results: The expression of CLCN1 and SCN4A genes was significantly increased in patients carrying the PLIN4 mutation compared with control subjects. Similarly, when patients were stratified according to the presence or absence of myotonia, both groups showed a trend toward increased expression of these genes compared with controls. However, these changes at the transcriptional levels were not associated with similar changes in protein expression, as no significant differences in protein levels were detected between control subjects and patients, regardless of myotonia. Together, these data suggest that the pathogenesis of myotonia is more likely related to functional alteration of ion channels rather than to changes in their expression levels. In addition, SCN5A gene expression was similar between patients and controls, indicating that the altered muscle excitability is not a consequence of impaired muscle innervation. Conclusion: This study provides a first insight into the myotonic phenomenon observed in a subset of patients affected by PLIN4-related myopathy. Our data suggest that myotonia might be driven by functional dysregulation of ion channels, secondary to structural and proteostasis abnormalities induced by PLIN4 aggregates, rather than alterations in their expression. Additional studies are needed to further elucidate the relationship between PLIN4 protein aggregates and ion channel regulation, leading to the identification of potential therapeutic targets for the management of myotonia in patients affected by PLIN4-related myopathy. This work was funded by the Italian Ministry of Health and the European Union (Project code: PNRR-MR1-2023-12377360).

Prof. Nicholas Johnson Virginia Commonwealth University, Richmond, United States Background: Myotonic dystrophy type 2 (DM2) is a rare, multisystemic, autosomal dominant disorder characterised by proximal muscle weakness, myalgia, fatigue, and functional limitations. Despite overlapping features with myotonic dystrophy type 1 (DM1), DM2 presents a unique clinical and symptom profile, notably lacking excessive daytime sleepiness and presenting with severe myalgic pain and slower disease progression. Current clinical outcome measures inadequately capture these DM2-specific features. Methods: Here we enrolled a pilot study seeking to adopt other composite outcome measures such as the Northstar assessment for the muscular dystrophies and assess the impact on RNA splicing in myotonic dystrophy type 2. In addition, the myotonic dystrophy clinical research network (DMCRN) has developed several composite measures that it seeks to implement to prepare this patient population for future clinical trials. Results: Myotonic dystrophy type 2 is a slowly progressive condition that affects proximal muscles. Pilot data support the adoption of the Northstar assessment for the muscular dystrophies as an approach to capture these symptoms. Muscle biopsies revealed changes in RNA splicing consistent with those seen in myotonic dystrophy type 1. Further studies are required to assess the correlation of these splicing events and functional endpoints. Conclusion: Myotonic dystrophy type 2 is a progressive disorder that may benefit from the development of clinical outcome assessments and biomarkers to support the development of new therapeutics. The studies proposed will prepare the field for clinical trials in the near future.

Dr. Konstantina Tetorou 1,2 , Dr. Monica Rebeca Gil Garzon 1 , Mr. Alex Kavanagh 2 , Ms. Nicha Songsliph 2 , Mr. Shashwat Guha 1 , Ms. Ayana Withana 2 , Ms. Jenny Vartianen 1 , Ms. Wing Sum Chu 1 , Ms. Camila Vallve Maine 1 , Mr. Darren Chambers 2,3 , Dr. Riccardo Privolizzi 1 , Prof. Simon Waddington 4,5 , Dr. Simon Beggs 6,7 , Prof. Joanne Ng 1 , Prof. Francesco Muntoni 1,2 1 Genetic Therapy Accelerator Centre, UCL Queen Square Institute of Neurology, London, United Kingdom. 2 Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 3 Dubowitz Neuromuscular Centre, Division of Neuropathology, UCL Queen Square Institute of Neurology, London, United Kingdom. 4 Gene Transfer Technology Group, EGA Institute for Women's Health, University College London, London, United Kingdom. 5 Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 6 Neuroscience, Physiology and Pharmacology, UCL, London, United Kingdom. 7 Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, United Kingdom Background: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in X-linked DMD gene, resulting in disruption of functional dystrophin protein production. DMD patients exhibit progressive muscle weakness and 44% DMD individuals also experience intellectual disability and/or neurobehavioral complications, such as autism spectrum disorder, attention deficit hyperactivity disorder, and anxiety. These latter complications are due to deficiency of different dystrophin isoforms in the brain differentially affected by the location of the DMD gene mutation. The brain involvement is recapitulated in DMD mouse models with mutations differentially affecting Dp427, Dp140 dystrophin isoforms and displaying enhanced fear response with increased anxiety- and depressive-like behaviours. Previous preclinical studies have shown partial restoration of dystrophin in the brain with antisense oligonucleotide (ASO) therapy delivered intracerebroventricular (ICV) resulted in partial amelioration of neurobehavioural phenotypes but low levels of Dp427 restoration. To further address therapeutic approaches for brain dystrophin deficiency we generated Adeno-associated virus (AAV) gene therapy vector with neuronal targeted micro-dystrophin and evaluated neurobehavioural efficacy in mdx52 mice lacking both Dp427 and Dp140 isoforms. Methods: We treated neonatal male mdx52 at P1 with ICV or intravenous (IV) 5x10vg/pup and 4x11vg/pup respectively of AAV.micro-dystrophin, controls were untreated male mdx52 and wildtype littermates n=15 per group). We performed a battery of neurobehavioural tests between 8-12 weeks including fear response, elevated zero maze, open field, light-dark box, balance beam and Catwalk XT. We also used simple western (WES) to quantify micro-dystrophin and dystrophin’s interacting proteins in the brain. Results: We demonstrated statistically significant improvement of emotional reactivity related behaviours in treated compared to untreated mdx52 littermates. Some behaviours were restored to wildtype levels showing improved efficacy compared to previous ICV ASO studies. Micro-dystrophin protein levels showed a rostro-caudal gradient with 60% wild-type levels in hippocampus and midbrain, with 10% in the cerebellum after ICV delivery and between 10-40% in all brain areas with IV delivery. Conclusion: This is the first preclinical therapeutic study demonstrating brain targeted micro-dystrophin improves the neurobehavioural deficits observed in DMD mouse model with ICV and IV delivery.

Ms. Ilse de Laat , Dr. Karlijn Bouman, Dr. Sanne Vincenten, Dr. Saskia Houwen - van Opstal, Dr. Corrie Erasmus, Prof. Jan Groothuis, Mr. Donnie Cameron, Prof. Nicol Voermans Radboud university medical center, Nijmegen, Netherlands Background: Laminin- α2-related muscular dystrophy (LAMA2-MD) and selenoprotein N-related congenital myopathy (SELENON-RM) are rare congenital muscle disorders characterized by delayed motor development, slowly progressive axial muscle weakness, early-onset spinal rigidity, and respiratory insufficiency. Currently, no curative treatment options are available, however, promising preclinical studies are being performed. Clinical and functional outcome measures often show little change over short-term follow-up. In contrast, muscle magnetic resonance imaging (MRI) has shown diagnostic and prognostic value in other congenital muscle disorders, making it a promising additional outcome measure. However, no prospective quantitative MRI studies have been performed yet in LAMA2-MD and SELENON-RM. Cross-sectional imaging studies have shown an inconsistent pattern in LAMA2-MD and more uniform involvement in SELENON-RM without correlations to clinical features. Hereby, we present the one-year follow-up muscle MRI data from the LAST STRONG study, a natural history study aiming to identify suitable outcome measures and reach trial readiness for LAMA2-MD and SELENON-RM. Methods: Patients underwent a whole-body MRI at baseline and one-year follow-up using a 1.5 tesla MRI system. The protocol included ‘Dixon’ imaging and T2-weighted STIR. In a subset of lower extremity muscles, polygonal region of interests (ROIs) were drawn to derive fat-fraction maps and cross-sectional areas. Motor function was assessed using the Motor Function Measures-32 and graded and timed function tests. Results: Data analysis is currently ongoing. At the congress, patterns of muscle involvement and longitudinal changes in quantitative muscle MRI, including fat-fraction and cross-sectional area, and their correlations with clinical and functional outcome measures will be presented. Conclusion: This prospective natural history study will provide important longitudinal quantitative muscle MRI data in LAMA2-MD and SELENON-RM patients. The findings are expected to clarify muscle involvement patterns, and determine if muscle MRI is a sensitive outcome measure for future clinical trials.

Prof. Nils Erik Gilhus University of Bergen, Bergen, Norway. Haukeland University Hospital, Bergen, Norway Background: Many MG women abstain from having children or have fewer children than they would have had without their MG. Main reasons are worries about MG worsening in pregnancy and after giving birth, outcome for the child because of mother's MG autoantibodies and drugs crossing the placenta, MG hereditary aspects, and long-term physical ability to care for a child. General birth rates are going down world-wide, and mother's age when giving birth is increasing. All MG women in reproductive age should receive precise information on pregnancy and puerperium, and all aspects that may lead to worries should be addressed. Methods: The impact of MG on pregnancy, puerperium, and the child, and the impact of pregnancy and puerperium on the MG have been addressed in many studies. Registry-based studies usually include large cohorts with little selection bias, but lack detailed clinical information. Most registry-based studies are able to include relevant control groups. Single- or multicentre hospital populations are prone to selection bias, they tend to include fewer patients, and typically they do not include control populations. The Nordic countries have excellent nationwide health registries, including birth registries. The presentation will include data from various sources. Results: Pregnancy is recommended when the MG is in a stable and well-controlled phase. Thymectomy performed before pregnancy leads to a less severe MG during pregnancy. In most MG women, the disease shows no or mild fluctuations during pregnancy. However, up to one third report a temporary deterioration. Some also improve. Myasthenic crisis during pregnancy is very rare. In puerperium, an MG deterioration is common. Therefore, relatively fast-acting therapy should be considered in this phase, either initiation or increasing the dose. Mycophenale mofetil, methotrexate, and cyclophosphamide are teratogenic and should not be used by women in reproductive age. Pyridostigmine, corticosteroids in low doses, and azathioprine can be continued during pregnancy. IVIg and plasma exchange are regarded as safe emergency treatments. Neonatal myasthenia occurs in 10-15% of children with MG mothers. This is not related to mother's MG severity. Malformations and the FARAD syndrome is rare, with 46 children reported in a large multicentre study. MG women has an increased chance for Cesarean section. This is mostly due to worries that vaginal delivery might be too demanding physically. However, ordinary vaginal birth is recommended for the large majority of MG women. Most pregnancy complications have a similar frequency with and without MG. Conclusion: All MG women in reproductive age should receive precise information about pregnancy and giving birth. Pregnancies should be planned when the MG is stable and well-controlled. Thymectomy should usually be performed before pregnancy, and drug treatment should be adapted to a potential pregnancy. Regular follow-up of the MG mother and her baby, including ultrasound examinations, should be performed during pregnancy. Vaginal delivery is preferred in the large majority. However, all MG women should give birth in a hospital with experience in emergency neonatal care including respiratory support due to the risk of neonatal myasthenia and FARAD. MG should not be a reason for abstaining from having children.

Dr. Fiammetta Vanoli 1,2 , Dr. Artur Drużdż 3 , Dr. Ali A. Habib 4 , Dr. Dale J. Lange 5 , Dr. Hiroyuki Naito 6 , Prof. Robert Pascuzzi 7 , Prof. Sabrina Sacconi 8 , Dr. Kimiaki Utsugisawa 9 , Prof. John Vissing 10 , Dr. Tuan Vu 11 , Dr. Jiann-Horng Yeh 12,13,14 , Mr. Joel Baldwin 15 , Dr. Thais Tarancón 16 , Dr. Vera Bril 17 1 Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS, Instituto Nazionale Neurologico Carlo Besta, Milan, Italy. 2 Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy. 3 Department of Neurology, Municipal Hospital, Poznań, Poland. 4 MDA ALS & Neuromuscular Center, Department of Neurology, University of California, Irvine, Orange, CA, United States. 5 Lange Neurology, New York, NY, United States. 6 Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Hiroshima, Japan. 7 Neurology Department, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, United States. 8 Université Côte d'Azur, Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France. 9 Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. 10 Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 11 Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, United States. 12 Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. 13 College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. 14 Department of Neurology, Kaohsiung Medical University, Kaohsiung, Taiwan. 15 UCB, Slough, United Kingdom. 16 UCB, Madrid, Spain. 17 Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada Background: Anti-muscle-specific tyrosine kinase antibody-positive (MuSK Ab+) generalised myasthenia gravis (gMG) is a rare and often severe subtype of myasthenia gravis (MG). The Phase 3 MycarinG ( NCT03971422 ) study demonstrated that six once-weekly rozanolixizumab infusions showed clinically meaningful improvements in MG-specific outcomes versus placebo in adults with gMG. Patients could then enrol in open-label extensions MG0004 ( NCT04124965 ) then MG0007 ( NCT04650854 ), or MG0007 directly. Here, we evaluate the efficacy and safety of repeated rozanolixizumab cycles in patients with MuSK Ab+ gMG. Methods: In MG0004, patients received chronic, once-weekly rozanolixizumab for ≤52 weeks. In MG0007, after an initial cycle of rozanolixizumab, subsequent cycles were administered upon symptom worsening, at the investigator’s discretion. Final data (7 mg/kg or 10 mg/kg) were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 for patients with ≥2 symptom-driven cycles (efficacy pool), and across MycarinG and MG0007 for patients with ≥1 treatment cycle (safety pool). Efficacy outcomes included mean change from baseline (CFB) to Day 43 per cycle, and weighted means across Cycles 1–13 for MG Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scores. Results: Overall, 12/129 (9.3%) patients who received ≥2 symptom-driven rozanolixizumab cycles had MuSK Ab+ gMG. In patients with MuSK Ab+ gMG, the weighted-mean MG-ADL scores across 13 cycles were 10.4 at baseline and 5.2 at Day 43. Weighted-mean CFB in MG-ADL total score across 13 cycles was −5.2, with mean (standard deviation) CFB ranging from −3.0 (3.6; n=8; Cycle 5) to −7.0 (3.5; n=12; Cycle 1). For QMG, the weighted-mean scores at baseline and Day 43 were 16.8 and 9.4, respectively. Weighted-mean CFB in QMG total score was −7.3, ranging from −5.0 (n=2; Cycle 13) to −10.6 (6.0; n=8; Cycle 3). In patients with MuSK Ab+ gMG and ≥1 treatment cycle (n=18), 14 (77.8%) reported treatment-emergent adverse events (TEAEs); most TEAEs were mild or moderate. Conclusion: Patients with MuSK Ab+ gMG who received rozanolixizumab treatment consistently had improvements from baseline in MG-ADL and QMG scores across cycles, with an acceptable safety profile.

Assoc. Prof. Yutaka Ohsawa 1 , Prof. Shin-ichiro Nishimatsu 1 , Assoc. Prof. Masahiro Fujino 2 , Prof. Yoshihide Sunada 1 , Prof. Masahito Mihara 1 1 Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. 2 Kyushu Women’s Junior College, Jiyugaoka 1‑1, Yahata Nishi, Kitakyushu, Fukuoka 807-858, Japan Background: The longevity protein α-Klotho is a critical determinant of aging; its deficiency precipitates a shortened lifespan and diverse senescent phenotypes, including sarcopenia. We previously demonstrated that circulating α-Klotho functions as an endogenous inhibitor of transforming growth factor (TGF)-β　superfamily members, such as myostatin, GDF11, activin, and TGF-β1 (Ohsawa, Am J Pathol 193, 2023). While a small-molecule compound suppressing these TGF-βs restored sarcopenia in α-Klotho (-/-), its clinical application is limited by potential cardiovascular risks. Methods: In this study, we investigated whether targeted inhibition of a single ligand, myostatin, is sufficient to rescue the senescent phenotypes in the α-Klotho (-/-) mice. By crossing the α-Klotho (-/-) mice with the transgenic mice overexpressing myostatin prodomain [MSTN Pro (+/-) Tg], we achieved ligand-specific suppression of myostatin activity. Results: The resulting α-Klotho (-/-)/MSTN Pro  (+/-) Tg mice exhibited significantly increased muscle mass, enhanced grip strength, and greater absolute contractile force. At the molecular level, myostatin blockade attenuated Smad2 phosphorylation and downregulated the senescence marker  Cdkn1a (p21) expression in skeletal muscle. Notably, myostatin inhibition significantly extended the median survival of the mice (15.2±2.2 vs. 10.5±1.9 weeks; n=17, P <0.05). Conclusion: These results indicate that specific myostatin blockade not only alleviates sarcopenia but also promotes longevity in a systemic senescence model, thereby providing safe therapeutic potential of myostatin-targeted interventions for age-related disorders.

Dr. Gordon Smith 1 , Dr. Nicholas Silvestri 2 , Ms. Cynthia Qi 2 , Dr. Hongbo Yang 3 , Dr. Andrea Corse 4 , Dr. Ali Habib 5 , Dr. Tuan Vu 6 , Dr. Gil Wolfe 7 , Dr. Lingyun Li 2 , Dr. Sun Lee 3 , Dr. Yujie Wu 3 , Dr. Dongni Ye 3 , Dr. Dustin Nowacek 2 , Dr. Jamie Aldridge 2 , Dr. Arash Mahajerin 2 , Dr. Glenn Philips 2 , Dr. James Howard 4 1 Virginia Commonwealth University School of Medicine, Richmond, VA, United States. 2 argenx US Inc., Boston, MA, United States. 3 Analysis Group, Inc, Boston, MA, United States. 4 University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States. 5 University of California, Irvine, Irvine, CA, United States. 6 University of South Florida Morsani College of Medicine, Tampa, FL, United States. 7 University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States Background: Long-term steroids in generalized myasthenia gravis (gMG) is associated with considerable complications. Efgartigimod, the first FcRn antagonist approved in the United States (US) for adults with AChR antibody-positive gMG, offers opportunities for steroid-sparing treatment. Although the MGFA International Consensus Guidance and clinical trial evidence support the potential for reducing steroids with efgartigimod, real-world physician tapering behaviors – specifically when, how, and to what extent neurologists taper steroids – remain poorly characterized. This study examined physician-reported tapering strategies and corresponding patient-level steroids tapering outcomes among individuals with gMG initiating efgartigimod in routine US clinical practice. Methods: STRIVE-gMG is a retrospective chart review of patients with gMG who were receiving steroids at the time of efgartigimod initiation and completed at least two efgartigimod treatment cycles. Data are collected from neurologists in a specialty panel and from participating medical centers. In addition to patient-level data, participating neurologists reported their typical steroids tapering strategies at practice level, including timing, tapering speed, and target dose. Data collection is ongoing, and this interim analysis reflected initial data obtained from the neurologist panel. Results: As of November 10, 2025, 15 neurologists contributed data. Participating physicians had an average of 17.3 years of experience treating gMG and managed an average of 23 gMG patients receiving efgartigimod since its approval in 2021. Regarding typical tapering practice, most neurologists (73.3%) reported initiating steroids tapering once a stable clinical response to efgartigimod was achieved, suggesting broad alignment on timing of tapering. However, tapering speed and tapering goals varied, reflecting highly individualized decision-making. Faster tapering (>5 mg/month) was adopted by 46.7% of physicians, whereas 33.3% preferred a slower approach (≤5 mg/month) and 13.3% reported adjusting tapering based on clinical response. Target steroids doses also differed: while the majority targeted a complete discontinuation (33.3%) or low-dose maintenance (0-5 mg/day; 40.0%), some targeted 5-10 mg/day (6.7%) and others indicated variable goals tailored to patient specific factors (13.3%). Forty-one patient charts were abstracted by these neurologists. All patients were AChR positive. At efgartigimod initiation, patients had a mean age of 48.9 years and a mean disease duration of 3.7 years. Most (87.8%) had MGFA class II–III disease, and they had been on their current steroids regimen for an average of 1.1 years (range of 0-6.8 years). All patients tapered steroids following efgartigimod initiation, with mean prednisone-equivalent dose declining from 30.4 mg/day to 4.0 mg/day at 18 months. By the end of follow-up, 68.3% had discontinued steroids entirely and an additional 19.5% had tapered to ≤5 mg/day while remaining on efgartigimod. Conclusion: Most neurologists identified achievement of a stable clinical response to efgartigimod as the point at which steroids tapering should begin; however, meaningful variation was reported in typical tapering speed and final target dose. These patterns indicate the absence of a standardized tapering protocol and the use of individualized approaches influenced by both patient factors and physician judgment. Across these diverse tapering strategies, substantial reductions in steroids dose were achieved following efgartigimod initiation, supporting its role as an effective steroid-sparing treatment option.

Dr. Tatsuya Abe 1 , Dr. Kei Okuba 2 , Dr. Hitoshi Kawasaki 2 , Dr. Syugo Fujita 2 , Dr. Yasuo Ito 2 , Dr. Genko Oyama 2 , Dr. Tomihiro Imai 1 1 Department of Neurology, National Hospital Organization Hakone Hospital, Odawara, Japan. 2 Department of Neurology, Saitama Medical University, Moroyama, Japan Background: In recent years, off-label intramuscular injections of botulinum neurotoxin type A (BoNT/A) for cosmetic purposes have become widely prevalent in East Asia to improve visual appearance. However, the actual number of patients receiving this treatment is not fully understood, and attention must be paid to undesirable side effects. This paper reports complications associated with these BoNT/A injections. A 24-year-old woman presented to our hospital approximately 30 days after receiving a total of 800 U of botulinum toxin type A (BoNT/A) for cosmetic purposes via intramuscular injection, complaining of fatigue, dysphagia, inability to raise her arms, and dyspnea. Weakness was observed in the neck flexor muscles, deltoid, trapezius, and quadriceps femoris. Grip strength decreased to approximately 10 kg. Jaw clenching and shoulder muscle weakness fluctuated during the day. Serological tests were negative for anti-AchR and MuSK antibodies, whereas respiratory function test noted a significant reduction in vital capacity. Methods: We performed electromyography (EMG) 30 days after her symptom was revealed, to evaluate and diagnose the pathology, including nerve conduction study, and repetitive nerve stimulation. Given the possibility of an immune-mediated neuromuscular junction disorder could not be ruled out, IVIG and pyridostigmine were administered as symptomatic therapy. Subsequent outpatient follow-up revealed that improvement in fatigue took approximately 90 days. In addition, follow up EMG was undergone 180 days after symptom onset. Results: EMG demonstrated a marked decrease in compound muscle action potential (CMAP) amplitude. Low-frequency repetitive nerve stimulation (LF-RNS) in the nasalis and trapezius muscles revealed an abnormal decrement of the CMAP. Furthermore, this decrement of CMAP manifested as “progressive decrement” toward the latter part of the evoked response and was accentuated not only by exercise loading but also by high-frequency repetitive nerve stimulation (HF-RNS). A second EMG study performed 180 days after symptom onset showed increased CMAP amplitude in the nasalis muscle and trapezius muscle compared to the previous examination, and abnormal decrement was improved in LF-RNS at rest. However, accentuated “progressive decrement” was still observed after exercise loading and after HF-RNS. In addition, needle EMG showed short duration and polyphasic MUPs with normal recruitment, and single-fiber EMG revealed a marked increase in jitter in the deltoid muscle. Conclusion: Clinicians should be aware of the risks associated with intramuscular injections of BoNT/A for cosmetic purposes and should consider the possibility of severe botulism, including respiratory dysfunction, occurring as a side effect. This case highlights important electromyographic features of iatrogenic botulism following BoNT/A intramuscular injection and suggests the potential for persistent symptoms even after recovery. Furthermore, “progressive decrement” following exercise loading or HF-RNS may be useful in identifying iatrogenic presynaptic impairment caused by botulinum toxin type A injection into muscles.

Dr. Kuo-Ting Wei 1 , Dr. Ya-Fen Liu 1 , Prof. Hong-Yo Kang 1,2 1 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. 2 Center for Hormone and Reproductive Medicine Research, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Background: Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked neuromuscular disorder caused by CAG trinucleotide repeat expansion in the androgen receptor (AR) gene, resulting in an expanded polyglutamine (polyQ) tract within the AR protein. Ligand-dependent misfolding and aggregation of polyQ-AR lead to progressive lower motor neuron degeneration and muscle atrophy. Despite advances in understanding SBMA pathogenesis, the mechanisms underlying selective neuromuscular vulnerability remain incompletely defined, and disease-modifying therapies are currently lacking.This study aimed to develop and evaluate proteolysis-targeting chimeras (PROTACs) as a targeted protein degradation strategy for eliminating pathogenic polyQ-AR. We sought to assess their efficacy in cellular and in vivo SBMA models and to elucidate the molecular pathways underlying PROTAC-mediated polyQ-AR degradation. Methods: A series of AR-targeting PROTACs were evaluated in neuron-2a cells stably expressing AR-97Q and in SBMA transgenic mice. PolyQ-AR protein levels were assessed following PROTAC treatment, with proteasome involvement examined using MG132 inhibition. Isobaric tags for relative and absolute quantitation (iTRAQ)–based proteomics were employed to identify pathways associated with protein degradation. Functional outcomes were assessed using grip strength, rotarod performance, body weight monitoring, and survival analysis. Histological analyses of skeletal muscle and spinal anterior horn were performed to evaluate neuromuscular pathology. Results: PROTAC treatment markedly reduced aggregated AR-97Q protein levels in both cellular and tissue models, an effect reversed by proteasome inhibition with MG132. Mechanistically, PROTACs enhanced K48-linked polyubiquitination of polyQ-AR, promoting proteasomal degradation. In SBMA transgenic mice, PROTAC administration significantly improved muscle strength, motor coordination, and body mass, and prolonged survival. Histopathological analyses revealed substantial attenuation of neurogenic muscle atrophy in treated animals. Conclusion: These findings demonstrate that PROTAC-mediated degradation of polyQ-expanded AR effectively ameliorates molecular, functional, and histopathological features of SBMA. Targeting pathogenic AR through selective ubiquitination and proteasomal degradation represents a promising therapeutic strategy for SBMA and potentially other polyglutamine-associated neurodegenerative disorders.

Assoc. Prof. eun bin cho 1,2 , Mr. Bongseong Kim 3 , Prof. Kyungdo Han 3 , Dr. Seung Ho Choo 4 , Asst. Prof. Soonwook Kwon 5 , Prof. Dong Wook Shin 6 , Prof. Ju-Hong Min 4 1 Department of Neurology, College of Medicine, Gyeongsang National University, Jinju, Korea, Republic of. 2 Gyeongsang National University Changwon Hospital, Changwon, Korea, Republic of. 3 Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea, Republic of. 4 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of. 5 Department of Neurology, Inha University Hospital, Incheon, Korea, Republic of. 6 Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School, Seoul, Korea, Republic of Background: Prodromal manifestations of amyotrophic lateral sclerosis (ALS) remain incompletely characterized at the population level. Methods: In a nationwide Korean case–control study using National Health Insurance data (2011–2021), 9,435 individuals with ALS and 94,350 age-, sex-, and index year–matched controls were analyzed. Adjusted rate ratios (aRRs) for 23 pre-diagnostic medical conditions were estimated across 0–1, 1–2, 2–5, and 5–10 years before ALS diagnosis using Poisson regression. Temporal trajectories of log-transformed aRRs over ten consecutive 1-year intervals were evaluated using linear regression with false discovery rate (FDR) correction. Results: Radiculopathy (5–10 years: aRR 1.11, 95% CI 1.06–1.17; annual percentage change [APC] 16.8%), obstructive sleep apnea (2.67, 2.03–3.52; 15.4%), depression (1.49, 1.38–1.61; 14.9%), insomnia (1.12, 1.03–1.21; 11.4%), anxiety (1.32, 1.24–1.41; 11.3%), constipation (1.12, 1.04–1.22; 9.3%), and diabetes mellitus (1.06, 1.00–1.11; 6.7%) demonstrated significant progressive enrichment up to a decade before diagnosis (FDR p<0.05). Other fractures and benign prostatic hyperplasia demonstrated progressive enrichment beginning 2–5 years before diagnosis (1.32, 1.13–1.54; 8.8% and 1.19, 1.09–1.29; 6.7%, respectively). In contrast, anemia (5–10 years: 1.21, 1.08–1.35) and asthma (5–10 years: 1.18, 1.05–1.32) exhibited early enrichment without consistent temporal escalation. Schizophrenia and bipolar disorder also exhibited early enrichment with heterogeneous, non-monotonic patterns. Conclusion: A defined cluster of psychiatric, sleep-related, and musculoskeletal conditions, along with constipation and diabetes mellitus, shows long-standing and progressively increasing enrichment up to a decade before ALS diagnosis, supporting their role as prodromal features or early manifestations of ALS. In contrast, anemia and asthma show early and sustained elevation without progressive escalation, suggesting potential underlying biological associations.

Miss Louise Iterbeke 1 , Dr. Lotte Huysmans 2,3 , Dr. Kobe Bamps 4,5 , Dr. Ronald Peeters 6 , Ms. Veerle Goosens 6 , Prof. Frederik Maes 2,3 , Prof. Patrick Dupont 7 , Prof. Kristl Claeys 1,8 1 Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI) and Leuven Institute for Rare Diseases (Leuven.IRD), Leuven, Belgium. 2 Department ESAT/PSI, KU Leuven, Leuven, Belgium. 3 Medical Imaging Research Center, University Hospitals Leuven, Leuven, Belgium. 4 Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. 5 Department of Cardiology, University Hospitals Leuven, Leuven, Belgium. 6 Department of Radiology, University Hospitals Leuven, Leuven, Belgium. 7 Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium. 8 Department of Neurology, University Hospitals Leuven, Leuven, Belgium Background: Adult-onset Myotonic Dystrophy type 1 (DM1) is a progressive multisystemic disorder primarily characterized by distal muscle weakness and myotonia. As disease-modifying therapies advance, clinical trials require reliable, non-invasive and sensitive outcome measures. In this longitudinal study, we delineated the natural history of adult-onset DM1 and identified robust outcome measures for future clinical trials by assessing quantitative muscle MRI, clinical, and patient-reported outcome measures in patients with adult-onset DM1. Methods: Thirty-three patients with adult-onset DM1 and 33 age- and sex-matched healthy controls were assessed at baseline, 12 months, 18 months and 24 months. Quantitative muscle MRI of the lower limbs included 6-point Dixon imaging to quantify proton density fat fraction (PDFF %) and water T2 (T2 H2O ) to evaluate disease activity in the muscles. A convolutional neural network enabled automated 3D segmentation of 18 proximal and 10 distal leg muscles. Clinical outcome measures included Motor Function Measure-32 (MFM32), 6-Minute Walk Distance (6MWD), 10-Meter Walk Test (10MWT), 30-Second Sit-to-Stand (30SSS), 9-Hole Peg Test and hand opening time (myotonia). Strength was measured by Medical Research Council Sum Score (MRCSS), handgrip, key pinch and tip pinch strength and peak cough flow. Patient-reported outcomes (PROM) included DM1-ActivC, Brief Pain Inventory (BPI), Individualized Neuromuscular Quality of Life (INQoL), and Fatigue and Daytime Sleepiness Scale (FDSS). Results: Three patients completed the baseline visit only for medical reasons and were excluded from further analyses. Baseline MRI revealed significant higher PDFF (%) in patients with DM1 compared to their matched controls (Distal leg: 31.8% vs 5.9%, p<0.001; Proximal leg: 13.0% vs 7.6%, p<0.001). In patients, muscle fat replacement followed a distinct pattern. Early and severe fat replacement in the posterior distal leg (soleus, gastrocnemius), sparing of the popliteus and tibialis posterior, and progressive involvement of the anterolateral distal and proximal leg. Longitudinal analysis showed significant increases in PDFF (%) across 9/10 distal leg muscles and 15/18 proximal leg muscles at 12, 18, and 24 months. The distal leg muscles demonstrated the largest 24-month mean change (+3.5%, p<0.001), with the flexor hallucis longus muscle showing the highest effect size (SRM = 1.7). Proximal leg muscles showed a smaller but significant progression (+1.5% at 24 months, p<0.001). Conversely, T2 H2O remained stable over time. Patients with adult-onset DM1 scored significantly worse on all clinical outcome measures compared to their controls, and demonstrated progressive, significant deterioration in motor function (MFM32) and muscle strength (MRC sum score), with significant declines detected as early as 6 months. DM1-activC significant deteriorated at 12, 18, and 24 months (-5.6, p<0.01; -6.2, p<0.001; -10.3, p<0.001). The total quality of Life, measured by the INQoL, showed significant decline at 12 and 18 months (5.4, p<0.05; 6.9, p<0.01). Leg PDFF (%) correlated significantly with functional measures (10MWT, 6MWD, MFM32, 30SSS, MRC sum score) but was independent of CTG repeat length. Conclusion: Muscle MRI fat fraction, MFM32, MRC Sum Score, DM1-ActivC and INQoL emerged as sensitive and robust outcome measures to monitor the disease progression in adult-onset DM1. These measures are well-suited for implementation in future clinical trials to show therapeutic effect.

Dr. Zabeen Mahuwala 1 , Dr. Ruben Faelens 2 , Dr. Belén Valenzuela Jiménez 3 , Dr. Martine Neyens 2 , Dr. Yaowei Zhu 4 , Dr. Jocelyn H. Leu 4 , Dr. Marie Fitzgibbon 5 , Dr. Sindhu Ramchandren 6 , Dr. Juan-Jose Perez Ruixo 2 1 Department of Neurology, University of Kentucky, Lexington, United States. 2 Johnson & Johnson, Beerse, Belgium. 3 Johnson & Johnson, Madrid, Spain. 4 Johnson & Johnson, Spring House, PA, United States. 5 Johnson & Johnson, Raritan, NJ, United States. 6 Johnson & Johnson, Titusville, NJ, United States Background: In generalized myasthenia gravis (gMG), immunoglobulin G (IgG)-based autoantibodies attack the neuromuscular junction, causing muscle weakness. Nipocalimab, a fully human neonatal fragment crystallizable receptor (FcRn) blocker, prevents IgG recycling and thus lowers levels of circulating IgG antibodies, including pathogenic autoantibodies, thereby improving symptoms of gMG. We explored the longitudinal relationship between IgG level and Myasthenia Gravis-Activities of Daily Living (MG-ADL) score using semi-mechanistic pharmacometrics modeling with data from clinical studies of nipocalimab in gMG and healthy volunteers. Methods: Data from five phase 1, one phase 2, and one phase 3 (Vivacity-MG3) clinical studies were analyzed to characterize pharmacokinetics ([PK]; 3,429 serum nipocalimab concentrations [n=277]), pharmacodynamics ([PD]; 4,441 serum IgG concentrations [n=421] and 1,247 FcRn receptor occupancy data [n=78]). To establish the longitudinal relationship between IgG and MG-ADL, 2,317 absolute change from baseline (CFB) MG-ADL scores were analyzed in seropositive (anti-acetylcholine receptor, anti-muscle-specific receptor tyrosine kinase, anti-lipoprotein receptor-related protein-4) participants with gMG (n=220). A previously developed nonlinear mixed-effects model was used. The effects of baseline demographics and clinical characteristics on PK, PD, and MG-ADL parameters were investigated. Results: The previous model captured serum nipocalimab and total serum IgG concentrations of the phase 3 data well. MG-ADL CFB drug effect was linearly related to IgG %CFB at 0.28 points per 10% IgG %CFB. In the patient population, this resulted in approximately 2-points MG-ADL reduction for the nipocalimab-induced 70% IgG reduction when adjusted for placebo. The slope of the regression line was dependent on baseline MG-ADL score. Age, body weight, race, ethnicity, sex, autoantibody status, gMG background therapy and gMG duration did not have a clinically relevant impact. Conclusion: The model confirmed that the IgG %CFB drives nipocalimab effect on MG-ADL. These results support that total serum IgG reduction is a good predictor for efficacy in gMG, allowing for comparison of clinical effect across FcRn inhibitors.

Assoc. Prof. Paola Imbrici, Dr. Alessandro Giovanni Cerchiara, Dr. Brigida Boccanegra, Assoc. Prof. Paola Mantuano, Prof. Antonella Liantonio, Assoc. Prof. Ornella Cappellari, Prof. Annamaria De Luca Department of Pharmacy-Drug Sciences, University of Bari, Bari, Italy Background: Ion channel dysfunction underlies a wide spectrum of neuromuscular and pain disorders, including inherited skeletal muscle channelopathies, neuropathic pain syndromes, and Duchenne muscular dystrophy (DMD) (Cerchiara Biomed Pharm 2025; Cerchiara Ann N Y Acad Sci 2024). Robust and reproducible electrophysiological platforms are essential both for preclinical drug discovery and for elucidating genotype–phenotype correlations, particularly in diseases characterized by marked genetic heterogeneity. This study aimed (i) to evaluate automated patch clamp as a reliable tool for drug screening on voltage-gated sodium channels, focusing on the Nav1.7 channel and its modulation by mexiletine (Mex), and (ii) to investigate genotype–phenotype correlations in DMD by characterizing ion channel function and expression in patient-derived myogenic cell lines. Methods: Automated whole-cell recordings were performed using the Patchliner platform. For Nav1.7 pharmacology, sodium currents were studied in TE671 cells endogenously expressing Nav1.7 and in HEK293 cells stably expressing human Nav1.7, assessing voltage-dependent, tonic, and use-dependent block by Mex. For DMD studies, two immortalized myogenic cell lines derived from patients DMD1 (harbouring a nonsense mutation in exon 59) and DMD2 (carrying a deletion spanning exons 48–50) and a healthy control line (hWT) were analyzed during differentiation. Electrophysiological parameters were combined with real-time PCR to evaluate ion channel function and gene expression. Results: Mex produced comparable voltage-dependent, tonic, and use-dependent block of Nav1.7 currents in both TE671 and HEK293 cells, with similar IC₅₀ values under different holding potentials and stimulation frequencies. Mex also induced a dose-dependent hyperpolarizing shift of steady-state inactivation in both models, confirming its state-dependent mechanism of action. In DMD1/2 myogenic cells, membrane capacitance was reduced compared to control during differentiation. Inward current density increased with differentiation only in hWT, while both dystrophic cell lines showed stable inward currents over time. Outward currents increased during differentiation in all cell lines. Notably, expression of several ion channel genes ( SCN4A , SCN5A , CACNA1S , KCNJ2 , KCNQ4 ) was reduced in DMD1 myotubes, compared to DMD2 and hWT cells, indicating mutation-specific phenotypic differences. Conclusion: Automated patch clamp is a powerful and versatile approach for both drug screening and functional phenotyping of ion channel disorders. The platform reliably captured the state-dependent block of Nav1.7 by mexiletine and validated the two cell models for analgesic drug discovery. Furthermore, Patchliner enabled the identification of mutation-specific electrophysiological and molecular phenotypes in DMD, supporting its utility for genotype–phenotype correlation studies and the development of personalized therapeutic strategies.

Assoc. Prof. Jinwoo Park 1,2 , Prof. Byung-Jo Kim 1 1 Korea University, Seoul, Korea, Republic of. 2 Vanderbilt University, Nashville, United States Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem neurodegenerative disorder with involvement of the autonomic nervous system. However, the characteristics of cardiovascular autonomic dysfunction and their clinical relevance across disease stages remain incompletely defined. The Valsalva maneuver provides a physiologically grounded assessment of baroreflex-mediated autonomic control and may offer sensitive biomarkers for ALS-related autonomic involvement. Methods: In this cross-sectional study, 27 drug-naïve patients with ALS (El Escorial criteria: possible, n = 3; probable, n = 13; definite, n = 11) and 24 age- and sex-matched healthy controls were enrolled. Cardiovascular autonomic function was evaluated using baroreflex sensitivity indices (adrenergic [BRSa] and vagal [BRSv]), pressure recovery time (PRT), heart rate variability during deep breathing (HRVdb), and the Valsalva ratio (VR). Head-up tilt testing (HUTT) was also performed. Clinical severity and disease burden were assessed using the ALS Functional Rating Scale–Revised (ALSFRS-R) and disease duration. Results: In this cross-sectional study, 27 drug-naïve patients with ALS (El Escorial criteria: possible, n = 3; probable, n = 13; definite, n = 11) and 24 age- and sex-matched healthy controls were enrolled. Cardiovascular autonomic function was evaluated using baroreflex sensitivity indices (adrenergic [BRSa] and vagal [BRSv]), pressure recovery time (PRT), heart rate variability during deep breathing (HRVdb), and the Valsalva ratio (VR). Head-up tilt testing (HUTT) was also performed. Clinical severity and disease burden were assessed using the ALS Functional Rating Scale–Revised (ALSFRS-R) and disease duration. Conclusion: Patients with ALS demonstrate early-stage sympathetic hyperactivity, reflected by elevated adrenergic baroreflex sensitivity, which appears to attenuate with disease progression. Pressure recovery time may serve as a marker of disease severity and cumulative disease burden. Autonomic parameters, particularly those derived from the Valsalva maneuver, show strong discriminatory potential and may be useful as biomarkers for early detection and staging of ALS.

Dr. Chiara Fiorillo 1,2 , Dr. Monica Traverso 3 , Dr. Stefania Dallorso 2 , Dr. Simona Baldassari 3 , Dr. Matteo Cataldi 2 , Prof. Lino Nobili 1,2 1 Department of Neuroscience, University of, Genova, Italy. 2 Pediatric Neurology, Gaslini Children Hospital, Genova, Italy. 3 Medical Genetics, Gaslini Children Hospital, Genova, Italy Background: SNAPC4 (small nuclear RNA-activating protein complex- 4) encodes the DNAbinding subunit of the snRNA-activating protein complex (SNAPc), which is required for transcription of RNA polymerases and splicing processes. Biallelic variants in SNAPC4 gene have been recently associated with a novel neurodevelopmental condition (NEDRSO, MIM 620515) featuring microcephaly, eye defects, abnormal movements, and brain atrophy. Here, we report a novel patient harboring recessive SNAPC4 variants presenting with a distinctive clinical phenotype of lower motor neuron disease. Methods: We collected clinical, electrophysiological, imaging, and genetic evaluation of a patient followed at the IRCCS Istituto Giannina Gaslini (Genoa, Italy) for long-standing progressive distal amyotrophy of lower limb due to axonal motor neuropathy. The diagnostic assessment included nerve conduction studies, brain and spine MRI, lower limb muscle MRI, and Whole Exome Sequencing (WES) to achieve a molecular diagnosis. Results: A 13-year-old patient was admitted to our clinical center for a diagnostic definition of gait disturbances. During infancy, he was noted to be clumsy by the parents, with a tendency to fall. At the age of 8 years, his parents noticed a slowly worsening of his walking skills requiring ambulatory support and since age 13, the use of a wheelchair for outdoor activities. Neurological examination showed wide-based gate, lower limb hyporeflexia, diffuse muscle weakness and reduced muscle mass in the lower limbs. The patient was able to walk only for few steps with unilateral support. Extended blood tests were normal except for high serum CK levels (700 U/L at rest, normal <170). Brain and spine MRI were normal. Nerve conduction studies showed axonal degeneration of motor fibers. Trio-exome sequencing identified biallelic variants in SNAPC4 in the proband: the maternal c.1436T>C, p.(Ile1479Thr) and the paternal c.1889_1899del, p.(Val630Glyfs*76) classified according to ACMG guidelines as of uncertain significance and likely pathogenetic respectively. In cultured patient’s fibroblasts using a commercially available anti-SNAPC4 antibody we observed a partially reduced protein expression in patient’s cells compared to healthy, age and sexmatched controls by western blotting. Conclusion: SNAPC4 variants have been previously detected in association with neurodevelopmental impairment, motor regression and progressive ascending spasticity. The features observed in our case, suggestive of a distal spinal muscular atrophy (dSMA) expand the phenotype of the emerging SNAPC4-related disorders and suggest SNAPC4 playing a possible role in motorneuron disease of children with or without intellectual impairment.

Dr. Jeffrey Allen 1 , Dr. Luis Querol 2 , Dr. Filip Eftimov 3 , Assoc. Prof. Stojan Peric 4 , Assoc. Prof. Tina Dysgaard 5 , Prof. Yusuf A. Rajabally 6 , Assoc. Prof. Thomas Harbo 7 , Prof. Eduardo Nobile-Orazio 8 , Assoc. Prof. Hans Katzberg 9 , Dr. David Cornblath 10 , Dr. Jon Katz 11 , Dr. James Sheffield 12 , Mr. Luke Hickey 12 , Dr. Bethany Beazley 12 , Dr. Nuria Carrillo 12 , Dr. Richard Lewis 13 1 University of Minnesota, Minneapolis, United States. 2 Hospital de la Santa Creu, Barcelona, Spain. 3 Amsterdam UMC, Amsterdam, Netherlands. 4 University of Belgrade, Belgrade, Serbia. 5 University of Copenhagen, Copenhagen, Denmark. 6 University of Aston, Birmingham, United Kingdom. 7 Aarhus University Hospital, Aarhus, Denmark. 8 Università degli Studi di Milano, Milan, Italy. 9 Institute of Medical Science, Toronto, Canada. 10 Johns Hopkins University School of Medicine, Baltimore, United States. 11 California Pacific Medical Center, San Francisco, United States. 12 Dianthus Therapeutics, New York, United States. 13 Cedars Sinai Medical Center, Los Angeles, United States Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder in which complement dysregulation contributes to pathogenesis. Claseprubart (DNTH103) is a potent monoclonal antibody that selectively binds to active C1s, inhibiting the classical complement pathway. CAPTIVATE Phase 3 study ( NCT06858579 ) evaluates claseprubart in a broad population of adults aged 18–75 with a diagnosis of CIDP. Methods: CAPTIVATE is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study assessing the efficacy and safety of claseprubart in adults aged 18–75 with a diagnosis of CIDP per 2021 EAN/PNS guidelines confirmed by an independent adjudication panel. Eligible participants are responders to standard-of-care (SOC) therapy (immunoglobulins [Ig] or oral corticosteroids [OCS]), refractory to SOC, or treatment-naïve. In SOC responders, Ig will be discontinued 1 week before dosing and OCS tapered and continued. Part A is open-label with an initial intravenous loading dose followed by biweekly subcutaneous claseprubart up to 13 weeks. Responders in Part A (≥1-point improvement in adjusted Inflammatory Neuropathy Cause and Treatment [INCAT]) are randomized (N=64/arm) into a placebo-controlled, double-blind period for 52 weeks (Part B). The primary endpoint is time to relapse in Part B with key secondary endpoints evaluating Inflammatory Rasch-built Overall Disability Scale (I-RODS) and grip strength changes. Those who complete or relapse (≥1-point worsening in adjusted INCAT) in Part B may enter an optional open-label extension (up to 104 weeks). Upon discontinuation, participants enter a 40-week safety follow-up. Results: CAPTIVATE was launched in 2025 and is actively enrolling participants in North and South America, Europe, and Asia. Conclusion: CAPTIVATE is an innovative, rigorous Phase 3 study evaluating claseprubart, an active C1s inhibitor administered as a convenient biweekly injection, in CIDP. The design prioritizes patient safety, avoids complete washout of SOC, minimizes exposure to ineffective therapy, and provides continued access as part of an optional open-label extension.

Miss Annabel Sen , Dr. Kevin Chesmore, Dr. Florian Barthelemy, Dr. Sophie Renegarajan, Assoc. Prof. Stanley Nelson, Assoc. Prof. Carrie Miceli UCLA, Los Angeles, United States Background: Skeletal muscle is a cellularly complex and plastic tissue that responds to local injury by recruiting and expanding immune cells, fibroblasts and other muscle resident cells to guide satellite cell-mediated repair of damaged multinucleated myofibers. In Duchenne muscular dystrophy (DMD), lack of dystrophin leads to chronic muscle damage, immune infiltration, dysregulation of repair, fibro-fatty replacement, and loss of muscle function. Our understanding of the cell and molecular mechanisms regulating dystrophy and repair remain incomplete, especially in humans. Cell-cell communication using single cell and single nucli sequencing can reveal how myofibers interact with surrounding immune cell-types leading to pathogenicity. These communication networks as well as analysis into downstream signaling targets can reveal novel insights into the mechanism of dystrophinopathies. Furthermore, the identification of unique cell populations that create autoimmune disruptions can be investigated for novel therapeutic interventions. Methods: Muscle biopsies from the Miceli and Nelson lab BioBank were submitted for single-cell and single-nucleus sequencing. Raw count matrices were filtered to remove low-quality cells or nuclei, doublets, and ambient RNA, then normalized and subjected to dimensionality reduction and graph-based clustering. Clusters were annotated using canonical markers to identify myogenic lineages, fibroblast, endothelial and smooth muscle cells, macrophages, T and B lymphocytes. To quantify intercellular communication, curated ligand–receptor databases and a probabilistic framework, such as NicheNet and OmniPath, were applied to cluster-averaged expression profiles. For each sender–receiver pair, ligand activity scores were computed, predicted target genes were inferred in receiver cells, and interactions were ranked based on expression, specificity, and concordance with downstream transcriptional programs. Differential expression analyses between DMD and control within each major cell type were used to identify disease-associated signaling. Gene set enrichment and pathway analyses highlighted inflammatory, fibrogenic, and regenerative pathways, while transcription factor activity and regulatory network modeling linked upstream ligands to downstream effectors in myogenic and immune populations. Results: Single-cell and single-nucleus profiling revealed a marked expansion of pro-inflammatory macrophages, cytotoxic and regulatory T cells, and fibroblasts in DMD compared with controls, consistent with chronic immune activation and fibro-fatty remodeling. Ligand–receptor analysis demonstrated an enrichment of inflammatory cytokine and chemokine interactions from macrophages and T cells to myofibers, satellite cells, and fibroblasts in DMD muscle. Fibroblasts in DMD displayed upregulation of distinct ligands and receptors, suggesting profibrotic signaling in the dystrophic niche. Dystrophic myonuclei exhibited transcriptional signatures of heightened stress, cytokine responsiveness, and impaired differentiation, including activation of pathways involved in apoptosis, interferon signaling, and aberrant regeneration. Downstream target gene analyses linked specific immune ligands to altered transcriptional programs in myogenic populations, revealing candidate axes through which the diseased niche perpetuates myofiber instability. Conclusion: Transcriptomic mapping of human dystrophic muscle reveals a profoundly remodeled inflammatory and fibrogenic niche in which specific ligand–receptor circuits between immune cells, fibroblasts, and myogenic populations drive chronic degeneration, impaired repair, and nominate discrete signaling axes and altered cell states as tractable therapeutic targets in Duchenne muscular dystrophy.

Assoc. Prof. Gulten Ozturk 1 , Assoc. Prof. Elif Acar Arslan 1 , Prof. Olcay Unver 1 , Dr. Bilgihan Bikmazer 1 , Dr. Hakki Akbeyaz 1 , Prof. Bilge Bilgen Geckinli 2 , Dr. Zeynep Yilmaz 1 , Dr. Kiymet Kecelioglu Binnetoglu 1 , Dr. Seyme Iyisenyurek 1 , Prof. Dilsad Turkdogan 1 1 Marmara University Department of Pediatric Neurology, Istanbul, Turkey. 2 Marmara University Department of Medical Genetics, Istanbul, Turkey Background: Limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous neuromuscular disorders characterized by progressive proximal weakness and marked clinical variability. Phenotypic overlap and variable age at onset often lead to delayed genetic confirmation. We aimed to describe the clinical features and diagnostic journey of genetically confirmed pediatric LGMD patients followed at our center Methods: Medical records of patients with LGMD were retrospectively reviewed. Only genetically confirmed cases were included. Results: Sixteen patients were included (9 female, 56%). The cohort’s average age was 13.4±5.5 years (median 12.5; range 6–23). Age at presentation was 50.3±41.6 months (median 60; range 0–132), and age at genetic diagnosis was 8.93±4.03 years (median 5.5; range 2.5–15). The diagnostic interval averaged 4.75±3.02 years (median 4; range 1–13). The most common initial finding was asymptomatic hyperCKemia, followed by hypotonia, neuromotor developmental delay, and progressive proximal weakness. Patients with normal creatine kinase (CK) levels experienced longer diagnostic delays. Muscle biopsy and electromyography supported myopathy but were not informative for specific genetic etiology. Pathogenic variants were identified in CAPN3 (n=3), SGCA (n=4), SGCB (n=2), ANO5 (n=2), POMT1 (n=1), HMGCR (n=1), TTN (n=2), and JAG2 (n=1) . A muscular dystrophy gene panel was most commonly used (68.7%), followed by whole-exome sequencing and single-gene testing. Prematurity-related complications and normal CK were major confounding factors contributing to diagnostic delay. Conclusion: Early recognition of LGMD in children with proximal weakness and/or hyperCKemia may reduce diagnostic delay and enable timely genetic testing.

Dr. Erica Frezza 1,2 , Dr. Marzia Nuccetelli 3 , Dr. Ilaria Petitta 1 , Dr. Mariangela Goglia 1 , Dr. Giulia Greco 1 , Dr. Francesco Gruosso 1,2 , Dr. Giovanni Vietri 1,2 , Dr. Laura Boffa 4 , Dr. Diego Centonze 4,2 , Dr. Roberto Massa 1,2 1 Unit of Neuromuscular Diseases, Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy. 2 IRCCS Neuromed, Pozzilli, Italy. 3 Department of Laboratory Medicine, Fondazione Policlinico Tor Vergata, Rome, Italy. 4 Neurology Unit, Fondazione Policlinico Tor Vergata, Rome, Italy Background: Myotonic dystrophy type 2 (DM2) is a multisystem disorder in which central nervous system involvement is increasingly recognized. However, the cognitive–behavioral profile of DM2 and its relationship with circulating biomarkers of neurodegeneration remain poorly defined. Notably, plasma phosphorylated tau (pTau-181) has not previously been investigated in DM2. Methods: Patients with genetically confirmed DM2 were consecutively recruited. All participants underwent a comprehensive clinical assessment including motor performance (6-Minute Walk Test [6MWT], quantitative muscle testing [QMT] sum score, Quick Motor Function Test [QMFT]), fatigue and sleep questionnaires, and cognitive and behavioral evaluation using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Plasma levels of neurofilament light chain (NfL), pTau-181 and GFAP were measured. Descriptive statistics, group comparisons, and correlation analyses corrected for multiple comparisons (false discovery rate, FDR) were performed. Results: Seventeen DM2 patients were included (58.8% females), with a mean age of 47.5 ± 19.3 years. Cognitive impairment was observed in 46.7% of patients, predominantly affecting language, memory, verbal fluency, and executive functions, while visuospatial abilities were relatively preserved. Behavioral changes were mild, with apathy being the most frequent feature (44%). No significant sex-related differences were detected across clinical, cognitive, or biomarker measures. Patients with pathological NfL levels (40%) showed significantly worse global and domain-specific cognitive performance, along with higher plasma pTau-181 and GFAP concentrations. FDR-corrected correlation analyses revealed strong associations between older age, reduced muscle strength, cognitive dysfunction, behavioral impairment, and increased NfL and pTau-181 levels. Conclusion: DM2 is characterized by a clinically relevant cognitive–behavioral involvement closely linked to age, muscle weakness, and biomarkers of neurodegeneration. Elevated NfL and pTau-181 levels were associated with cognitive impairment, supporting an early neurodegenerative component in DM2 and identifying plasma pTau-181 as a potential marker of central nervous system involvement in this disease.

Prof. Makito Hirano 1 , Dr. Makoto Samukawa 1 , Ms. Chiharu Isono 2 , Dr. Tomoyasu Matsubara 3 , Prof. Yuishin Izumi 4 , Dr. Yuko Saito 3 , Dr. Shigeo Murayama 3 , Prof. Yuji Higashimoto 5 , Assoc. Prof. Mamoru Nagano 6 , Prof. Laura P. W. Ranum 7 , Prof. Yoshitaka Nagai 1 1 Department of Neurology, Kindai University, Faculty of Medicine, Sakai, Japan. 2 Division of Rehabilitation Medicine, Kindai University Hospital, Sakai, Japan. 3 Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan. 4 Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan. 5 Department of Rehabilitation Medicine, Kindai University Faculty of Medicine, Sakai, Japan. 6 Department of Anatomy, Kindai University Faculty of Medicine, Sakai, Japan. 7 Center for Neurogenetics, Department of Molecular Genetics & Microbiology, College of Medicine, McKnight Brain Institute, Genetics Institute and Fixel Institute, University of Florida, Gainesville, United States Background: We previously identified non-coding CTA/CTG repeat expansions (>50 repeats) in the gene causative for spinocerebellar ataxia type 8 (SCA8) in ∼3% of Japanese patients with sporadic ALS. Seven patients with SCA8-related ALS so far accumulated in our cohort (N = 230). Three patients (43%) had bulbar-onset ALS, and two (29%) had cervical-onset ALS with acute bulbar palsy, while among non-SCA8-related ALS patients 20% presented with bulbar onset and 3% with cervical onset. This study was aimed to clarify swallowing functions in patients with SCA8-associated ALS and in an SCA8-transgenic mouse model with 121 CTA/CTG repeats. Methods: Videofluorography (VF) was used to evaluate swallowing functions in five of the seven patients. For the evaluation of swallowing functions in mice, a barium contrast agent identical to that used for humans was administered orally to one-year-old-mice, followed immediately by anesthesia and computed tomography analyses. We also conducted pathological analyses in one patient and in heterozygous and homozygous mouse models. Results: VF examination revealed oral and pharyngeal phase disorders in all patients, with severe aspiration confirmed in 2 of 5 patients. In mice, no aspiration was observed in wild-type, but aspiration was observed in significantly more mice (50%) among heterozygotes or homozygotes with severer tendency in homozygotes (p < 0.05, Kruskal-Wallis test and post-hoc analysis). Pathological analyses in an autopsied patient revealed the degeneration of the neurons in the hypoglossal nucleus with phosphorylated TDP43 accumulation in the remaining neurons. In homozygous mice, the number of motor neurons in the hypoglossal nucleus was reduced. Conclusion: We found that repeat expansions in the gene for SCA8 affected swallowing functions in humans as well as in mouse models. We propose that swallowing function may serve as a biomarker for SCA8-related ALS for future therapeutic interventions.

Dr. Fatemeh Rezania 1,2 , Mr. Murray Worner 1 , Dr. Lauren Ross 1,2 , Ms. Linda Seiderer 1 , Ms. Natasha Willems 1 , Assoc. Prof. Patrick Waters 3 , Mr. Jake Canning 3 , Dr. Ezgi Bakircioglu-Duman 3 , Assoc. Prof. David Szmulewicz 4,2 , Assoc. Prof. Leslie Roberts 1,2 1 St Vincent's Hospital, Melbourne, Australia. 2 The University of Melbourne, Melbourne, Australia. 3 University of Oxford, Oxford, United Kingdom. 4 The Royal Victorian Eye and Ear Hospital, Melbourne, Australia Background: The prevalence of myasthenia gravis (MG) is increasing, and delayed diagnosis is associated with substantial morbidity. Early ocular involvement is common, so we investigated whether optokinetic nystagmography (OKN) could improve diagnostic accuracy. Methods: We recruited 31 individuals from the Neurophysiology Department at St Vincent’s Hospital, Melbourne, presenting with ptosis and/or diplopia. Diagnostic assessment comprised single-fibre electromyography (SFEMG) of the orbicularis oculi, repetitive nerve stimulation (RNS) of the nerve to the nasalis muscle, ice-pack testing when ptosis was present, and serological testing using radioimmunoprecipitation assay (RIPA) and live cell-based assays (LCBA). Definite MG was identified in 12/31 participants based on positive serology and/or electrophysiology, while 4/31 were classified as probable MG based on a clear therapeutic response to acetylcholinesterase inhibitor therapy +/- corticosteroids despite negative serological and electrophysiological testing. The remaining 15 participants were determined to have alternative diagnoses. All participants underwent OKN testing using binocular videonystagmography (VNG), recording eye-movement velocities during a 60-second visual tracking task. Results: Of the 16 patients with MG, 9 (56%) were positive for acetylcholine receptor (AChR) antibodies using RIPA, while 10 (63%) were positive using LCBA. Combined RIPA and LCBA testing identified AChR antibodies in 11 of 16 MG patients (69%). SFEMG was abnormal in 57% (8/14) of patients with MG and normal in those without. Facial RNS was abnormal in 27% (4/15) of MG patients and none of those without. Notably, all individuals with abnormal neurophysiological findings were seropositive, except for one patient who was SFEMG-positive and seronegative. In participants with ptosis, ice-pack testing was positive in 40% (6/15) with MG compared with 9% (1/11) without. OKN yielded interpretable recordings in 12/16 with MG and 10/15 without; remaining recordings were uninterpretable due to excessive blinking, anatomical factors, severe ophthalmoplegia, or difficulty complying with the task requirements. OKN testing demonstrated significantly lower velocities and greater beat-to-beat variability in MG subjects ( P <0.05). Decrement in OKN response - calculated as the percentage change between maximum and minimum OKN velocities - was significantly greater in MG than in non-MG participants for both eyes ( P <0.001). ROC analysis showed 92% sensitivity and 89% specificity for the left eye at a 77.5% threshold and 100% sensitivity and 89% specificity for the right eye at a 72% threshold. Using the mean decrement of both eyes yielded 100% sensitivity and 90% specificity at a 76% cut-off (P < 0.0001). Subgroup analysis demonstrated similar thresholds for definite (75.8%) and probable MG (76.6%), with identical sensitivity (100%) and specificity (90%). Conclusion: In this small cohort, combining LCBA with RIPA improved sensitivity for AChR antibody detection from 56% to 69% in 16 patients with MG with ocular manifestations. OKN metrics demonstrated promising diagnostic performance, with 100% sensitivity and 90% specificity, although the interpretable recording rate was 71% due to participant-related factors. Single-fibre EMG showed lower sensitivity than expected, likely reflecting the small sample size. Overall, these results highlight the potential utility of OKN-based measures as a non-invasive adjunct in the evaluation and diagnosis of MG.

Dr. MEHAR SHARMA , Dr. Aishwarya Dhall, Dr. vaishali suri AIIMS, delhi, India Background: Congenital myopathies are rare muscle diseases, predominantly present at birth as generalised hypotonia, floppy infants and non-progressive muscle weakness. This is a heterogeneous group, and many gene variations are described. Methods: During a period of 11 years, 2997 muscle biopsies were received in our tertiary referral centre for various reasons. Various modalities like histochemistry, immunohistochemistry, ultrastructural examination and NGS was performed for diagnosis. Results: Based on ultrastructural examination 8 cases were diagnosed as nemaline myopathy comprising of less than 1% of all muscle diseases. Age ranged from 5months to 60 years ( mean age 19 years) and onset of symptoms is variable. NGS show variations in ACTA1 gene 1 case, Nebulin 2 cses, KLHL 1 in 1 patient, TTN in 2 cases, KBTBT in 1 case and KLHL 1 patient Conclusion: Morphological changes in Nemaline rod myopathy are consistently uniform but molecular variations are heterogenous. Predominantly present in early life but can present at any age. This molecular spectrum of nemaline rod myopathy is expanding.

Dr. Hyung Jun Park 1 , Dr. Yunjung Choi 2 , Dr. Young-Chul Choi 1 , Dr. Bum Chun Suh 3 , Dr. Sang Beom Kim 4 , Dr. Jeong Hee Cho 5 , Dr. Woo-Kyung Kim 6 , Dr. Yang-Ki Minn 7 1 Department of Neurology, Gangnam Severance Hospital, Younsei University College of Medicine, Seoul, Korea, Republic of. 2 Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea, Republic of. 3 Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of. 4 Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea, Republic of. 5 Department of Neurology, National Health Insurance Service Ilsan Hospital, Goyang, Korea, Republic of. 6 Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic of. 7 Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic of Background: Distal myopathies are a group of clinically and genetically heterogeneous myopathies characterized by progressive weakness and atrophy of the distal muscles, with 24 causative genes identified. Distal myopathy-3 (MPD3) was first described in a large Finnish pedigree in 2003, and its causative gene, HNRNPA1 , was later identified in 2021. Here, we describe two unrelated Korean families with autosomal dominant distal myopathy, in whom we identified a pathogenic exon 10 deletion in HNRNPA1 . Methods: We reviewed clinical characteristics, electromyography, laboratory findings, and muscle biopsy results of affected individuals from two unrelated families. PacBio Revio long-read sequencing and Sanger sequencing were used to detect a deletion in HNRNPA1. Results: In family MF1594, the proband, a 42-year-old man, developed hand muscle weakness at 13 years of age. Muscle weakness and atrophy were pronounced in the intrinsic hand and forearm muscles, but only mild ankle dorsiflexor weakness was observed without leg muscle atrophy. A muscle biopsy revealed no pathological abnormalities. The other affected family members exhibited similar clinical courses. They developed hand weakness in mid-adolescence followed by lower-limb involvement, including steppage gait in the third decade. Asymmetric involvement was consistently observed and mild neck weakness and dysphagia were noted. The course was indolent; one affected individual remained ambulatory with ankle–foot orthoses at 71 years, with largely preserved proximal strength. In family MF443, the proband, a 68-year-old woman, reported hand weakness beginning 8 years of age. The disease progressed extremely slowly; however, writing and fine motor skills became difficult after 40 years of age, and foot drop developed at 45 years. Affected relatives followed a similar trajectory; despite severe weakness, one individual retained limited ambulation into the mid-sixties. Dysarthria and dysphagia were absent. Muscle biopsies demonstrated myopathic changes, with rimmed vacuoles identified in one severely affected individual. Long-read sequencing of probands from two unrelated families identified a 317-base pair deletion in HNRNPA1 ( NM_031157.4 : c.1063+74_*4+40del; NP_112420.1 :p.Gly304Asnfs*4) spanning exon 10. Sanger sequencing identified breakpoint junctions and confirmed the co-segregation of the deletion with the affected members of families MF443 and MF1594. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), encoded by HNRNPA1 , is an RNA-binding protein involved in RNA metabolism and interacts with several proteins implicated in a spectrum of neuromuscular and neurodegenerative disorders. Two MPD3 phenotypes have been reported: a classic adult-onset autosomal dominant distal myopathy in Finnish families featuring distal hand weakness and gait disturbance with frequent stumbling and asymmetric involvement, and a rare childhood-onset form characterized by rapidly progressive, generalized myopathy. Our findings further support a genotype–phenotype correlation whereby exon 10 deletions are associated with a slowly progressive, hand-predominant distal phenotype. Conclusion: This is the first report of HNRNPA1 -associated distal myopathy in Korea. Our findings expand the known geographic and ethnic spectrum of HNRNPA1 -related myopathies, indicating that this disorder is not confined to the Finnish population but represents a globally distributed neuromuscular disease entity.

Ms. Jin Wang 1,2 , Dr. Stefanie Meyer 1 , Dr. Janek Gröhl 3 , Ms. Luca Eisenblätter 1 , Ms. Paula Schwabe 1 , Ms. Hannah Bruex 1 , Ms. Alica Stobbe 1 , Ms. Meret Dreyer 1 , Ms. Katharina Kief 1 , Prof. Mathias Bähr 1 , Dr. Stefanie Glaubitz 1 , Dr. Jana Zschüntzsch 1 1 University Medical Center Goettingen, Clinic for Neurology, Robert-Koch-Straße 40, 37075 Goettingen, Goettingen, Germany. 2 University Medical Center Goettingen, Heart & Brain Center Goettingen, Robert-Koch-Straße 42, 37075 Goettingen, Goettingen, Germany. 3 ENI-G, a Joint Initiative of the University Medical Center Göttingen and the Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany, Goettingen, Germany Background: Myotonic dystrophy type 2 (DM2) is a multisystem neuromuscular disorder characterized by progressive muscle involvement with substantial inter-individual heterogeneity. The emergence of targeted therapies highlights the urgent need for objective, non-invasive biomarkers to support disease monitoring and therapeutic evaluation. Multispectral optoacoustic tomography (MSOT) is a hybrid imaging modality combining laser excitation with ultrasound detection to visualize endogenous chromophores such as collagen, hemoglobin, and lipids, thereby enabling non-invasive quantitative assessment of muscle microstructure without the need for contrast agents. Methods: In this prospective, cross-sectional study, we enrolled eight genetically confirmed DM2 patients and six age- and sex-matched healthy volunteers (HV). Recruitment of additional healthy controls is ongoing. MSOT imaging of selected skeletal muscles was performed using the Acuity Echo system (iThera Medical GmbH, Munich, Germany). Imaging parameters related to tissue composition were extracted as candidate biomarkers. Clinical evaluation included standardized strength testing (Medical Research Council scale, handgrip dynamometry), functional performance measures (6-minute walk test (6MWT), timed up and go test (TUGT)), and patient-reported outcomes (ACTIVLIM, EQ-5D, SSQ). Analyses covering between-group comparisons and exploratory correlations between MSOT-derived metrics and clinical severity are ongoing. Results: The interim analyses includes eight DM2 patients and six HV. MSOT imaging was successfully completed and well tolerated in all participants. Participants were predominantly female in both cohorts, DM2=6/8 (75.0%) vs HV=5/6 (83.3%) with a mean age of 59.0±16.5 years in DM2 and 53.0±13.1 years in HV. In the preliminary results, BMI differed between groups, with an average BMI of 29.0±7.6 in DM2 compared to 26.1±4.1kg/m² in HV. DM2 patients showed impaired mobility compared to HV (6MWT: DM2= 438.5±116.7m, HV=548.3±71.3 m; TUGT: DM2=8.6±4.0s, HV=5.6±0.5s). Quantitative analysis of MSOT-derived parameters is ongoing, and detailed results will be presented at the meeting. Conclusion: This study represents the first application of MSOT imaging in DM2. MSOT offers a feasible, non-invasive method for assessing muscle involvement and may provide complementary insights to established clinical and functional outcome measures.

Dr. Eleftheria Kokkinou 1 , Assoc. Prof. Vasiliki Zouvelou 2 , Dr. Marina Katsalouli 1 , Dr. Elissavet Georgiadou 3 , Dr. Evangelia Lykopoulou 3 , Dr. Doxa-Eleni Sareidaki 1 , Dr. Iasonas-George Stamatakis 1 , Dr. Anna Moustafellou 1 , Dr. Sotiris Giouroukos 3 , Prof. Roser Pons 3 1 Department of Neurology, Children's Hospital “Agia Sofia”, Athens, Greece. 2 Medical School, National and Kapodistrain University of Athens, Eginition Hopsital, Athens, Greece. 3 First Department of Paediatrics, Medical School, National and Kapodistrian University of Athens, Children's Hospital “Agia Sofia”, Athens, Greece Background: Myasthenia Gravis (MG) associated with anti-muscle-specific kinase (MuSK) antibodies is a rare subtype of autoimmune MG, particularly uncommon in the paediatric population under 5 years of age. It is often characterized by predominant bulbar, respiratory, and facial muscle weakness and can be refractory to standard treatments. Rituximab, a B-cell depleting monoclonal antibody, has shown efficacy in adult MuSK-MG but its use in very young children is limited. This case highlights the successful use of rituximab in a toddler with severe anti-MuSK MG. Methods: Case Presentation Results: A previously healthy 2-year-old girl presented with ptosis, facial weakness, nasal speech, and feeding difficulties over two weeks. Examination revealed fatigable weakness of facial and bulbar muscles, generalized hypotonia, and minimal limb involvement. No respiratory distress was noted. Antibody testing confirmed the presence of anti-MuSK antibodies; acetylcholine receptor antibodies were negative. Initial management with pyridostigmine and corticosteroids yielded minimal improvement. Given the refractory nature and the persistence and severity of symptoms, rituximab was initiated. The patient showed significant clinical improvement within 3 weeks of starting rituximab, with resolution of ptosis and improved swallowing. Steroids were tapered over the following 3 months, and pyridostigmine was gradually discontinued. At 5-year follow-up, she remained in sustained clinical remission, was off all medications, and had regained appropriate weight and developmental milestones. Conclusion: This case illustrates that early recognition and targeted immunotherapy with rituximab can lead to excellent outcomes in paediatric anti-MuSK MG, even in very young children. Rituximab should be considered in refractory or severe MuSK-positive MG cases in children. Long-term follow-up is essential to monitor for relapse and manage potential immunosuppressive risks.

Ms. Anna Nalepa 1,2 , Ms. Kalina Hajok 1 , Ms. Małgorzata Myszka 1 , Ms. Ewa Jakubczak 1 , Ms. Urszula Waśniowska 1 , Dr. Olga Mucha 1 , Dr. Urszula Florczyk-Soluch 1 , Assoc. Prof. Józef Dulak 1 , Assoc. Prof. Agnieszka Łoboda 1 1 Jagiellonian University, Kraków, Poland. 2 Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland Background: Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by mutations in the DMD gene, leading to dystrophin deficiency and progressive skeletal and cardiac muscle damage. Hydrogen sulfide (H 2 S), once considered toxic, is now recognized as a cytoprotective gasotransmitter. We previously found altered expression of H 2 S-producing enzymes in dystrophic muscles, suggesting H 2 S deficiency may contribute to DMD pathogenesis 1 . Methods: Using two murine DMD models ( mdx and D2. mdx ), we tested H 2 S supplementation via  fast- (NaHS) and slow-releasing (GYY4137) donors, and genetic overexpression of the H 2 S-producing enzyme cystathionine γ-lyase (CTH). Results: NaHS altered the expression of DMD-related genes and proteins but did not improve muscle function 2 . In contrast, GYY4137 significantly enhanced exercise capacity and reduced muscle damage markers, such as lactate dehydrogenase (LDH), creatine kinase (CK), and osteopontin (OPN). Histological, gene, and protein analyses of the gastrocnemius muscle and diaphragm revealed decreased inflammation and fibrosis, along with reduced necrosis, improved muscle regeneration, and enhanced angiogenesis. The upregulation of phosphorylated AMPKα and cytoprotective and antioxidant heme oxygenase-1 (HO-1) and mitochondrial superoxide dismutase (SOD2), together with anti-apoptotic effects manifested by reduced caspase-3 levels and increased AKT phosphorylation, was evident after the treatment with a slow releaser of H 2 S. Overall, GYY4137 ameliorated DMD progression in the skeletal muscle 3 and exerted cardioprotective effects. CTH overexpression also modulated key DMD hallmarks. Conclusion: These results demonstrate that increasing H 2 S levels confers protection against DMD pathology and highlight the therapeutic potential of H 2 S-based strategies for slowing disease progression and developing mechanism-based interventions. Acknowledgements: This work was supported by grant #2019/35/B/NZ3/02817 (to AŁ) from the National Science Centre. References: 1. Mucha O.; Myszka M.; Podkalicka P.; Świderska B.; Malinowska A.; Dulak J.; Łoboda A.Proteome Profiling of the Dystrophic mdx Mice Diaphragm. Biomolecules,  2023,  13 , 1648. 2. Myszka M.; Mucha O.; Podkalicka P.; Waśniowska U.; Dulak J.; Łoboda A. Sodium hydrosulfide moderately alleviates the hallmark symptoms of Duchenne muscular dystrophy in mdx  mice. Eur J Pharmacol,  2023 , 955 , 175928. 3. Myszka M.; Jakubczak E.; Mucha O.; Hajok K.; Waśniowska U.; Nalepa A.; Dulak J.; Łoboda A. GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Attenuates Skeletal Muscle Abnormalities in a Murine Model of Duchenne Muscular Dystrophy.  Antioxid Redox Signal,   2025,  43 , 115-137

Mr. Lok Man WAN , Ms. Irene Heung Lan CHAN, Mr. Wai Kin CHING Occupational Therapy Department, North District Hospital, Hong Kong Background: Motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS), progressively impairs speech and motor function while typically preserving cognition. Demoralization and suicidal ideation rates significantly exceed those in advanced cancer, yet communication barriers severely restrict access to psychosocial interventions. These inequities limit holistic care, leading to loss of autonomy, social isolation, and diminished quality of life. Artificial Intelligence (AI) voice synthesis and immersive technology offer targeted solutions to restore naturalistic expression, meaningful engagement, and equitable support in advanced MND. The objective of this study was to apply AI voice synthesis and immersive technology to advance equity and autonomy in advanced MND. Drawing on occupational therapy's enabling occupation framework, the platform integrated patient-specific voice synthesis with eye-gaze-navigated immersive memory re-creation to enable independent exploration of cherished memories, preserve personal identity, facilitate authentic communication, and support precise expression of needs and emotions, ultimately enhancing quality of life and access to person-centered care. Methods: A single-case exploratory design followed a 58-year-old participant with advanced ALS (preserved cognition, anarthria, eye-gaze dependent) over 12 weeks in an occupational therapy-led intervention. The co-designed platform featured: (1) AI voice synthesis from the patient's preserved recordings to retain auditory identity and enable natural, emotive narration; (2) immersive, photo-realistic virtual re-creation of a treasured personal memory; and (3) real-time eye-tracking for autonomous navigation. Sessions progressed from calibration to self-directed exploration, reflective storytelling via synthesized voice, and creation of shareable family narratives. Data were collected through semi-structured interviews, usage logs, and the McGill Quality of Life Questionnaire (MQOL), analyzed thematically and descriptively for feasibility, expressive efficacy, autonomy restoration, and quality-of-life outcomes. Results: The participant independently navigated the immersive memory environment and utilized AI voice synthesis to narrate experiences, emotions, and preferences in a rich, context-embedded manner. This enabled multimodal, naturalistic expression of needs and healthcare priorities. MQOL scores improved notably in existential wellbeing (+32%) and perceived support (+36%). Thematic analysis highlighted restored autonomy through self-guided immersion, reinforced self-identity via personal historical reconnection, and greater confidence in articulating needs. No adverse cognitive or emotional effects occurred. Family members reported enhanced insight and relational closeness through shared synthesized content. Conclusion: AI voice synthesis combined with immersive technology offers a feasible, low-burden approach to advancing equity and autonomy in motor neuron disease. By preserving identity, enabling independent engagement with meaningful memories, and supporting natural tone and pronunciation in expressing needs and emotions, it reduces frustration and embarrassment from slurred speech, mitigates social isolation, promotes equitable access to tailored psychosocial care, and markedly improves quality of life despite severe physical disability. Guided by occupational therapy principles, this patient-centered innovation shows strong potential as a transformative model for progressive neurological conditions and merits larger-scale evaluation for broader implementation.

Dr. Otto Jesus Hernandez Fustes 1 , Miss Nathalia Faria 1 , Miss Bruna Maçaneiro 1 , Dr. Claudia Suemi Kamoi Kay 1 , Dr. Renata Dal-Pra Ducci Cirino 1 , Dr. Paulo Jose Lorenzoni 1 , Dr. Paula Raquel do V.P. Rodrigues 1 , Dr. Luiza Fraga 1 , Dr. Rosana Herminia Scola 1 , Dr. Paula Silvia Rosignoli 2 1 Universidade Federal do Paraná, Curitiba, Brazil. 2 Secretaria da Saúde do Paraná, Curitiba, Brazil Background Introduction: Amyotrophic Lateral Sclerosis (ALS) is a chronic, degenerative, and progressive disease that primarily affects upper and lower motor neurons. It has an unknown, multifactorial etiology and an invariably fatal outcome. Epidemiological studies have reported a prevalence ranging from 0.8 to 10.32 cases per 100,000 people. This variability can be explained by methodological differences, changes in diagnostic criteria over time, and the lack of adequate disease notification systems in several countries, such as Brazil. Incidence studies, which show less variability because they can only be conducted under optimal conditions of disease documentation, report rates between 1.5 and 2.5 cases per 100,000 people per year. However, most epidemiological studies have been conducted in North America and Europe. Therefore, it is essential to seek data from other regions of the world to better understand the distribution and potential determinants of the disease. The objective of this study was to determine the incidence and prevalence of individuals with amyotrophic lateral sclerosis in the population of Curitiba from 2019 to 2024. Methods: This study employed a cross-sectional cohort design. Demographic data, including sex and age, were obtained from the State Health Department for patients with ALS receiving treatment in the municipality of Curitiba. The public health system provides treatment with riluzole, prescribed by neurologists, to all patients diagnosed with ALS. Results: Curitiba is the capital of the state of Paraná, located in southern Brazil, with an area of 435.036 km². It is situated at 25°25′40″ south latitude and 49°16′23″ west longitude, with a north–south extension of 35 km and an east–west extension of 20 km. According to 2022 data from the Brazilian Institute of Geography and Statistics (IBGE), the city has a population of 1,773,718 inhabitants. During the study period (2019–2024), 159 patients receiving riluzole treatment were identified. The estimated prevalence ranged from 2.46 to 3.80 cases per 100,000 inhabitants, showing an upward trend over time, with a peak observed in 2024 (68 active cases). Annual incidence ranged from 0.06 to 0.22 new cases per 10,000 inhabitants. A male predominance was observed, accounting for 59.7% of the sample (95 patients), with an approximate male-to-female ratio of 1.5:1. The mean age at treatment initiation was 63.4 years, ranging annually from 60.8 to 65.4 years, and was slightly higher in males than in females. Conclusion: Data from Curitiba corroborate global epidemiological patterns, demonstrating incidence and prevalence rates consistent with the literature. Male predominance and the affected age range reinforce the classic disease profile. The observed increase in prevalence rates in recent years suggests possible improvements in diagnosis, increased patient survival, or greater access to pharmacological treatment provided by the public health system. These findings highlight the importance of continuous registry systems for planning healthcare actions aimed at rare neurodegenerative diseases.

Prof. Corrado Angelini 1 , Prof. Giovanna Cenacchi 2 , Dr. Paola Tonin 3 , Dr. Alicia Rodriguez 4 , Asst. Prof. Gaetano Vattemi 3 1 University of Padova, Padova, Italy. 2 University of Bologna, Bologna, Italy. 3 Hospital of Verona, Verona, Italy. 4 University of Deusto, Bilbao, Spain Background: LGMD subtypes are highly variable in terms of age of onset, speed of disease progression, and overall severity; at a histopathological level, their common feature is progressive muscle degeneration with connective tissue substitution, CK is elevated and degenerative changes are found in muscle (biopsy,MRI) although they do not share a common pathological mechanism .The incidence for all forms is 1:100,000 and LGMD are divided into two major subgroups: autosomal dominant forms (LGMD type D) and autosomal recessive (LGMD type R).We report here a novel Slovakian patient with all these clinical features and entertain anhypthesis regarding the “locking “ symptoms that LGMD1F/D2 patients experience. Methods: An open quadriceps muscle biopsy was done and histochemistry and electron microscopy analized. Needle EMG in muscles m. vastus lateralis l.dx., m. rectus femoris .sin., m. deltoideus .sin. shows findings of a chronic neurogenic lesion. m. biceps brachii l.dx. with a normal finding. MEP examionation In the upper and lower limbs, with bilateral cortical stimulation, total and central latencies are normal, findings are bilaterally symmetrical – so far, no convincing signs of conduction disorder in the corticospinal tract to the lower limbs. WHOLE BODY MRI: The upper limbs and legs remained outside the measured volume. Muscle structures appear to be adequately symmetrically configured, without focal atrophies, without apparent focal signal intensity changes in terms of edema or fatty transformation. Subcutaneous adipose tissue is also adequately configured, symmetrical, and without focal changes. Results: A male patient, 31 years old, living in Slovakia, was found to be affected by a sporadic form of LGMD-TNPO3 related: a pathogenic stop codon variant c.2686 in a heterozygous state in the TNPO3 gene and a c23335 heterozygous mutation in the gene WASHC5 associated to spastic paraplegia type 8. Clinically, he developed in the third decade a weakness compatible with LGMD syndrome; he had a Gowers’ sign and difficulty walking. A detailed genetic analysis of the family showed that his parents did not carry the mutation and appeared healthy. An important clinical feature was that the patient had been frequently suffering since as a child had a lot of infections, and such an unfortunate feature persisted in adulthood. He often had sinusitis, a sore throat, and frequent headaches. His immune system is weak, but specific immune tests showed no specific disorders. He was also affected by Lyme disease and had to be treated for two years with antibiotics to eradicate the Borrelia. This treatment resulted in several gastrointestinal symptoms: for 8 years, he had daily diarrhea and/or constipation. Muscle biopsy showed COX-negative fibers on electron micoscopy abnormal nuclei (figure), fragmented cristae in mitochondria, and signs of autophagy. Conclusion: The combination of biopsy and clinical data supports the hypothesis that LGMD-D2 is caused by several possible mechanisms likely involving nuclear transport and myofibrillar network; the interplay with infection appears to be because TNPO3 directly participates in nuclear import and infection of HIV-1.

Ms. Aurélie Hazotte 1 , Ms. Linda Baptista 1 , Mr. Stéphane Boyer 1 , Dr. Rabye Ouaja 2 1 LFB Biotechnologies, Les Ulis, France. 2 LFB Biomédicaments, Les Ulis, France Background: Quality by Design (QbD) is a systematic approach for incorporating quality into pharmaceutical products. This analysis examines the link between the application of QbD and the long-term purity profile of IQYMUNE®, a plasma-derived intravenous immunoglobulin (IVIg). Methods: The development of IQYMUNE® was reviewed in accordance with a defined QbD process. This included defining a target product quality profile, identifying critical quality attributes such as purity and key impurities, and conducting risk assessments. Subsequent manufacturing data relating to the purity profile of IQYMUNE® were evaluated over the last decade (2016-2025). Results: Purity was a primary driver of the QTPP. The QbD process designed and optimized multiple manufacturing steps (e.g., caprylic acid fractionation, chromatography) specifically to achieve high purity by removing impurities. The control strategy, derived from QbD outputs, combined process controls at critical steps with end-product testing. Over a decade after IQYMUNE® launch, analysis of 387 batches shows a mean purity of 99.01% (SD=0.42), with a 95% confidence interval between 98.70% and 99.33%, demonstrating exceptional process stability and output consistency (Figure 1). The high level of purity of IQYMUNE®, sustained over the years after obtaining its initial marketing authorization, is a direct consequence of its QbD foundation. The systematic, science-based approach ensured deep process understanding, established a robust control strategy, and maintained product quality over its lifecycle. This case underscores QbD's value in achieving predictable, long-term quality for complex therapeutics. Conclusion: The sustained, exceptional purity of IQYMUNE® over time is a direct result of its foundational Quality by Design development. This demonstrates that a systematic QbD approach successfully builds and maintains high, consistent product quality throughout a product's lifecycle.

Prof. Jong Seok Bae Kangdong Sacred Heart Hospital, Seoul, Korea, Republic of Background: Diabetic polyneuropathy (DPN) affects over 50% of diabetic individuals worldwide and represents a major microvascular complication. Early detection and risk stratification are critical, yet conventional risk factors alone do not fully explain DPN development. This systematic review synthesizes evidence on emerging biomarkers that enhance DPN risk prediction and early detection. This study systematically reviews biomarkers associated with DPN risk prediction and early detection, categorized by pathophysiological mechanisms. Methods: A comprehensive search of MEDLINE and Embase (2009–2024) using terms related to diabetic neuropathy, biomarkers, glycemic variability, insulin resistance, dyslipidemia, and systemic inflammation identified studies examining associations between novel biomarkers and DPN development. Studies were stratified by biomarker category: (1) glycemic variability, (2) insulin resistance indices, (3) lipid variability, and (4) systemic inflammatory markers. Risk of bias was assessed using the Newcastle-Ottawa Scale. Results: Twenty-eight studies met inclusion criteria. Four major biomarker categories emerged: (1) Glycemic Variability—Coefficient of variation in fasting plasma glucose (CV-FPG) and HbA1c variability (CV-HbA1c) independently predicted DPN (HbA1c cutoff 15.15%, sensitivity 66.7%, specificity 65.7%); hemoglobin glycation index (HGI) showed no association; (2) Insulin Resistance—Estimated glucose disposal rate (eGDR) showed promise, while direct DPN outcome data for the triglyceride-glucose (TyG) index remain limited; (3) Lipid Variability—Visit-to-visit variability in HDL cholesterol, triglycerides, and remnant cholesterol associated with increased DPN risk; (4) Systemic Inflammation—Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) demonstrated independent DPN associations. Conclusion: Multiple pathophysiologically distinct biomarker categories improve DPN risk prediction beyond conventional parameters. Integration of these indices may enhance clinical risk stratification. Future prospective studies with standardized DPN diagnostic criteria across diverse populations are needed for clinical implementation.

Prof. Marco Sandri University of Padova, Padua, Italy Background: Maintaining the integrity of organelles and proteins despite the cellular stresses that arise from environmental pressure is essential for life. The time-dependent accumulation of cellular damage is widely considered to be the general cause of cellular degeneration and disease onset. Alteration of the protein quality control, called the loss of proteostasis, contributes to impairment of macromolecule and organelle function and is considered among the primary hallmark of aging, morbidity and mortality. Postmitotic tissues such as brain and striated muscles are particularly vulnerable to changes of proteostasis. Methods: By using genetic approaches for gain and loss of function experiments as well as transgenic mice we have shown that the regulation of protein and organelles turnover is under the control of transcription factors belonging to different signalling pathways. Moreover, to identify novel players in ageing sarcopenia we screened transcriptomic data sets and identified a novel autophagy regulator gene that is required for a healthy ageing. Results: Our findings showed that the the shape of mitochondrial network and impaired proteostasis in muscles regulates signalling pathways that not only promote sarcopenia but also a secretory pattern to induce sterile systemic inflammation, tissue senescence and organism premature ageing. These alterations in bioenergetics and proteostasis are linked to life styles and I will describe why physical activity and exercise are beneficial for human health, while sedentary life and inactivity are one of the major detrimental behaviours of industrialized societies that contribute to mortality and morbidity Conclusion: We have started to dissect the molecular insights that promote sarcopenia. These results enable us to identify blood biomarkers that predict the risk of sarcopenia onset and unhealthy ageing

Dr. Mélanie Flaender, Dr. Louise Griveau , Ms. Marine Foray, Ms. Eve Duchemin-Pelletier, Ms. Caroline Roelants, Dr. Bianca Freytag, Dr. Erwann Ventre, Dr. Joanne Young CYTOO SA, Grenoble, France Background: Muscle wasting is associated with genetic, metabolic, and chronic disorders, including muscular dystrophy, sarcopenia, type 2 diabetes, cancer cachexia, and chronic kidney disease. Loss of muscle mass and function is also an emerging concern with the growing use of GLP-1R agonists for obesity treatment. One strategy to counter muscle loss is bimagrumab, an injectable anti-catabolic monoclonal antibody that blocks myostatin/activin type II receptors (ACTRIIA and B), key negative regulators of skeletal muscle growth. Bimagrumab has shown clinical efficacy by increasing muscle mass across diverse populations, including patients with sporadic inclusion body myositis, sarcopenia, and during weight loss. Identification of an oral small-molecule inhibitor targeting this clinically validated pathway would therefore represent a therapeutic advance, enabling simpler and more scalable manufacturing. Methods: Experiments were conducted using the in vitro MyoScreen drug discovery platform. This human skeletal muscle system combines highly reproducible, micropatterned primary myotubes (healthy and disease-derived) in 96- or 384-well formats with high-content imaging and quantitative multiparametric readouts. The platform is specifically designed to assess clinically relevant endpoints with low variability and high sensitivity, including myotube differentiation and fusion index, myotube size, atrophy rescue, contractility, acetylcholine receptor clustering, calcium flux, glucose uptake, protein synthesis, autophagy accumulation and mitochondrial dysfunction. Target identification and validation were performed using a siRNA-mediated knockdown strategy within a myostatin-induced muscle wasting model implemented on MyoScreen. Candidate intracellular effectors were selected based on their ability to rescue muscle size and impaired differentiation following knockdown. Small molecule inhibitors of the myostatin/activin signaling axis were screened across healthy and multiple atrophy-induced muscle models Results: Most current therapies targeting the activin/myostatin pathway are biologics directed against soluble ligands or extracellular receptor domains. We instead prioritized small-molecule inhibitors acting against intracellular components of the signaling cascade, given the potential for improved specificity and reduced off-target effects. Target validation identified ALK5/TGFβR1 as a strong downstream mediator of myostatin-induced muscle wasting with knockdown significantly increasing fusion index and myotube size. A panel of ten literature-reported ALK5/TGFβR1 inhibitors was subsequently evaluated for hypertrophic-inducing activity in healthy human myotubes. One compound displayed superior potency and selectivity, robustly promoting hypertrophy with no detectable cytotoxicity. This ALK5/TGFβR1 antagonist preserved muscle size and differentiation in other MyoScreen atrophy myotube models (TGFb, TNFa, dexamethasone-induced), and was more effective than the clinical benchmark reference, bimagrumab. Further characterization revealed other positive effects such as increased myotube contractility and maturation, augmented acetylcholine receptor clustering, elevated calcium flux, and upregulation of the late myogenic marker, myosin heavy chain. These structural and functional improvements were accompanied by increased basal and insulin-stimulated glucose uptake. Conclusion: Collectively, the data indicates that selective ALK5/TGFβR1 inhibition drives skeletal muscle hypertrophy and a transition toward a more mature and metabolically active phenotype, highlighting ALK5/TGFβR1 as a potential intracellular target for muscle-preserving therapies. These findings also establish MyoScreen as a clinically translatable human muscle platform that robustly models disease-relevant muscle states and recapitulates myofiber rescue by established standards such as bimagrumab. Importantly, this platform approach enables efficient discovery and in-depth characterization of next-generation drug candidates aimed at preserving muscle health.

Dr. Elena Rossini 1 , Dr. Laura Tufano 1 , Dr. Valentina Vera 1 , Dr. Antonio Lauletta 2 , Dr. Stefania Morino 3 , Dr. Luca Leonardi 3 , Assoc. Prof. Matteo Garibaldi 3 , Assoc. Prof. Giovanni Antonini 2 , Dr. Laura Fionda 3 1 Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), SAPIENZA University of Rome, Rome, Italy, Rome, Italy. 2 NESMOS Department, Sapienza University of Rome and UniCamillus-St. Camillus International University of Health Science, Rome, Italy., Rome, Italy. 3 Neuromuscular Disease Center, Sant'andrea Hospital, Rome, Italy., Rome, Italy Background: Complement inhibitors increase susceptibility to infections by capsular-bearing bacteria, particularly Neisseria meningitidis , requiring mandatory vaccination. Non-capsulated Neisseria species are typically commensals of the upper respiratory and urogenital tracts and lack certain virulence factors, which limits the occurrence of invasive disease in humans. Nevertheless, a range of infections attributed to these organisms—including endocarditis, meningitis, pneumonia, peritonitis, and septic arthritis—have been reported in both immunocompromised and otherwise healthy Methods: We describe the clinical presentation, management, and outcome of a patient with acetylcholine receptor positive (AchR+) thymoma-associated generalized myasthenia gravis (gMG), who developed Neisseria mucosa sepsis while receiving ravulizumab therapy. Additionally, a systematic literature review was conducted to identify published cases of invasive infections caused by uncommon Neisseria species in patients treated with complement inhibitors. Extracted data included underlying disease, immunocompromised status, infecting Neisseria species, clinical severity, treatment, outcomes, and reported vaccination or prophylactic strategies when available. Results: The 25-year-old patient was receiving ravulizumab infusions every 8 weeks, azathioprine 150 mg daily, and prednisone 15 mg daily. She was fully vaccinated for Neisseria meningitidis serogroup B and ACYW135, with booster doses administered over time. She was hospitalized for an acute febrile illness with neutropenia, rapidly progressing to septic shock requiring vasoactive support. Blood cultures were positive for Neisseria mucosa . Her last ravulizumab infusion had been administered 7 weeks earlier. Azathioprine therapy was discontinued. She was successfully treated with intravenous ceftriaxone, with complete resolution of symptoms after 10 days of therapy. A systematic literature review identified 10 additional cases of invasive infections caused by uncommon Neisseria species, including N. sicca (3), N. mucosa/subflava (2), N. cinerea (2), N. mucosa (2), and N. subflava (1), in patients receiving complement inhibitors. Underlying conditions included MG (2), atypical hemolytic uremic syndrome (aHUS; 1), hemolytic uremic syndrome (HUS; 3), classic paroxysmal nocturnal hemoglobinuria (PNH; 2), PNH with aplastic anemia (1), and catastrophic antiphospholipid antibody syndrome (CAPS; 1). Six patients were variably immunocompromised. Five cases progressed to sepsis and one to septic shock. All patients recovered with prompt antibiotic therapy and no reported sequelae however, comprehensive data on vaccination schedule and eventual prophylactic therapy were unavailable for most of the patients Conclusion: These cases highlight that patients treated with complement inhibitors may remain at risk for invasive infections caused by unusual and non-capsulated Neisseria species, despite anti-meningococcal vaccination. Continuous monitoring of the epidemiology of Neisseria infections, including the collection of international registry data, is needed to better understand their prevalence and the factors that may predispose to their occurrence.

Dr. João Guilherme de Toledo Justo 1 , Dr. Eduardo Hummelgen 1 , Miss Lara Godoy 2 , Prof. Sara Giampá 3 , Prof. Otto Hernandez Fustes 2,4 1 Hospital do Rocio, Campo Largo, Brazil. 2 Universidade Federal do Paraná, Curitiba, Brazil. 3 Biologix Institute, São Paulo, Brazil. 4 Hospital de Reabilitação, Curitiba, Brazil Background Introduction: Neuromuscular diseases (NMDs) comprise a group of disorders that topographically affect the spinal cord, nerve roots, plexuses, peripheral nerves, the neuromuscular junction, and muscles. Respiratory system involvement in these diseases may lead to acute and/or chronic respiratory failure related to weakness of the respiratory musculature. Chronic restrictive respiratory failure is the most common ventilatory disorder in chronic neuromuscular diseases, characterized by pulmonary hypoventilation, with nocturnal hypoventilation being the earliest clinical manifestation. Nocturnal oximetry is a simple method for screening and diagnosing nocturnal hypoventilation and has proven to be more comfortable, inexpensive, and accessible, as it objectively measures intermittent hypoxia. Objectives: To analyze and compare features detectable by nocturnal oximetry in patients with NMDs. Methods: Ambulatory nocturnal oximetry was performed using a wireless oximeter (Oxistart, Biologix Sistemas Ltd., Brazil) with an embedded accelerometer, placed on the second digit. The Oxistart firmware acquires 100 samples per second, generating beat-to-beat raw SpO₂ data with a resolution of 0.1%. A moving time average of four cardiac beats was applied. Data obtained by Oxistart are transferred via a smartphone application to the cloud, where they are automatically analyzed using a proprietary algorithm. The following variables were analyzed: age, oxygen desaturation index (ODI), number of desaturations, time spent at specific oxygen saturation levels, and sleep apnea. The study was approved by the Ethics Committee of the Workers’ Hospital Complex (approval number: 7,501,240). Patients received detailed explanations regarding the study and the examination protocol and subsequently signed an informed consent form. Results: Twenty-two consecutive patients with confirmed diagnoses were evaluated and divided into two groups: one with polyneuropathies and another with other NMDs, with 11 patients in each group, predominantly male (54.55%). The mean ODI was higher in the polyneuropathy group (25.1) compared with the other NMD group (18.9), as was the number of desaturations (144.5 vs. 122.8). Regarding sleep apnea classification, the proportion of patients classified as severe was identical in both groups (18.18%). In the polyneuropathy group, a higher number of patients were classified as normal (4 patients; 36.36%). Conclusion: Nocturnal oximetry showed abnormalities in 72.7% of the patients studied. There were no statistically significant differences in the analyzed variables between the two groups. These preliminary results support the continuation of this study to determine the value of nocturnal oximetry in NMDs as a tool for the early detection of hypoxemia.

Mr. Matthias Schelfhout 1 , Mr. Jayant A. Soekhradj 2,3 , Dr. Hermien E. Kan 2,3 , Dr. Erik H. Niks 3,4 , Dr. Liesbeth De Waele 1,5 , Dr. Sam Geuens 1,5 , Dr. Rosanne Govaarts 2,3 1 Department of Development and Regeneration, KU Leuven, Leuven, Belgium. 2 C.J. Gorter MRI Center, Radiology, Leiden University Medical Center, Leiden, Netherlands. 3 Duchenne Center Netherlands, Leiden, Netherlands. 4 Department of Neurology, Leiden University Medical Center, Leiden, Netherlands. 5 Child Neurology, University Hospitals Leuven, Leuven, Belgium Background: Duchenne (DMD) and Becker (BMD) muscular dystrophy are muscle wasting diseases caused by a mutation on the X-chromosome leading to absent or reduced dystrophin production. Currently, there is no cure for DMD and BMD. Symptomatic treatment consists of corticosteroids, ventilation and multidisciplinary care management. Dystrophin is well characterized in muscle tissue, but its involvement in the brain remains unclear. Imaging studies have mainly shown smaller gray matter volumes and less structured white matter in DMD patients compared to healthy controls. These brain alterations likely result from dystrophin deficiency and/or corticosteroid treatment. As no overview currently exists of this rapidly evolving field, a comprehensive and preregistered systematic review was conducted to highlight current knowledge and guide future research. Methods: The systematic review was conducted following PICO criteria, which were applied within PUBMED, EMBASE, and Web of Science. After deduplication, studies underwent title-abstract and full text screening, supported by Rayyan, an AI-powered tool. Eligibility of studies at these stages was determined using the PICO criteria. Next, a backwards reference check was performed on the remaining articles to identify additional eligible studies not captured in the initial search. Finally, data extraction and a quality check (using the JBI critical appraisal tool for cross-sectional studies) of the included papers was conducted. The screenings, data extraction and quality check were conducted by two independent reviewers to ensure reliability, disagreements were resolved through discussion or consultation of a third independent reviewer. Results: This process resulted in 36 included papers, with the reference check indicating no missed papers. The results show an increase in neuroimaging publications from 1977 to 2025 in the DMD and BMD population, especially in exploratory structural research. Most recent publications (<5 years) are of high quality, associates with other clinical measures and considers possible confounding factors like age, mutation and corticosteroid treatment. Despite this, some recent publications still lack the inclusion of these confounding factors. Further interpretation of the results is currently in progress and will be available for ICNMD 2026. Conclusion: This systematic review highlights the growing interest for neuroimaging research in DMD and BMD. Exploratory structural research has provided valuable insights in understanding brain alterations of patients with DMD and BMD compared to healthy controls. Future work should try to address more specific, hypothesis-driven questions in associating neuroimaging findings to clinical symptoms, for example behavioral problems, language and cognitive impairments.

Dr. Hyunjin Kim 1 , Mr. Ben Thompson 2 , Mr. Jinhyeong Kim 3 , Prof. Jung-Joon Sung 4 , Prof. Eleanora Aronica 5 , Prof. Junho Kim 3 , Prof. Jeong Ho Lee 6 1 Asan Medical Cener, Seoul, Korea, Republic of . 2 University College London, London, United Kingdom . 3 Sungkyunkwan University, Suwon, Korea, Republic of . 4 Seoul National University Hospital, Seoul, Korea, Republic of . 5 Amsterdam UMC, Amsterdam, Netherlands . 6 Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of Background: Amyotrophic lateral sclerosis (ALS) is a clinically and molecularly heterogeneous neurodegenerative disease, with most sporadic cases lacking an identified cause. While familial ALS is linked to germline mutations, the contribution of somatic mutations arising during neurodevelopment remains poorly understood in the onset of sporadic ALS. We aimed to investigate whether somatic mutations arising during brain development contribute to sporadic ALS, and to define their molecular characteristics and potential pathogenic role. Methods: We performed whole-genome sequencing (∼60× coverage) on approximately 1,000 primary motor cortex neurons per brain from 27 sporadic ALS cases and 8 neurotypical controls. Neurons were isolated using laser capture microdissection to ensure cell-type specificity. Matched neuronal and peripheral tissue (liver) whole-genome sequencing data were compared to identify somatic variants. Variant calling was performed using Mutect2, Strelka, and MosaicForecast, and only single-nucleotide variants detected by at least two of these callers were included in the final callset. Mutational signatures and variant allele fractions were analyzed to infer timing and mechanisms of mutation accumulation. Results: We observed a significantly increased burden of somatic single-nucleotide variants (sSNVs) in a subset of ALS cases corresponding to the ‘ALS-Oxidative stress’ molecular subtype identified in previous transcriptomic studies. Gene set enrichment analysis demonstrated that these mutations were enriched in genes involved in neurogenesis. Mutational signature analysis revealed enrichment of COSMIC SBS36-like (oxidative damage) and SBS44-like (defective mismatch repair) signatures in high-burden ALS neurons, while absent in controls and bulk motor cortex. Genes harboring these mutations were preferentially expressed during fetal neurodevelopment, suggesting a developmental window of vulnerability to oxidative stress–associated DNA damage. Conclusion: Our findings support a model in which early neurodevelopmental oxidative stress promotes focal vulnerability in motor neurons, as reflected by associated clonal somatic mutations. This work highlights the importance of somatic mosaicism and developmental origins in ALS pathogenesis and suggests that targeting oxidative stress pathways during critical developmental periods may hold potential for prevention or early intervention in susceptible individuals.

Dr. Umberto Manera ALS Centre, 'Rita Levi Montalcini', Department of Neuroscience, University of Turin, Turin, Italy Background: Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MND) are characterized by rapid progression and multidimensional burden affecting motor, respiratory, cognitive, and psychosocial domains. Traditional endpoints such as survival and clinician-administered scales (e.g., ALSFRS-R) only partially capture the patient experience. Patient-reported outcomes (PROs) and PROMs provide a complementary, patient-centered perspective, capturing quality of life, symptoms, and daily functioning. The rise of digital medicine and decentralized clinical trials (DCTs) enables remote, frequent, and real-world PRO collection, particularly relevant for patients with limited mobility. However, challenges remain in validation, integration with objective biomarkers, and ensuring reliability and adherence. Methods: We discussed in a structured review of PROMs used in ALS, including ALSFRS-R (patient-reported versions), ROADS, ALSAQ-40, and EQ-5D, focusing on psychometric properties and suitability for remote use. Evidence from observational cohorts and clinical trials incorporating PROs was analyzed, comparing remote versus in-clinic data collection. We evaluated digital platforms (apps, web portals, telemedicine) for usability, adherence, and data quality, and reviewed the integration of PROs within decentralized and hybrid trial designs. Correlations between PROs and clinical outcomes (e.g., progression, respiratory function, survival) were assessed, along with strategies to address missing data and reporting bias. Insights from real-world clinical practice in ALS digital monitoring were also included. Results: PROs capture key aspects of disease burden often missed by clinician-based measures, including fatigue, emotional well-being, and social impact. Patient-reported functional scales show strong correlation with clinician-administered assessments, supporting their reliability. Frequent digital PRO collection improves resolution of disease trajectories and patient stratification. In DCTs, PROs enable remote endpoint collection, increasing accessibility and inclusivity while reducing patient burden. Adherence is generally good but declines in advanced disease, requiring caregiver support and adaptive tools. Limitations include variability in reporting, missing data, and digital access disparities. Integration with objective biomarkers enhances interpretability. Regulatory acceptance of PRO-based endpoints is growing but still evolving. Conclusion: PROs are central to a more patient-centered approach in ALS and MND research and care. Combined with digital medicine, they enable continuous, real-world monitoring and support decentralized trial models, improving inclusion and engagement. Their integration with multimodal data (wearables, biomarkers) can enhance disease modeling and personalized care. Future priorities include validation of digital PROMs, standardization, and improved accessibility across disease stages. Collaboration among stakeholders will be essential to establish PROs as robust endpoints in clinical trials. Overall, PROs bridge the gap between clinical measures and lived experience, offering a critical tool to advance research and improve outcomes in ALS.

Dr. Shahar Shelly 1 , Dr. Marianna Lalla 2 , Dr. Yang Zhao 2 , Dr. Linda Rehaume 2 , Dr. Jennifer Cross 2 , Dr. Tuan Vu 3 1 Rambam Medical Center, Haifa, Israel. 2 Dianthus Therapeutics, New York, United States. 3 University of South Florida, Tampa, United States Background: In generalized myasthenia gravis (gMG), pathogenic antibodies activate the classical complement pathway, culminating in membrane attack complex (MAC)-mediated injury at the neuromuscular junction (NMJ). Levels of complement components (C3) have been associated with disease severity in animal models. C5 inhibitors block MAC formation and improve clinical outcomes, without reducing the upstream inflammatory fragments (C3a, C3b), which potentially drive NMJ injury and amplify immune responses in addition to MAC formation. We determined whether active C1s (aC1s) inhibition by claseprubart (DNTH103) suppresses generation of C3a, C3b and MAC in comparison with C5 inhibitor ravulizumab. Methods: MAC formation was quantified using the Wieslab® Complement Classical Pathway assay in 1% normal human serum (NHS). C3a in supernatants was measured by ELISA and C3b deposition on sensitized human red blood cells in 5% NHS was assessed by flow cytometry. For each assay, we tested dilution series of claseprubart, ravulizumab, and an isotype control. Results: In head-to-head assays, claseprubart and ravulizumab produced comparable inhibition of MAC formation, confirming similar downstream blockade. Only upstream aC1s inhibition with claseprubart resulted in near-complete reduction of C3a and C3b levels, while ravulizumab did not. Findings were reproduced across three independent experiments, supporting a mechanistic upstream (aC1s)-downstream (C5) inhibition distinction. Conclusion: Upstream aC1s inhibition with claseprubart prevented MAC formation and reduced C3a and C3b levels, demonstrating broader inflammatory control beyond C5 blockade. Thus upstream inhibition may provide both pathological and immunological advantages.

Miss Farah J. Walter 1 , Miss Caterina M. Wendel 1 , Miss Daniela Grote 2 , Dr. Simone Thiele 1 , Mrs Eva Malm 1 , Mrs Monika Bischoff 2 , Dr. Gert Bischoff 2 , Asst. Prof. Stephan Wenninger 1 , Prof. Maggie C. Walter 1 1 Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, Munich, Germany. 2 Center for Nutritional Medicine and Prevention, Barmherzige Bruder Hospital, Munich, Germany Background: A multidisciplinary approach is the key element in the management of patients with neuromuscular diseases. Individuals are frequently at risk of overweight, with an increased risk of undernutrition or malnutrition along with ongoing loss of muscle mass and function. Despite the essential role of nutrition in metabolic health and preserving muscle mass, there is only insufficient evidence regarding the specific nutritional requirements of neuromuscular patients and the efficacy of targeted interventions. Methods: Nutritional status and body composition of patients with spinal muscular atrophy (SMA), facioscapulohumeral muscular dystrophy (FSHD), and Becker muscular dystrophy (BMD) will be assessed at baseline and longitudinally, patients will be individually educated and counselled on nutrition and nutritional interventions, and will regularly have BIA measurements, fill specific nutrition protocols followed by a high-protein diet, in case of overweight with a calorie-reduced high-protein diet, in case of underweight or malnutrition by adding high-caloric drink food, along with regular SMA-assessments following disease-specific protocols. The aim is to evaluate the impact of the nutritional intervention on general health, quality of life, lung function and motor function, along with correlation of current disease-modifying therapy (DMT), gastrointestinal side effects, and nutrition. Results: Preliminary analyses demonstrate significant variability in nutritional status within the cohort. The data suggest that adherence to the nutritional intervention is significantly influenced by individual habits and disease-specific functional impairments. Furthermore, initial correlations have been identified between specific nutritional patterns and clinical-functional parameters. Conclusion: Nutritional factors are a critical yet often overlooked component in the management of neuromuscular diseases. The findings underscore the importance of personalized approaches over generic recommendations. Further research is needed to refine these correlations, evaluate long-term effects, and establish a foundation for evidence-based clinical guidelines.

Dr. Shiny Joy, Dr. Rajesh kumar Singh , Dr. Jasmine Parihar, Dr. Animesh Das, Dr. Arunmozhimaran Elavarasi, Dr. Anu Gupta, Dr. Ayush Aggarwal, Dr. Awadh Kishor Pandit, Dr. Vishnu VY, Dr. Deepti Vibha, Dr. Ajay Garg, Dr. Rohit Bhatia, Dr. Achal kumar Srivastava, Dr. Manjari Tripathi AIIMS, DELHI, India Background: Myasthenia Gravis (MG) is an autoimmune disorder that impairs neuromuscular transmission among those affected, 15-20% of patients experience a myasthenic crisis (MC) at least once in their lives. Methods: This ongoing prospective observational study included patients with MG in crisis or impending crisis (IMC) and assessed their outcome after 3 months. Results: 55 consecutive patients of myasthenic crisis (MC) and impending myasthenic crisis were recruited. Mean age was 44.84 ± 15.04 years, with male 60%. Out of 55 patients, 39 (70.09%) initially had generalized MG, 7 (12.7)% had ocular MG, 3(5.5%) had bulbar MG, and 6 (10.9%) had oculo-bulbar MG. Acetylcholine receptor (AchR) antibodies were positive in 42( 76.4%), while anti-MuSK antibodies were positive in 9 (16.4%). Thymic abnormalities were present in 27 (49.1%). 46 patients (83.6%) presented with IMC and 9 with direct MC (16.4%). However, out of 46 patients of IMC, 16 further developed MC during admission. So, total no of crisis patients were 25(45.5%) and IMC were 30 (54.5%). The mean duration from conversion to IMC to MC was 2.40 ± 2.79 days. Infection was leading cause of IMC and MC seen in 25 patients (45.5%). Thymectomy was done in 21 patients (38.2%). Infection as a cause was independent predictor of conversion from impending MC to MC (OR 3.0 [1.02- 9.03], p=0.04). The three-month mortality was in 5( 9.1%), with infection as a leading cause. Conclusion: This study showed that infection was an independent predictor in progression from impending MC to MC.

Assoc. Prof. Carola Hedberg-Oldfors 1 , Dr. Ali Zeki Bedir 2 , Dr. Kittichate Visuttijai 1 , Dr. Eva Michael 3 , Prof. Anders Oldfors 1 1 Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden. 2 Department of Pediatric Neurology, İstanbul Medeniyet University / Göztepe Research and Training Hospital, Istanbul, Turkey. 3 Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden Background: Nemaline myopathy is a rare congenital neuromuscular disorder characterized by the presence of nemaline rods in skeletal muscle fibers. Pathogenic variants in several genes have been implicated in its etiology, most notably NEB and ACTA1 , which encode thin filament proteins of the sarcomere. Currently, no curative treatment exists for nemaline myopathy, highlighting the urgent need to identify disease-modifying targets to support therapeutic development. Proteomic profiling of affected muscle tissue represents an emerging and promising research approach that, in combination with genomic analyses, may facilitate the identification of dysregulated proteins and molecular networks. Such insights can advance the understanding of disease pathobiology and enable the discovery of novel biomarkers and therapeutic targets in neuromuscular disorders. The objective in this study was to identify dysregulated proteins and altered cellular pathways in infant muscle tissue across the two most common genetic forms of nemaline myopathy, which present with similar clinical phenotypes and muscle biopsy histopathology. Methods: In this study, quantitative nanoscale liquid chromatography–tandem mass spectrometry (LC–MS³) with labeled protein analysis was performed on skeletal muscle samples obtained from five unaffected controls and seven affected patients diagnosed with nemaline myopathy caused by pathogenic variants in NEB or ACTA1 . To minimize age-related effects, only infant patients were included, and all muscle samples were collected via open biopsy from living individuals. The mean age at biopsy was 5.4 months (range, 2–19 months). Among the patients, three harbored de novo dominant ACTA1 variants, while four were compound heterozygous for NEB variants. Pathway enrichment and protein–protein interaction analyses were conducted using multiple bioinformatic tools and web-based resources, including ProteoMap and STRING. Results: A total of 4,846 proteins were identified and quantified across all samples, of which 183 exhibited significant dysregulation. Protein–protein interaction analysis revealed nine upregulated, muscle-specific proteins: ALPK3, ANKRD2, CSRP3, FBXO40, LMOD2, NRAP, TRIM54, TRIM63 and XIRP1. Pathway analysis further demonstrated increased activity of protein synthesis and proteasomal degradation pathways, accompanied by a downregulation of glycolytic processes. Furthermore, bioinformatic analysis revealed no proteins with significantly different expression levels between the two patient groups. This finding supports the concept that mutations in different genes may be associated with very similar phenotypes, not only from a clinical and morphological perspective but also regarding protein dysregulation. This finding implies that there may be therapeutic approaches that can be efficient irrespective of the underlying genetic defect in nemaline myopathy. Conclusion: This study identifies key dysregulated proteins and cellular pathways in the skeletal muscle of infants with nemaline myopathy. These findings underscore the value of proteomic profiling in elucidating disease pathobiology and suggest that the identified proteins merit further investigation as potential therapeutic targets for nemaline myopathy.

Prof. Nalini Atchayaram 1 , Dr. Dipti Baskar 1 , Dr. seena vengalil 1 , Dr. Kiran Polavarapu 2 , Dr. Muddassu Keerthipriya 1 , Dr. Saraswati Nashi 1 , Dr. S G Thenral 3 , Dr. V L Ramprasad 3 , Dr. sanjana Angadi 1 1 National Institute of Mental Health and Neurosciences, Bangalore, India. 2 CHEO-RI, ottawa, Canada. 3 MEDGENOME, Bangalore, India Background: Limb-girdle-muscular-dystrophy type 3(LGMD3; OMIM #608099) is a rare autosomal recessive disorder caused by pathogenic variants in the SGCA gene (OMIM *600119), which encodes α-sarcoglycan, which is a critical component of the dystrophin–glycoprotein complex. Disruption of this leads to progressive muscle fiber damage and weakness. While numerous SGCA variants are reported, data on recurrent or founder mutations in the Indian population remain sparse. Methods: We analyzed the clinical, biochemical, and molecular characteristics of seven unrelated Indian patients diagnosed with LGMD3 . Detailed clinical evaluation included age at onset, distribution of muscle weakness, disease progression, family history, and ambulatory status. Next-generation sequencing(n=8) was performed to identify disease-causing variants. Approximately 200ng of DNA was fragmented (250bp inserts), exome-capture enriched, and sequenced on a NovaSeq (Illumina, CA) with paired-end reads to an average depth of 80-100x. SNVs/Indels were annotated using VEP (Ensembl human gene model) and incorporating allele frequencies from population databases(1000 Genomes, GnomAD, TOPmed), in silico predictions (PolyPhen‐2, SIFT, Mutation Taster2, LRT, REVEL, SpliceAI, etc.), and disease databases (OMIM, ClinVar, HGMD). Copy number variants were called using the Exomedepth method. Clinically significant variants was prioritized based on minor allele frequency, published disease associations, support from ≥ 2 in silico prediction tools, proband clinical features, and classified according to ACMG guidelines. RNA extracted from muscle tissue was processed for mRNA PolyA capture and sequenced on the Illumina NovaSeq X Plus platform(2×150 bp). Data was analyzed using RNA-Seq pipeline integrating GATK-based variant calling, differential expression, and aberrant splicing analysis. Results: The M:F=4:3, ages ranging from 18-58 years. The median age onset and duration at presentation are 23 years(range: 16–38), and 5 years(range: 2–20). All presented with progressive limb girdle weakness. A consistent and notable finding across patients was weakness of the latissimus dorsi and rhomboideus muscles. None demonstrated cardiac or respiratory involvement. Additional clinical features included scapular winging, calf hypertrophy, ankle contractures, macroglossia, and sensorineural hearing loss, highlighting phenotypic variability. Serum CK ranged from 1111-3654 IU/L. Disease progression was slow, and all patients remained ambulant at presentation. All eight patients were homozygous for the shared intronic SGCA variant c.37+6T>C [ NC_000017.11 ( NM_000023.4 ): c.37+6T>C], located near the 5' splice site of intron 1. This rare variant, affecting a highly conserved nucleotide was absent in population databases (1000 Genomes, TOPMed, gnomAD), segregated with the disease in one family, showing homozygosity in affected siblings and heterozygosity in an unaffected parent, consistent with autosomal recessive inheritance. This variant, predicted to cause aberrant splicing (SpliceAI = 0.5). mRNA testing to confirm the variant pathogenicity is being conducted. The variant's recurrence in unrelated families suggests a founder effect or population-specific origin. Conclusion: This study identifies a recurrent homozygous SGCA splice-site variant, c.37+6T>C, as a cause of LGMD3 in Indian patients. This expand the genetic and phenotypic spectrum of SGCA-related muscular dystrophy and underscores the importance of considering population-specific variants. Recognition of this recurrent mutation has significant implications for molecular diagnosis, genetic counselling and development of targeted screening approaches in the Indian population.

Dr. Yong Lin Wang 1 , Dr. Chao Zhu 1 , Dr. Mahima Kapoor 1 , Prof. Gary Cutter 2 , Assoc. Prof. Carolina Barnett-Tapia 3 , Prof. Helmut Butzkueven 1 , Dr. WenWen Zhang 1 , Dr. Gabor Lovas 4 , Dr. Csilla Rozsa 4 , Prof. Jeannine Heckmann 5 , Assoc. Prof. Stefan Blum 6 , Dr. Laurie McLaughlin 6 , Dr. Katherine Buzzard 7 , Dr. Yi Chao Foong 8 , Prof. Elisabeth Chroni 9 , Asst. Prof. Dimitra Veltsista 9 , Dr. Belinda Cruse 10 , Dr. Mina Botrous 1 , Dr. Stephen Reddel 11 , Assoc. Prof. Mastura Monif 1 , Assoc. Prof. Anneke van der Walt 1 1 School of Translational Medicine, Monash University, Melbourne, Australia. 2 Department of Biostatistics, University of Alabama in Birmingham, Birmingham, United States. 3 Division of Neurology, Department of Medicine, University Health Network and University of Toronto, Toronto, Canada. 4 Department of Neurology, Jahn Ferenc Hospital, Budapest, Hungary. 5 Neurology Research Group, Neuroscience Institute, University of Cape Town, Cape Town, South Africa. 6 Neurology, Princess Alexandra Hospital, Wooloongabba, Australia. 7 Department of Neurosciences, Box Hill Hospital, Box Hill, Australia. 8 Neurology, Royal Hobart Hospital, Tasmanian Health Service, Hobart, Australia. 9 Neuromuscular Unit, Neurology Department, University of Patras, Patras, Greece. 10 Neurology, Royal Melbourne Hospital, Melbourne, Australia. 11 Brain and Mind Centre, Camperdown, Australia Background: The role of rituximab in the treatment of myasthenia gravis (MG), particularly among patients with acetylcholine receptor (AChR) antibody positivity, remains uncertain due to limited randomized controlled evidence and heterogeneous observational data. While rituximab is often used in refractory MG, its comparative effectiveness against other non-steroidal immunosuppressive therapies (NSISTs) requires further clarification. Methods: We conducted a retrospective cohort study of AChR-antibody-positive MG patients treated with rituximab or a second NSIST. The primary outcome was time to achieving a composite clinical endpoint representing a patient acceptable symptom state (PASS): Myasthenia Gravis Composite (MGC) score ≤ 3, daily corticosteroid dose ≤ 5 mg prednisolone equivalent, and no rescue therapy use in the preceding month. To reduce confounding by indication and improve causal comparability between treatment groups, inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline covariates. Cox regression was applied to estimate the effect of treatment on time to achieving composite endpoint. Results: 169 patients entered into the time-to-event analysis, and after IPTW adjustment, baseline characteristics between treatment groups were well balanced. There was no statistical difference in the hazard ratio between rituximab compared to a second NSIST in achieving the composite clinical outcome (HR = 1.27, 95% CI 0.66-2.45, p = 0.48). Sensitivity analyses yielded consistent findings. Conclusion: In this IPTW-adjusted analysis, rituximab did not improve attainment of clinical improvement compared to a second NSIST in AChR-antibody-positive MG.

Dr. Mathieu Horeau 1,2 , Dr. Camilla Pezzini 1,2 , Assoc. Prof. Roberta Sartori 1,2 , Prof. Marco Sandri 1,2 1 Veneto Institute of Molecular Medicine, Padova, Italy. 2 Università di Padova, Department of Biomedical Sciences, Padova, Italy Background: Duchenne muscular edystrophy is a severe and fatal X-linked disease, characterized by the lack of dystrophin, leading to structural fragility of muscle fibers and promoting a pro-catabolic metabolic imbalance. To date, no curative treatment is available, partly due to the difficulty in restoring full dystrophin expression and developing non-immunogenic approaches. Reactivation of utrophin, a paralog of dystrophin that is naturally downregulated by microRNAs (miRNAs), has shown strong potential to compensate for dystrophin deficiency. This project aims to address three major challenges to 1) reactivate utrophin expression to compensate for the loss of dystrophin, 2) inhibit pro-catabolic pathways to promote muscle growth, 3) develop non-immunogenic vectors for effective and tolerable combination therapy. We hypothesize that our combinatory multitarget therapy could simultaneously restore muscle structural integrity and prevent/ reverse muscle wasting and the associated loss of function. Methods: Taking into consideration that this project only started a few months ago, we will focus solely on Aims 2 and 3. Aim 2: To reduce the expression of MuRF1 and FOXO1/3, key players in muscle catabolism, short hairpin RNAs targeting MuRF1 and FOXO1/3, alone or in combination, were electroporated into the tibialis anterior muscle of wild-type mice. Aim 3: We developed myotropic liposomes derived from C2C12 murine myoblast cells carrying antisense oligonucleotides against MuRF1. To date, wild-type mice were injected intramuscularly (TA) with 10¹¹ particles. After 24 and 72 hours, and 7 days, the tibialis anterior muscles were collected, and MuRF1 protein and mRNA expression were assessed. Results: Our preliminary data for Aim 2 highlight that, in WT animals, combined electroporation of AAV-MYO-shMuRF1 and AAV-MYO-shFOXO1/3 in the tibialis anterior muscle leads to a reduction in the expression of MuRF1 (−24%; P = 0.04), FOXO1 (−36%; P = 0.002), and FOXO3 (−39%; P = 0.03) genes. This reduction is associated with muscle hypertrophy, characterized by a 30% increase in the cross-sectional area (P = 0.03) of the tibialis anterior, which is not significantly observed with non-combinatorial treatments. For Aim 3, we observe, after only 7 days, a downregulation of the MuRF1 transcript (−46%; P = 0.038) and a slight but non-significant decrease in protein expression (−10%). Conclusion: Our objective is now to move to pathological conditions for Aim 2. We are currently testing this approach in pre-symptomatic (3-week-old) MDX mice using adeno-associated virus vectors with a muscle-specific serotype (AAV9-MYO2/3) to deliver our AAV-MYO-shRNA against FOXO1/3 or MURF1. Concerning Aim 3, we are now moving to a systemic approach to evaluate muscle specificity and efficiency in targeting whole-body muscle while avoiding off-target effects.

Dr. Kristl G. Claeys 1,2 , Dr. Arjun Seth 3 , Dr. Ali A. Habib 4 , Dr. Yessar Hussain 5 , Dr. Gregory Sahagian 6 , Dr. Elena Cortés-Vicente 7,8 , Dr. Jeffrey Guptill 9 , Dr. Li Liu 9 , Dr. Rosa H. Jimenez 9 , Dr. Sirine Bougamra 9 , Dr. Delphine Masschaele 9 , Dr. Renato Mantegazza 10 , Dr. Andreas Meisel 11 , Dr. Fang Sun 12,13 , Dr. Shahram Attarian 14 1 University Hospitals Leuven, Leuven, Belgium. 2 KU Leuven, Leuven, Belgium. 3 Northwestern University, Chicago, United States. 4 University of California, Irvine, United States. 5 Austin Neuromuscular Center, Austin, United States. 6 The Neurology Center of Southern California, Carlsbad, United States. 7 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 8 Biomedical Research Institute Sant Pau, Barcelona, Spain. 9 argenx, Ghent, Belgium. 10 Fondazione IRCCS Istituto Neurologico Carlo Besta (Emeritus), Milan, Italy. 11 Charité – Universitätsmedizin Berlin, Berlin, Germany. 12 University of Pittsburgh School of Medicine, Pittsburgh, United States. 13 Northwestern University Feinberg School of Medicine, Chicago, United States. 14 Timone Hospital University, Marseille, France Background: Efgartigimod, a human immunoglobulin G1 Fc fragment that blocks the neonatal Fc receptor, was well tolerated and efficacious when administered in fixed-cycles or every-other-week (Q2W) dosing to participants with generalized myasthenia gravis (gMG) during Part A of the Phase 3b ADAPT NXT study ( NCT04980495 ). Part B of ADAPT NXT investigated the long-term efficacy, safety, and tolerability of efgartigimod in participants with gMG receiving Q2W or every-third-week (Q3W) dosing. Methods: Participants were randomized 3:1 to Q2W or fixed-cycles dosing of 10 mg/kg efgartigimod for 21 weeks in Part A. Fixed-cycles dosing involved 4 once-weekly infusions followed by a 4-week intertreatment period. In Part B, all participants received Q2W dosing during a 105-week extension. Participants could switch to Q3W dosing, depending on clinical assessment. Results: Sixty-five participants (of 69 in Part A [94.2%]) continued treatment in Part B; 57.8% (37/64) transitioned to Q3W dosing, and 59.5% (22/37) remained on Q3W dosing. Average Q3W treatment duration was 382 days. Mean Myasthenia Gravis Activities of Daily Living (MG-ADL) total score improvements were sustained through Week 126. Overall, 81.2% (56/69) of participants experienced an MG-ADL improvement of ≥5 points, and 56.5% (39/69) achieved minimal symptom expression (MSE; MG-ADL score, 0-1) at any time during the study. In Part B, 51.6% (32/62) achieved MSE. Efgartigimod was well tolerated across dosing regimens; no new safety signals were observed. Data from the final analysis of ADAPT NXT will be presented at the conference. Conclusion: Efgartigimod demonstrated sustained clinical benefits in participants with gMG during long-term treatment while remaining well tolerated across different dosing schedules.

Prof. Olimpia Musumeci , Dr. Ignazio Arena, Dr. Selene Drago, Dr. Cristian Usbergo, Prof. Carmelo Rodolico, Prof. Antonio Toscano University of Messina, Messina, Italy Background: Second-generation enzyme replacement therapies (ERTs) are now available in clinical practice for the treatment of Late-Onset Pompe Disease (LOPD). Most data about their efficacy and safety came from clinical trials, while long term data on real word settings are still limited. Herein, we present real-life clinical outcomes in a cohort of eight LOPD patients treated with avalglucosidase. Methods: We performed a longitudinal analysis of motor and respiratory functions in eleven LOPD patients followed at the Unit of Neuromuscular disorders of Messina, who received avalglucosidase for at least one year. Parameters assessed included six-minute walking test (6MWT) and forced vital capacity (FVC), which were measured at baseline (corresponding to the start of second-generation ERT) and every 12 months. Results: The cohort mean age was 61.3 years (range 12–82) and included six males and five females. 10/11 patients were ERT-experienced, whereas one was ERT-naïve. All received avalglucosidase-alfa. The mean follow-up duration under second-generation ERT was 3.5 years (range 1–8 years). The mean 6MWT at baseline was 355 m, increasing to 370.5 m at the last follow-up. Regarding respiratory function, the mean baseline FVC% was 68.5%, increasing to 73.8% at the last follow-up, with a mean change of +5.3%. Individual patient trajectories showed that 10/11 patients stabilized or improved in at least one functional parameter. Conclusion: To provide real-life data is critical for understanding long-term treatment effects outside controlled trial environments. About 10/11 improved or stabilized, one pt who switched from alglucosidase-alfa to avalglucosidase-alfa after a period of gradual decline, did not inverted this trend after switching, likely due to limited residual muscle function. Notably, ERT-naïve pt had stable motor and respiratory function over eight years with avalglucosidase-alfa. 5/11 patients showed improvement in both outcome measures. However, the small sample size did not allow to determine whether specific subgroups (e.g., age, ERT-naïve vs. ERT-experienced) might have differential benefit from second-generation therapies. Longer follow-up in larger cohort is warranted to confirm this positive trend.

Prof. Alessio Signori 1 , Dr. Erika Schirinzi 2 , Prof. Fiore Manganelli 3 , Prof. Dario Cocito 4 , Dr. Yuri Falzone 5 , Prof. Chiara Briani 6 , Prof. Anna Mazzeo 7 , Prof. Angelo Schenone 8 , Dr. Vincenzo Di Stefano 9 , Dr. Giuseppe Cosentino 10 , Prof. Girolama Alessandra Marfia 11 , Dr. Luana Benedetti 8 , Dr. Marinella Carpo 12 , Prof. Massimiliano Filosto 13 , Dr. Luca Leonardi 14 , Dr. Marco Luigetti 15 , Dr. Sabrina Matà 16 , Dr. Giuseppe Piscosquito 17 , Dr. Tiziana Rosso 18 , Dr. Marta Lucchetta 19 , Prof. Gabriele Siciliano 2 , Prof. Giuseppe Lauria Pinter 20 , Prof. Maurizio Inghilleri 21 , Dr. Teresa Cantisani 22 , Dr. Francesca Notturno 23 , Dr. Dario Ricciardi 24 , Prof. Francesco Habetswallner 24 , Dr. Elisa Vegezzi 25 , Dr. Alberto De Lorenzo 26 , Dr. Claudia Lozi 26 , Dr. Alessandro Salvalaggio 27 , Dr. Camilla Strano 5 , Dr. Luca Gentile 7 , Dr. Giorgia Mataluni 11 , Prof. Filippo Brighina 9 , Dr. Barbara Risi 13 , Dr. Loris Poli 28 , Dr. Francesca Forcina 29 , Dr. Federica Moret 21 , Dr. Fabrizio Canale 30 , Dr. Emanuele Cassano 31 , Dr. Eleonora Della Bella 20 , Prof. Eduardo Nobile-Orazio 26 , Prof. Pietro Emiliano Doneddu 26 1 Department of Health Sciences, University of Genoa, Genoa, Italy. 2 Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Pisa, Italy. 3 3.Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy. 4 Dipartimento Scienze Cliniche e Biologiche, Università di Torino, Turin, Italy. 5 Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. 6 Neurology Clinic, Department of Neurosciences, University of Padova, Padua, Italy. 7 Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 8 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy. 9 Department of Biomedicine, Neuroscience, and Advanced Diagnostic (BIND), University of Palermo, Palermo, Italy. 10 Department of Brain and Behavioral Sciences, University of Pavia, Campus della Salute, Policlinico San Matteo, Pavia, Italy. 11 Dysimmune Neuropathies Unit, Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy. 12 ASST Bergamo Ovest-Ospedale Treviglio, Treviglio, Italy. 13 Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy. 14 Neuromuscular and Rare Disease Centre, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), SAPIENZA University of Rome, Sant'Andrea Hospital, Rome, Italy. 15 Department of Neurosciences, Università Cattolica del Sacro Cuore, Rome, Italy. 16 Department of Neurological and Psychiatric Sciences, Azienda Ospedaliero-Universitaria di Careggi, Florence, Italy. 17 Neurology Unit, University Hospital “San Giovanni di Dio e Ruggi d'Aragona”, Salerno, Italy. 18 UOC di Neurologia, Ospedale San Bassano, Vicenza, Italy. 19 UOC Neurologia, Ospedale Santa Maria della Misericordia, Rovigo, Italy. 20 Unit of Neuroalgology, IRCCS Foundation 'Carlo Besta' Neurological Institute, Milan, Italy. 21 Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy. 22 Servizio di Neurofisiopatologia, Azienda Ospedaliera di Perugia, Perugia, Italy. 23 Servizio di neurofisiopatologia, Ospedale SS di Pescara, Perugia, Italy. 24 Clinical Neurophysiology Unit, Cardarelli Hospital, Naples, Italy. 25 Neuroimmunology Laboratory and Neuroimmunology Research Section, IRCCS Mondino Foundation, Pavia, Italy. 26 Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy. 27 Neurology Clinic, Department of Neurosciences, University of Padova, Padua, Italy. 28 Unit of Neurology, ASST Spedali Civili, Brescia, Italy. 29 Neuromuscular and Rare Disease Centre, Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), SAPIENZA University of Rome, Sant'Andrea Hospital, Rome, Italy. 30 Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy. 31 Neurology and Stroke Unit, Ospedale del Mare, ASL Napoli 1 Centro, Naples, Italy Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, heterogeneous, and treatable immune-mediated neuropathy. Research in CIDP is constrained by low prevalence, small cohorts, and restricted data sharing due to privacy regulations, limiting reproducibility and secondary analyses. Synthetic data (SD) generated through regression-based and generative artificial intelligence models offer a potential solution by preserving the statistical structure of real-world datasets while eliminating re-identification risk. Methods: To validate the use of regression-based synthetic data derived from the Italian CIDP Registry, using a previously published multicenter case–control study on lifestyle and dietary factors as a reference framework. We aimed to determine whether SD could accurately reproduce (i) marginal distributions of variables, (ii) univariable associations with CIDP risk, and (iii) the multivariable joint structure of key predictors. We analyzed the matched dataset of 390 individuals (195 CIDP cases, 195 controls) from the original study. Synthetic datasets were generated using the synthpop package in R, stratified by sex to preserve the original 1:1 matching scheme. Binary and multinomial regression models were used to synthesize predictors and outcome variables. Fidelity was assessed through information-theoretic distance measures (Total Variation, Jensen–Shannon, Hellinger), χ² tests with Cramér’s V, and propensity score mean squared error (pMSE). Privacy was evaluated using exact match rates and nearest-neighbor Hamming distances. Univariable and multivariable logistic regression models were replicated in real and synthetic datasets. Results: The synthetic data preserved case–control balance and sex distribution. Marginal distributions closely matched the real data, with minimal discrepancies confined to a few multi-level dietary variables. Distance metrics and goodness-of-fit tests indicated high fidelity (Total Variation typically 0.01–0.05; Cramér’s V ≤0.09). No identical matches between real and synthetic records were observed; nearest-neighbor analyses showed low disclosure risk (median Hamming distance 5). Univariable associations with CIDP risk were highly concordant between datasets. Protective effects of higher fish and rice intake were preserved in both univariable and multivariable models (e.g., fish intake: real OR 0.52 vs SD OR 0.44; rice intake: real OR 0.45 vs SD OR 0.43). Conclusion: Regression-based synthetic data generated from the Italian CIDP Registry reliably preserve the statistical structure and clinically meaningful associations of real-world case–control data, while effectively eliminating the risk of patient re-identification. This strategy overcomes key barriers imposed by small sample sizes and data-sharing constraints in rare diseases, enabling secure dissemination of high-fidelity datasets. By facilitating independent validation, secondary analyses, and innovative study designs, synthetic data provide a robust foundation for collaborative, reproducible, and precision-oriented research in CIDP and other rare peripheral neuropathies.

Dr. Dulce Peris-Moreno 1 , Ms. NATALIA RIEDEL 2,3,4 , Mr. ALBERTO GARCÍA-MARTÍN 3 , Mr. JORGE ESPINONSA-ESPINOSA 5 , Dr. ARIADNA BARGIELA 3 , Prof. RUBÉN ARTERO 2,3,4 1 Ciberer, Iscill, Madrid, Spain. 2 BIOTECMED, UNIVERSITY OF VALENCIA, VALENCIA, Spain. 3 INCLIVA, VALENCIA, Spain. 4 CIBERER, ISCIII, MADRID, Spain. 5 Universidad Particular Internacional SEK, QUITO, Ecuador Background: Myotonic dystrophy type 1 (DM1) is a rare genetic disorder caused by an expansion of a non-coding CTG repeat in the DMPK gene, leading to the sequestration and translational repression of MBNL proteins and resulting in severe muscle dysfunction, including myotonia, atrophy and weakness. We recently identified the RNA-binding protein Musashi-2 (MSI2) as a critical contributor in DM1 pathology: MSI2 is overexpressed in the disease and represses miR-7 biogenesis, disrupts autophagy regulation and exacerbates muscle loss. Targeting MSI2 may therefore complement strategies that directly neutralize toxic CUG-expanded RNA. In this study, we explored MSI2 as a therapeutic target using antisense oligonucleotides (ASOs) to knockdown its expression in vitro and in vivo . Methods: A total of 127 ASOs targeting MSI2 mRNA were designed in silico . Based on bioinformatics criteria and to achieve maximal coverage of transcript sequences through non-overlapping tiling, 27 candidates were selected for secondary in vitro profiling in human DM1 myotubes (hDM1-myo), from which the best candidate ASOs were chosen for detailed evaluation. In hDM1-myo, we quantified MSI2 silencing, myogenic fusion (desmin immunostaining) and transcriptomic changes. For in vivo studies, the best candidate ASOs were administered subcutaneously to HSA LR mice to assess MSI2 knockdown across tissues, with MSI2 protein levels quantified by Jess simple western and ASOs levels by hybridization-based ELISA. After detecting insufficient skeletal-muscle delivery, ASO chemistry was further optimized, and the new design was re-evaluated for MSI2 silencing in skeletal muscle and other tissues, as well as for renal and hepatic tolerability. Results: Initial in vitro screening identified 27 MSI2-directed ASOs, from which the best candidates were selected for in-depth analysis. In hDM1-myo, MSI2 silencing by these ASOs produced marked phenotype improvement, including a >75% increase in myogenic fusion capacity. Transcriptomic analyses showed restoration of pathways associated with muscle function and cytoskeletal integrity. In HSA LR mice, systemic administration of ASOs in a single dose significantly reduced MSI2 levels in non-muscular tissues such as liver, but skeletal-muscle uptake and knockdown were limited. ELISA quantification confirmed that this limitation reflected poor ASO delivery to skeletal muscle. Subsequent optimization of ASO chemistry together with additional dosing frequency and concentration, substantially enhanced MSI2 silencing in skeletal muscle as well as in other tissues, without evidence of renal or hepatic toxicity at the tested doses. In a dedicated durability study, one candidate ASO achieved sustained Msi2 silencing in liver and skeletal muscle for at least 45 days post-treatment indicating a durable Msi2 knockdown in vivo . Conclusion: MSI2 silencing with ASOs induces robust in vitro improvements in DM1 myotubes, including enhanced myogenic fusion and transcriptional recovery of muscle-structural pathways, supporting MSI2 as a relevant therapeutic target in DM1. In vivo , the studies highlight delivery to skeletal muscle as a critical bottleneck but also show that appropriate chemical optimization can markedly improve MSI2 knockdown in muscle without overt toxicity and with sustained target engagement. Together, these findings identify MSI2 as a promising therapeutic target in DM1 and support MSI2-directed ASOs, while highlighting the need to optimize skeletal-muscle delivery to enable clinical translation

Dr. Julie Paik Johns Hopkins University, Baltimore, United States Background: Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases with variable clinical manifestations and outcomes. Early diagnosis and timely initiation of therapy are critical to prevent irreversible muscle damage and systemic complications. However, treatment selection remains challenging due to disease heterogeneity, limited comparative data, and the absence of standardized treatment pathways. A subset of patients develops refractory disease, underscoring the need for more effective and targeted therapies. Methods: This presentation provides a state-of-the-art review of treatment strategies for IIM, with a focus on dermatomyositis and immune-mediated necrotizing myopathy. Evidence is drawn from randomized controlled trials, prospective cohort studies, and emerging data on targeted therapeutics. Practical treatment approaches for newly diagnosed and refractory patients are discussed, incorporating clinical phenotype, autoantibody profiles, and organ involvement. Results: In newly diagnosed IIM, glucocorticoids in combination with steroid-sparing immunosuppressive agents remain the foundation of therapy, with intravenous immunoglobulin and other agents used in selected patients. Recent advances in targeted therapies are reshaping the treatment landscape, particularly in dermatomyositis. Recently reported phase 3 trial data evaluating JAK/STAT pathway inhibition demonstrate clinically meaningful improvements in disease activity and provide new options for patients with refractory disease. In this setting, biologic and targeted therapies are increasingly used following inadequate response to conventional immunosuppression. Integration of clinical features with serologic and imaging data is improving patient stratification and guiding therapeutic decisions. Conclusion: The treatment landscape of IIM is rapidly evolving with the emergence of targeted therapies and increasing availability of high-quality clinical trial data. While therapeutic decision-making remains individualized, recent advances offer new opportunities to improve outcomes, particularly in refractory disease. Ongoing multicenter studies will be critical to define optimal treatment strategies and support a more precision-based approach to care.

Dr. Sang Beom Kim 1 , Dr. Bum Chun Suh 2 , Dr. Yang-Ki Minn 3 , Dr. Hee-Jung Song 4 , Dr. Jin Yong Lee 1 1 Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Korea, Republic of. 2 Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of. 3 Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic of. 4 Department of Neurology, Chungnam National University Sejong Hospital, Sejong, Korea, Republic of Background: Carpal tunnel syndrome (CTS) is recognized as the most prevalent form of entrapment neuropathy. It occurs due to the compression of the median nerve as it passes beneath the transverse carpal ligament in the wrist. Typical clinical manifestations include numbness, tingling in the fingers, and significant pain that often intensifies at night. In chronic or advanced stages, patients may experience thenar atrophy and a noticeable decline in fine motor skills. While diagnosis is generally based on patient history and electrodiagnostic tests, such as nerve conduction studies, these standard tests do not always capture the full clinical picture. When results from nerve conduction tests appear normal despite persistent symptoms, neurosonography becomes an essential tool for identifying rare anatomical abnormalities or nerve tumors that might be mimicking CTS. Methods: This case involves a 66-year-old female housewife who sought medical attention for a ten-year history of stabbing pain and numbness in her left palm. Her condition had deteriorated significantly over the final year. Her symptoms were particularly triggered by hand-clapping and were notably worse during the night. These symptoms led to functional impairments, including difficulty holding a book while reading, challenges opening glass bottle caps, and difficulty lifting or maneuvering a shopping cart. Despite these challenges, physical examination showed no observable muscle atrophy in her thumb. Her medical history included hyperlipidemia, for which she took atovastatin, but she had no history of tobacco or alcohol use. Neurological testing revealed a mild decrease in grip strength in her left hand. Both Phalen’s sign and Tinel’s sign were positive in the left hand. Because CTS was the primary suspicion, an upper extremity nerve conduction study was performed; however, the results were entirely normal. To investigate further, clinicians performed neurosonography to evaluate the anatomical integrity of the median and ulnar nerves. The ultrasound revealed that the cross-sectional area of the median nerve was mildly increased, measuring 10.7 mm2 at the left carpal tunnel. The wrist:forearm ratio was also slightly elevated at 1.5. Most importantly, the scan identified a hypoechoic mass measuring 3.8 x 8.4 mm in the symptomatic region of the left palm. A subsequent MRI of the hand provided more detail, showing a heterogeneously contrast-enhancing mass measuring 2.3 x 1.6 x 1.1 cm located between the third metacarpal and the flexor tendons. Results: The patient was referred for surgical excision, where a white mass measuring 2.2 x 1.5 x 1.3 cm was successfully removed. Histopathological analysis confirmed the mass was positive for S-100 but negative for other markers like SMA and CD 34. This confirmed a diagnosis of schwannoma, a benign nerve sheath tumor, with no evidence of malignancy. Ten months following the surgery, the patient’s recovery was complete. Her motor skills returned to normal, and the persistent numbness, tingling, and pain were entirely resolved. Conclusion: This case underscores the importance of using neurosonography for differential diagnosis when standard electrodiagnostic results are inconclusive.

Dr. Sukru Karali 1 , Mrs Barbara Domanska 1 , Dr. Natasa Savic 2 , Dr. Miriam Freimer 3 , Mr. Gilles Vinçonneau 2 1 UCB, Slough, United Kingdom. 2 UCB, Bulle, Switzerland. 3 Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, United States Background: Zilucoplan is a complement component 5 inhibitor approved for treatment in patients with generalised myasthenia gravis (gMG). It is currently self-administered with a pre-filled syringe. Auto-injectors (AIs) are self-administration devices designed to automatically inject a defined dose of medication, which may be a preferred option for some patients. The zilucoplan AI is button-free and contains a pre-filled syringe enclosed in the device so that the needle is not visible. The objective of this human factors validation study was to assess use-related safety and effectiveness of the zilucoplan AI. Methods: Participants were divided into 5 categories: patients with gMG or those exhibiting ocular symptoms (injection-experienced and injection-naïve); caregivers (injection-experienced and injection-naïve); and healthcare professionals (HCPs). Participants were required to simulate use of the AI by injecting into a manikin (HCPs and caregivers) or skin pad attached to their body (patients) in a simulated use environment, without training. Instructions for Use (IFU) were available, but participants were not directed to use them. Results: In total, 100 participants were recruited in the United States of America (injection-experienced patients, n=21; injection-naïve patients, n=22; injection-experienced caregivers, n=25; injection-naïve caregivers, n=17; and HCPs, n=15). Overall, 90% (n/N=90/100) of participants performed a successful injection with the AI on their first attempt, without training. Observed use errors did not introduce new risks beyond those previously assessed during risk management. The use errors were attributed to prior experience with other injection devices, IFU layout and use environment influences; minor changes were made to the IFU to address these use errors. Conclusion: The data from this human factors validation study demonstrate that the zilucoplan AI is safe and effective for use in patients with gMG. No new hazards or use-related risks were identified. Funding: UCB.

Savas Tsolakidis , R Schmidhammer Background: Peripheral neuropathic pain (PNP) is a debilitating condition affecting 7-10% of the global population, characterized by hyperalgesia, allodynia, and burning sensations that significantly impair quality of life and contribute to psychological comorbidities. Posttraumatic and postsurgical scarring of peripheral nerves represents a major causative factor, leading to loss of nerve gliding properties, local fibrosis, and compression. While pharmacological treatments remain first-line therapy, surgical intervention may be warranted when scarring is the primary etiology. Objective: This 20-year retrospective analysis evaluates the efficacy of local perforator-based gliding tissue flaps in reducing post-neurolysis neuropathic pain in patients with peripheral nerve scarring. Methods: A retrospective analysis was conducted examining a total of 67 patients who underwent neurolysis combined with local perforator-based gliding tissue flap reconstruction over a 20-year period. The study primarily assessed pain reduction outcomes following this surgical technique. Results: Patients with pain duration 1 year decreased from 7.5 to 3.0. Mean gliding tissue flap size was 3,899 mm². Upper extremity nerves were most commonly affected (ulnar nerve: 21 cases; radial: 14; median: 8) Conclusion: This study provides evidence supporting the use of local perforator-based gliding tissue flaps as a surgical treatment option for patients with post-traumatic or post surgical peripheral nerve scarring causing neuropathic pain. The technique addresses the underlying pathophysiology by restoring nerve gliding properties and reducing compression.

Dr. Nicola Molitierno 1 , Dr. Delia Gagliardi 1 , Dr. Mosè Parisi 1 , Dr. Alberto Lerario 2 , Dr. Patrizia Ciscato 2 , Dr. Letizia Bertolasi 2 , Dr. Simona Zanotti 2 , Dr. Laura Napoli 2 , Dr. Michela Ripolone 2 , Assoc. Prof. Claudia Maria Cinnante 3 , Prof. Stefania Corti 4,5 , Prof. Giacomo Pietro Comi 1,5 , Dr. Daniele Velardo 2 1 IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy. 2 IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, Italy. 3 IRCCS Istituto Auxologico Italiano, Section of Neuroradiology, Department of Radiology and Diagnostic Imaging, Milan, Italy. 4 IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Disease Unit, Milan, Italy. 5 Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy Background: Anti-HMGCR immune-mediated necrotizing myopathy is a rare autoimmune disease characterized by severe proximal muscle weakness, markedly elevated creatine kinase levels, and specific autoantibodies. Despite consensus recommendations, the lack of standardized criteria for therapeutic stratification represents a significant clinical challenge, particularly given the increasing recognition of phenotypic heterogeneity ranging from aggressive acute forms to chronic presentations. This study aimed to characterize a monocenter cohort and develop objective criteria for therapeutic decision-making and prognostic stratification. Methods: We retrospectively analyzed 24 patients with anti-HMGCR myopathy diagnosed between 2014-2025. Clinical assessment included MMT-8 scoring, serum CK levels, anti-HMGCR antibody titers, and muscle MRI with semi-quantitative analysis of edema (STIR sequences) and fibro-adipose replacement (T1 sequences). Patients received either single induction therapy (high-dose corticosteroids alone) or multiple induction therapy (corticosteroids plus immunosuppressants and/or intravenous immunoglobulins). Patients were evaluated at 3, 6, and 12 months, with outcomes defined based on CK levels and muscle strength. Statistical analysis included univariate and multivariate logistic regression to identify predictors of therapeutic choices and treatment response. Results: The cohort (median age 64.5 years, 58.3% female) showed significant demographic differences based on statin exposure: statin-exposed patients were older (66 vs 43 years) while statin-naive patients were predominantly young females. Through a retrospective evaluation of the therapeutic choices made in our cohort, we identified clinical, laboratory and imaging parameters that guided the selection between corticosteroid monotherapy and combined immunosuppressive induction therapy. Multivariate analysis of these parameters enabled development of a therapeutic algorithm integrating baseline CK levels, MMT-8 scores, and MRI edema scores (AUC=0.889, p=0.04), achieving 79.2% accuracy in predicting the need for multiple induction therapy. The application of this approach produced comparable results at 12 months between the two groups, (complete response: 50% vs 60%, p=0.697), suggesting an effective balancing between different disease severity through optimal therapeutic intensity for each patient. Prognostic analysis identified three significant baseline predictors of complete response: older age at onset, diagnostic delay (paradoxically favorable when adjusted for age and structural damage), and degree of fibro-adipose replacement on MRI (AUC=0.909, p=0.009). The unexpected finding regarding diagnostic delay supports the existence of distinct phenotypes with different biological activity and progression rates. During follow-up, persistent muscle edema on MRI and need for rescue immunoglobulin therapy predicted suboptimal response (AUC=0.898, p=0.009). Exploratory antibody kinetics analysis (n=8) revealed correlations between the percentage reduction in antibody titre and CPK values at 6 months (rho =-0.810, p=0.022) and 12 months (rho =-0.762, p=0.037). The rate of antibody reduction correlated significantly with complete clinical response (rho =0.771, p value=0.025). Conclusion: This study supports a multiparametric approach for personalized management of anti-HMGCR myopathy, integrating easily measurable clinical, biochemical, and imaging parameters. The developed therapeutic algorithm enables objective stratification, while identification of baseline and follow-up prognostic factors facilitates early recognition of non-responders. These findings underscore the phenotypic heterogeneity of anti-HMGCR myopathy and highlight the importance of tailored therapeutic strategies in improving patient outcomes.

Dr. Paz Castro 1 , Dr. Laura Carrera-García 2 , Dr. Vanessa Ejarque 3 , Dr. Ana María León 4 , Mrs Cristina Puig 5 , Mrs Carmen Álvarez 1 , Dr. Jorge Mauriño 1 , Mrs Sofía García-López 1 , Dr. Andrés Nascimento 2 1 Medical Department, Roche Farma, Madrid, Spain. 2 Neuromuscular Unit, Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain. 3 Department of Gastroenterology, Hepatology and Nutrition, Hospital San Joan de Déu, Barcelona, Spain. 4 Phoniatrics and Speech Therapy Unit, Hospital Universitari Vall d´Hebron, Barcelona, Spain. 5 Institut de Recerca Sant Joan de Déu, Barcelona, Spain Background: Bulbar dysfunction is a frequent and clinically relevant complication in spinal muscular atrophy (SMA), affecting quality of life and health outcomes. Systematic assessment is limited by a lack of standardized tools; addressing these gaps is crucial for optimizing comprehensive patient-centred-care. This study describes the current management for bulbar dysfunction in SMA patients in Spain. Methods: A non-interventional, cross-sectional pilot study was conducted including healthcare professionals (HCPs) with expertise in SMA. Participants were invited to the study by the national SMA registry CuidAME and completed a structured electronic survey, including information regarding their demographic characteristics, and practice-related variables. A descriptive analysis was conducted. Results: The study included 37 HCPs (62.2% female), primarily pediatric neurologists (37.8%) and neurologists (21.6%), with a mean of 9.6 years ± 5.8 of experience. Most (86.5%) work in multidisciplinary teams at public, tertiary centers (89.2%). HCPs placed great importance (mean 8.9/10) on bulbar function and the systemic effect of disease modifying treatments (mean 8.7/10). While 56.8% of HCPs gave a high priority to bulbar function, motor evaluation still received more dedication (2.8/6). The most widely recognized bulbar domains were dysphagia (97.3%), voice and speech (89.2%), and fatigability (89.2%) which directly aligned with the main aspects evaluated: dysphagia (97.3%), voice and speech 89.2% and fatigue (83.8%). Swallowing assessment is a common practice (94.4%), performed by speech-language therapists (82.4%) and gastroenterologists (70.6%), particularly in SMA types 1 and 2. Evaluation combines instrumental methods (videofluoroscopy: 96.8%) with non-instrumental scales (Functional Oral Intake Scale: 55.9%, Egen Klassifikation 2: 50.0%), with intervention programs available in 85.3% of these centers. The evaluation is specifically performed in SMA type 1 (94.1%) and SMA type 2 (82.4%) patients. It is noteworthy that only 47.1% perform it in type 3 and 32.4% in presymptomatic patients. Voice and speech evaluations are conducted in 59.5% of centers, with 77.3% of them offering specific interventions. HCPs working in centers with a multidisciplinary team more frequently used instrumental assessment of bulbar function (93.5% vs. 50%; p=0.022), and videofluoroscopy (87.5% vs. 40%; p=0.037) compared to their counterparts, and were more likely to recommend bulbar rehabilitation (87.1% vs. 33.3%; p=0.013). Regarding professional well-being, participants predominantly showed high empathy (45.9%) and openness in evidence-based innovations (27.0%). Bulbar prioritization is associated with a significantly higher total empathy (Jefferson Scale of Empathy) score (p=0.032). Openness to Innovations is significantly associated with a lower procrastination (Pure Procrastination Scale) score (p=0.030). Conclusion: This study suggests strong awareness and commitment among HCPs managing bulbar function in SMA, characterized by a multidisciplinary approach and established evaluation and rehabilitation. However, motor evaluation still dominates time, and dysphagia evaluation is critically limited in SMA Type 3 and presymptomatic patients. A significant correlation links bulbar prioritization with higher medical empathy. Standardization of assessment protocols is still required to optimize care across the full SMA spectrum.

Assoc. Prof. Seung Woo Kim , Mr. Ye Joon Jung, Prof. Ha Young Shin Yonsei University College of Medicine, Seoul, Korea, Republic of Background: Myasthenia gravis (MG) is an antibody-mediated autoimmune neuromuscular disorder in which B-cell–driven immune responses play a central pathogenic role. Bruton’s tyrosine kinase (BTK) is a key intracellular signaling molecule downstream of the B-cell receptor and is essential for B-cell activation, differentiation, and survival. Although BTK inhibition has emerged as a promising therapeutic strategy in antibody-mediated autoimmune diseases, the expression and activation status of BTK in human MG, particularly in relation to clinical disease activity and thymic pathology, remain unknown. This study aimed to investigate BTK expression and activation in peripheral blood and thymic tissue from patients with acetylcholine receptor (AChR) antibody–positive MG and to examine their associations with clinical disease activity. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 40 patients with AChR antibody–positive MG and 11 healthy controls. Thymic tissue samples from 22 patients who underwent thymectomy were analyzed. Total BTK and phosphorylated BTK (p-BTK) expression in peripheral B-cell subsets were assessed by intracellular flow cytometry, and BTK expression in thymic tissue was evaluated using immunohistochemistry. Clinical data, including MG subtype, Myasthenia Gravis Activities of Daily Living (MG-ADL) score, and recent clinical course, were collected at the time of sampling. Patients were classified as being in remission, having stable symptomatic disease, or experiencing recent clinical worsening. Associations between BTK or p-BTK expression and clinical variables were evaluated using univariate and multivariate linear regression analyses. Results: Total BTK and p-BTK expression in PBMCs did not differ significantly between MG patients and healthy controls. However, when patients with MG were stratified by disease status, total BTK expression was higher in patients having generalized symptoms than those in remission (median 19953.5 [Q1–Q3, 15415.8–24403.5] vs 14876.5 [11064.5–15693.3]; p = 0.039). Phosphorylated BTK demonstrated a stepwise increase from remission (111.2 [55.8–264.5]) to ocular MG (352.5 [204.3–681.5]) and generalized MG (612.0 [354.7–782.8]), with significantly higher levels in patients having generalized symptoms compared with healthy controls (294.0 [130.0–567.0]; p = 0.049). Patients with recent clinical worsening showed markedly increased p-BTK expression compared with those in remission (673.0 [322.0–1,044.0] vs 133.0 [62.7–249.0]; p = 0.008). In multivariate analysis adjusting for current prednisolone use and thymectomy status, recent clinical worsening was independently associated with increased p-BTK expression (β = 0.43, p = 0.012), whereas total BTK expression was not. Although p-BTK expression was modestly associated with MG-ADL scores in univariate analysis (p = 0.046), this association was not retained after adjustment for recent disease activity. Immunohistochemical analysis showed BTK expression in 9 of 22 thymic specimens (40.9%), predominantly localized around lymphoid follicular structures. Conclusion: Activation of BTK signaling, reflected by p-BTK expression, is associated with recent clinical worsening of MG, whereas total BTK expression shows limited clinical relevance. The localization of BTK expression to disease-relevant thymic immune microenvironments further supports a role for BTK signaling in MG immunopathogenesis. These findings provide human tissue–based evidence that BTK activation reflects active immune processes in MG and support BTK signaling as a biologically relevant therapeutic target.

Prof. Jorge A. Bevilacqua Universidad de Chile, Santiago, Chile Background: Palliative and supportive care for neuromuscular disorders (NMDs) faces complex, structural, cultural, and clinical-scientific challenges in developing countries. Some of them are universal; however, unlike in high-income countries, where services are relatively integrated, a lack of visibility persists in low-and middle-income countries, leaving many patients without any specific diagnosis, treatment, or support. These challenges encompass at least five main critical areas: health infrastructure and public policies; late and misdiagnosis; access to treatments and symptom management; training of healthcare personnel and fragmentation of general and specialized care; caregiver burden; and psychosocial support. The lack of prioritization of rare diseases, particularly NMDs, on most public health agendas often leads to a lack of registries, preventing us from assessing the magnitude of the problem and planning appropriate healthcare resource allocation and strategies accordingly. The existing palliative care infrastructure, often basic and insufficient, typically focuses on more common, urgent, or visible illnesses, such as cancer, or multiple sclerosis, neglecting rare and progressive NMDs. In most developing countries, timely diagnosis presents an enormous clinical and logistical challenge. NMDs are often mistaken for more common conditions. The lack of specialists and the absence of specific diagnostic tools leads to long diagnostic odysseys. Once diagnosed, the disease are often at an advanced stage, and access to therapy is limited, hindering timely management and treatment. Disease-modifying therapies are often inaccessible or unavailable in the public sector, requiring legal action to obtain them, resulting in delays and loss of the therapeutic windows for prescription, additionally to the administrative burden put on the medical team's shoulders. Taken together, this forces palliative care teams to focus exclusively on symptom management with basic resources. Furthermore, a significant knowledge gap exists between both general practitioners and specialists, who do not associate NMDs with palliative care, perceiving them solely as “end-of-life care.” Additionally, multidisciplinary care is only accessible in large cities and is virtually nonexistent in rural areas. In contexts where institutionalized care is unavailable, the responsibility falls almost exclusively on the family, often on women or children. The absence of universal health insurance systems or government subsidies on the other hand, forces families to cover prohibitive costs with their own scarce resources. Conclusion: Palliative and supportive care for patients with NMDs faces challenges that are exacerbated in low-income developing countries. Several strategies have been identified to address these challenges effectively. Integrated home-based palliative care has emerged as a viable and effective model. Civil society organizations constitute another strategy that not only helps raise awareness about these diseases but also provides social support networks and community education. There is a clear and urgent need for a paradigm shift: to move from considering palliative care as a luxury of high-income countries to reading it as an essential component of the treatment of neuromuscular diseases at a universal level; secondly, to move from medicine centralized in medical specialties to one centered on the patient's health problem as the central axis of the healthcare team's strategy to treat it through the implementation of integrated multidisciplinary approaches including transition.

Prof. Jorge Arturo Diaz-Ruiz 1,2 , Prof. Sandra Milena Castellar-Leones 1,2,3 , Prof. Edicson Ruiz-Ospina 1,2 , Dr. Cristian Correa-Arrieta 2 , Dr. Eduardo Echeverry 4 , Dr. Diana Ramirez-Montaño 4 , Dr. Juan David Lopez 5 , Dr. Diana Luzuriaga-Carpio 6 , Dr. Dario Zambrano-Vera 7 , Dr. Daniel César Chávez 8 , Dr. Edison Vasquez 8 , Dr. Ana Laura Castro 9 , Dr. Juan Pablo Muñoz 10 , Prof. Fernando Ortiz-Corredor 1,2,3 1 Universidad Nacional de Colombia, Bogota, Colombia. 2 CIFEL, Bogota, Colombia. 3 Hospital Universitario Nacional de Colombia, Bogota, Colombia. 4 Clinica Imbanaco, Cali, Colombia. 5 Fundación Valle de Lili, Cali, Colombia. 6 Hospital General Manuel Ygnacio Monteros-IESS, Loja, Ecuador. 7 Hospital de Especialidades Carlos Andrade Marín-IESS, Quito, Ecuador. 8 Hospital Teodoro Maldonado Carbo-IESS, Guayaquil, Ecuador. 9 Hospital Universal Cartago, Cartago, Costa Rica. 10 Caja Costarricense de Seguro Social, Alajuela, Costa Rica Background: Identifying the transition from asymptomatic carrier to symptomatic disease in hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) remains a clinical challenge. Standard neurological examinations and clinical scales may miss early nerve involvement, whereas neuromuscular ultrasound can detect structural nerve changes at subclinical stages. This study aims to characterize the chronological pattern of nerve hypertrophy and to identify the earliest sites of structural involvement in a Latin American hATTR-PN cohort. Methods: We conducted a multicenter study of 105 transthyretin (TTR) mutation carriers from Colombia, Costa Rica, and Ecuador. Clinical status was assessed using the Neuropathy Impairment Score (NIS), classifying participants as asymptomatic (NIS = 0; n = 82) or symptomatic (NIS > 0; n = 23). The cohort included 58 women (55.2%), and multiple TTR genotypes were represented, mainly Ser43Asn (33.3%), Val50Met (24.8%), and Val142Ile (22.9%). We measured the cross-sectional area (CSA) of 14 nerve sites by neuromuscular ultrasound, encompassing distal and proximal segments of the median, ulnar, tibial, peroneal, sural, brachial plexus, and vagus nerves. To account for demographic differences, CSA values were converted into adjusted Z-scores using generalized additive models controlling for age, sex, country, and mutation group. We then estimated age-related trajectories for each nerve and defined the onset of structural hypertrophy as the age at which the adjusted Z-score crossed 0.5. Results: Ultrasound revealed a clear distal-to-proximal pattern of nerve hypertrophy. The median nerve at the wrist had the earliest modeled onset of structural involvement (57.4 years), followed by the tibial nerve at the ankle (73.0 years). Subsequent sites of involvement included the median nerve at the elbow (75.8 years), the ulnar nerve at the elbow (80.1 years), the vagus nerve (80.1 years), the peroneal nerve (81.5 years), the median nerve at the axilla (85.8 years), and the ulnar nerve at the forearm (87.2 years). In symptomatic individuals, CSA was significantly larger at key distal sites. The largest hypertrophy occurred at the median nerve at the wrist (mean Z = 0.90), followed by the tibial nerve at the ankle (Z = 0.72) and the sural nerve (Z = 0.70). Intermediate enlargement was noted at the median and ulnar nerves at the elbow, whereas proximal structures such as the brachial plexus showed minimal or no hypertrophy. By contrast, asymptomatic carriers had adjusted Z-scores near zero across all sites, despite early trajectory changes in the most susceptible nerves. Conclusions: In this Latin American cohort, ultrasound-detected nerve hypertrophy followed a consistent distal-to-proximal pattern, with the median nerve at the wrist as the earliest site of structural involvement. Detecting enlargement at this location in carriers with normal neurological examinations may indicate early structural conversion. Focusing on these high-susceptibility distal nerves could provide a pragmatic framework for ultrasound surveillance in hATTR-PN.

Dr. Rebecca Leung 1,2,3 , Dr. Laurie McLaughlin 1 , Dr. Kristen Lefever 1 , Dr. Lori Mackay 1 , Assoc. Prof. Stefan Blum 1 1 Princess Alexandra Hospital, WOOLLOONGABBA, Australia. 2 Queensland Children's Hospital, South Brisbane, Australia. 3 Sunshine Coast University Hospital, Birtinya, Australia Background: Juvenile myasthenia gravis (JMG) is a rare antibody-mediated disorder of the neuromuscular junction, with clinical manifestations ranging from isolated ocular involvement to severe generalized weakness that may be life-threatening and require ventilatory support. While many patients respond to conventional immunosuppressive therapies, a subset experience persistent or refractory disease. Emerging targeted therapies, including complement component C5 inhibition and neonatal Fc receptor (FcRn) antagonism, have demonstrated efficacy in adults with refractory generalized myasthenia gravis (gMG); however, data in adolescents with severe JMG remain limited. Methods: NA Results: Case: We describe an adolescent female with severe, treatment-refractory JMG associated with malignant thymoma, who demonstrated a marked clinical response to complement inhibition. The patient was initially diagnosed with a complex thymic cyst at age 12, managed with incomplete surgical resection. At age 17, she re-presented with a four-month history of progressive generalized weakness, dysarthria, recurrent falls, and ptosis. Investigations confirmed anti–acetylcholine receptor antibody–positive (AChR-Ab+) gMG. Chest imaging demonstrated residual thymic tissue, and repeat resection identified a WHO type B3 thymoma with invasion into the lung and pericardium. Surgical margins were positive, and the patient subsequently received 30 fractions of adjuvant radiotherapy. Over the following months, she experienced severe generalized disease, with Myasthenia Gravis Composite (MGC) scores ranging from 11 to 21, and three myasthenic crises requiring intensive care admission. This occurred despite aggressive immunotherapy, including high-dose oral prednisolone (up to 50 mg daily), intravenous immunoglobulin, plasma exchange, and rituximab. Ongoing disease activity remained highly disabling, with MGC scores 6 months after therapy initiation of 8–10 at outpatient review, resulting in school absenteeism and significant functional limitation. Treatment-related complications included herpes zoster infection, right subsegmental pulmonary emboli requiring anticoagulation, iron-deficiency anaemia, and corticosteroid-related adverse effects, including Cushingoid features (20 kg weight gain, and hyperglycaemia). Zilucoplan, a subcutaneous, self-administered macrocyclic peptide inhibitor of complement component C5, was initiated approximately nine months after diagnosis. Within three months, the patient’s MGC score improved to 0, allowing plasma exchange to be tapered and discontinued. Oral prednisolone was successfully reduced to 8 mg daily. Disease remission was sustained, with persistent MGC scores of 0, enabling full return to school and regular physical activity, including weight training. Zilucoplan was well tolerated, with no reported adverse effects over a nine-month treatment period. Conclusion: This case demonstrates the efficacy and tolerability of complement C5 inhibition with zilucoplan in an adolescent patient with severe, thymoma-associated, AChR-Ab+ refractory gMG. Complement inhibition may represent a valuable therapeutic option in selected cases of refractory JMG, facilitating disease control and substantial reduction in exposure to conventional immunosuppressive therapies.

Prof. Birouk Nazha 1 , Assoc. Prof. Tamaoui Leila 1 , Prof. Bouhouche Ahmed 2 1 Department of Neurophysiology, hospital of specialities, university hospital Ibn Sina, Mohamed V university, Rabat, Morocco. 2 Laboratory of Neurogenetics, hospital of specialities, university hospital Ibn Sina, Mohamed V university, Rabat, Morocco Background: Congenital myasthenic syndrome is due to mutations in the genes encoding the proteins of neuromuscular junction either in post-, pre-, or intra-synaptic components. The clinical presentation is usually in favour of myasthenia with ophtalmoparesis and muscle weakness exacerbated by exercise but pseudo-myopathic presentation is possible. Age at onset is usually congenital with possibly congenital respiratory distress and delayed motor millstones. Some patient can experience first symptoms later on and possibly at adult age. The aim of this study is to analyse clinical, electrophysiological, genetic and therapeutic aspects in a cohort of 13 cases belonging to 8 Moroccan Families. Methods: All patients underwent clinical evaluation for neonatal hypotonia, respiratory and/or feeding issues at birth, ptosis and ophtalmoparesis at birth, motor millstones development and main clinical symptoms (distribution of muscle weakness in limbs, bulbar, facial and ocular muscles), functional disability and orthopaedic deformations. All patients had nerve conduction study and 3 Hz repetitive nerve stimulation for NMJ abnormalities. Genetic study consisted of exome analysis. Patients received symptomatic treatment and were followed up during 1 to 24 years. Results: 13 patients belonging to 8 families were studied. All parents were 1 st degree consanguineous except in one family. 3 families had more than one affected member. Onset of the disease was congenital in 9 cases, under 3 years in 3 cases and adult age in 1 case. We identified 3 different genotypes and phenotypes. 5 families (8 patients) had homozygous mutation in epsilon subunit of acetylcholine receptor (CHRNE) with 3 different and rare pathogenic variants identified. The p.Asn452GlufsTer4 mutation was the most frequent and concerned 3 different families. The p.Gly355AlafsTer30 mutation was diagnosed in one family (3 patients) and the NP_000071 .1p? pathogenic variant in 1 family. These 5 families had similar phenotype with ptosis and ophtalmoparesis noticed at birth in most cases, all patients had moderate phenotype with walking distance limit at 100 to 500 m. All patients were noticeably improved with anticholinesterases and became asymptomatic except for ptosis and ophtalmoparesis. One family with 3 affected members had homozygous DOK7 novel mutation (p.Leu389ProfsTer66). All had congenital onset with stridor, feeding difficulties and delayed age of walking. The phenotype was severe in 2 cases with respiratory restrictive syndrome leading to death in one case. The two remaining were dramatically improved under salbutamol with sustained effect. One patient had heterozygous pathogenic variant in CHRNA1 (pGly173Ser), he was normal at birth and harboured first symptoms at the age of 35 years with progressive and bilateral weakness of writs and fingers extensors. Nerve conduction study showed bifid motor action potentials with postsynaptic conduction block. The patient had partial improvement with salbutamol and fluoxetine. Genetic study is still ongoing in a patient. Conclusion: The CHRNE homozygous mutations were the most frequent with one novel homozygous mutation. One family had a novel DOK 7 homozygous pathogenic variant with typical reported phenotype. Only one patient, with a novel heterozygous CHRNA1 pathogenic variant, had a particular phenotype with late onset fingers and writs extensors which is rarely reported.

Prof. Fiore Manganelli Department of Neuroscience, Reproductive and Odontostomatological Science - University of Naples 'Federico II', Naples, Italy Background: Peripheral neuropathies represent a heterogeneous group of disorders embracing mononeuropathies, multineuropathies and polyneuropathies, with diverse etiologies including metabolic, toxic, inflammatory, hereditary, and infectious causes. Because of their clinical variability, establishing an accurate diagnosis requires a structured and stepwise diagnostic approach integrating clinical, electrophysiological, and laboratory data. Methods: The diagnostic approach to peripheral neuropathy is based on a systematic evaluation including detailed clinical history, neurological examination, and neurophysiological study. Nerve conduction studies and electromyography are used to define the pattern of nerve involvement (axonal vs. demyelinating, motor vs. sensory, focal vs. diffuse). Laboratory investigations are tailored according to the clinical and electrophysiological findings and may include metabolic, autoimmune, infectious, and genetic testing. Additional tools such as imaging, cerebrospinal fluid analysis, or nerve biopsy are considered in selected cases. Results: A structured diagnostic algorithm allows the identification of the neuropathy pattern and guides targeted investigations, improving diagnostic accuracy and reducing unnecessary tests. Neurophysiology plays a central role in classifying neuropathies and identifying potentially treatable forms such as inflammatory neuropathies. The integration of clinical and laboratory data facilitates differentiation between acquired and hereditary conditions and supports appropriate therapeutic decisions. Conclusion: A stepwise and multidisciplinary diagnostic strategy is essential for the accurate evaluation of peripheral neuropathies. Early recognition of the neuropathy pattern through clinical and neurophysiological assessment enables timely etiological diagnosis and improves patient management, particularly in treatable neuropathies.

Dr. Katherine Schutze 1,2 , Mr. Ruby Shehatha 3 , Ms. Kelly Beer 3,4 , Ms. Tanya Smith 4 , Mr. Matthew Bagg 2,5 , Ms. Althea Doverty 3,4 , Prof. Merrilee Needham 2,3,4,6 , Mr. Ian Cooper 3,4 1 Sir Charles Gairdner Hospital, Nedlands, Australia. 2 Notre Dame University, Fremantle, Australia. 3 Perron Institute, Nedlands, Australia. 4 Murdoch University, Murdoch, Australia. 5 Neuroscience Research Australia, Rendwick, Australia. 6 Fiona Stanley Hospital, Murdoch, Australia Background: Large language models (LLMs) have demonstrated safety and effectiveness in exercise prescription for the general population, though their advice is often less comprehensive than that of physiotherapists. Their potential value may be greater in rare disease populations, where access to specialist expertise is limited. Inclusion Body Myositis (IBM) is a rare inflammatory myopathy affecting older adults, characterised by a distinct pattern of muscle involvement and specific resistance exercise recommendations. The accuracy, safety, and appropriateness of LLM-generated exercise advice for individuals with IBM has not previously been evaluated. Methods: This study evaluated responses generated by ChatGPT to six predefined questions addressing muscle involvement, resistance exercise prescription, and strategies to reduce falls in individuals with IBM. Twelve physiotherapists from around the world participated, with clinician experience in IBM management averaging 9.2 years. Reviewers rated each response using a five-point rubric ranging from “comprehensive and accurate” to “wrong and unsafe.” Results: ChatGPT’s responses were judged to be safe and mostly accurate in five of the six assessed domains. Most responses demonstrated appropriate clinical reasoning and alignment with current IBM management principles, though they frequently lacked depth or specificity. Performance was strongest in general descriptions of muscle involvement and standard resistance exercise principles. Accuracy was reduced when prescribing exercise for individuals without antigravity movement, where advice was more limited and occasionally vague. Conclusion: ChatGPT generally provided safe and mostly accurate advice related to exercise prescription and falls management in individuals with IBM, though comprehensiveness was variable. In some domains, performance was notably strong, highlighting the potential of LLMs as adjunct tools in rare disease exercise prescription where specialist access is limited. Future studies may consider whether LLMs can be used to generate individualised longitudinal regimens. Whilst LLMs may be useful in the design of a program but the responsibility for safe exercise prescription remains with the human prescriber.

Dr. Margaux Poleur 1 , Dr. Stéphanie Delstanche 1 , Dr. Manon Hustinx 1 , Mr. Guillaume Parinello 2 , Ms. Noor Benmhammed 1 , Ms. Thao Nguyen Le Lam 2 , Ms. Camille Bisson 2 , Mr. Nicolas Bovy 1 , Dr. Céline Cluzeau 2 , Ms. Charline Dubois 1 , Mr. Damien Eggenspieler 2 , Prof. Laurent Servais 3,4 1 University department of neurology, CHR Citadelle, Liege, Belgium. 2 Sysnav, Vernon, France. 3 Department of Paediatrics, University and University Hospital of Liege, Liege, Belgium. 4 University of Oxford, Oxford, United Kingdom Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and is characterized by marked genetic and phenotypic heterogeneity, predominantly affecting distal muscles and sensory function. Progression is typically slow and often occurs over several decades. Current clinical outcome measures lack robustness and sensitivity to detect change over the course of a clinical trial. Wearable digital health technology (wDHT) enables passive collection of ambulation data in daily living. The qualification of a wDHT-derived variable, stride velocity 95 th centile (SV95C), as a primary endpoint in Duchenne muscular dystrophy by the European Medicines Agency raised interest in applying similar approaches in other neuromuscular disorders. We hypothesized that SV95C and digital variables derived from the same wDHT, Syde, could provide a representative and sensitive assessment of motor function in daily life of patients with CMT. Methods: Patients with CMT were enrolled in two natural history studies, ActiLiege-Next and ActiLiege-Adult, and underwent clinical evaluation every 6 months. Participants wore one sensor at each ankle daily for the first 3 months and then for 1 month every 6 months. We started by investigating a portfolio of digital outcomes including SV95C, maximal walking distance (WD95C), and number of strides per hour (NbStrides/h) and will expand to other variables that could better evaluate gait impairment due to distal weakness. The reliability of digital measures was assessed by comparing two 2-week periods of each recording month using intraclass correlation coefficient (ICC). Discrimination between patients and controls (enrolled in a separate cohort) was determined using a Mann Whitney U test. Correlations of digital measures with 6-minute walk test (6MWT), 10-meter walk test (10MT), CMT examination score version 2 (CMTESv2), and overall neuropathy limitation score (ONLS) were tested using Spearman’s rank correlation coefficient. Longitudinal changes were assessed using Wilcoxon signed-rank test. Results: To date, 24 patients were enrolled (median age [range]: 36 years [6-85]) and compared to 45 healthy volunteers (40 years [5-84]). Most subjects were adherent to wearing the ankle sensors: >85% of them recorded at least 50 hours of data at baseline. Analysis of the first 12 enrolled patients showed that SV95C reliability was excellent with intraclass correlation coefficients of 0.99 for patients and 0.90 for controls at baseline, whereas reliability of WD95C and NbStrides/h varied between 0.64 and 0.99. Mean baseline SV95C was significantly higher in controls than in patients (p<0.001), but WD95C and NbStrides/h baseline values were similar between the two groups. SV95C correlated strongly with 6MWT (r = 0.70), 10MT (r = −0.94), ONLS (r = −0.75), and CMTESv2 (r = −0.52). Preliminary longitudinal analysis in the first 3 patients with 6-month follow-up data showed limited changes from baseline for both digital and conventional clinical measures. All available longitudinal results will be presented at the congress. Conclusion: Further work is needed to confirm the good metric properties observed for SV95C in a larger population, to evaluate sensitivity to detect change versus gold standards and to expand the set of valid wearable-derived variables with measures meaningful for CMT.

Asst. Prof. HALLAL SIHAM 1 , Dr. BENCHAABI OUISSEM 2 , Prof. NOUIOUA SONIA 2 , Prof. YARGUI LYECE 1 1 CHU MUSTAPHA, ALGIERS, Algeria. 2 EHS CHERCHEL, BLIDA, Algeria Background: Spinal muscular atrophy (SMA) is a form of motor neuron disease caused by a mutation in the survival motor neuron of gene (SMN1), which results in a wide disease spectrum affecting children and adults. There are four subtypes of SMA depending on age of onset and maximum acquired motor function. Spinal Muscular Atrophy (SMA) in adults (often Type 4) is a genetic condition causing progressive muscle weakness, typically starting after age 18 with slow progression, usually mild, affecting leg muscles first, but with normal life expectancy and rare impact on breathing/swallowing, managed with physical therapy, supportive care. Methods: Our work represents a retrospective descriptive study of 10 years of diagnosis spinal muscular atrophy in adults (January 2015- December 2025), performed in the only referral laboratory that diagnoses SMA in Algeria by amplification with ACRS method to search a deletion homozygote of exon 7. Results: We analyze a total of 1620 patients , which 526 cases were confirmed as SMA. The frequency of the disease in our series was 33% 21 % of them are type 4, with an average age of symptoms apparition at 31 years. 42 % of our patients were born into a consanguineous marriage. The most frequent reasons for consultation were functional impotence of the lower limbs, and fatigue, and fasciculations. Conclusion: The adult form of SMA is a frequently suspected etiology in neuromuscular consultations. Diagnosing adult SMA involves ruling out other neuromuscular conditions with tests like EMG, muscle enzyme assay, and DNA testing, focusing on symptoms like progressive muscle weakness. In our country treatments were not yet available, management is multidisciplinary, with a key goal of avoid disability, preventing complications like scoliosis, respiratory issues.

Dr. Ignazio Giuseppe Arena , Dr. Selene Francesca Anna Drago, Dr. Cristian Usbergo, Prof. Vincenzo Macaione, Prof. Mhammed Aguennouz, Prof. Carmelo Rodolico, Prof. Antonio Toscano, Prof. Olimpia Musumeci University of Messina, Messina, Italy Background: Primary mitochondrial myopathies (PMMs) are disorders of oxidative phosphorylation characterized by predominant muscle involvement, impaired energy production, and reduced exercise tolerance. Identifying clinically meaningful outcome measures remains a major challenge in neuromuscular practice and clinical research. Methods: To assess functional performance tests, patient-reported outcome measures (PROMs), laboratory biomarkers, and clinical scales in patients with PMMs evaluated during routine clinical follow-up, and to explore associations among these measures. Results: Forty patients with genetically confirmed PMMs (19 with mtDNA mutations, including single deletions, and 21 with nDNA mutations) were evaluated during routine clinical follow-up over a four-year period. All patients underwent functional assessments including the Six- or Twelve-Minute Walk Test (6MWT, 12MWT), Timed Up and Go test (TUG), Five Times Sit-to-Stand test (5XSTS), spirometry, and the Newcastle Mitochondrial Disease Adult Scale (NMDAS). Patient-reported outcome measures addressing physical function and daily activity were also collected. Twenty patients additionally underwent cardiopulmonary exercise testing (CPET) according to standardized protocols, with assessment of peak oxygen uptake (VO₂peak), maximal workload (Wmax), and ventilatory and cardiovascular responses. Laboratory evaluations included serum levels of GDF15, FGF21, and neurofilament light chain (sNfl). Associations between functional, clinical, patient-reported, and laboratory variables were explored using non-parametric correlation analyses. Conclusion: In PMM patients evaluated in a clinical setting, functional performance tests and PROMs provide complementary information on disease burden and functional limitation. The 12MWT reflected objective exercise capacity assessed by CPET, while serum neurofilament light chain was associated mostly with neurological involvement and overall clinical severity. These findings support a multidimensional approach to patient assessment in primary mitochondrial myopathies.

Dr. Sophie Lehnerer 1 , Dr. Raffaele Iorio 2,3 , Dr. Francisco JR de Rivera Garrido 4 , Dr. Mazen M Dimachkie 5 , Dr. Lea Gerischer 6,7 , Dr. Séverine Bieuvelet 8 , Dr. Loïc Carment 8 , Miss Blandine Landrieu 8 , Miss Natacha Pesic-Heuvrard 8 , Miss Noura Sellami 8 , Dr. Saad Zinaï 8 , Dr. Elina Järvinen 9 , Dr. John Vissing 10 , Prof. Pascal Laforêt 11 1 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Berlin, Germany. 2 Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy; Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 3 Neurology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 4 Reference Unit of Hereditary Ataxias and Paraplegias, Department of Neurology, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. 5 Department of Neurology, University of Kansas Medical Center, Kansas City, United States. 6 Department of Neurology With Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin,, Berlin, Germany. 7 Neuroscience Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 8 Ad Scientiam, Paris, France. 9 Merck OY, Espoo Finland,an affiliate of Merck KGaA, Darmstadt, Germany. 10 Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 11 Nord-Est/Ile-de-France Neuromuscular Reference Center, UMR 1179, Neurology Department, Raymond-Poincaré Hospital, Garches, FHU PHENIX, UVSQ Paris-Saclay University, Garches, France Background: Generalized Myasthenia Gravis (gMG) is a heterogeneous antibody-mediated disease characterized by a fluctuating and fatigable muscle weakness, making it difficult for people with gMG to predict or recall day-to-day fluctuations. Digital health technologies could enhance disease monitoring by integrating wearable sensors, electronic patient-reported outcomes (ePROs) and active assessments to provide objective, longitudinal data. We have developed an innovative investigational medical device combining passive monitoring via the ActiGraph LEAP (physical activity, sleep, heart and respiratory rate), smartphone-based active functional tests (ptosis, dysarthria, upper, lower limb and respiratory muscle weakness) and ePROs (MG-ADL; MG-QoL-15r; NeuroQoL fatigue and infection tracking). By combining the passive day-to-day, active digital tests, and standardized clinical questionnaires, we aim to depict a comprehensive portrayal of gMG. In this regard, the international Harmony 360 study ( NCT07323316 ) is designed to assess the feasibility of using this tool to detect changes in disease trajectory over 12 months. Methods: HARMONY 360 is a prospective, single-arm, multi-center, exploratory study enrolling 100 adults with gMG in five European countries (Denmark, France, Germany, Italy and Spain) over 12 months. Participants will attend in-clinic visits at Day 0 (inclusion visit), Day 180 and Day 360 (exit visit), during which socio-demographic, clinical data, and Quantitative MG (QMG) scores will be collected. Between visits, participants will wear the ActiGraph LEAP continuously, complete monthly active test sessions (morning and evening), and ePROs twice a month (Figure). Results: Recruitment is scheduled to begin in April 2026, with a planned study duration of 12 months. Conclusion: HARMONY 360 study will describe the feasibility of our investigational tool in capturing and predicting changes in disease trajectory in people with gMG using continuous passive and active data. Findings will inform optimization of the device and a subsequent validation study toward more personalized generalized Myasthenia Gravis care.

Dr. Tanya Stojkovic 1 , Dr. Marc Bitoun 2 1 APHP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 2 Inserm, Sorbonne University, research center of Myology, Paris, France Background: Hereditary neuromuscular diseases include a broad range of genetic disorders affecting muscle, peripheral nerve, or both. Traditionally, hereditary myopathies (such as muscular dystrophies, congenital and metabolic myopathies) were distinguished from hereditary neuropathies (like Charcot-Marie-Tooth disease). However, increasing recognition of overlapping forms where muscle and nerve involvement coexist and intertwine is challenging this distinction. High-throughput molecular biology techniques over the last 20 years have identified mutations in the same gene causing both neuropathies and myopathie Methods: Diagnosis involves a multidisciplinary approach including clinical evaluation,biomarkers such as creatine kinase levels, electrophysiology (EMG showing both neurogenic and myogenic patterns), muscle biopsy disclosing in some cases mixed neurogenic and myopathic features, and muscle imaging . Advances in exome and genome sequencing increasingly highlight overlaps between genes associated with myopathies and neuropathies. Temporality and spatial distribution of muscle involvement vary; neurogenic damage may appear before myopathy or vice versa, and different muscles may be differently affected. Results: Several genes illustrate this overla: • Mitochondrial genes (e.g., MELAS, MERRF syndromes) that cause sensory and motor neuropathies along with muscle weakness. • LMNA (encoding nuclear lamins A/C) and DNM2 (encoding dynamin 2), where mutations can lead to either Charcot-Marie-Tooth neuropathy or myopathy depending on the mutation. • BAG3, DES, CRYAB, mutated in both myofibrillar myopathies and isolated or combined neuropathies. • Genes such as VCP, MATR3, SQTM1, and TIA1 involved in multisystem proteinopathies affecting nerve, brain, muscle, and bone. • HSPB8 and SPTAN1, primarily linked to distal motor neuropathy, also implicated in distal and axial myopathies or mixed neurogenic-myogenic phenotypes. Conclusion: Advances in high-throughput sequencing have revealed that mutations in a single gene can manifest as neuropathic, myopathic, or mixed neuro-myopathic phenotypes. This genetic overlap highlights the complexity of neuromuscular disease pathophysiology, where the same molecular defect can differently affect muscle and nerve tissues depending on factors such as cell type metabolism, energy dependence, or cytoskeletal structure.Future progress in sequencing technologies and bioinformatics will likely uncover additional overlapping genes and mechanisms, further blurring the boundaries between neuropathies and myopathies and opening new avenues for understanding and treating these complex diseases.

Dr. Otto Hernandez Fustes 1,2 , Dr. Carlos Arteaga Rodriguez 3,4 , Dr. Hélio Ghizoni Teive 1 1 Federal University of Paraná, Curitiba, Brazil. 2 Clinics Complex Hospital at Federal University of Paraná, Curitiba, Brazil. 3 Positivo University, Curitiba, Brazil. 4 Pontifical Catholic University of Paraná, Curitiba, Brazil Background: The term “ataxia” refers to a lack of coordination in movements and was recognized in nineteenth-century medicine, initially as a manifestation of other neurological diseases. In 1863, the German physician Nicolas Friedreich made the first clinical description of a familial hereditary ataxia, characterized by childhood onset, autosomal recessive inheritance, and progressive neurological symptoms. Then in 1893, the French neurologist Pierre Marie identified another type of hereditary ataxia with a late-onset autosomal dominant pattern, distinct from that described by Friedreich. These contributions established the conceptual foundations for hereditary ataxias today. In Cuba, during the second half of the nineteenth century (colonial period), local physicians began documenting cases of “locomotor ataxia,” a term coined by Duchenne de Boulogne in 1864. Cuban Heredoataxia, the original description of spinocerebellar ataxia type 2 (SCA2), is an autosomal dominant inherited neurodegenerative disease that affects the central nervous system, particularly the cerebellum, brainstem, and spinal cord. Methods: This qualitative, historical-descriptive study analyzes the historical aspects of Cuban Heredoataxia. Methodological Procedures a) Literature and Documentary Review A systematic review of the scientific and documentary literature was conducted, including articles indexed in PubMed, SciELO, LILACS, and Google Scholar. The keywords used were: Cuban Heredoataxia, spinocerebellar ataxia type 2, history of medicine in Cuba, Cuban population genetics, and neurodegenerative diseases. b) Interviews with Experts Results: Spinocerebellar ataxia type 2 (SCA2) has a worldwide distribution, with its first clinical description in 1971, in India, by Wadia & Swami. However, SCA2 is most frequently found in Cuba (in the province of Holguín) and is recognized worldwide as Cuban heredoataxia. In 1989, Orozco et al. published an outstanding paper on SCA2 describing its clinical, neuropathological, and biochemical features. This article proposes a historical analysis of Cuban Heredoataxia, based on a bibliographical and documentary review, with an understanding of the scientific path of research since its identification in the 1970s related to contemporary research strategies. The role of the four main Cuban researchers—Estrada, Valles, Orozco, and Pérez—is highlighted in the recognition of this rare disease. Conclusion: The first Cuban contributions to understanding Cuban Heredoataxia, currently known as spinocerebellar ataxia type 2, range from the historical identification of cases and families in Holguín to detailed clinical descriptions and large-scale population studies. The contributions of Cuban neurologists, supported by international collaborations, allowed delineation of the clinical profile, genetic pattern, and regional concentration of the disease. Cuban Heredoataxia offers a unique case in the history of Latin American medicine, combining high local incidence, a structured medical response, and a socially engaged approach. The historical study of the disease allows reflection on the links between genetics, territory, and public policies, highlighting the role of science in contexts of limited resources.

Dr. Omar Keritam 1,2 , Dr. Raphael Wurm 1,2 , Dr. Daniel Bormann 1,2 , Mr. Felix Gruber 3 , Dr. Martin Krenn 1,2 , Dr. Gudrun Zulehner 1,2 , Dr. Jakob Rath 1,2 , Prof. Fritz Zimprich 1,2 , Prof. Hakan Cetin 1,2 1 Department of Neurology, Medical University of Vienna, Vienna, Austria. 2 Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria. 3 Austrian Federation of Social Insurances, Vienna, Austria Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by the progressive loss of motor neurons, leading to muscle weakness, respiratory failure, and ultimately death within a few years of disease onset. In Austria, the average annual incidence and prevalence of ALS between 2009 and 2011 were 3.2/100,000 person-years and 9.1/100,000 persons, respectively. Although recent studies suggest that the global burden of the disease has increased over past decades, the trajectory of epidemiological metrics in Austria after 2011 remain unknown. Methods: Hospital discharge records and riluzole prescription databases were used to identify ALS cases between 2016 and 2023. The capture–recapture method was then applied to estimate the incidence and prevalence of ALS in Austria. Survival was analysed in dependence of age, gender, and riluzole/physiotherapy. Furthermore, the relationship between disease prevalence and the ratio of deaths to prevalent cases (death-to-case ratio) in a given year was analysed using Pearson’s correlation. Results: A total of 3,344 patients were identified during the study period, of whom 44.3% were female. While the corrected annual incidence remained stable (5.2/100,000 person-years in 2016 and 4.8/100,000 person-years in 2023), the prevalence increased steadily over the same period, rising from 8.6 to 14.5/100,000 individuals. Median survival was 605 days (95% CI 569-638). Younger age at diagnosis, male sex and physiotherapy were associated with longer survival. The death-to-case ratio decreased during the study period, from 0.32 in 2016 to 0.22 in 2023, which correlated negatively with the corresponding prevalence numbers (r=-0.85, p=0.0019). Conclusion: In this study, we report on the epidemiology of ALS in Austria between 2016 and 2023. Notably, while the annual incidence remained stable over the study period, our findings indicate an increase of prevalence, most likely due to reduced mortality rates. Our results underscore the need for national healthcare policies to address the challenges posed by the growing disease burden.

Dr. Channa Hewamadduma 1,2 , Dr. Miriam Freimer 3 , Dr. M. Isabel Leite 4 , Dr. Angelina Maniaol 5 , Dr. Kimiaki Utsugisawa 6 , Dr. Michael D. Weiss 7 , Dr. Jos Bloemers 8 , Dr. Babak Boroojerdi 9 , Dr. Paul Mahoney 10 , Dr. Natasa Savic 11 , Dr. James Howard 12 1 Academic Neuromuscular Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom. 2 Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom. 3 Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Canada. 4 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. 5 Department of Neurology, Oslo University Hospital, Oslo, Norway. 6 Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan. 7 Department of Neurology, University of Washington Medical Center, Seattle, United States. 8 UCB, Brussels, Belgium. 9 UCB, Monheim, Germany. 10 UCB, Slough, United Kingdom. 11 UCB, Bulle, Switzerland. 12 Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, United States Background: Patients with generalised myasthenia gravis (gMG) experience fluctuating muscle weakness, leading to a diverse range of symptoms that can impact quality of life. In RAISE (Phase 3, NCT04115293 ), zilucoplan, a potent macrocyclic complement component 5 inhibitor, showed statistically significant and clinically meaningful improvements in myasthenia gravis (MG)-specific outcomes in patients with anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) gMG. These improvements were sustained over 120 weeks in the ongoing, Phase 3, open-label extension, RAISE-XT ( NCT04225871 ). This post hoc analysis assessed change in item scores for MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG) and MG Quality of Life 15-item revised (MG-QoL15r). Methods: In RAISE, adults with anti-AChR Ab+ gMG were randomised to self-administer once-daily placebo or zilucoplan 0.3 mg/kg. Adults who completed RAISE received zilucoplan 0.3 mg/kg in RAISE-XT. Analyses of MG-ADL, QMG and MG-QoL15r (interim data cut-off: 11 November 2023) included the proportion of patients showing no symptoms, improvement and no change from baseline to Week 12 (RAISE), and from double-blind baseline to Week 120 (RAISE-XT). Change from double-blind baseline (CFB) to Week 120, and safety, were assessed in RAISE-XT. Results: In RAISE, a greater proportion of patients improved from baseline to Week 12 or had no symptoms at Week 12 across MG-ADL items with zilucoplan than placebo ( Table 1 ). Improvements in the zilucoplan group further increased and were sustained in RAISE-XT to Week 120 ( Table 1 ). At Week 120 (n=73), mean (standard error) CFB for MG-ADL items was: chewing, −0.85 (0.09); swallowing, −0.75 (0.10); talking, −0.86 (0.10); breathing, −0.71 (0.09); double vision, −1.04 (0.14); eyelid droop, −1.44 (0.13); brush hair/teeth, −0.96 (0.11) and rise from chair, −0.79 (0.11). Similar results were observed for QMG and MG-QoL15r. Treatment-emergent adverse events occurred in 97.0% (n=194/200, RAISE-XT) of patients. Conclusion: Treatment with zilucoplan showed improvements in a greater proportion of patients across individual items in MG-specific outcomes at Week 12 versus placebo. During the extension study, the proportion of patients demonstrating these improvements further increased and were sustained through to Week 120. These data show that treatment with zilucoplan may provide benefit across a broad range of signs and symptoms of MG. Funding: UCB.

Prof. Sarah Hoffmann 1 , Dr. Sonja Katz 2 , Dr. Paolo Doksani 1 , Dr. Frauke Stascheit 1 , Dr. Jan D. Lünemann 3 , Dr. Jana Zschuentzsch 4 , Dr. Maike Stein 1 , Dr. Lea Gerischer 1 , Dr. Menekse Oezturk 5 , Dr. Meret Herdick 1 , Dr. Adela Della Marina 6 , Dr. Amani Suboh 1 , Miss Carla Dusemund 1 , Prof. Michael Schroeter 7 , Prof. Andreas Meisel 1 , Dr. Annabel M Ruiter 8 , Dr. Martijn R Tannemaat 8 , Dr. Sophie Lehnerer 1 1 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Neuroscience Clinical Research Center (NCRC) and Integrated Myasthenia Gravis Center, Berlin, Germany. 2 Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Wageningen, Netherlands. 3 Department of Neurology, University and University Hospital of Münster, Münster, Germany. 4 Department of Neurology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany. 5 Ruhr University Bochum, BG University Hospital Bergmannsheil, Department of Neurology, Bochum, Germany. 6 Department of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, Essen, Germany. 7 Department of Neurology, University Hospital Cologne, Cologne, Germany. 8 Department of Neurology, Leiden University Medical Center, Leiden, Netherlands Background: Despite epidemiological and clinical evidence for a relevant role of sex in autoimmune myasthenia gravis (MG), understanding of sex-related heterogeneity and its implications for care remains limited. This study aimed to assess sex-related differences in MG and evaluate machine learning (ML) models for sex prediction and delineation of sex-related clinical patterns using two independent registry-based populations. Methods: We combined conventional age-adjusted group comparisons with unsupervised (PCA/UMAP) and supervised (Random Forest Classifier) ML models to conduct a cross-sectional analysis of data from the German Myasthenia Gravis Registry (MyaReg), a multicenter national cohort including 1814 patients with autoimmune MG. We validated the predictive properties of our model using external data from the Dutch MG registry (n=419). Variables included age at disease onset and diagnosis, time to diagnosis, disease severity (QMG, MG-ADL), fatigue, antibody status, electrophysiological and pharmacological test results, therapeutic strategies, and comorbidities. Model explainability was assessed using SHAP. The main outcome was biological sex (female or male). Results: In MyaReg, 56.2% (n=1019) of patients were female. Compared with men, women were significantly younger at disease onset (mean 42.9 vs. 56.9 years) and had longer time to diagnosis (mean 2.2 vs. 0.9 years). Women also showed higher disease severity (QMG mean 7.8 vs. 5.1; MG-ADL mean 4.8 vs. 3.4), a higher rate of seronegative MG (20% vs. 13%), and more autoimmune comorbidities (38% vs. 13%). Unsupervised analyses revealed sex-related structure in the data (Figure 1A & 1B). Boruta identified seven key variables as sufficient for sex estimation. A Random Forest classifier trained on these features achieved reliable discrimination (ROC–AUC 0.734 in development cohort and 0.748 in validation cohort; figure 1C). SHAP analysis showed that sex estimation was primarily driven by younger age at disease onset and autoimmune comorbidity, followed by greater functional impairment (MG-ADL), diagnostic delay, history of thymectomy, fatigue, and affective symptoms (HADS) (Figure 1D). A subset of female patients misclassified as male (24%) exhibited an intermediate clinical pattern, sharing characteristics with the male cohort consistent with a phenotypic continuum. Conclusion: ML provides a framework to uncover sex-related signatures in MG, offering complementary insights to classical statistical comparisons. Our results reveal a reproducible, clinically meaningful pattern of sex-associated clinical features and emphasize the importance of considering both biological and clinical management related factors in understanding disease expression and access to care. ML-based methods may prove valuable in stratifying patients for personalized and equitable management in MG.

Dr. Otto Hernandez Fustes 1,2 , Dr. Ádria Rodrigues da Silva 2 , Dr. Cláudia Suemi Kamoi Kay 2 , Dr. Paulo Jose Lorenzoni 1,2 , Dr. Renata Dal-Pra Ducci Cirino 1,2 , Dr. Paula Raquel do Vale Pascoal Rodrigues 2 , Dr. Erika Christina Silva 2 , Dr. Rosana Hermínia Scola 1 1 Federal University of Paraná, Curitiba, Brazil. 2 Clinical Complex Hospital at Federal University of Paraná, Curitiba, Brazil Background: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disorder caused by mutations in the transthyretin (TTR) gene. Mutations in the TTR gene lead to structural instability of the protein, resulting in tetramer dissociation, release of mutant (or even wild-type) monomers, aggregation into amyloid fibrils, and extracellular deposition. These deposits compromise multiple organs, most notably the peripheral nervous system and the heart. Over 130 TTR variants have been identified, most of which are pathogenic. The most common worldwide is Val30Met—endemic in regions such as Portugal, Brazil. The clinical features of ATTRv-PN depend on the types of nerve fibers affected, which in turn are influenced by whether the disease presents with early-onset (<50 years) or late-onset (≥50 years), as well as by the disease stage. Methods: A case presentation. Results: An 82-year-old man with a history of hypertension, undergoing treatment for heart failure, presented with chronic diarrhea associated with hypotension, dehydration, and decline in overall condition. He reported a two-year history of progressive muscle weakness initially affecting the distal region of the right lower limb, later involving the contralateral limb, accompanied by paresthesias. Approximately one year prior, he developed difficulty grasping objects, dysphagia, dysphonia, and recurrent diarrheal episodes. Physical examination revealed tetraparesis, predominantly distal and slightly asymmetric, inability to ambulate, and axial instability while seated; absent patellar and Achilles reflexes; globally reduced tactile and pain sensation, more pronounced up to the knees and elbows, with loss of joint position sense and reduced vibration sense to the patellar level. Electroneuromyography revealed an axonal sensorimotor polyneuropathy. Minor salivary gland biopsy revealed material compatible with amyloid, and genetic testing for hereditary transthyretin (TTR) amyloidosis identified the V30M variant. Conclusion: In the present study, we draw attention to the late onset of clinical manifestations in ATTR with polyneuropathy (PN), presenting an 82-year-old man with a length-dependent, predominantly distal, asymmetrical axonal sensorimotor polyneuropathy associated with marked autonomic symptoms and cardiac involvement. In the context of hereditary transthyretin amyloidosis, recognizing late-onset cases is crucial, as these patients often present with manifestations that pose particular diagnostic challenges in primary healthcare settings. Such cases are frequently misdiagnosed as idiopathic axonal neuropathies or other more common conditions in the elderly population. Therefore, a high index of suspicion should prompt healthcare professionals to refer patients promptly to specialized centers.

Dr. Eleftheria Kokkinou , Dr. Doxa-Eleni Sareidaki, Dr. Iasonas-George Stamatakis, Dr. Anna Moustafellou, Mr. Dimitris Lignos, Mr. Nikolaos Mouzis, Mr. Kosmas Lymperatos, Ms. Miranta Pavlou, Ms. Ilianna Psichari, Ms. Ilianna Papadaki, Dr. Marina Katsalouli Department of Neurology, Children's Hospital “Agia Sofia”, Athens, Greece Background: Guillain-Barré Syndrome (GBS) is an acute immune-mediated neuropathy often triggered by infections. The most paediatric patients respond well to standard treatments. We present three cases of previously healthy children diagnosed with GBS. Methods: Case presentations Results: Case 1: A 7-year-old boy presented with sudden refusal to walk and severe bilateral leg pain beginning earlier that day. There was no history of trauma or systemic symptoms. On examination he demonstrated absent deep tendon reflexes in both legs. He was started on IVIG. Serologic testing revealed positive Parvovirus B19 IgM. The patient’s neurological function improved with physical therapy. After a 1 month hospitalization, he was discharged home with near-complete motor recovery and outpatient follow-up arranged for continued rehabilitation. Case 2: A 9-year-old male developed severe GBS (AMAN variant) and received timely standard treatment and intensive rehabilitation. Serologic test revealed positive Mycoplasma pneumoniae IgM. Despite receiving the above standard treatment and gradually neurological improvement, the patient had a prolonged hospital stay due to exhibition of signs of PTSD. Case 3: A 3-year-old female presented with rapid-onset quadriparesis and autonomic instability. Her neurological examination showed flaccid paralysis with areflexia. Stool cultures were positive for Campylobacter jejuni and both serum and cerebrospinal fluid (CSF) tested positive for anti-GT1a antibodies. The patient was treated with IVIG, PLEX and received intensive supportive care, including autonomic monitoring, nutritional support, and early physical rehabilitation. Gradual neurological recovery was observed and mechanical ventilation was weaned after clinical stabilization. Conclusion: These cases highlight the diverse clinical spectrum and variable outcomes of severe paediatric GBS, as well as they underscore the importance of early recognition, prompt immunotherapy and a multidisciplinary approach to optimize recovery.

Dr. Edouard Berling 1 , Dr. Ima Ebong 2 , Dr. Céline Tard 3 , Dr. Pascal Cintas 4 , Dr. Gaurav K Guliani 5 , Dr. Emmeline Lagrange 6 , Dr. Lindsay Malatesta 7 , Dr. Maud Michaud 8 , Dr. Aleksandra Nadaj-Pakleza 9 , Prof. Guillaume Nicolas 10 , Dr. Denis Ostrovskiy 11 , Dr. Yann Péréon 12 , Prof. Hélène Prigent 10 , Dr. Michael T Pulley 13 , Dr. Shruti M Raja 14 , Dr. Thomas Ragole 15 , Dr. Sabrina Sacconi 16 , Dr. Sara Takacs 17 , Dr. Clarissa Gorin 18 , Miss Aurore Balique-Laplanche 18 , Miss Noura Sellami 18 , Dr. Saad Zinaï 18 , Dr. Benjamin Yungher 19 , Dr. Bhaskar Dutta 19 , Dr. Loïc Carment 18 , Dr. Christophe A Scheiner 20 , Prof. Pascal Laforêt 10 1 APHP, Service de Neurologie, Hôpital Raymond Poincaré, Centre de Référence Nord‐Est‐Ile‐de‐France, FHU PHENIX, Garches, France. 2 Department of Neurology, University of Kentucky College of Medicine, Lexington, United States. 3 U1172, Centre de référence des maladies neuromusculaires Nord/Est/Île-de-France, service de Neurologie A, CHU de Lille, Lille, France. 4 Service de Neurologie, Centre de référence des Maladies Neuromusculaires, Toulouse University Hospital, Toulouse, France. 5 HealthPartners Institute, Bloomington. Department of Neurology, University of Minnesota, Minneapolis, MN HealthPartners Institute Neuroscience Research Center, St. Paul. Regions Hospital, Saint-Paul, United States. 6 Department of Neurology, Grenoble University Hospital, Grenoble, France. 7 Department of Neurology, Vanderbilt University Medical Center, Nashville, United States. 8 Centre de Référence des Maladies Neuromusculaires Nord-Est-Ile de France, Department of Neurology, University Hospital Centre, Nancy, France. 9 Centre de Référence des Maladies Neuromusculaires Nord-Est-Ile de France, Department of Neurology, University Hospital Centre, Strasbourg, France. 10 Nord-Est/Ile-de-France Neuromuscular Reference Center, UMR 1179, Neurology Department, Raymond-Poincaré Hospital, Garches, FHU PHENIX, UVSQ Paris-Saclay University, Garches, France. 11 Department of Neurology, Hofstra University, North shore, Mount Sinai School of Medicine. Neurological Associates of Long Island, Long Island, United States. 12 CHU Nantes, Reference Centre for Neuromuscular Disorders AOC, FILNEMUS, Euro-NMD, Hôtel-Dieu, Nantes, France. 13 College of Medicine-Jacksonville, Department of Neurology, University of Florida, Jacksonville, United States. 14 Department of Neurology, Box 3403, Duke University Medical Center, Durham, United States. 15 Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, United States. 16 Referral Centre for Neuromuscular Diseases, CHU Nice, Nice, France. 17 Department of Neurology. Indiana University School of Medicine, Indianapolis, United States. 18 Ad Scientiam, Paris, France. 19 Alexion, AstraZeneca Rare Disease, Boston, United States. 20 University of Tennessee Medical Center, Knoxville, United States Background: Generalized Myasthenia Gravis (gMG) is an autoimmune disease characterized by fluctuating and fatigable muscle weakness, making it essential to regularly assess symptom fluctuations outside of clinic visits. ME&MGTM is a software as medical device allowing remote and objective self-assessment of gMG symptoms through its five digital biomarkers My Eyelid, My Breathing, My Voice, My Arms and My Legs respectively measuring ptosis, respiratory function, dysarthria, upper and lower limb muscle weakness.In the ME&MGopen decentralized study, proof-of-concept was established with digital biomarkers’ scores correlating with the sub-scores of the MG Activities of daily living (MG-ADL) and MG quality of life 15-item scale-revised (MG-QoL15r) questionnaires. The ongoing DOMYA ( NCT05564936 ) study aims to validate ME&MG™ clinical performance by comparing individual’s Quantitative MG (QMG) sub-scores to home-measured ME&MG™ digital biomarkers’ scores in people with gMG and healthy controls. Methods: DOMYA recruited adult patients with anti-acetylcholine receptor antibody-positive gMG and healthy controls in France and the USA. Patients are monitored for one year with in-clinic visits at days 0, 90 and 365, along with monthly home-performed ME&MGTM active tests in the mornings and evenings. Healthy controls performed active tests in-clinic on day 0 and at home on day 1. Correlation coefficients between dBMKs and ptosis, speech, lung function, limb stretch sub-items of QMG, will be calculated to determine the clinical significance of dBMKs and, safety related to the medical device will be reported. Results: 94 people with gMG (France: 46; USA: 48) and 50 healthy controls (France: 22; USA: 28) have been recruited from 21 centers (France: 10; USA: 11). 23 patients (France: 10; USA: 13) completed the study with the remaining anticipated by October 2026. Conclusion: ME&MGTM digital biomarkers reliability, consistency and quality have been established in the ME&MGopen study. Validation of their clinical performance and safety in DOMYA will further support ME&MGTM adoption for objective tracking of gMG symptoms in routine practice supporting HCPs in monitoring the symptoms and in their decision-making processes.

Dr. Elke Schipani , Dr. B. Kalei Chang, Ms. JaNean Engelstad, Dr. William Litchy, Dr. Michelle Mauermann, Dr. B. Matthew Howe, Dr. Robert Spinner, Dr. P. James Dyck Mayo Clinic, Rochester, United States Background: Intraneural perineurioma is a rare, benign peripheral nerve tumor of youth that typically presents as a focal, motor-predominant neuropathy with axonal features. Demyelinating-appearing electrophysiologic findings and multifocal involvement are uncommon and may lead to a misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: A 15-year-old male presented with slowly progressive, asymmetric weakness involving the right upper and left lower limbs. Symptoms began around age 9 with right finger extensor weakness and exercise intolerance, with the eventual development of left foot drop. Despite prolonged treatment with IVIg and later subcutaneous immunoglobulin, disease progression was felt to have slowed but did not remit. Examination demonstrated high arched feet, a steppage gait, and distal predominant weakness in the right upper and left lower limbs, though mild, patchy weakness was noted in the other limbs. Reflexes were diminished in the right upper limb compared to the left, but lower limb reflexes were symmetric but diminished at the ankles. Sensation was essentially normal. Results: Serial nerve conduction studies over five years leading up to and inclusive of our evaluation demonstrated multifocal abnormalities, including low-amplitude or absent CMAPs and SNAPs, temporal dispersion, partial motor conduction block, slowed conduction velocities, prolonged distal latencies, and absent F-waves. Nerve conduction studies met the 2021 EAN/PNS electrodiagnostic criteria for motor conduction block, with >30% CMAP amplitude drop between the proximal and distal sites in two non-tibial nerves (ulnar and fibular) with preserved distal CMAP amplitudes (Figure 1A). Formal criteria for CIDP were not fulfilled due to the absence of qualifying temporal dispersion, prolongation of distal latencies, and widespread sensory demyelinating features. Needle EMG revealed chronic denervation with large polyphasic motor units and reduced recruitment affecting multiple elements of the right brachial plexus and, to a lesser degree, the left L4–5 distribution. MRI of the brachial and lumbosacral plexus demonstrated multifocal, fusiform nerve enlargement with marked T2 hyperintensity and avid, homogeneous enhancement involving the brachial plexus (Figure 1C) and bilateral sciatic nerves (Figure 1D), accompanied by denervation-related muscle edema and fatty atrophy. Extensive laboratory, CSF, genetic, and metabolic evaluations were unrevealing. Targeted fascicular biopsy of the right middle trunk revealed diagnostic features of intraneural perineurioma, including concentric perineurial cell proliferation with preserved nerve architecture and characteristic immunohistochemical staining (EMA-positive, S100-negative perineurial cells; Figure 1E-G). Conclusion: This case highlights multifocal intraneural perineurioma as an important mimic of demyelination, capable of producing conduction block–like electrophysiologic features and MRI findings suggestive of an acquired process. Recognition of the characteristic imaging pattern, treatment refractoriness, and pathologic confirmation is essential to avoid prolonged immunotherapy and to guide appropriate management.

Asst. Prof. Juhee Chae , Prof. Sun-Young Oh Department of Neurology, Jeonbuk National University College of Medicine and Hospital, Jeonju, Korea, Republic of Background: Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes mellitus. There is growing evidence that neuropathic processes from diabetes may affect not only peripheral somatic nerves but also the vestibular and autonomic systems. However, few studies have explored how DPN severity relates to different neurophysiological measures, including vestibular reflex parameters and autonomic sudomotor function. This study aimed to analyze associations between DPN severity and several neurophysiological measures: nerve conduction parameters, vestibular function, and autonomic function. Clarifying these associations may help us understand the complex mechanisms underlying DPN. Methods: In this cross-sectional study, we enrolled patients with DPN and healthy controls (HCs), and performed nerve conduction study, vestibular function tests (including cervical vestibular evoked myogenic potentials [cVEMP], ocular vestibular evoked myogenic potentials [oVEMP], and video head impulse test [vHIT]), as well as quantitative sudomotor axon reflex testing (QSART). We collected clinical data (age, gender, BMI, lipid profile, HbA1c, etc.). Standardized nerve conduction studies were performed, and composite scores for motor, sensory, and overall severity were calculated based on latency and amplitude abnormalities. Results: This study included 43 patients with DPN and 37 healthy controls. DPN showed a significantly higher age, diabetes duration, and prevalence of dyslipidemia and hypertension than HCs. DPN patients had significantly higher motor, sensory, and overall nerve conduction severity scores, longer cVEMP and oVEMP latencies, and reduced amplitudes. Within the DPN group, proximal leg QSART latency was associated with motor, sensory, and overall severity (r = 0.35–0.38, p = 0.012–0.024), while distal leg latency was significantly associated with sensory and overall severity (r = 0.31–0.38, p = 0.011–0.040). Increasing nerve conduction severity score was associated with delayed cVEMP latencies, and the overall severity score was correlated with both P1 (r = 0.30, p = 0.051) and N1 latencies (r = 0.26, p = 0.089). Vestibulo-ocular reflex gains were not correlated with DPN severity. Conclusion: Our findings show that disease severity in DPN is associated with latency-dominant neurophysiological abnormalities across the systems. An increase in the nerve conduction severity score was significantly correlated with QSART latencies, particularly in the lower extremity, a pattern consistent with the length-dependent manifestation of DPN. In addition, delays in cVEMP latencies suggest subclinical involvement of vestibulo-collic pathways in DPN. Together, these results indicate a significant association between DPN and vestibular dysfunction, potentially reflecting shared neuropathic mechanisms that concurrently affect multiple pathways and emphasize the value of integrated neurophysiological assessment in patients with DPN. A multimodal approach may improve characterization of disease severity and help identify individuals at increased risk of balance impairment and falls, thereby informing more comprehensive clinical evaluation and targeted management strategies.

Prof. Sa-Yoon Kang Department of Neurology, Jeju National University College of Medicine, Jeju, Korea, Republic of Background: Miller Fisher syndrome (MFS) is a rare immune-mediated neuropathy that commonly presents with progressive bilateral external ophthalmoplegia. Myasthenia gravis (MG) is also immune-mediated neuromuscular junction disorder characterized by fluctuating ocular symptoms. Methods: A 47-year-old woman presented with progressive binocular diplopia and blepharoptosis. She had headache and dizziness after a week later after the diplopia had started. Neurological examination revealed complete bilateral external ophthalmoplegia, ptosis and ataxia, but no areflexia. Cerebrospinal fluid analysis demonstrated no evidence of CNS infection. Results: A provisional diagnosis of MFS was made, and intravenous immunoglobulin therapy was initiated. After immunoglobulin treatment, ptosis was mildly improved, but diplopia was still remained. Repetitive nerve stimulation test demonstrated post-synaptic neuromuscular junction defects and nerve conduction studies showed mild slowing of sensory and motor nerves in bilateral upper extremities. Serological tests showed normal anti-GQ1b levels, but anti-acetylcholine receptor binding antibody was positive (titer: 6.91 nmol/L). So, we started oral steroids and acetylcholinesterase inhibitor therapy. After that, she showed much improvement of diplopia and ptosis. Conclusion: This case illustrates that MG can be seen similar to MFS, according to patient’s initial symptoms. Although the predominant ophthalmic features of MFS are complete bilateral external ophthalmoplegia, it should be recognized that myasthenia gravis has variable initial presentation. Such confounding neuro-ophthalmic features require a thorough history, neurological examination, neuroimaging, and serological testing.

Dr. David Gómez Andrés 1 , Prof. Valeria Sansone 2 , Dr. Andrea Parodi 3 , Dr. Odile Boespflug-Tanguy 4 , Dr. Natalie Goedeker 5 , Dr. Paolo Bettica 3 , Dr. Tracey Willis 6,7 , Prof. Eugenio Mercuri 8 1 Hospital Universitario Vall De Hebron, Barcelona, Spain. 2 The NeMO Clinical Center in Milan, Neurorehabilitation Unit, Milan, Italy. 3 Italfarmaco S.p.A., Milan, Italy. 4 APHP and Université Paris Cité, Paris, France. 5 Washington University, St. Louis, St. Louis, Missouri, United States. 6 The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, United Kingdom. 7 Chester University Medical School, Chester, United Kingdom. 8 Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy Background: Givinostat is an oral histone deacetylase inhibitor that was investigated in the phase 3, randomized, double-blind, placebo-controlled EPIDYS trial ( NCT02851797 ). In 2021 interim analysis of an ongoing, single-arm, open-label extension (OLE) study of the long-term safety, tolerability, and efficacy of givinostat ( NCT03373968 ), givinostat-treated patients showed a delay in median age at persistent loss of ambulation (LoA; ie, permanent inability to walk independently) compared with a matched, natural history corticosteroid-treated external control group. This analysis aimed to evaluate the effect of longer-term givinostat treatment, in combination with standard-of-care corticosteroids, on LoA in patients with DMD aged ≥6 years using data through the 2023 cutoff, which provided a larger patient population and an additional 2 years of follow-up since the previous interim analysis. Methods: The ongoing OLE study includes patients who completed a prior phase 2 givinostat study ( NCT01761292 ) or EPIDYS ( NCT02851797 ), as well as those who were screened but not randomized in EPIDYS. All patients who received ≥1 month of givinostat in combination with corticosteroids were included in the analyses. Median age at persistent LoA was calculated using Kaplan–Meier survival analysis in this population. Results: Among the 225 patients analyzed, 78 experienced persistent LoA. The median (95% CI) age at persistent LoA was 17.3 (15.5-18.1) years ( Figure ). Conclusion: This updated interim analysis evaluated LoA in patients with DMD with 2 additional years of data from the OLE. These updated OLE data suggest that givinostat consistently delays the onset of LoA in patients with DMD. Relative to published estimates from a meta-analysis reporting a median age at LoA of 11.0-13.4 years in patients treated with corticosteroids alone, the median age at persistent LoA with givinostat was 17.3 years, suggesting a delay in the loss of ambulation in patients treated with givinostat.

Dr. Karen Lynch 1 , Dr. Molly Scannell Bryan 2 , Dr. Karissa Gable 3 , Dr. Arjun Seth 4 , Dr. Pietro Emiliano Doneddu 5,6 , Dr. Yuyao Sun 7 , Dr. Jan C. Schuller 8 , Mrs Melissa Dupont 1 , Dr. Ashley Cogell 2 , Dr. Alex Seluzhytsky 1 1 Sanofi, Cambridge, MA, United States. 2 PicnicHealth, San Francisco, CA, United States. 3 Division of Neuromuscular Medicine, Duke University, Durham, NC, United States. 4 Northwestern Medicine, Chicago, IL, United States. 5 Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele (MI), Italy. 6 Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy. 7 University of Kentucky, Lexington, KY, United States. 8 Enovalife, Cœur Défense A – 110 Esplanade du Général de Gaulle – 92931 Paris La Défense Cedex, France Background: Despite standard-of-care treatments, people with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often experience residual disability, mobility limitations, and neurological deficits. These challenges increase the burden of regular, in-person clinical assessments required for clinical research. ORBIT-CIDP ( O bservational, R eal-world, D igital B iomarker, and I ntegrated T reatment O utcomes; NCT06968975 ), a first-of-its-kind study, addresses this gap by implementing an innovative telehealth-based approach that integrates artificial intelligence (AI), digital biomarkers, and patient-centric data collection methods. Here we aim to describe the ORBIT study. Methods: This study will characterize the clinical evolution, quality-of-life, and outcomes in people with CIDP using a direct-to–patient approach. The study will enroll 200 adults (≥18 years) from the United States with CIDP who have received therapy for ≥3 months and have residual disability, impairment, or neurologic deficits. Exclusion criteria include participation in interventional clinical trials. The primary objective is to characterize changes in disability over up to 2 years using the patient-reported Inflammatory Rasch-built Overall Disability Scale (IRODS) score. The secondary objective is to characterize change in disability by the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score, including assessing the reliability of virtually administered INCAT. The study will also assess novel digital biomarkers including video-AI movement assessments and insole-derived gait analysis. Results: To date, 124 participants have been enrolled in ORBIT-CIDP study. Of which 62.1% are female, 82.3% are white, and 89.5% are not Hispanic or Latino. Additional data will be presented at the congress. Conclusion: ORBIT-CIDP pioneers a direct-to–patient approach in CIDP research, enabling real world, disability assessment and feasibility of virtual INCAT administration. By integrating novel digital biomarkers- including AI-enabled video movement and insole-based gait analysis- this study reduces the burden of clinical visits while potentially validating remote monitoring methods, ultimately accelerating patient-centered research in CIDP.

Mr. Kevin Larimore 1 , Ms. Annie Greenslade 1 , Ms. Ara Yu 1 , Mr. Schwend Santos 1 , Mr. Muhammed Hamir 1 , Mrs Kristen Jahr 1 , Mrs Lucy Crockett 1 , Mr. Jeremy Van Vleet 1 , Mr. Bert Blank 1 , Mrs Huiyu Zhou 1 , Mrs Yulan Qi 1 , Mr. Joshua Henshaw 1 , Mr. Andrew Melton 1 , Ms. Kristin Obrochta-Moss 2 1 BioMarin Pharmaceutical Inc., Novato, CA, United States. 2 BioMarin Pharmaceutical Inc., Novato, United States Background: BMN 351 is an antisense oligonucleotide therapeutic designed to exclude DMD exon 51 during mRNA splicing in muscle and induce synthesis of functional, near full-length dystrophin protein in amenable patients with Duchenne muscular dystrophy (DMD). 351-201 ( NCT06280209 ) is an ongoing Phase 1/2 clinical trial of BMN 351 in boys with DMD. Three key pharmacodynamic biomarkers were measured in participant muscle biopsy tissue to evaluate early patient responses to treatment. Methods: DMD mRNA exon 51 skipping was measured by quantitative droplet digital PCR (ddPCR), while dystrophin protein expression was measured by quantitative immune-affinity ultra-performance liquid chromatography tandem mass-spectrometry (IA-UPLC-MS/MS) and semi-quantitative western blot. DMD mRNA exon 51 skipping provides a proximal measure of target engagement and pharmacodynamic activity. IA-UPLC-MS/MS data provides quantitative measurement of near full-length dystrophin protein expression resulting from DMD mRNA exon 51 skipping, while western blot analysis confirms IA-UPLC-MS/MS measurements and provides qualitative analysis of the size and diversity of the dystrophin protein isoforms present before and after treatment. The IA-UPLC-MS/MS method includes absolute quantitation of both dystrophin and alpha-actinin 2 proteins. The latter was used to normalize dystrophin data based on myofiber content in each biopsy. The absolute dystrophin and alpha-actinin 2 IA-UPLC-MS/MS measurements from each sample were used to calculate % of normal myofiber-normalized dystrophin concentrations relative to the median of a panel of 19 normal human muscle samples measured in triplicate, with data reported as % of normal. Results: The ddPCR data demonstrated dose-dependent increases in muscle DMD mRNA exon 51 skipping that correlated with dose-dependent increases in near full-length dystrophin protein measured by both IA-UPLC-MS/MS and western blot. Conclusion: Together, the data from these orthogonal methods provide a robust data set demonstrating early patient responses and support the potential for clinical benefit in patients treated with BMN 351.

Walter Demmel Background: Chronic neuropathic pain may respond inadequately to conservative treatments. For severe, therapy-refractory pain syndromes, peripheral nerve stimulation represents an effective therapeutic option, supported by recent advancements in implant technology and novel technical approaches.

Mrs Amadea Zupan 1 , Dr. Nataša Teran 2 , Mr. Matic Klopčič 1 , Prof. Lea Leonardis 1 1 Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia. 2 Clinical institute of genomic medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, phenotypically diverse hereditary muscular disorder that most commonly affects the facial muscles, the shoulder girdle, and the upper extremities. The disease progression, degree of impairment, and impact on quality of life vary significantly among individuals. The aim of this study was to retrospectively and prospectively evaluate the clinical status, functional impairment, and quality of life of Slovenian patients with FSHD. Methods: The study included 31 patients with genetically confirmed FSHD type 1 and a control group of healthy individuals. The analysis encompassed demographic and clinical data, functional scales (Vignos-Brooke Scale, FSHD Rating Scale, Comprehensive Clinical Evaluation Scale), and questionnaires (VAS, SWLS, WHOQOL-BREF, MoCA, Zarit Burden Interview). Additionally, upper limb range of motion (ROM) was assessed using a Python-based application, which utilizes a standard 2D camera and the MediaPipe library to automatically detect body landmarks—a more accessible and less time-consuming alternative to marker-based systems or Kinect sensors. Results: The median age of the patients was 46 years, with the disease onset at age 30. Half of the patients exhibited mild to moderate muscle impairment (FSHD Rating Scale ≤ 5), and the most frequent phenotype was myopathic D1. Regarding upper limb ROM, half of the FSHD patients achieved near-normal results (160°–180° in abduction and anteflexion), while the other half showed significant impairments, with values as low as 50° for abduction and 60° for anteflexion. Statistical analysis revealed a significant difference in ROM between FSHD patients and healthy controls. Better abduction capacity was moderately associated with higher scores in the physical health and social domains of the WHOQOL-BREF. However, upper limb function was not significantly correlated with overall life satisfaction. Furthermore, a strong correlation was observed between ROM and the Brooke Scale, confirming that greater ROM is positively associated with muscle strength scores. Conclusion: FSHD in the Slovenian population exhibits broad phenotypic and functional diversity. While most patients maintain a satisfactory quality of life, the presence of pain, comorbidities, and physical limitations necessitates individually tailored multidisciplinary management. Objective 2D measurement of the range of motion using the MediaPipe module proves to be a feasible, accessible, and clinically useful tool for supplementing disease monitoring and tracking progress in rehabilitation or treatment.

Dr. Fatemeh Rezania 1,2 , Dr. Lauren Ross 1,2 , Mr. Murray Worner 1 , Assoc. Prof. David Szmulewicz 3,2 , Assoc. Prof. Leslie Roberts 1,2 1 St Vincent's Hospital, Melbourne, Australia. 2 The University of Melbourne, Melbourne, Australia. 3 The Royal Victorian Eye and Ear Hospita, Melbourne, Australia Background: Vestibular neuropathies are often under-recognised in patients with peripheral neuropathy or ganglionopathy, as ataxia is frequently attributed solely to proprioceptive loss despite possible vestibular or cerebellar contributions. We investigated vestibular function across neuropathies and ganglionopathies using video head impulse testing (vHIT). We hypothesised that unrecognised vestibular involvement is common and that specific clinical or neurophysiological features could serve as red flags for vestibulopathy. Methods: We studied 30 patients with confirmed peripheral neuropathy or sensory ganglionopathy who underwent the Michigan Neuropathy Screening Instrument (MNSI) questionnaire and the Michigan Diabetic Neuropathy Score (MDNS) clinical examination, which included sensory, motor, and reflex testing, along with gait assessment and the Romberg test. Nerve conduction study findings were reviewed to define the neurophysiological phenotype and the number of abnormal nerves (NCS severity). Semicircular canal function was assessed using video head impulse testing (vHIT), which quantifies the vestibulo-ocular reflex (VOR). VOR gain, calculated as the eye/head velocity area ratio, was considered abnormal if <0.8 for horizontal canals or <0.7 for vertical canals. Results: Twelve of 30 participants (40%) had dysimmune neuropathy, while 7/30 (23%) had hereditary neuropathy, including 4 with RFC1 repeat expansion disorder, 2 with Charcot–Marie–Tooth disease type 1A (CMT1A), and 1 with hereditary neuropathy with liability to pressure palsies (HNPP). Three patients (10%) had metabolic/toxic/nutritional neuropathy, and 8 (26%) were idiopathic. Nineteen of 30 patients (63%) had abnormal VOR gain in at least one canal, including 4/4 (100%) with RFC1, 6/12 (50%) with dysimmune neuropathy, 2/3 (66%) with metabolic/toxic/nutritional neuropathy, 1/3 (33%) with CMT1A/HNPP, and 6/8 (75%) with idiopathic neuropathy. In multivariable logistic regression using NCS phenotype axes, none of the individual axes significantly altered the odds of vestibulopathy relative to the sensory, non–length-dependent, axonal baseline. However, this baseline composite phenotype showed a high absolute probability of vestibulopathy (OR 5.37, p=0.038). Consistently, in categorical NCS phenotype analysis, no single NCS pattern was directly associated with vestibulopathy (p>0.13). In univariate logistic regression, vestibulopathy was strongly associated with ataxia/Romberg positivity (OR 7.1, p=0.042), while neuropathy severity measures and disease duration did not predict vestibular involvement (p>0.3). Conversely, ataxia/Romberg positivity was associated with greater MDNS sensory score (OR 1.47, p=0.015), but not with MDNS motor score or other severity measures. VOR gain in individual canals or canal planes showed no association with disease duration or neuropathy severity (p>0.3), except for MDNS motor score, which showed a moderate positive correlation with higher (better) VOR gain for both lateral canals (p<0.05), with a similar but weaker pattern for vertical canals. Conclusion: Vestibulopathy is common in patients with peripheral neuropathy and ganglionopathy and clusters within the sensory ataxic phenotype rather than reflecting overall neuropathy burden. A composite sensory, non–length-dependent, axonal NCS pattern shows high baseline vestibular involvement, although no single NCS feature predicts vestibulopathy in isolation. Vestibular involvement is strongly associated with ataxia, while sensory burden predicts ataxia but not vestibulopathy directly, supporting an indirect, ataxia phenotype-mediated relationship. These findings support targeted vestibular screening and rehabilitation in patients with disproportionate sensory ataxia.

Assoc. Prof. Massimo Russo, Dr. Marcella De Luca, Dr. Angelica Squillaci, Prof. Antonio Toscano, Prof. Carmelo Rodolico, Prof. Anna Mazzeo, Prof. Sonia Messina Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy Background: Guillain–Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy and early identification of prognostic indicators is essential to optimize therapeutic strategies and management. We aimed to identify the association of clinical, neurophysiological and laboratory parameters with functional outcome at 6 months. We also evaluated the response to immunomodulatory treatments among different subtypes. Methods: We performed a single-center, retrospective observational study on patients consecutively admitted between 2015 and 2024 in a tertiary referral centre. Functional disability, muscle strength and autonomic symptoms were assessed using the Hughes Functional Grading Scale (HFGS), the Medical Research Council (MRC) sum score and the COMPASS-31 questionnaire. Neurophysiological studies allowed classification into Acute Inflammatory Demielinating Polyneuropathy (AIDP), Acute Motor Axonal Neuropathy (AMAN), Acute Motor and Sensory Axonal Neuropathy (AMSAN) or mixed forms. Laboratory parameters, including serum sodium, albumin, fibrinogen and neurofilament light chain (NfL) were analyzed. Treatment modalities included intravenous immunoglobulin and/or plasma exchange. Results: We included 50 patients (mean age at onset of 56, SD:19 yrs, M:F, 58% vs 42%). The clinical severity at admission was high [(HFGS score of 4 (IQR 3—4)]. Twenty-eight percent of patients exhibited dysphagia and 20% required ventilatory support. COMPASS-31 score was 23,SD:12. The average time from symptom onset to specific therapy was 7.5,SD:4 days. Neurofilament light chain (NfL) levels in CSF were 470.8 pg/mL, SD:378.1. Regarding the functional outcome at 6 months, the median Hughes score was 2 (IQR 2-3), and 62% of patients achieved autonomous walking (Hughes 1 point on the Hughes scale within 4 weeks). The factors found to be associated with an unfavourable outcome (HFGS >3 at 6 months) were: age >60 years (p=0.03), HFGS >4 at admission (p=0.01), time from onset to therapy >7 days (p=0.04), serum sodium 500 pg/mL (p=0.02). The correlation between the COMPASS-31 score and HFGS at nadir was modest (p= 0.22). Conclusion: This real-world study confirms the heterogeneity of GBS and supports the value of an integrated, multidimensional assessment combining clinical, neurophysiological, and laboratory data to improve prognostic stratification. Such an approach may facilitate earlier identification of high-risk patients, guide individualized management, and optimize follow-up strategies.

Miss Lauren Miguet 1 , Mr. Martijn De Merlier 1 , Prof. Kristl G. Claeys 1,2 1 Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium. 2 Department of Neurology, University Hospitals Leuven, Leuven, Belgium Background: Acetylcholine receptor antibody-positive (AChR-Ab+) generalized Myasthenia Gravis (gMG) often remains inadequately controlled by conventional therapies, negatively impacting patient-reported Myasthenia Gravis Activities of Daily Living (MG-ADL) scores. While advanced therapies like neonatal Fc receptor (FcRn) and terminal complement (C5) inhibitors show efficacy in clinical trials, these highly selected populations may not reflect the heterogeneity of routine clinical practice. A critical knowledge gap remains regarding the real-world effectiveness and treatment patterns of these novel agents in gMG. The study aims to assess the real-world utilization and clinical outcomes of efgartigimod in AChR-Ab+ gMG patients. We aim to characterize treatment patterns, clinical response, the potential for steroid-sparing effects and prolonged drug-free inter-cycle intervals in a cohort of adult patients with AChR-Ab+ gMG in whom conventional treatments have failed. Methods: We conducted a retrospective, single-center analysis of adult patients with AChR-Ab+ gMG treated with efgartigimod at our tertiary neuromuscular reference center in Leuven, Belgium. Effectiveness was primarily quantified by analyzing longitudinal MG-ADL scores, changes in daily corticosteroid doses, and the optimization of conventional treatments. To evaluate treatment utilization and long-term outcomes, we examined efgartigimod-free inter-cycle intervals, transitions to other advanced therapies, and the need for rescue therapies or hospitalization. In addition, medication-related adverse effects, comorbid conditions, and thymic status were documented. Results: The study cohort comprised 27 AChR-Ab+ gMG patients (14 male, 13 female) treated with efgartigimod. Median age was 56.0 years [IQR 34.0–66.5] and median disease duration was 7.0 years [IQR 3.5–14.0]. Thymectomy had been performed in 37% of patients due to hyperplasia (18.5%) or thymoma (18.5%). Patients had a median of 2.0 [IQR 1.0–2.5] lifetime myasthenic crises requiring rescue therapy. At baseline, patients presented with a median MG-ADL score of 8.0 [IQR 6.5-10.0] and Myasthenia Gravis Foundation of America (MGFA) severity was distributed across Grade II (26%), Grade III (59%), and Grade IV (15%), with 45% exhibiting predominantly bulbar symptoms (IIb, IIIb, IVb). The study followed patients for up to 7 treatment cycles. A total of 27 patients completed cycle 1, with 9 patients reaching cycle 7 at the time of analysis. Notably, the mean drug-free interval increased progressively from 3.63 weeks after cycle 1 to 4.57 weeks by cycle 7. A sustained reduction in disease burden was observed, evidenced by a consistent decrease in median MG-ADL scores, from 8.0 to 3.0 by cycle 7. In the total cohort, 77.8% of patients achieved a sustained clinical response, with the responder rate increasing to 88.9% among those who completed seven treatment cycles. Four patients (14.8%) switched to a C5-inhibitor zilucoplan, due to lack of response. Corticosteroid sparing was achieved in 48% of patients, while only 7.1% required a dose increase during efgartigimod treatment. Conclusion: In a real-world setting characterized by high disease burden and bulbar involvement, efgartigimod demonstrates significant clinical effectiveness and a steroid-sparing effect. These findings validate the use of FcRn inhibitors outside of clinical trial parameters and support individualized, cycle-based treatment strategies for refractory AChR-Ab+ gMG.

Dr. Benedikt Schoser Friedrich-Baur-Institute dep. of Neurology LMU Clinic, Munich, Germany Background: Neuromuscular disorder management is evolving through genomic medicine, digital health, and proactive strategies. The focus shifts from simply alleviating symptoms to implementing targeted, disease-modifying treatments, including genetic therapies and stem cell research. Precision medicine allows for personalized therapies based on genetic profiles, often combining agents like antisense oligonucleotides (ASOs) or gene vector therapy with protective or anti-inflammatory agents to enhance outcomes. Regenerative approaches involve stem cell and tissue engineering for muscle repair, driven by the development of muscle organoids, replacing earlier animal-driven strategies. AI and digital tools support diagnosis and ongoing monitoring through wearable devices and integrated electronic health data. Digital phenotyping with AI wearables enables real-world, long-term functional assessment, reducing the need for sporadic clinic visits. Diagnostic methods are advancing with multi-omic profiling to identify predictive biomarkers tailored to individuals. Standardized, multidisciplinary care pathways will ensure smooth pediatric-to-adult transitions and help reduce disparities. The use of new biomarkers in trials will speed up drug approval and access to therapies. Achieving these objectives requires collaboration among academia, industry, regulators, and patients living with neuromuscular disorders to lower barriers. Integrating technology into healthcare delivery aims to restore function and achieve remission in incurable muscle diseases. Conclusion: By 2030, advances in molecular science, digital infrastructure, and policies should usher in a “golden age” of neuromuscular medicine, providing equitable, life-changing therapies for our patients.

Assoc. Prof. Aysha Alshareef , Dr. Manal Alsulami, Assoc. Prof. Ahmad Abuzinadah King Abdulaziz University Hospital, Jeddah, Saudi Arabia Background: Tofersen is an antisense oligonucleotide designed to promote RNase-mediated degradation of SOD1 mRNA, leading to reduced synthesis of both wild-type and mutant SOD1 protein. It has shown promising results across different physical function scales. In this study, we evaluated the short-term outcome of tofersen on clinical paramters across physcial function scales including (Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale-Expanded (HFMSE), and the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Methods: A retrospective, single-center study analyzed 10 patients with genetically confirmed SOD1-ALS who received intrathecal tofersen. All patients carried the SOD1 D77V mutation. The mean age was 47 years (range 28–61), and patients received a mean of 14 intrathecal doses (range 7–24). Pre- and post-treatment scores were compared for RULM, HFMSE, and ALSFRS-R. Paired comparisons were performed using the Wilcoxon signed-rank test for non-normally distributed outcomes and paired t-tests where appropriate. Results: Nine patients had complete RULM and HFMSE data, and all ten had ALSFRS-R data. RULM showed a trend toward improvement (median change +1; Wilcoxon Z = –1.89, p = 0.059), but did not reach statistical significance. HFMSE changes were small and not significant (median change 0; p = 0.686). ALSFRS-R showed a slight numerical improvement (mean change +0.7 ± 2.8) without statistical significance (p = 0.454). Individual assessments showed improvement in ALSFRS-R scores in four out of ten patients. No patient demonstrated marked functional decline over the observation period. (Table 1) Conclusion: Tofersen was associated with stabilization of motor function across multiple clinical scales, with improvement observed in some patients. Importantly, all patients carried the SOD1 D77V mutation, a subtype linked to rapid functional decline, typically losing ∼0.8–1.0 ALSFRS-R points per month (∼10–12 points/year) in natural history. In contrast, our cohort showed a mean gain of +0.7 points over 3–6 months, and no patient experienced decline—an outcome highly unexpected for this aggressive genotype. Although statistical significance was not reached, likely due to the small sample size, this pattern of stability and improvement aligns with emerging observational data and suggests a clinically meaningful effect of tofersen even in severe SOD1 variants. Larger, genotype-stratified prospective studies are warranted to confirm these findings.

Dr. Maria Gontika , Dr. Chrysanthi Tsimakidi, Dr. Sotiria Stavropoulou- De Lorenzo, Dr. Aggeliki Psarra, Dr. Eirini-Anastasia Karydi, Dr. Dionysia Gkougka Penteli's Children Hospital, Athens, Greece Background: Juvenile seronegative generalized myasthenia gravis (MG) is rare and therapeutically challenging, particularly in patients with aggressive disease and poor response to conventional rescue therapies. Plasma exchange (PLEX) is effective but invasive and associated with possibly significant side-effects. Efgartigimod alfa, an FcRn antagonist that reduces circulating IgG levels and has a mechanism of action analogous to PLEX, represents a less invasive alternative; however, it is currently approved only for adult acetylcholine receptor antibody–positive MG. Methods: We report an adolescent female (born in 2009) followed since January 2025 for juvenile seronegative generalized MG. Initial symptoms consisted of fluctuating diplopia and left esotropia, first noted in 2021 and initially attributed to strabismus, for which surgical correction was performed in 2024. Following relapse of diplopia, particularly with fatigue, the patient was referred for neurological re-evaluation. Examination revealed fluctuating left ptosis, generalized limb weakness (predominantly left-sided), easy fatigability, and recurrent respiratory tract infections. Baseline scores were 11 on the Quantitative Myasthenia Gravis (QMG) scale and 7 on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale. Results: Diagnostic evaluation demonstrated negative MG-related antibodies, normal repetitive nerve stimulation and Desmedt testing, but a positive single-fiber EMG with increased jitter in the left orbicularis oculi muscle, along with a positive pyridostigmine test. Whole-genome sequencing was unremarkable, and thoracic MRI showed mild residual thymic tissue without thymoma. A diagnosis of juvenile seronegative generalized MG was established. Initial treatment included intravenous immunoglobulin (IVIg), pyridostigmine (up to 240 mg/day), and high-dose corticosteroids (prednisolone up to 1 mg/kg/day). Despite this, the patient developed a highly aggressive disease course with recurrent episodes consistent with impending myasthenic crisis, requiring frequent hospitalizations. IVIg provided only transient benefit, whereas PLEX induced marked and sustained improvement (QMG reduction from 12 to 3), identifying the patient as preferentially PLEX-responsive. However, repeated PLEX necessitated prolonged ICU admissions, and corticosteroid exposure resulted in early Cushingoid features and steroid-induced myopathy, highlighting the need for a steroid-sparing, less invasive therapy. Off-label treatment with efgartigimod alfa was initiated, and the patient received one full treatment cycle. At 3-month follow-up, she remains clinically stable, with a QMG score of 6 and an MG-ADL score of 4. These residual scores are largely attributable to constant diplopia, which cannot be fully or reliably assessed due to prior strabismus surgery. Prednisolone was successfully tapered to 25 mg/day without clinical deterioration, and no rescue therapy was required. Treatment was well tolerated, with no adverse events except for a mild upper respiratory tract infection. Conclusion: To our knowledge, this is the first reported case of juvenile seronegative generalized MG treated with efgartigimod alfa, representing a double off-label use. The excellent clinical response, meaningful steroid sparing, and favorable safety profile support efgartigimod alfa as a promising therapeutic option in aggressive juvenile seronegative MG, particularly in patients who are PLEX-responsive.

Ms. CHIHARU ISONO 1 , Prof. MAKITO HIRANO 2 , Asst. Prof. MAKOTO SAMUKAWA 2 , Prof. Kazumasa Saigoh 3 , Prof. Yuji Higashimoto 4 , Prof. Yoshitaka Nagai 2 1 Division of Rehabilitation Medicine, Kindai University Hospital, OSAKA, Japan. 2 Department of Neurology, Kindai University Faculty of Medicine, OSAKA, Japan. 3 Division of Clinical Genetics, Kindai University Hospital, OSAKA, Japan. 4 Department of Rehabilitation Medicine,Kindai University Faculty of Medicine, Japan, OSAKA, Japan Background: Mutations in SOD1 are the second most common cause of familial amyotrophic lateral sclerosis (ALS), found in approximately 20-30% of familial cases, as well as 2-3% of sporadic cases. While swallowing function in SOD1-related ALS is thought to be relatively preserved compared to non-SOD1-related ALS, its detailed findings remain largely unknown. The objective of this study was to assess swallowing function in patients with SOD1-ALS using videofluoroscopic examination (VF). Methods: Genetic testing in our cohort (116 sporadic cases and 10 familial cases) revealed that three patients with sporadic ALS and four with familial ALS had SOD1 mutations. VF were performed in three women with a mean age at onset of 53.7 ± 4.9 years, all of whom presented with lower-limb onset. VF evaluation was based on the scale established by the Japanese Society of Dysphagia Rehabilitation, which can separately evaluate oral and pharyngeal phases in addition to total scores, the international scale Dysphagia Outcome and Severity Scale (DOSS), and Penetration-Aspiration Scale (PAS). Results: Mild oral phase disorders were observed in the VF. Two patients had silent penetration without aspiration during the pharyngeal phase. All patients continued oral intake, and none developed aspiration pneumonia or required gastrostomy for feeding. Conclusion: In general, dysphagia is a critical factor affecting prognosis in ALS. Our study suggests that in SOD1-related ALS, swallowing function varies depending on the mutation and may be milder than expected for the duration of disease.

Dr. Nurit Birman Har-Noy 1 , Dr. Jacopo Luca Casiraghi 2 , Dr. Andrea Lizio 2 , Dr. Silvi Cadri 3 , Dr. Michela Coccia 3 , Dr. Andrea Barp 4 , Dr. Riccardo Zuccarino 4 , Dr. Filomena Caria 5 , Prof. Massimiliano Filosto 6 , Prof. Valeria Ada Sansone 1 1 Neurorehabilitation Unit University of Milan The NeMO Clinical Center, Milan, Italy. 2 Neuromuscular Omnicentre (NEMO), Fondazione Serena Onlus, Milan, Italy. 3 Neuromuscular Omnicentre (NEMO), Fondazione Serena Onlus, Ancona, Azienda Ospedaliero-Universitaria Delle Marche, Ancona, Italy. 4 Neuromuscular Omnicentre (NEMO), Fondazione Serena Onlus, Trento, Ospedale Riabilitativo Villa Rosa, Pergine Valsugana Italy, Trento, Italy. 5 Neuromuscular Omnicentre (NEMO), Fondazione Serena Onlus, Brescia, Italy. 6 NeMO-Brescia Clinical Center for Neuromuscular Diseases; Department of Clinical and Experimental Sciences, University of Brescia; ERN Euro-NMD Center ASST Spedali Civili, Brescia, Italy, Brescia, Italy Background: Patient-reported outcome measures (PROs) are essential for assessing disease burden and tracking changes over time. Neuromuscular diseases exhibit heterogeneous phenotypic presentations. A preliminary exploratory study at the NeMO Center in Milan (77 patients with FSHD and BMD) suggested that episodes of transitory symptom worsening may be a clinically relevant phenomenon. This expanded multicenter study investigates the prevalence, characteristics, and impact of self-reported episodes of transitory neuromuscular symptom worsening in patients with facioscapulohumeral muscular dystrophy (FSHD) and Becker muscular dystrophy (BMD), compared to healthy controls. Methods: We developed a patient-reported questionnaire and distributed it anonymously online in April and May 2025 to adult patients with FSHD and BMD followed at the NeMO Center in Milan, Italy. In July 2025, the study was expanded to additional NeMO centers in Italy (Ancona, Brescia, and Trento). A further group of 18 healthy controls also completed the questionnaire. Symptoms of fatigability, focal muscle weakness, and pain were classified as episodic if they occurred in addition to chronic neuromuscular impairment, lasted 1–14 days, and returned to baseline or near-baseline levels. Results: A total of 145 patients responded (104 FSHD, 41 BMD). Overall, 58 patients (40%) reported episodes of transitory symptom worsening, significantly higher than healthy controls (3/18, 17%). Episodes were reported by 43% of FSHD and 32% of BMD patients. Within the FSHD group, 87% of patients who reported episodes had baseline pain or fatigue, compared with 68% who had baseline symptoms but no episodes. Only FSHD patients reported episodes lasting longer than 7 days (20% experienced 8-14 day episodes), demonstrating greater heterogeneity in episode duration. The annual frequency was higher in FSHD: 29% experienced more than 6 episodes per year, compared with only 8% of BMD patients. Episodes interfered with daily routine in 62-68% of patients, with 41-57% requiring increased bed rest and 24-43% reducing social activities. Importantly, 50-62% changed their ongoing routine after episodes. Disease-specific triggers emerged: excessive physical activity predominated in BMD (87.5%) and FSHD (60%), while psychological stress was more common in FSHD (50%) and climate changes in BMD (62.5%). Conclusion: This multicenter study confirms that transitory symptom worsening is a clinically relevant phenomenon in FSHD and BMD, significantly more often than in healthy controls. Episodes substantially impact daily living and lead to behavioral modifications. FSHD patients experience a higher annual burden due to increased frequency and longer duration of episodes. Disease-specific trigger patterns suggest different underlying mechanisms. These findings support the development of PROs that capture symptom fluctuations, not only progressive decline. Clinical trial implications include performing baseline assessments multiple times, using digital measures and wearables for continuous patient monitoring, or incorporating questions about current versus baseline status into trial PROMs. Personalized interventions such as adjusted physical activity and psychological support are suggested. Larger studies are needed to validate these findings and explore prevention strategies.

Mr. Matthias Schelfhout 1 , Mr. Jayant A. Soekhradj 2,3 , Dr. Lara M. Wierenga 4,5 , Dr. Hermien E. Kan 2,3 , Dr. Rubén Miranda 6 , Dr. Liesbeth De Waele 1,7 , Dr. Sam Geuens 1,7 , Dr. Rosanne Govaarts 2,3 1 Department of Development and Regeneration, KU Leuven, Leuven, Belgium. 2 C.J. Gorter MRI Center, Radiology, Leiden University Medical Center, Leiden, Netherlands. 3 Duchenne Center Netherlands, Leiden, Netherlands. 4 Institute of Psychology, Leiden University, Leiden, Netherlands. 5 Leiden Institute for Brain and Cognition, Leiden, Netherlands. 6 Department of Psychobiology and Methodology in Behavioral Sciences, Complutense University of Madrid Rector Royo Villanova s/n, Madrid, Spain. 7 Child Neurology, University Hospitals Leuven, Leuven, Belgium Background: Duchenne muscular dystrophy (DMD) is a muscle wasting disease caused by a mutation on the X-chromosome, resulting in the absence of full-length dystrophin production. Neuroimaging studies have mainly shown smaller gray matter volumes and less structured white matter in patients with DMD compared to age- and sex-matched healthy controls. These alterations are thought to arise from dystrophin deficiency and/or long-term corticosteroid treatment, which remains a standard of care treatment in DMD. While corticosteroids are beneficial for muscle function, they are also associated with pubertal delay. Brain structure is known to change during puberty. Differences in brain volumes reported in studies using age-matched controls may thus partly reflect differences in puberal status rather than effects of dystrophin deficiency or corticosteroid exposure alone. Accounting for pubertal development, for example by using puberty matched controls, may improve the interpretation of neuroimaging findings in DMD. To address this problem, we investigated differences in grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) volumes between DMD and healthy controls while controlling for age and puberty. Methods: Retrospective data from 37 DMD patients and 21 healthy controls, collected at LUMC/UL (The Netherlands) and KUL/UZL (Belgium) were analyzed. Data variables included pubertal status (based on clinical files and expert opinion), age, corticosteroid treatment, mutation type and T1 MRI data. Volumes were standardized by the intracranial volume (ICV), which was transformed on the log-scale for small and symmetric differences. A linear model (ANCOVA) was fitted with log(GM/ICV) ratio as outcome, group (DMD vs. healthy controls) as main predictor, adjusting for age and pubertal status. Identical ANCOVA models were applied to the log(WM/ICV) and log(CSF/ICV). All model assumptions were checked and met. For interpretation purposes, estimates were transformed to the percentage scale. Results: When adjusting for age and puberty, the log(GM/ICV) was not significantly different for group (p = 0.70) with DMD patients having a lower GM on average by -0.6% with a 95% CI [-3.8;2.7]. However, group differences were significant for the log(WM/ICV) (p<0.01) with DMD patients having a lower WM on average by -9.9% with a 95% CI [-12.6;-7.1] and log(CSF/ICV) (p<0.01) with DMD patients having a higher CSF on average by 29.8% with a 95% CI of [14.4;47.2]. Conclusion: These findings show volumetric differences between patients with DMD and healthy controls in WM and CSF, but not in GM, when adjusting for age and puberty. This is in contrast with previous research utilizing age-matched healthy controls showing volumetric differences in GM, suggesting an effect of puberty on GM volumetric differences. Future imaging research should try to account for puberty when comparing DMD with healthy controls.

Dr. Stefano Previtali 1,2 , Dr. Nicolas Deconinck 3,4 , Dr. Liesbeth DeWaele 5 , Dr. Kevin Flanigan 6 , Dr. Chamindra Laverty 7 , Dr. Jeehun Lee 8,9 , Dr. Hugh McMillan 10 , Dr. Perry Shieh 11 , Dr. Ian Woodcock 12,13 , Dr. Soma Ray 14 , Dr. Dazhe Wang 14 , Dr. Douglas Kerr 14 , Dr. Maria Naylor 14 , Dr. Michaela Guglieri 15 1 IRCCS San Raffaele Scientific Institute, Milan, Italy. 2 Vita-Salute San Raffaele University, Milan, Italy. 3 Neuromuscular Reference Center UZ Gent, Gent, Belgium. 4 Hôpital des Enfants Reine Fabiola (HUB), Brussels, Belgium. 5 University Hospitals Leuven,, Leuven, Belgium. 6 Nationwide Children's Hospital, Columbus, Ohio, United States. 7 UC San Diego Health, San Diego, CA, United States. 8 Samsung Medical Center, Seoul, Korea, Republic of. 9 Sungkyunkwan university School of Medicine, Seoul, Korea, Republic of. 10 Children's Hospital of Eastern Ontario, Ottawa, Ontario;, Canada. 11 University of California, Los Angeles, United States. 12 Murdoch Children’s Research Institute, Parkville, Victoria, Australia. 13 The Royal Children’s Hospital, Melbourne, Australia. 14 Dyne Therapeutics, Waltham, MA, United States. 15 Royal Victoria Infirmary, Newcastle University, Newcastle-Upon-Tyne, United Kingdom Background: Individuals with DMD pathogenic variants amenable to exon 51 skipping have significant unmet needs, despite approved treatments. Zeleciment rostudirsen (z-rostudirsen, also known as DYNE-251) leverages the transferrin receptor, TfR1, to deliver an exon 51 skipping Phosphorodiamidate Morpholino Oligomer (PMO) to muscle with the goal of producing near-full length functional dystrophin. Methods: In the Multiple Ascending Dose (MAD) portion of the Phase 1/2 DELIVER trial ( NCT05524883 ), 54 participants received z-rostudirsen or placebo every 4 or 8 weeks for 6 months. Following dose selection, 32 participants were randomized 3:1 to receive 20 mg/kg Q4W z-rostudirsen or placebo for 6 months in a registrational expansion cohort (REC). After the placebo-controlled period, participants entered an open-label Long Term Extension (OLE/LTE) and transitioned to 20 mg/kg Q4W, as applicable. Results: The REC met its primary endpoint, demonstrating a statistically significant increase in mean muscle content-adjusted dystrophin at 6 months compared to baseline (5.46% vs. 0.83% of normal, respectively, p <0.0001). Trends in functional improvement were observed across multiple clinical endpoints at 6 months including Time to Rise (TTR) velocity, 10 Min Walk Run (10MWR) velocity, North Star Ambulatory Assessment (NSAA), Stride Velocity 95 Centile (SV95C), Performance of Upper Limb (PUL) 2.0, and Forced Vital Capacity Percent Predicted (FVC%p). Sustained improvements from baseline in these measures were also observed through 18 months of treatment in participants who enrolled in the MAD at 20 mg/kg Q4W and through 24 months of treatment in participants who enrolled in the MAD at 10 mg/kg Q4W and transitioned to 20 mg/kg Q4W in the OLE/LTE. As of August 19, 2025, z-rostudirsen had a favorable safety and tolerability profile based on data from 86 participants enrolled in DELIVER and followed for up to 36 months. Conclusion: Data from the DELIVER trial, including robust dystrophin expression, trends in functional improvement, favorable safety profile, and convenient dosing support the potential of z-rostudirsen to address the unmet needs of individuals with DMD pathogenic variants amenable to exon 51 skipping.

Dr. Claudia Vinciguerra 1 , Dr. Carmen Erra 2 , Dr. Liliana Bevilacqua 1 , Dr. Dario Ricciardi 2 , Dr. Francesco Tuccillo 2 , Dr. Francesco Habetswallner 2 , Prof. Paolo Barone 1 1 Neurology Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84131 Salerno, Italy., Salerno, Italy. 2 Clinical Neurophysiology Unit, Azienda Ospedaliera di Rilievo Nazionale-Cardarelli, Naples, Italy., Naples, Italy Background: Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), defined by acute respiratory failure requiring ventilatory support. Impending myasthenic crisis (IMC) describes a rapidly progressive clinical deterioration associated with a high risk of respiratory impairment if prompt therapeutic intervention is not started. In patients with acetylcholine receptor (AChR) antibody–positive MG, complement activation and subsequent membrane attack complex–mediated damage at the neuromuscular junction play a pivotal pathogenic role, rendering complement inhibition a rational therapeutic approach. However, evidence supporting the use of the C5 inhibitor zilucoplan in acute or peri-critical settings remains limited. Methods: We report two cases of Italian patients with AChR-positive MG who developed severe, treatment-refractory disease exacerbations. One patient experienced a full-blown MC requiring non-invasive ventilatory support, while the second presented with an IMC characterized by rapidly progressive bulbar dysfunction. In both cases, zilucoplan was initiated at a dose of 32.4 mg administered subcutaneously once daily following an poor response to standard rescue therapies, including high-dose corticosteroids and intravenous immunoglobulin (IVIg); one patient had additionally failed multiple prior biologic treatments. Clinical efficacy was assessed using the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores, together with functional and respiratory evaluations performed before and after treatment initiation. Patients were closely monitored during hospitalization or outpatient management and throughout early follow-up to evaluate clinical outcomes and treatment safety. Results: The first case involved a 38-year-old man with thymoma-associated MG, refractory to IVIg, plasma exchange, and several targeted therapies. Following initiation of zilucoplan, he exhibited rapid and marked improvement in bulbar and respiratory function within seven days, allowing discontinuation of non-invasive ventilation and safe resumption of oral feeding. The second patient, an 81-year-old man with severe bulbar symptoms and imminent respiratory deterioration, achieved complete resolution of dysphagia and dysphonia within ten days of treatment, thereby avoiding hospital admission and ventilatory support. Conclusion: Both patients maintained sustained clinical stability during continued zilucoplan therapy, with no treatment-related adverse events observed. These cases suggest that zilucoplan may induce a rapid, robust, and sustained clinical response in patients with refractory AChR-positive MG during both established myasthenic crisis and impending crisis. Its continuous complement inhibition and easy subcutaneous administration may represent significant advantages in both acute rescue and longer-term disease management. Early initiation of zilucoplan may help prevent progression from IMC to MC. Prospective studies are warranted to better define its optimal timing, efficacy, and positioning in the management of MG-related crises.

Dr. Jamie Lim 1 , Dr. Roeland Vanhauwaert 1 , Dr. Karolien Van Huynegem 1 , Dr. Ann Swijsen 1 , Prof. Jan Verschuuren 2 , Prof. Maartje Huijbers 2 , Prof. Steven Burden 3 1 argenx, Ghent, Belgium. 2 Leiden University Medical Center, Leiden, Netherlands. 3 Massachusetts General Hospital, Boston, United States Background: The agrin-LRP4-MuSK signaling pathway is essential for neuromuscular junction (NMJ) establishment, maintenance, and function. Diseases that disturb the structure or function of the NMJ cause debilitating and potentially life-threatening neuromuscular conditions such as congenital myasthenic syndromes (CMS), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA). CMS can be caused by genetic mutations in the agrin-LRP4-MuSK-DOK7 pathway, which impact development and function of the NMJ. An early pathological feature of ALS is NMJ disassembly, which can cause motor dysfunction and paralysis even in the absence of motor neuron loss. SMA is caused by mutations in SMN1 which disrupt the NMJ and lead ultimately to motor neuron loss. Current treatments for CMS can lose effectiveness and be associated with central nervous and cardiovascular system-associated side effects following long-term use. Current therapies for ALS offer only modest benefits for survival or motor function, and while targeted therapies for SMA are effective, functional rescue is incomplete. There remains an unmet need for treatment options that improve NMJ stability and muscle function, and slow disease progression in patients with CMS, ALS, and SMA . MuSK agonist antibodies have been shown to preserve neuromuscular synapses in animal models of CMS, ALS and SMA and may offer potential benefit for these and other neuromuscular diseases. Methods: Adimanebart (ARGX-119) is a humanized agonistic monoclonal antibody that specifically binds and activates MuSK. Adimanebart is in clinical development as a potential targeted therapy to treat CMS, ALS, and SMA. Results: Agrin, released from motor nerve terminals, binds LRP4 to stimulate LRP4-MuSK association leading to the phosphorylation and activation of MuSK. Recruitment of DOK7 to phosphorylated MuSK further stimulates MuSK dimerization and phosphorylation, resulting in AChR clustering and functional synaptic transmission. Adimanebart binds MuSK, independent of agrin, to promote MuSK dimerization, phosphorylation, and activation, and to stimulate AChR clustering. This leads to a stabilized NMJ and improved synaptic transmission, which could potentially improve or even restore muscle function in patients with neuromuscular disorders such as CMS, ALS, and SMA. This proposed mechanism of action underpins the rationale for the evaluation of adimanebart during ongoing clinical studies in CMS, ALS, and SMA. A phase 1b, double-blinded, randomized, placebo-controlled study ( NCT06436742 ) is investigating the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of adimanebart in adult participants with DOK7-CMS (N=16). reALiSe ( NCT06441682 ) is a phase 2a, double-blinded, randomized, placebo-controlled clinical trial investigating the safety and tolerability, preliminary efficacy, pharmacokinetics, and immunogenicity of adimanebart in ∼60 adult patients with ALS. SPARKLE ( NCT07287982 ) is a phase 2, double-blinded, randomized, placebo-controlled, active-treatment extension study designed to assess the safety, tolerability, efficacy, pharmacokinetics, and immunogenicity of adimanebart in pediatric participants (5 to <18 years of age) with SMA. Conclusion: By stabilizing and preserving NMJ and motor neuron function, facilitating synaptic transmission and promoting motor endplate integrity, adimanebart has therapeutic potential to improve muscle function in patients with CMS, ALS, and SMA.

Dr. Hara Jeon National Health Insurance Service Ilsan Hospital, Goyang, Korea, Republic of Background: Gait training robots are categorized into exoskeleton-type, end-effector-type, and wearable-type devices. It is well established that robot-assisted gait training (RAGT) is beneficial for patients with Guillain-Barré syndrome (GBS) who experience gait disorders. RAGT requires training by selecting an appropriate type of gait training robot, considering the patient's functional level; however, there is no established protocol for this. In this study, we would suggest which gait training robot is appropriate for patients with GBS depending on the patient's gait function. Methods: The gait training robots used for patients were as follows. We applied an exoskeleton-type Walkbot, an end-effector type Morning Walk, and a wearable-type Angel Legs according to the patients’ functional level. The patient's functional level was classified using the Functional Ambulation Categories (FAC) and Berg Balance Scale (BBS). For 24 patients with GBS who received RAGT, the types of gait training robots applicable to the patients were summarized according to their functional level. Results: There were 10 patients who applied Walkbot, 12 patients who applied Morning Walk, and 2 patients who applied Angel Legs. The FAC of patients who applied the Walkbot was 0∼1, and their average BBS was 4.5 points. The FAC of patients who applied the Morning Walk was 1∼3, and their average BBS was 7.9 points. The FAC of patients who applied the Angel Legs was 2 and 3, and their average BBS was 22.5 points. The application range of the Walkbot was suitable for FAC 0 to 1. If the patient can control the trunk somewhat, the Walkbot could provide gait experience even in cases where lower limb strength was zero. Morning Walk and Angel Legs were suitable for patients with FAC 1 to 3, and if body weight support was consistently measured less than 10% during RAGT using Morning Walk, the gait training robot was changed to Angel Legs. However, Angel Legs, which is a mobile gait training robot, requires higher balance ability compared to fixed gait training robots such as Walkbot or Morning Walk. Conclusion: By investigating the scope of application of exoskeleton, end-effector, and wearable-type gait training robots according to GBS patients’ functional level, the continuity of RAGT could be suggested. In the future, there will be a need to develop more precise training protocols for GBS patients according to their functional level and the type of gait training robot.

Prof. Ivan Barbov 1,2 , Dr. Goce Kalcev 2 1 University Clinic of Neurology, Skopje, North Macedonia, Skopje, North Macedonia. 2 National Alliance for Neuromuscular diseases and Neuroscience, GANGLION Skopje, 1000 Skopje, Republic of North Macedonia, Skopje, North Macedonia Background: The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) is a disease-specific tool used to assess quality of life in individuals with neuromuscular disorders, evaluating symptom severity and functional limitations. Methods: The sample included thirty adult patients with various neuromuscular disorders. A t-test was performed to examine differences in measured variables between participants with and without a family history of neuromuscular disease. Results: The measured variables in the section of the symptoms were: scores of the muscle weakness, pain, fatigue, locking of the muscles, droopy eyelids, double vision, and swallowing difficulty separately. The measured variables of the section life domains were: score of activities, independence, social relationships, emotions, and body image. A score for the quality of life, another measured variable, is also derived from the individual scores in this section using a particular formula. The measured variables in the section of the treatment effects were perceived treatment effects and expected treatment effects. The t-test results indicate that most measured variables did not differ significantly between individuals with and without a family history of neuromuscular disease. Some variables (pain, locking of the muscles, independence and expected treatment effects) approach significance, indicating potential trends that may warrant further investigation. Conclusion: Findings from this preliminary assessment indicate that the presence of a family history of neuromuscular disease does not significantly affect the measured variables within the studied sample.

Mr. Matthias Opsomer 1,2 , Dr. Jilmen Quintiens 3 , Ms. Elena Paravisi 3 , Dr. Thomas Anijs 3 , Mr. Herman Borghs 4 , Mr. Walter Coudyzer 5 , Ms. Tine de Cuyper 4 , Mr. Herman Peeters 4 , Dr. Veerle Goosens 5 , Prof. Marian Dejaeger 4 , Prof. Patrick Dupont 6 , Prof. Harry van Lenthe 3 , Prof. Kristl G. Claeys 1,2 1 Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium. 2 Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 3 Biomechanics Section, Department of Mechanical Engineering, Leuven, Belgium. 4 Metabolic Bone Center, University Hospitals Leuven, Leuven, Belgium. 5 Department of Radiology, University Hospitals Leuven, Leuven, Belgium. 6 Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a slowly progressive muscle disorder caused by contraction of the D4Z4 repeat on chromosome 4q35. While muscle degeneration is well-characterized, osteoporosis and fracture risk are often underestimated and conventional dual-energy X-ray absorptiometry (DXA) may not capture early microarchitectural changes. Photon-counting computed tomography (PCCT) offers a low-dose, rapid method to evaluate bone mineral density (BMD) and microarchitecture. We aim to evaluate baseline and 12-month longitudinal changes in bone health and fracture risk and identify clinical and biochemical predictors of bone loss in adults with FSHD1. Methods: Adults with FSHD1 were prospectively examined at baseline and 12 months. Bone health was assessed via DXA (lumbar spine, bilateral hips), PCCT, vertebral fracture assessment (VFA), and serum markers (BetaCTx, P1NP, vitamin D, PTH). Clinical and functional evaluation included fall history, FRAX® scores, disease severity scales. Patient-reported outcome measures comprised ActivLim and FSHD-Rasch-built overall disability scale (FSHD-Rods) and clinical outcome measures Timed Up and Go (TUG), Motor Function Measure 32 part D1 (MFM32-D1), 4-stairs climb test, and 6-minute walk test (6MWT), and Biodex® knee extension and flexion peak isometric strength. Results: Baseline assessment of 60 patients (mean age 52.1 ± 15.7 years, 55.0% female, mean number of D4Z4 repeats 7.2 ± 1.8) revealed that 56.7% had osteopenia and 21.7% osteoporosis. Prior fractures were reported in 50.8% of patients. Fall frequency was high with 63.3% reporting at least one fall per year). Mean DXA T-score was -0.53 ± 1.33 (spine), and -1.32 ± 0.98 (femoral neck). VFA detected mild asymptomatic vertebral fractures in three patients. Baseline 10-year FRAX® risk for major osteoporotic fractures (5.9%) and hip fractures (1.5%) increased to respectively 6.5% and 1.7%, after including DXA-derived BMD in the FRAX® score. BMD was symmetrical between left/right (p=0.45), dominant/non-dominant (p=0.59), and the strongest/weakest limbs (p=0.43). Among patients not on anti-osteoporosis therapy, 12-month spine and hip BMD remained stable (p=0.77 and p=0.11). However, bone turnover significantly decreased, in both bone resorption (BetaCTx -66.12 ng/L, p=0.04) and bone formation markers (P1NP -6.73 µg/L, p=0.04), independent of stable vitamin D (p=0.38) and PTH (p=0.13) levels. Regarding clinical predictors, TUG was the strongest objective predictor of 1-year hip Z-score decline (R=-0.46, p=0.003), while ActivLim was the primary patient-reported predictor (R=0.33, p=0.047). Similar trends were observed across other functional measures, including MFM32-D1 (R=0.32, p = 0.05), total FSHD Clinical Score (R=-0.31, p=0.06), FSHD-RODS (R =0.28, p=0.09), FSHD Clinical Severity Score (R =-0.29, p=0.09) and 6MWD (R=0.28, p=0.09). Conversely, bone turnover markers, number of repeat units, calcium intake and the changes in the outcome measures did not predict 1-year bone changes. Analysis of PCCT is ongoing and will be presented at the congress. Conclusion: Adults with FSHD1 exhibit high osteoporosis prevalence, frequent falls, and suppressed bone turnover. Baseline mobility (TUG, ActivLim) predicted 12-month hip Z-score changes, while D4Z4 length and blood biomarkers did not. This suggests functional mobility drives skeletal integrity in FSHD1, highlighting the need for proactive bone screening, fall prevention, and mobility-maintaining interventions like physical therapy.

Dr. Bruno Graziosi 1 , Dr. Enzo Pellacani 1 , Dr. Thaina Louise Rodrigues 1 , Dr. Pedro Fontana 2 , Dr. Carolina Correia 2 , Dr. Ana Marina Silva 1 , Dr. Alessandra Tolentino 1 , Dr. Roseli Corazzini 1 , Dr. David Feder 1 , Dr. Alzira Carvalho 1 1 Centro Universitário FMABC, Santo André, Brazil. 2 Hospital Universitário Oswaldo Cruz, Recife, Brazil Background: The increasing availability of genomic sequencing has revealed that more than one monogenic disorder may coexist in a single individual, a phenomenon increasingly recognized as a relevant diagnostic challenge in clinical genetics. Large cohorts demonstrate that approximately 4–7% of molecularly diagnosed patients harbor multiple independent genetic conditions, directly challenging the classical application of Occam’s razor in the neuromuscular discipline. We report two unrelated patients evaluated in a tertiary neuromuscular center in whom comprehensive genomic testing disclosed coincident molecular diagnoses explaining complex phenotypes. Methods: Case 1. A 39-year-old woman developed progressive proximal weakness, dysarthria, dysphonia, fasciculations, hyperreflexia, and muscle atrophy over six months, consistent with combined upper and lower motor neuron involvement. Electroneuromyography demonstrated a preganglionic pattern. Genetic testing identified a variant of uncertain significance in FUS , located in a functionally relevant domain previously associated with sporadic and familial amyotrophic lateral sclerosis, and a pathogenic splice-site variant in NF1 . The patient fulfilled diagnostic criteria for amyotrophic lateral sclerosis and also presented multiple café-au-lait macules and cutaneous neurofibromas. Brain and spinal MRI demonstrated multiple nerve sheath tumors consistent with schwannomas. These findings supported two independent molecular diagnoses: FUS -associated amyotrophic lateral sclerosis and neurofibromatosis type 1. Case 2 A one-year-old male infant presented with congenital hypotonia, generalized weakness, dysphagia, and early respiratory failure requiring prolonged invasive ventilation, followed by partial recovery with nocturnal ventilatory dependence. Examination revealed elongated facies, facial paresis, ophthalmoparesis, proximal limb weakness, cleft palate, pectus carinatum, scoliosis, cryptorchidism, short neck, low posterior hairline, and limited cervical mobility. Serum creatine kinase was normal. Electromyography demonstrated a myopathic pattern. Muscle biopsy revealed centrally located nuclei and necklace fibers. Whole-exome sequencing identified a pathogenic variant associated with Klippel–Feil syndrome, while chromosomal microarray demonstrated a pathogenic Xq28 deletion involving MTM1 , confirming X-linked myotubular myopathy. Both molecular diagnoses were necessary to explain the combined neuromuscular and skeletal phenotype. Results: These cases underscore the growing relevance of coincident molecular diagnoses in contemporary neuromuscular practice and highlight the limitations of strict diagnostic parsimony when applied to patients with complex or multisystem phenotypes. Traditionally, Occam’s razor has guided clinical reasoning toward a single unifying diagnosis; however, the expanding use of comprehensive genomic testing has revealed that multiple independent monogenic disorders may coexist and jointly shape the clinical presentation. Conclusion: These observations reinforce the importance of phenotype-driven, hierarchical interpretation of genomic data, in which discordant or “excess” clinical features prompt reconsideration of diagnostic assumptions rather than being dismissed as atypical manifestations. Recognizing coincident molecular diagnoses is not merely an academic exercise; it has direct implications for prognosis, surveillance strategies, genetic counseling, and family planning. As genomic technologies become increasingly accessible, clinicians must remain vigilant to cognitive biases and embrace a diagnostic framework that accommodates molecular multiplicity in neuromuscular disease.

Ms. Wanqing Wu 1,2 , Dr. Jing Wu 3 , Ms. Malin Petersson 1,2 , Ms. Ann Eriksson-Dufva 1,2,4 , Prof. Fang Fang 3 , Prof. Fredrik Piehl 1,2,4 , Assoc. Prof. Susanna Brauner 1,2,4 1 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 2 Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 3 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 4 Department of Neurology, Karolinska University Hospital, Stockholm, Sweden Background: Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder characterized by fluctuating muscle weakness. Azathioprine has long been recommended as first-line treatment by international guidelines. However, recent randomized trials indicate a beneficial effect of several biological therapies. In Sweden, a rapid transition from azathioprine to B cell-depletion (rituximab) as preferred first-line treatment occurred around 2015. Leveraging this change, we were able to compare outcome while minimizing treatment bias. Our aim is to compare the effectiveness of azathioprine and rituximab as first-line IST in MG patients using clinical data from the Swedish MG registry (MG-reg). Methods: We included adult MG patients from MG-reg who initiated azathioprine (n=156) or rituximab (n=91) as first-line treatment after 2005 and followed them until data withdrawal. The primary efficacy measure was relapse, identified by the use of rescue treatment. Incidence rate ratios (IRRs) were estimated using quasi-Poisson regression, adjusting for age at treatment initiation, sex, and disease duration. Analyses were performed using both intention-to-treat (ITT) and per-protocol (PP) approaches. Results: Patients receiving rituximab were younger (57.9 vs. 62.5 years, p=0.002) and were more often Early-onset MG (24.1% vs. 9.6%, p=0.062). By year 1, 28.2% of azathioprine users and 12.1% of rituximab users had switched or added another ISTs; and after two years the proportions were 30.8% and 26.4%, respectively. By ITT, relapses occurred in 23.1% vs 14.3% of patients in year 1 and 8.9% vs 11.2% in year 2 (azathioprine vs rituximab). Adjusted IRRs for relapse in the first and second year with rituximab were 0.59 (95% CI: 0.31, 1.08) and 1.13 (95% CI: 0.48, 2.61), respectively. By PP, the relapse incidence was 298 vs. 167 per 1,000 person-years by year 1 and 194 vs. 149 per 1000 person-years by year 2. Adjusted IRRs for rescue treatment in the first and second year with rituximab were 0.55 (95% CI: 0.22, 1.23) and 0.71 (95% CI: 0.27, 1.61), respectively. Analysis of long-term follow up is ongoing. Conclusion: Rituximab was associated with lower relapse frequency and fewer therapy switches in the first year compared with azathioprine, suggesting a faster onset of effect and greater effectiveness. Further studies are needed to identify predictors of treatment response and assess benefit–risk balance over extended follow-up.

Dr. Paolo Doksani 1 , Miss Marlene Wolfsgruber 2 , Prof. Fritz Zimprich 2 , Dr. Hakan Cetin 2 , Dr. Martin Krenn 2 , Asst. Prof. Romana Höftberger 2 , Asst. Prof. Lukas Weigl 3 , Dr. Meret Herdick 1 , Dr. Amani Suboh 1 , Miss Carla Dusemund 1 , Prof. Andreas Meisel 1 , Prof. Sarah Hoffmann 1 , Dr. Inga Koneczny 2 1 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Neuroscience Clinical Research Center (NCRC) and Integrated Myasthenia Gravis Center, Berlin, Germany. 2 Department of Neurology, Division of Neuropathology and Neurochemistry, Medical University of Vienna, Vienna, Austria. 3 Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria Background: Seronegative myasthenia gravis (SNMG) represents a clinical challenge, as approximately 10–15% of MG patients remain antibody-negative on routine testing despite clinically typical myasthenic features. This diagnostic gap is associated with diagnostic uncertainty, delayed diagnosis, and limited access to targeted immunotherapies. Cell-based assays (CBAs) have demonstrated increased diagnostic yield. However, a substantial proportion of SNMG patients remains antibody-negative even with extended CBA testing. In such cases, antibody binding to NMJ-associated structures may provide evidence of autoimmunity and increase diagnostic confidence, even without antigen identification. The MYA-DACH study assesses the prevalence of autoimmune signals in SNMG patients from the D-A-CH region (Germany, Austria, Switzerland) using live (L-CBA) and fixed (F-CBA) cell-based assays for clustered AChR- and MuSK-antibody detection, complemented by a human muscle cell-based assay for autoimmunity screening. Methods: MYA-DACH is a multicenter cross-sectional study testing samples from adult and pediatric patients with clinically characteristic myasthenic syndromes and negative routine antibody testing (AChR; MuSK and LRP4 where available). Samples were collected between November 2023 and February 2026. Using L-CBA and F-CBA, we assessed the prevalence of autoantibodies against clustered AChR and MuSK. To assess autoimmunity beyond known antigen targets, persistently seronegative sera in L-CBA testing were screened for antibody binding using an NMJ model based on primary human skeletal muscle cells with agrin-induced AChR clustering. This interim analysis focuses on baseline characteristics of 275 and antibody prevalence of 466 out of 500 collected samples. Recruitment and sample collection are complete, while final antibody analyses and comprehensive clinical correlations are ongoing, with updated results to be presented at ICNMD. Results: As of Dezember 2025, 466 serum samples were collected. The cohort is predominantly female (69.8%) with a mean age of 51.7 years. Mean age at disease onset was 44.6 years, with a mean diagnostic delay of 2.7 years. Most patients had generalized MG (76.9%), while 23.1% presented with purely ocular symptoms. Diagnostic features frequently supported autoimmune MG, including positive repetitive nerve stimulation (34.3%), abnormal single-fiber EMG (26%), and a positive oral pyridostigmine test (85.2%). L-CBA detected antibodies against clustered AChR in 4,78% (22/466) and MuSK antibodies in 1.52% (6/466) of previously seronegative classified patients. Of the L-CBA–positive samples, 86.4% (19/22) of AChR-positive sera were confirmed by fixed CBA, whereas none of the MuSK-positive samples (0/5) showed reactivity, indicating a higher sensitivity of the L-CBA. Among samples remaining negative on L-CBA, 6.3% (24/382) demonstrated antibody binding to NMJ-associated structures on human myotubes. Conclusion: The interim results from the MYA-DACH study demonstrate the prevalence of detectable AChR or MuSK autoantibodies identified by live and fixed cell-based assays in seronegative myasthenia gravis is relatively low compared with published international cohorts, but consistent with previous German data. Beyond antigen-specific antibodies, additional NMJ-associated antibody binding on human muscle cells supports autoimmune involvement in a subset of patients. Ongoing analyses will address clinical correlations with specific assay results, comparing patients with and without detectable signals for autoimmunity.

Dr. Luca Kunsztler 1 , Dr. Daniela Leone 1 , Dr. Claudia Brogna 1,2 , Dr. Sonia Messina 3 , Dr. Valeria Ada Maria Sansone 4 , Dr. Antonio Di Muzio 5 , Dr. Giulia Norcia 1 , Dr. Beatrice Berti 1 , Dr. Sophia Paolucci 1 , Dr. Anna Capasso 1,2 , Dr. Chiara Arpaia 1,2 , Dr. Marianna Villa 1 , Dr. Gianpaolo Cicala 1,2 , Dr. Romina Venditti 1,2 , Dr. Giorgia Coratti 1,2 , Dr. Eugenio Maria Mercuri 1,2 , Dr. Marika Pane 1,2 1 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 2 Università Cattolica del Sacro Cuore, Rome, Italy. 3 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 4 The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan- ERN for Neuromuscular Diseases, Milan, Italy. 5 Department of Neuroscience, Imaging and Clinical Sciences, “G. D'Annunzio” University, Chieti, Italy Background: Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disease caused by dystrophin gene mutations, affecting 1 in 3600 live male births. Typically diagnosed between ages 3-5 years with waddling gait, calf hypertrophy, and difficulty climbing stairs, the disease follows a predictable pattern of functional decline after age 7. Improved standards of care and early glucocorticoid treatment have significantly altered the natural history, affecting both survival and timing of functional milestone loss. Recent mutation-specific therapies, including antisense oligonucleotides for exon skipping and nonsense mutation treatments, show promising results. However, longitudinal data remain crucial for understanding genotype-specific progression and providing external controls for evaluating new pharmacological approaches. A 2013 three-year longitudinal study provided prospective functional data but lacked comprehensive genotype information. Methods: Following the original 2013 Telethon-funded study, participating centers continued data collection using identical criteria and structure, accumulating over 100 additional patients with three-year follow-up data and extended observations in the original cohort. The project is funded by the Grant “Unione europea–Next Generation EU–PNRR M6C2–Investimento 2.1 Rafforzamento e potenziamento della ricerca biomedica del SSN–PNRR-MR1-2023-12377031_CUP C53C23001220007”. This project aims to: develop a structured national electronic case report form (CRF) incorporating comprehensive functional data; migrate existing data from electronic datasets and clinical notes into the CRF; analyze three-year data from an expanded cohort exceeding 200 patients; conduct extended follow-up analysis beyond three years; evaluate non-ambulant patient outcomes; and identify prognostic indicators by analyzing functional trajectories one to three years preceding loss of ambulation. Results: By August 31, 2025, two meetings were held among participating units to establish common terminology through a data dictionary and identify appropriate variables for CRF development. This process involved identifying ambulant and non-ambulant patients with genetically confirmed DMD who had at least three years of consecutive natural history data at each center, reviewing their scheduled follow-up appointments, and identifying deceased patients with at least three years of consecutive data. Protocols were defined for blood sample collection, storage, and shipment to Unit 1 for genetic analysis. Nine-milliliter EDTA blood samples were collected for DNA extraction and real-time PCR analysis to evaluate potential genetic modifiers (osteopontin, LTBP4, etc.) in known DMD modifier loci, specifically SNPs of LTBP4, SPP1, CD40, and THBS1 genes. During routine follow-up visits, all eligible patients with a genetic DMD diagnosis were enrolled, and new clinical, functional, respiratory, and cardiologic data were collected according to DMD care standards guidelines. The CRF includes clinical history interviews, functional assessments (6MWT, NSAA, and PUL2.0 for ambulant patients; PUL2.0 for non-ambulant patients), and laboratory and instrumental examinations (2D echocardiogram, resting electrocardiogram, 24-hour Holter ECG monitoring, spirometry, polysomnography, nocturnal oximetry) according to international DMD care standards guidelines. As of the interim analysis, 170 patients meeting the original inclusion criteria have been consecutively enrolled following informed consent during routine clinical visits, with ongoing enrollment and data collection. Conclusion: This initiative will advance understanding of genotype-specific disease progression, ultimately supporting improved clinical trial design and patient care in DMD.

Prof. Chiara Briani Department of Neurosciences, University of Padova, Padova, Italy Background: The peripheral nervous system may be involved at any stage in the course of hematological diseases. Paraproteinemic neuropathies and those related to lymphoproliferative diseases are the most common. The different underlying mechanisms include chemotherapy neurotoxicity, direct nerve infiltration (neurolymphomatosis), infections, immune-mediated (especially IgM paraproteinemic neuropathies), paraneoplastic or metabolic processes and nutritional deficiencies. Some clinical findings, such a focal or diffuse involvement, symmetric or asymmetric pattern, presence of pain may point to the correct diagnosis. Besides a thorough medical history and neurological examination, neurophysiological studies, cerebrospinal fluid analysis, nerve biopsy (in selected patients with suspected lymphomatous infiltration) and neuroimaging techniques are needed for a proper diagnostic workup.

Dr. Arjun Seth 1 , Dr. Andrew Lerman 2 , Dr. Anneleen Remmerie 3 , Dr. Arne De Roeck 3 , Dr. Katerina Anokhina 3 , Dr. Arie Gafson 3 , Dr. Yessar M. Hussain 4 1 Northwestern Medicine, Chicago, United States. 2 Grove Neurology, Miami, United States. 3 argenx, Ghent, Belgium. 4 Austin Neuromuscular Center, Austin, United States Background: Efgartigimod is a human immunoglobulin G1 antibody Fc fragment that blocks FcRn, reducing pathogenic IgG autoantibody levels. Results from the ADHERE trial ( NCT04281472 ) demonstrated a significant, clinically meaningful benefit of efgartigimod PH20 subcutaneous (SC) in participants with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), regardless of prior CIDP therapy. Participants in ADHERE underwent a washout period during which they were required to show disease worsening before initiation of efgartigimod. Since disease worsening is not required for efgartigimod initiation outside of the clinical trial setting, research on the transition from intravenous immunoglobulin (IVIg) to efgartigimod without disease worsening will inform clinical practice. This phase 4, open-label, multicenter trial ( NCT06637072 ) in the US investigated whether transitioning to efgartigimod PH20 SC within 1 week after last IVIg dose is a safe and effective approach in CIDP. Methods: Twenty-three participants ≥18 years of age diagnosed with CIDP and treated with stable IVIg doses (0.5–2 g/kg once every 3–6 weeks for ≥3 doses) were enrolled. After a ≤3-week screening period, participants received efgartigimod PH20 SC 1000 mg once weekly for a 12-week treatment period within 1 week of stopping IVIg. The primary endpoint was the percentage of participants who continued receiving efgartigimod PH20 SC during the treatment period. Secondary endpoints included changes from baseline in quality-of-life assessments, perception of disease improvement/severity, treatment satisfaction, and safety/tolerability. Following study completion, participants may have received treatment at the investigator’s discretion per their routine clinical practice and completed a safety follow-up visit 4 weeks after the final study dose of efgartigimod PH20 SC. Results: The study commenced December 10, 2024. Last patient last visit is expected by end of February 2026. Topline results will be reported. Conclusion: This study evaluated an approach to transitioning from IVIg to efgartigimod PH20 SC within 1 week after last IVIg infusion in patients with CIDP.

Dr. Chad Heatwole 1 , Ms. Preshetha Kanagaiah 1 , Mrs Jennifer Weinstein 1 , Ms. Christina Shupe 1 , Ms. Charlotte Engebrecht 1 , Ms. Judith Monickaraj 1 , Ms. Anika Varma 1 , Mr. Spencer Rosero 2 , Ms. Charlotte Irwin 1 , Ms. Karnavaal Al-Rubayie 1 , Ms. Alicia Brockt 1 , Mrs Peggy Auinger 1 , Mrs Debra Guntrum 1 , Dr. Emma Ciafaloni 1 1 University of Rochester, Rochester, United States. 2 University of Utah, Salt Lake City, United States Background: In preparation for upcoming therapeutic trials with patients with Duchenne muscular dystrophy (DMD), there is a need for sensitive outcome measures that can detect clinically relevant changes in disease burden overtime. To satisfy this need we previously developed and validated the regulatory-grade caregiver-reported DMDCR-HI as a potential outcome to serially quantify patient disease burden. The DMDCR-HI can be used for ambulatory or non-ambulatory patients and consists of individual subscales that measure the symptomatic domains most important to patients, as reported by the caregiver. Additional information is needed regarding the performance metrics of the DMDCR-HI in the context of a longitudinal clinical study. Methods: We are in the process of conducting   a 24-month, remote, longitudinal study with caregivers and individuals with DMD. Caregivers of   individuals with DMD are completing the DMDCR-HI, the Proxy-Reported PedsQL (PedsQL), an outcome preference survey, and a global impression of change questionnaire at 6-month intervals. As part of this study, we are evaluating: 1) the ability of the DMDCR-HI to measure disease progression in DMD; 2) the survey preference for the DMDCR-HI compared to the PedsQL; and, 3) the meaningful score difference of the DMDCR-HI and its subscales. Results: 92 DMD caregivers (mean child age: 12.3 years (range: 2 to 21)) enrolled at baseline. After 12 months, the DMDCR-HI total score demonstrated a 5.15 point change from baseline (p-value:0.0068) in addition to detecting disease progression in the following subscales: shoulder and arm function (10.46 points, p-value:0.0002), gastrointestinal health (9.48 points, p-value:0.0115), heart health (7.33 points, p-value:0.0256), activity participation (7.27 points, p-value:0.0085), mobility (6.94 points, p-value:0.0157), ambulation (6.83 points, p-value:0.0134), finger and hand function (6.29, p-value:0.0131), breathing (6.03 points, p-value:0.0183), and core and truncal strength (5.20 points, p-value:0.05). The PedsQL did not demonstrate any significant change over 12 months. A total of 65% of caregivers preferred the DMDCR-HI over the PedQL (p-value:0.03). Figure 1 shows 12-month data regarding caregiver preferences for the DMDCR-HI vs. the PedsQL. To date, all 12-month data has been collected with participants currently completing their 18 month and final 24-month assessments. Meaningful score difference data based on final data collection is forthcoming. Conclusion: The DMDCR-HI is a validated outcome measure that is able to quantify point-in-time multifactorial disease burden in patients with DMD. Longitudinally, the DMDCR-HI is able to detect disease progression over a 12-month period and is preferred by users. Data from our study will provide insight into what a meaningful change in DMDCR-HI score is, and will be useful when interpreting changes in DMDCR-HI scores during future therapeutic and regulatory trials.

Dr. Nancy L. Kuntz 1 , Dr. Rahul Gentyala 2 , Dr. Julie Coats 3 , Dr. Atsuki Hashimoto 4 , Dr. Astrid Blaschek 5 , Dr. Wolfgang Müller-Felber 5 , Dr. Carsten G. Bönnemann 6 , Dr. Barbara K. Smith 7 , Dr. Andrea Seferian 8 , Dr. Lucy James 3 , Dr. Perry B. Shieh 9 , Dr. James J. Dowling 10 1 Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, United States. 2 Astellas Pharma Global Development, Inc., Northbrook, IL, United States. 3 Astellas Gene Therapies, South San Francisco, CA, United States. 4 Astellas Pharma Europe Ltd., Addlestone, United Kingdom. 5 Department of Paediatric Neurology and Developmental Medicine, Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany. 6 National Institute of Health, Bethesda, MD, United States. 7 University of Florida, Gainesville, FL, United States. 8 Institute of Myology, French National Centre for Scientific Research, Paris, France. 9 University of California Los Angeles, Los Angeles, CA, United States. 10 Penn Medicine, Philadelphia, PA, United States Background: X-linked myotubular myopathy (XLMTM) is a life-threatening, rare, congenital muscle disease with no approved therapies. The ASPIRO trial assessed the safety and efficacy of resamirigene bilparvovec (rAAV8-desmin-hMTM1), a gene replacement therapy that expresses human MTM1 in muscles, in children with XLMTM. With up to 4.6 years of follow-up (primary analysis), 16/24 dosed participants achieved ventilator independence and 19/24 had improved motor function compared with baseline, with 8 walking independently and 15 sitting independently. Here, results from ASPIRO with >5 years of follow-up are reported. Methods: ASPIRO ( NCT03199469 ) is an open-label, international, multicenter, dose-escalation trial. Male children aged <5 years with XLMTM requiring mechanical ventilator support were included. Participants received one intravenous infusion of resamirigene bilparvovec at 1.3 × 10 14 vector genomes (vg)/kg bodyweight (lower-dose cohort) or 3.5 × 10 14 vg/kg bodyweight (higher-dose cohort). The primary efficacy outcome was change from baseline to week 24 in hours of daily ventilator support. Other important efficacy outcomes included ventilator independence and motor milestones. ASPIRO stopped enrollment after 1 participant in the lower-dose and 3 in the higher-dose cohorts died; at time of death, all had cholestatic liver failure following gene therapy. During long-term follow-up, 1 participant in the lower-dose cohort withdrew from the study. Follow-up to 10 years of the remaining 19 participants (lower-dose cohort, n=5; higher-dose cohort, n=14) is ongoing. Results: As of data cutoff, June 20, 2025, median follow-up was 5.51 years (range, 0.18–7.25) for all participants (N=24; lower dose [n=7]: 6.96 years [range, 0.18–7.25]; higher dose [n=17]: 5.07 years [range, 0.28–6.48]). Among evaluable participants (n=19), 5/6 (83.3%) in the lower-dose cohort and 10/13 (76.9%) in the higher-dose cohort had ventilator independence at month 60. Most participants (n=11) achieved ventilator independence ≤1.5 years of treatment, but others (n=4) achieved independence ≥2 years after treatment. Of the 4 participants without ventilator independence, 3 required fewer hours of ventilator support daily at month 60 compared with baseline (Figure). At month 60, 5/6 (83.3%) and 12/13 (92.3%) evaluable participants demonstrated functionally independent sitting for ≥30 seconds in the lower-dose and higher-dose cohorts, respectively; 5 (83.3%) in the lower-dose and 7 (53.8%) in higher-dose cohorts were also walking independently at that time. Since the 4 deaths reported in the primary analysis, there were no additional deaths. In the overall safety analysis (N=24), 2 participants in the lower-dose cohort and 7 in the higher-dose cohort had serious treatment-related hepatobiliary adverse events (AEs), all of which had first onset 6–162 days post-dosing. Four participants had treatment-related hepatobiliary AEs that had onset ≥1 year post-dose; all had grade 1, 1 also had grade 2. Myocarditis was a treatment-related AE in 1 participant in each cohort, consistent with the primary analysis. Conclusion: With up to 7.25 years of follow-up, most children with XLMTM who received resamirigene bilparvovec continued to show improvements in respiration and motor function. Since the primary analysis, 4 additional participants began walking independently and 1 achieved independent sitting. During long-term follow-up, no further deaths were reported, and resamirigene bilparvovec demonstrated a favorable safety profile.

Dr. Laura Ferraiuolo 1 , Dr. Erin Hurley 1 , Dr. Mark Stahl 1 , Dr. Gretchen Thomsen 1 , Ms. Hana Julazadeh 1 , Dr. Jannigje Kok 1 , Dr. Cleide Dos Santos Souza 1 , Ms. Ashley Fox 2 , Mr. Ryan Weiss 1 , Dr. Vivian Ko 1 , Ms. Haydee Gutierrez 1 , Ms. Melissa McAlonis-Downes 3 , Mr. Robert Cano 1 , Dr. Binh Chu 1 , Dr. Angélique Braen 4 , Dr. Junguo Zhou 4 , Dr. W. David Arnold 5 , Dr. Stephen J. Kolb 2 , Dr. Allan Kaspar 1 , Dr. Brian Kaspar 1 1 Insmed Gene Therapy LLC, San Diego, CA, United States. 2 Ohio State University Wexner Medical Center, Columbus, OH, United States. 3 University of California, San Diego, CA, United States. 4 Insmed Incorporated, Bridgewater, NJ, United States. 5 University of Missouri, Columbia, MO, United States Background: INS1202 is an engineered adeno-associated virus 9 (AAV9) vector that drives expression of a short hairpin RNA (shRNA) construct targeting human superoxide dismutase 1 ( SOD1 ) mRNA, being evaluated for the potential treatment of amyotrophic lateral sclerosis (ALS). Methods: SOD1 G93A mice treated with single ascending doses of INS1202 or vehicle via intracerebroventricular administration at postnatal day (p)1 were assessed for disease onset and survival, motor skills, and muscle force through p200 (scheduled study end). Plasma neurofilament levels were evaluated at p50, p120, and p200 in all animals alive at the respective timepoints. Tissues were collected for biodistribution, histological examination, and protein analysis. Nonhuman primates (NHPs) were administered single ascending doses of INS1202 or vehicle via lumbar intrathecal injection to assess biodistribution and safety in a 3-month GLP-compliant toxicology study. To assess efficacy in a human disease in vitro model, astrocytes directly reprogrammed from SOD1-ALS (n=1) and sporadic ALS (n=10) human patient fibroblasts were treated with INS1202 or vehicle and co-cultured with healthy control mouse GFP-positive motor neurons (MNs). Results: SOD1 G93A mice treated with INS1202 (n=7-12/sex/group) showed a dose-dependent improvement in median survival. Median age at death in the vehicle control group was p130, while 93% of mice in the highest dose group were still alive at study end (p200). INS1202-treated SOD1 G93A mice gained and sustained physiological weight (p<0.0001), retained muscle function per the rotarod test (p<0.0001), and retained muscle force per the muscle physiology Aurora system (p<0.0001). Additionally, compared with vehicle-treated mice, INS1202-treated SOD1 G93A mice exhibited significantly lower plasma neurofilament levels at three timepoints: p50, when mice are asymptomatic (p<0.01, n=6/group), p120±10 when vehicle-treated mice showed signs of paralysis (p<0.001, n=12-15/group), and at p200, end of study. INS1202 treatment of SOD1 G93A mice preserved lumbar MN numbers (n=6/group, p=0.0006) and preserved staining intensity of IBA1 (n=4/group, p<0.0001) and GFAP (n=6/group, p<0.0001) in-line with levels observed in wild-type mice. At the highest dose, INS1202 treatment reduced the levels of human mutant SOD1 protein (n=6/group, p<0.0001) by 46% in the lumbar spinal cord of SOD1 G93A mice. In the 3-month GLP-compliant NHP toxicology study, biodistribution via droplet digital PCR (ddPCR) demonstrated vector genome delivery to all spinal cord segments, brainstem, and motor cortex, with lower distribution to peripheral organs including liver, compared with what is reported with intravenous administration of AAV9. INS1202 was well tolerated at all doses with single intrathecal administration in NHPs and the No-Observed-Adverse-Effect Level was determined to be the highest dose evaluated. Additionally, INS1202 treatment was neuroprotective in astrocyte-MN co-cultures from patients with SOD1-ALS, as well as in co-cultures from 7 of 10 patients with sporadic ALS negative for SOD1 and other known mutations. Conclusion: Administration of INS1202 improved survival and motor function and ameliorated hallmarks of neurodegeneration in SOD1 G93A  mice. INS1202 was well tolerated in NHPs and showed potential for treating patients with SOD1-ALS and sporadic ALS negative for SOD1 and other known mutations. Based on these efficacy and safety data, three ascending doses of INS1202 are being evaluated in a phase 1 first-in-human clinical trial.

Dr. Andrea Sipos 1 , Dr. Endre Pál 1 , Dr. Dávid Varga 1 , Dr. Nándor Hajdú 2 , Miss Réka Héjas 1 , Mrs Brigitta Ruszin-Perecz 1 1 UPMS, Pécs, Hungary. 2 ELTE, Budapest, Hungary Background: Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and is characterized by progressive muscle weakness and impaired muscle relaxation (myotonia). The disease typically presents with early distal muscle involvement followed by a gradual distal-to-proximal progression. Myotonia contributes substantially to functional impairment. Methods: Patients with myotonic dystrophy type 1 underwent a standardized, multimodal evaluation encompassing neuromuscular function, functional performance, and patient-reported outcomes. Muscle strength was assessed using Manual Muscle Testing (MMT) with Medical Research Council–based scoring and complemented by quantitative hand-held dynamometry. Myotonia was evaluated using clinical assessments and functional relaxation tests. Upper limb dexterity was measured with the Nine-Hole Peg Test (9HPT), and lower limb function and walking capacity with the Six-Minute Walk Test (6MWT). Activity limitations and disability were captured using the DM1-Activ scale and the DM Disability Scale. Health-related quality of life was assessed with the SF-36, mood with the Beck Depression Inventory (BDI), and cognitive function with the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Examination. Results: Longitudinal linear mixed-effects models revealed clear progression of muscular impairment. After correction for multiple comparisons, 35 of 62 outcomes (56.5%) demonstrated significant annual change. Distal lower limb muscles were most affected: ankle dorsiflexion declined ∼0.25 points/year bilaterally (padj < .001). Upper limb strength also deteriorated, with shoulder elevation decreasing 0.17–0.20 points/year (padj < .001), and the composite MIRS score increased over time. Hand grip strength declined 0.38–0.40 kg/year (p< 0.001). In contrast, 9HPT, 6MWT, and myotonia relaxation tests showed no significant longitudinal change. Cognitive function, assessed by MoCA and Addenbrooke’s Cognitive Examination, remained largely stable (MoCA β = −0.37/year), as did SF-36 subscales and the DM1-Activ scale (β = −0.06/year). Only the activities of daily living subscale of the DM1 Disability Scale showed modest but significant worsening (β = 0.19/year). Other self-reported outcomes, including fatigue, social participation, and depressive symptoms remained stable. Conclusion: These results confirm that DM1 is characterized by progressive muscular weakness, particularly in distal lower limb and proximal upper limb muscles, while functional performance, cognitive function, quality of life, and most patient-reported outcomes remain relatively preserved. Objective strength measures, including manual muscle testing (MMT) parameters and hand grip dynamometry, were the most sensitive indicators of disease progression. Integrating quantitative neuromuscular assessments with patient-reported outcomes provides a comprehensive understanding of disease trajectory and is essential for monitoring progression and evaluating therapeutic interventions in myotoniy dystrophy type 1.

Dr. Amanda Maccarrone 1,2 , Dr. Lorenzo Chiarella 3,4 , Dr. Noemi Brolatti 5 , Mr. Simone Morando 5 , Dr. Ramona Cordani 3,6 , Ms. Antonella Iadarola 6 , Dr. Marco Veneruso 3,6 , Dr. Chiara Panicucci 5 , Prof. Carlo Minetti 6 , Prof. Martino Ruggieri 1 , Prof. Claudio Bruno 5,6 , Prof. Pasquale Striano 2,6 , Prof. Lino Nobili 3,6 , Dr. Marina Pedemonte 2 , Dr. Federica Trucco 2,6 1 Unit of Pediatric Clinic, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. 2 Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. 3 Child Neuropsychiatry Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy. 4 . Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. 5 Centre of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy. 6 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy Background: Sleep-disordered breathing (SDB) is a clinically relevant complication of Duchenne muscular dystrophy (DMD), encompassing obstructive and central events and nocturnal hypoventilation. Sleep is a vulnerable period during which respiratory abnormalities may precede daytime pulmonary decline. The association between sleep abnormalities, motor and respiratory functional decline, and biological dysregulation remain poorly defined in DMD. This study aims to characterize sleep disorders in DMD, pathogenesis and their role as disease biomarkers. Methods: DystREST is an ongoing prospective, single-center observational study. All participants underwent a standardized assessment including pulmonary (forced vital capacity, FVC; peak cough flow, PCF) and motor function tests (NSAA, PUL), overnight cardiorespiratory polygraphy (PG) with transcutaneous monitoring of gas exchange (oxycapnography, measuring tcPCO₂, SaO₂). Validated sleepiness questionnaires (PSQI, Epworth Sleepiness Scale, MEQ, Respicheck) were administered and objective assessment of circadian rhythm was conducted via actigraphy and salivary melatonin levels. Clinical data, including age, ambulatory status, genotype, age at loss of ambulation (LOA), age at peak FVC and PCF, initiation of nocturnal non-invasive ventilation (NIV), comorbidities, and ongoing therapies were correlated with sleep disorders. Results: Twenty male patients with genetically confirmed DMD have been enrolled to date. Age range was 8-32 years (mean 19.1). Preliminary results showed normal PG and nocturnal gas exchange findings in 17/20; 7 of these were already on NIV, supporting its effectiveness in maintaining adequate nocturnal ventilation. PG identified SDB in 3/20 patients, with a predominance of obstructive events (2 out of 3); none of these three patients exhibited nocturnal hypoventilation. One ambulant, non-ventilated patient aged 10.8 years, showed combined central and obstructive events. Two non-ambulant, non-ventilated patients (aged 15 and 24.5 years, respectively) presented obstructive sleep apnea. The 15-year-old patient showed a more severe respiratory pattern and was affected by severe obesity. In the subgroup of non-ventilated patients, pulmonary function was compared between subjects with and without SDB. No statistically significant differences were observed in FVC (p = 0.33), FVC% (p = 1.00), or peak expiratory flow (p = 0.22). However, despite the lack of statistical significance, patients with SDB consistently exhibited lower values. There was a statistically significant positive correlation between age at peak absolute FVC and age at LOA (p = 0.005), indicating parallel progression of respiratory and motor decline. In a Cox proportional hazards model, later LOA was associated with a reduced hazard of NIV initiation (hazard ratio per year = 0.94, p = 0.59), although this association did not reach statistical significance. No significant correlations were observed between SDB severity and motor impairment or pulmonary function. PG findings were not significantly associated with self-reported sleep disturbances. Analyses of potential circadian rhythm abnormalities recorded via actigraphy and salivary melatonin are ongoing. Conclusion: Preliminary findings from the DystREST study suggest that clinically relevant SDB may occur in patients still ambulant, with normal pulmonary function and in the absence of hypoventilation and may therefore be overlooked. Ongoing in-depth analysis of polygraphy data using diaphragm-specific SDB metrics may further enhance phenotypic characterization and the use of sleep as stage-specific disease biomarker in DMD.

Prof. Enrico Bertini 1 , Prof. Maria Mazurkiewicz-Bełdzińska 2 , Prof. Laurent Servais 3,4 , Prof. Michelle A Farrar 5 , Dr. Dmitry Vlodavets 6 , Dr. Edmar Zanoteli 7 , Prof. Mohammad Al-Muhaizea 8 , Prof. Alexandra PQC Araújo 9 , Dr. Leslie Nelson 10 , Miss Manni Kuthiala 11 , Dr. Ksenija Gorni 12 , Dr. Heidemarie Kletzl 13 , Dr. Francis Warren 14 , Dr. Eleni Gaki 14 , Mr. Dave Summers 14 , Dr. Marianna Manfrini 12 , Prof. Richard S Finkel 15 1 Research Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children’s Research Hospital IRCCS, Rome, Italy. 2 Department of Developmental Neurology, Chair of Neurology, Medical University of Gdańsk, Gdańsk, Poland. 3 MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, United Kingdom. 4 Division of Child Neurology, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège & University of Liège, Liège, Belgium. 5 Sydney Children’s Hospital Network and UNSW Medicine, UNSW Sydney, Sydney, Australia. 6 Russian Children Neuromuscular Center, Veltischev Clinical Pediatrics and Pediatric Surgery Research Institute of Pirogov Russian National Research Medical University, Moscow, Russia. 7 Department of Neurology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. 8 Neuroscience Centre of Excellence, King Faisal Specialist Hospital & Research Center-Riyadh, Riyadh, Saudi Arabia. 9 Pediatrics Department, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 10 Department of Physical Therapy, University of Texas Southwestern Medical Center, Dallas, TX, United States. 11 Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland. 12 PDMA Neuroscience, F. Hoffmann-La Roche Ltd, Basel, Switzerland. 13 Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland. 14 Roche Products Ltd, Welwyn Garden City, United Kingdom. 15 Center for Experimental Neurotherapeutics, St Jude Children’s Research Hospital, Memphis, TN, United States Background: Risdiplam is a centrally and peripherally distributed, oral survival of motor neuron 2 ( SMN2 ) pre‑mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). RAINBOWFISH ( NCT03779334 ) is a global, open-label, single-arm, multicentre, Phase 2 study assessing the efficacy, safety, pharmacokinetics and pharmacodynamics of risdiplam in infants with genetically diagnosed and presymptomatic SMA from birth to 6 weeks of age (at first dose), regardless of SMN2 copy number or baseline compound action potential (CMAP). Methods: RAINBOWFISH enrolled 26 infants: eight infants had two SMN2 copies, 13 infants had three SMN2 copies and five infants had ≥4 SMN2 copies. The primary efficacy (PE) population (n=5) had two SMN2 copies and baseline CMAP amplitudes ≥1.5 mV. Drug dosage was adjusted to achieve a target exposure of approximately 2,000 ng∙hr/mL. This analysis assesses the efficacy and safety of risdiplam in children with presymptomatic SMA after 3 years of treatment. Results: The primary endpoint was met after 12 months of risdiplam treatment, with 4/5 (80%) infants in the PE population able to sit without support for ≥5 seconds (Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition [BSID-III]). Twenty-three children completed 3 years of treatment with risdiplam (data cut-off: 10 February 2025). The vast majority of children who reached Year 3 (21/23, 91%) were able to sit, stand and walk without support, and once achieved, no children lost any abilities. All children who completed 3 years of risdiplam treatment were able to swallow and 96% of children were fed exclusively orally. Cognitive function and speech development were similar to that of typically developing children without SMA in the same age range. There were no treatment-related serious adverse events reported up to Year 3. No child required respiratory support outside of an illness and the majority of children (21/26) did not require any hospitalisations up to Year 3. There were no withdrawals from treatment between Years 2 and 3. Conclusion: The majority of children treated with risdiplam before the onset of SMA symptoms, maintained motor milestones and bulbar function and showed cognitive skills similar to children without SMA after 3 years of treatment.

Dr. Marie Goret, Dr. Thomas Arbogast, Miss Gwenaelle Piccolo, Dr. jocelyn laporte IGBMC, Inserm U1258, Strasbourg University, Illkirch, France Background: Charcot–Marie–Tooth disease (CMT) comprises genetically heterogeneous peripheral neuropathies for which no disease-modifying therapy is currently available. Among these, recessive MTMR2 mutations cause CMT4B1, a severe demyelinating neuropathy characterized by focal myelin outfoldings and aberrant mTORC1 signaling in Schwann cells, while dominant loss-of-function mutations in DNM2 lead to intermediate or axonal CMT. Although MTMR2 and DNM2 belong to distinct molecular families, both regulate phosphoinositide-dependent membrane trafficking and cytoskeletal dynamics, suggesting convergence on shared pathogenic pathways. Methods: Using complementary mouse models, we investigated the contribution of DNM2 dosage and activity to CMT pathophysiology and assessed gene-modulation strategies as therapeutic proof-of-concepts. Results: In MTMR2-deficient mice, transcriptomic and biochemical analyses revealed a coordinated downregulation of DNM2 and its functional partners in peripheral nerves, concomitant with mTORC1 hyperactivation. Genetic and AAV-mediated upregulation of DNM2, either ubiquitously or selectively in Schwann cells, significantly improved neuromuscular performance, restored mechanical sensitivity, reduced paranodal myelin outfoldings, and normalized mTORC1 signaling in sciatic nerves, establishing DNM2 as a disease modifier in CMT4B1. In parallel, we addressed dominant DNM2-CMT caused by the common K562E mutation. By combining refined disease models that unmask Schwann-cell autonomous pathology with post-symptomatic AAV9-mediated DNM2 supplementation, we show that DNM2-CMT neuropathy primarily arises from early Schwann-cell dysfunction and exhibits limited reversibility once myelination defects are established. These data highlight a narrow temporal and quantitative therapeutic window for DNM2 augmentation. Importantly, genetic rebalancing of DNM2 activity—either by combining loss- and gain-of-function DNM2 alleles or by modulating BIN1, a negative regulator of DNM2—rescues both neuropathic and myopathic phenotypes of a DNM2-CMT mouse model, normalizing nerve architecture and motor function. Conclusion: Collectively, our results support a unifying model in which precise tuning of DNM2 activity is critical for peripheral nerve homeostasis. They provide strong proof-of-concept that gene-modulation strategies targeting the DNM2 pathway, delivered through transgenesis or AAV vectors, represent a promising and broadly applicable therapeutic avenue for genetically distinct forms of CMT, while emphasizing the need for cell-type specificity, dosage control, and early intervention.

Dr. Maria Sframeli 1 , Dr. Noemi Brolatti 2 , Asst. Prof. Federica Trucco 3,4 , Dr. Elena La Rosa 1 , Dr. Rita Lauro 1 , Dr. Roberto Materia 1 , Dr. Marisa Maniaci 1 , Dr. Natalia Longoni 1 , Dr. Ibrahim Said 1 , Dr. Cosimo Allegra 1 , Dr. Marina Pedemonte 3 , Dr. Claudio Bruno 2,4 , Prof. Sonia Messina 1 1 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 2 Center of Translational and Experimental Myology and Maternal and Child Health, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 3 Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 4 Department of Neuroscience, Rehabilitation, Ophthalmology Genetics, University of Genoa, Genoa, Italy Background: Risdiplam is an available treatment of all patients with spinal muscular atrophy (SMA). Although the respiratory impairment is inevitably progressive also in later-onset SMA, no studies report the effect of this drug on respiratory function. Methods: We report a case series of 14 patients, followed at two Italian tertiary referral centers with long-term disease duration and treated with risdiplam for more than 5 years. We describe changes in respiratory and motor function and the need for non-invasive ventilation (NIV). Results: Patients (mean age: 19,7 years, range: 14-28), 11 SMA2 (78,6%) and 3 SMA3 (21,4 %), were sitter (57,1%) or non-sitter (43,9%). The Hammersmith Functional Motor Scale Expanded (HFMSE) score was ≤ 8 in 13/14 patients, and did not show significative changes after treatment (p=0.9). Mean FVC at baseline was 1,27 l (SD:1,02). After more than 5 years (mean follow-up 5,3 years) the mean FVC improved significantly (1,41 l; SD: 1,06, p=0.04). Overall 4 patients (28%) showed minimal FVC decrease (-0,12 l; p=0.09), while the other 10 patients (72%) showed a significative improvement in FVC (+0,24; p=0.009). None of the patients on NIV at baseline (n=8) required changes in ventilation regime at follow-up. Conclusion: We report longer-term respiratory follow-up in treated patients and, for the first time, an improvement in commonly used pulmonary function tests, in contrast to motor functional outcome measures. Therefore, we propose to explore a high responsiveness of the FVC, mostly in severely affected SMA patients, in which commonly used motor functional outcome measures might not detect changes (PNRR-MR1-2022-12376937).

Dr. Jeffrey A Allen 1 , Dr. Claudia Sommer 2 , Dr. Manuel Nunez 3 , Dr. Karen M. Lynch 3 , Dr. Yi Lu 4 , Dr. Li Xiong 3 , Dr. Miguel Alonso Alonso 3 , Dr. Asif Paker 3 , Dr. Luis Querol 5,6 1 Department of Neurology, Division of Neuromuscular Medicine, University of Minnesota, Minneapolis, Minnesota, United States. 2 Neurologische Klinik und Poliklinik, Universitätsklinikum Würzburg, Würzburg, Germany. 3 Sanofi, Cambridge, MA, United States. 4 Sanofi R&D, Evidence Generation and Decision Science, Cambridge, MA, United States. 5 Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau (IR SANT PAU), Barcelona, Spain. 6 Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain Background: Riliprubart, a first-in-class, humanized IgG4-monoclonal antibody, selectively inhibits activated-C1s in classical complement pathway and is self-administered subcutaneously. Phase 2 trial demonstrated encouraging efficacy and safety in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Adapted from the established multiple sclerosis model, GBS|CIDP Foundation has proposed Immune Neuropathy-No Evidence of Disease Activity (IN-NEDA) as a composite endpoint tailored for CIDP with IN-NEDA-1 defined as no patient-perceived change and either no decline in disability or no decline in impairment while IN-NEDA-2 requires no patient-perceived change and no decline in both disability and impairment for a duration of 6 months or more. This framework offers structured outcome assessment, to guide treatment decisions and enhance patient care through disability/impairment evaluation. The goal of this study was to conduct an exploratory analysis of Phase 2 results of riliprubart applying the proposed IN-NEDA framework. Methods: NCT04658472 , an open-label, Phase 2 trial evaluated riliprubart across three groups: Standard-of-care (SoC)-Treated, SoC-Refractory and SoC-Naïve. Participants underwent 24-week treatment (Part-A) with optional 52-week treatment-extension (Part-B). This post-hoc analysis evaluated durability of non-deterioration in (trial) participants using a composite approach incorporating disability and impairment scales aligned with the IN-NEDA framework. Results: Findings exploring different approaches will be presented at the congress. Conclusion: These results will help illustrate the applicability of the IN-NEDA framework in CIDP, supporting its role as a comprehensive approach for assessing sustained disease control.

Dr. Marco Guglielmi 1 , Dr. Eleonora Pacucci 1 , Dr. Valeria Delmonte 1 , Dr. Gianni Difonzo 1 , Dr. Eustachio D'Errico 2 , Dr. Teresa Francavilla 2 , Dr. Angela Fraddosio 2 , Dr. Stefania Cataldo 2 , Dr. Antonio Iaffaldano 2 , Prof. Damiano Paolicelli 1 1 University of Bari “Aldo Moro”, Bari, Italy. 2 Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy Background: A 66-year-old male with a history of arterial hypertension, obstructive sleep apnea syndrome, remote Hodgkin lymphoma and cognitive dysfunction diagnosed as Alzheimer’s disease in 2017 (which fully resolved within 8 months since onset) presented with a subacute onset of motor weakness, spasticity and diffuse and abundant fasciculations beginning in March 2025. This presentation raised suspicion for a peripheral nerve hyperexcitability disorder. Methods: During hospitalization, the patient underwent neurological examination, blood tests, cerebrospinal fluid (CSF) analysis, electromyography (EMG), motor evoked potentials (MEPs), somatosensory evoked potentials (SEPs), and brain and spine MRI with and without contrast. Therapeutic intervention with intravenous immunoglobulins (IVIG, 0.4 g/kg/day for 5 days) was administered. Results: Neurological examination revealed paraparesis with spasticity, hyperreflexia and widespread fasciculations. EMG demonstrated diffuse persistent fasciculations and myokymias and sporadic acute denervation activity, suggesting peripheral nerve hyperexcitability in combination with lower motor neuron involvement. MEPs showed abnormal corticospinal tract conduction, while SEPs revealed preserved sensory conduction. MRI imaging and CSF analysis were unremarkable. Blood tests showed positive anti-LGI1 autoantibodies. Following IVIG therapy, a mild clinical improvement was observed, particularly in muscle tone and frequency of fasciculations. The combination of diffuse fasciculations, EMG findings of peripheral hyperexcitability, absence of structural CNS pathology, partial clinical response to immunotherapy and previous transient cognitive dysfunction supported a diagnosis of Morvan syndrome. The sporadic presence of acute denervation signals raised consideration for concomitant lower motor neuron dysfunction, but no alternative etiology was identified. Furthermore, we performed a review of 21 cases published in English literature (papers found by bibliographic search on PubMed and Google Scholar on January 9, 2026). Out of 21 patients, 6 (29%) had cognitive symptoms at the time of diagnosis and no patient ever experienced a spontaneous resolution of cognitive symptoms. The most common symptoms were insomnia (19 out of 21 patients, 90%), followed by dysautonomia (18 out of 21 patients, 86%), paresthesias, muscle cramps, limb weakness and REM sleep behavioural disorder. 19 out of 21 patients (90%) tested positive for anti-VGKC autoantibodies. Conclusion: The clinical, neurophysiological and radiological findings were most compatible with Morvan syndrome. Immunoglobulin therapy produced partial symptomatic improvement. The patient was discharged with symptomatic and immunomodulatory treatmentand a follow-up plan including serial laboratory and clinical monitoring. Furthermore, the literature review suggests that a spontaneous resolution of cognitive symptoms is unlikely in Morvan syndrome, therefore more data is needed in order to fully understand the prevalence of this phenomenon.

Dr. Te-Wei Wang 1,2 , Asst. Prof. Mao-Yuan Su 1 , Assoc. Prof. Mei-Fang Cheng 1 , Dr. Hsueh-Wen Hsueh 1 , Prof. Ming-Chang Chiang 3 , Prof. Yen-Hung Lin 1 , Prof. Jyh-Ming Jimmy Juang 1 , Assoc. Prof. Shiou-Ru Tzeng 4 , Prof. Sung-Tsang Hsieh 4,1 , Prof. Chi-Chao Chao 1 1 National Taiwan University Hospital, Taipei City, Taiwan. 2 National Taiwan University Hospital Hsin-Chu Branch, Hsinchu County, Taiwan. 3 National Yang Ming Chiao Tung University, Taipei City, Taiwan. 4 National Taiwan University, Taipei City, Taiwan Background: Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by various TTR gene mutations. Recent advances in disease-modifying therapies for ATTRv have heightened the clinical significance of early diagnosis and intervention. Cardiac involvement is a common presentation of late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This study explored phenotypes of cardiac amyloidosis and their clinical and neurological correlates in the premanifest stage. Methods: Premanifest carriers with the transthyretin p.A117S variant were enrolled. Healthy controls and ATTRv-PN patients with stage 1 polyneuropathy disability (PND) were enrolled for comparison. Cardiomyopathy was evaluated by echocardiography, 99m Tc-pyrophosphate (PYP) single-photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum N-terminal prohormone of brain natriuretic peptide (pro-BNP). Neuropathy was assessed using clinical questionnaires, skin biopsy, neurophysiology, and quantitative sensory testing. Differences between groups were compared using the Kruskal–Wallis test or Fisher’s exact test. Multivariable linear regression models were applied to adjust for age and sex. Multiple comparisons were corrected by the false discovery rate (FDR) method. Results: Thirty-two carriers with transthyretin variants (31 p.A117S, 17 men, median age 47) were enrolled, along with 63 controls (34 men, median age 51 years) and 11 ATTRv-PN patients (9 p.A117S, 7 men, median age 64 years). None of the carriers had polyneuropathy, while 38% had carpal tunnel syndrome (CTS) and 16% had increased radiotracer uptake on 99m Tc-PYP SPECT imaging. Based on the normal references from the healthy controls (the mean plus 2 standard deviations), abnormally increased extracellular volume (ECV) was noted in 25% of the carriers, prolonged myocardial native T1 in 11%, and increased left ventricular mass index (LVMi) in 6%. Compared with controls, carriers demonstrated a greater ECV (β 1.87%, 95% CI 0.76–2.98%, p=0.0025), longer native T1 (β 15.51 msec, 95% CI 1.7–29.32, p=0.0282) and greater LVMi (β 4.16 g/m²; 95% CI, 0.65–7.67; p=0.0208) on CMR, indicating subclinical cardiac amyloidosis. ATTRv-PN patients had markedly greater amyloid burden across these cardiac imaging. Among carriers, CMR myocardial interstitial and hypertrophic parameters were significantly correlated with large- and small-fiber nerve degenerations. Higher 99m Tc-PYP SPECT uptake was associated with increased pro-BNP, native T1, ECV, autonomic and sensory dysfunction, and presence of CTS. Conclusion: Subclinical cardiomyopathy, as shown by nuclear medicine imaging and CMR, is common and linked to neuropathic changes among carriers carrying predominant p.A117S variant, and may facilitate early and accurate diagnosis and intervention for ATTRv-PN.

Prof. Andrea Malaspina UCL Queen Square MND Centre, Institute of Neurology, London, United Kingdom Background: Capturing the presymptomatic phase of ALS through the lens of subtle clinical and molecular changes preceding phenoconversion is of critical importance. This effort is central to understanding risk, enabling early intervention and developing preventative treatment strategies. Reducing the incidence of ALS must not be underestimated, as it represents a major burden on health systems and society, requiring substantial investment in specialised end-of-life care. Apart from gene-silencing approaches benefiting a small minority of people living with ALS (plwALS), therapeutic development has recently stalled, contributing to a sense of hopelessness among patients and carers. Although significant progress has been made over the past 10–15 years in defining the clinical and molecular framework of presymptomatic disease, a complete picture of the stepwise or linear changes leading to disease onset remains elusive. Methods: Here, we evaluate the methodological approaches used over the past two decades to study the presymptomatic stage of ALS. This has included work to understand genetic susceptibility and the broader genetic architecture of a disease with a lifetime risk of approximately 1 in 300 in the general population. Epidemiological studies of large ALS cohorts have enabled multistep modelling of disease development. In parallel, increasingly sensitive methodologies for detecting subtle molecular changes preceding clinical onset have led to the identification of biomarkers that, individually or in combination, show strong predictive value when incorporated into multivariate models of disease onset. Results: These investigative efforts have yielded several key advances: the development of multistep population-based models; transformative progress in disease stratification and identification of the prodromal phase in mutation carriers through measurement of neurofilament light chain in biological fluids; and, more recently, the identification of biomarker panels capable of robustly predicting disease initiation. These panels are based on analyses of plasma and cerebrospinal fluid samples from presymptomatic mutation carriers, as well as large longitudinal population studies employing high-sensitivity platforms such as Simoa and Olink. Conclusion: The future holds further promise. Continued expansion of longitudinal clinical datasets and biobanked biological samples, alongside the development of increasingly sensitive detection technologies, will enable deeper exploration of additional disease dimensions, including the proteome and metabolome. These advances, coupled with ongoing refinement of genetic and epigenetic frameworks, are expected to further elucidate the earliest stages of ALS and support the development of effective preventative strategies.

Dr. Jhee LEE Department of Neurology, Seoul National University Hospital, Seoul, Korea, Republic of Background: Young-onset amyotrophic lateral sclerosis (yALS), defined by symptom onset before age 45, may differ from typical-onset ALS in genetic architecture, phenotype, and trajectory. We characterized the clinical features, genetic findings, and outcomes of yALS at a large tertiary center in Korea. Methods: We retrospectively reviewed consecutive patients diagnosed with ALS at the Department of Neurology, Seoul National University Hospital between 01/01/2025 and 12/31/2025. Of 109 total ALS cases, 18 met the age-at-onset criterion for young-onset ALS (yALS; <45 years). Diagnosis adhered to the revised El Escorial and Gold Coast (2019) criteria. Standardized workup included neurological examination, electrophysiology, neuroimaging, and targeted laboratory testing to exclude mimics. An ALS multigene panel was performed in 15 of the 18 yALS patients using next-generation sequencing, and repeat-primed PCR was used to test for C9orf72. Results: Of 109 patients with ALS, 18 (16.5%) met criteria for young-onset ALS (yALS), with a male-to-female ratio of 3:1. Limb onset was the predominant presentation; bulbar onset was observed in two patients, both of whom were men. Genetic testing identified variants most frequently in SOD1 (n = 3) and FUS (n = 2). Variants of uncertain significance were detected in seven patients. No C9orf72 repeat expansions were identified. Conclusion: In this single-center cohort, yALS accounted for 16.5% of ALS cases. Pathogenic or potentially relevant variants were enriched in SOD1 and FUS . Clinically, yALS was characterized by predominantly limb-onset disease.

Dr. Linda Kusner , Dr. Henry Kaminski George Washington University, Washington, United States Background: Thymomas are unique among neoplasms for their strong association with autoantibody-mediated diseases with the highest occurrence of acetylcholine receptor antibody-positive myasthenia gravis (thymoma associated MG, TAMG). A major contributor to this pathogenesis is disruption of thymic epithelial cell function, which impairs T cell development and central immune tolerance through a deficiency in the autoimmune regulator (AIRE) protein. While autoantibodies targeting striated muscle proteins, the ryanodine receptor, and potassium channels have been described, the full scope of autoreactivity remains incompletely defined. Methods: To address this, we applied a broad, unbiased profiling approach. Serum samples from 43 patients with TAMG and 18 healthy, non-autoimmune controls were analyzed by molecular indexing by self-assembly to characterize the autoreactome, assessing over 16,000 full-length proteins and nearly 400,000 peptide sequences for autoreactive antibodies. Results: Both TAMG subjects and controls demonstrated substantial autoreactivity, ranging from 62 to 623 protein-targeted autoantibodies per individual. Although no consistent pattern of autoreactivity distinguished the TAMG cohort, a subset of patients exhibited high levels of antibodies directed against multiple type I interferons. Within this subgroup, all patients had antibodies against TRIM46 and P2X4 which have not previously been identified in TAMG. Analysis of the subpopulation did not reveal association with thymoma WHO classification or clinical characteristics. Conclusion: These findings support widespread disruption of immune tolerance in TAMG, particularly affecting antigen processing and regulatory T-cell function. Further investigation into the functional significance of these autoantibodies may provide insight into disease mechanisms.

Dr. Paola Alberti University of Milano-Bicocca, Monza, Italy Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) represents a significant complication arising from cancer treatment, often resulting in sensory, motor, and autonomic dysfunctions that impact patients’ quality of life. A translational approach to CIPN integrates preclinical and clinical research, bridging laboratory findings with patient care. Preclinical studies employ morpho-functional techniques to elucidate axonal damage mechanisms, focusing on ion channel dysfunctions and nerve excitability, while clinical investigations explore epidemiological trends and therapeutic interventions. This strategy facilitates the development of targeted diagnostic tools and novel therapies, ultimately improving outcomes for individuals undergoing chemotherapy.

Prof. Laurent Servais University of Oxford, Oxford, United Kingdom. University of Liege, Liege, Belgium Background: This is a joined session ICNMD/WMS Methods: We will present the perspective of treatment inequity from an European perspective Results: We will discuss issues like relocation, lottery and crowd funding Conclusion: To assess treatment access inequity needs the involvement of all actors, including physicians, policy makers, scientific society, patients advocacy and pharma company. It needs multimodal action including standard of care development, education to the management of rare diseases, early diagnosis to allow early treatment and of course differential costing of innovative medications.

Dr. Marija Meznaric 1 , Prof. Corrado Angelini 2 1 University of Llubjana, Llubjana, Slovenia. 2 University of Padova, Padova, Italy Background: A common form of limb girdle muscular dystrophy is dysferlinopathy, presenting as LGMDR R2 /2 B or distal Miyoshi myopathy, which shows a different clinical course. They are caused by mutations in the DYSF gene encoding the protein dysferlin, a transmembrane sarcolemmal and T-tubule protein that has a role in the repair of sarcolemma. To the best of our knowledge, dysferlin expression in different skeletal muscles has not been studied so far. We investigated by western blot dysferlin myosin ratio in human skeletal muscles, biceps brachii and tibialis anterior, and rat muscles, the slow soleus, and fast extensor digitorum longus ( EDL). Methods: Slow and fast muscles in the man and the rat were examined for dysferlin by Western Blot. The ratio was higher in human neuromuscular controls in the biceps brachii versus the tibialis. Histochemistry was performed for Myosin heavy chain isoforms, SDH, and NADH-TR. Results show in humans a trend towards a higher amount of dysferlin in fast skeletal muscle compared to slow, which might be relevant for the different course observed in LGMDR 2 2 B and Miyoshi myopathy Results: The ratio was higher in human neuromuscular controls in the biceps brachii than in the tibialis anterior. In rat muscles, the ratio was significantly higher in SOL than in EDL. A positive correlation was found between the area proportion of type 1 fibres and dysferlin expression, and a negative correlation for type 2, subtypes of type 2, and hybrid fibres was found. Differential dysferlin expression in human and rat fast and slow skeletal muscles is of interest and might be relevant to explain the clinical course of LGMD-R2. Our results show in humans a trend towards a higher amount of dysferlin in fast skeletal muscle compared to slow, which might be relevant for the different course observed in LGMDR R2 /2 B and Miyoshi myopathy Conclusion: Our western blot results have discovered a different ratio of dysferlin and myosin in slow and fast muscles. This might imply a metabolic role of dysferlin,(Figure) besides the repair, on type 1 fibres that are rich in mitochondria and lipids, and in type 2 fibres with abundant T tubules

Prof. Jungim Suk Department of Neurology, Catholic University of Daegu, School of Medicine, Daegu, Korea, Republic of Background: Centronuclear myopathy (CNM) is a rare hereditary myopathy characterized by centrally located muscle fiber nuclei. Usual EMG finding is myopathic motor unit potentials without spontaneous activity. Myotonic discharge without clinical myotonia can be seen in polymyositis, acid maltase deficiency, and so on. Methods: We reported a case of CNM with electrical myotonia. Results: A 30-year-old man presented with progressive limb weakness. Neurologic examination revealed mild ptosis and proximal limb weakness. Neither spontaneous or percussion myotonia nor muscle atrophy was observed. In the electrophysiologic examinations, motor and sensory conduction studies were normal; needle electromyogram showed numerous myotonic discharges. CNM was confirmed by gene test without muscle biopsy. Next generation sequencing revealed a heterozygous substitution (c.1948G>A; p.Glu650Lys) in the DNM2. Conclusion: This case suggests that DNM2 -related CNM may present electrical without clinical myotonia. The diagnosis of CNM should be considered in patients with myotonic discharges of an unknown cause.

Dr. Rohit Aggarwal 1 , Dr. Anthony A. Amato 2 , Dr. Ingrid E. Lundberg 3 , Dr. Andrew L. Mammen 4 , Dr. Jiri Vencovský 5 , Mr. Sebastian Rodriguez 6 , Dr. Paul Duncombe 6 , Dr. Bas van der Woning 6 , Dr. Hector Chinoy 7,8 1 University of Pittsburgh Medical Center, Pittsburgh, United States. 2 Brigham and Women’s Hospital Harvard Medical School, Boston, United States. 3 Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 4 Muscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, United States. 5 Institute of Rheumatology, Research Department, and Department of Rheumatology, 1st Medical Faculty, Charles University, Prague, Czechia. 6 argenx, Ghent, Belgium. 7 Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom. 8 Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom Background: Idiopathic inflammatory myopathy (IIM), a rare, debilitating, systemic rheumatic disease, has limited treatment options. Efgartigimod is a human immunoglobulin G1 (IgG1) antibody Fc fragment, with increased affinity for the neonatal Fc receptor (FcRn), that selectively reduces IgG by blocking FcRn-mediated IgG recycling without impacting antibody production or other parts of the immune system. Efgartigimod does not lower albumin levels and does not increase low-density lipoprotein cholesterol levels. The ALKIVIA trial assessed the safety and efficacy of subcutaneous (SC) efgartigimod versus placebo in individuals with active IIM receiving background therapy. Interim data from the open-label extension ALKIVIA+ trial are reported. Methods: In ALKIVIA ( NCT05523167 ; a seamless phase 2/3, randomized [1:1], double-blinded, placebo-controlled, parallel-group, multicenter trial), adults received weekly efgartigimod (1000 mg) co-formulated with recombinant human hyaluronidase (rHuPH20) SC (EFG) or placebo rHuPH20 SC (PBO). After the 24-week placebo-controlled period, eligible participants either enrolled in ALKIVIA+ ( NCT05979441 ) and received EFG or entered a 56-day safety follow-up. The ALKIVIA+ primary endpoint is long-term safety and tolerability (treatment-emergent adverse events [TEAEs], serious adverse events [SAEs], and adverse events of special interest [infections]). Secondary endpoints include changes over time in the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) Myositis Response Criteria’s Total Improvement Score (TIS); the proportion of participants with minimal (TIS ≥20), moderate (TIS ≥40), and major (TIS ≥60) clinical improvement over time; and changes from baseline in Physician Global Assessment of Disease Activity (MDGA), Patient Global Assessment of Disease Activity (PGA), Patient Global Impression of Severity (PGI-S), and manual muscle testing-8 (MMT8). Results: In ALKIVIA, 89 participants received EFG (n=47) or PBO (n=42), with 69 entering ALKIVIA+ at Week 24; 35 continued EFG (EFG-EFG; mean age: 57.7 years, mean time since diagnosis: 4.60 years), and 34 switched to EFG (PBO-EFG; 54.9 and 4.81 years, respectively). At Weeks 24 to 52, for PBO-EFG, TIS increased from 38.96 to 49.62, and for EFG-EFG, it remained stable (50.67 to 52.19) (Image 1A). At Week 52, minimal, moderate, and major TIS improvements were achieved by 93.8% versus 93.9%, 75.0% versus 66.7%, and 37.5% versus 33.3% of EFG-EFG versus PBO-EFG participants, respectively. Mean changes from baseline in MDGA, PGA, and MMT8 scores at Week 52 were similar for participants receiving EFG-EFG versus PBO-EFG (–3.56 vs –3.10, –2.56 vs –1.89, and 16.3 vs 17.1, respectively). At Week 28, PGI-S symptoms improved in 9.4% versus 26.0% of those receiving EFG-EFG versus PBO-EFG and worsened in 15.6% versus 8.8% of participants in these groups, respectively. The incidence of adverse events was comparable between EFG-EFG (TEAE: 33/35 [94.3%], SAE: 7/35 [20.0%]) and PBO-EFG (TEAE: 31/34 [91.2%], SAE: 6/34 [17.6%]) (Image 1B). In general, the incidence of TEAEs was consistent for both groups. Only 1 severe infection was noted in the EFG-EFG group. Generally, the TEAE incidence remained consistent throughout ALKIVIA and ALKIVIA+. Conclusion: Interim ALKIVIA+ data show a favorable safety profile over 52 weeks for EFG, with notable improvements in efficacy for participants who switched to EFG. These findings support the ongoing phase 3 evaluation of EFG in ALKIVIA+.

Miss Martina Esposito 1,2 , Dr. Andrea Armani 3 , Dr. Davide Steffan 2 , Dr. Leonardo Nogara 1,2 , Prof. Bert Blaauw 1,2 , Dr. Paolo Grumati 4 , Dr. Sofia De Felice 5 , Prof. Laura Cendron 5 , Prof. Marco Sandri 1,2 1 Università degli Studi di Padova, Department of Biomedical Sciences, Padova, Italy. 2 Veneto Institute of Molecular Medicine, Padova, Italy. 3 Institute of Neuropathology, UZH, Zurich, Switzerland. 4 Telethon Institute of Genetic and Medicine (TIGEM), Napoli, Italy. 5 Università degli Studi di Padova, Department of Biology, Padova, Italy Background: Skeletal muscle health and function are guaranteed by a finely tuned balance between synthesis of new proteins and degradation of damaged structures and organelles. However, under catabolic conditions degradative processes exceed de novo protein synthesis and organelle biogenesis leading to muscle atrophy, which is regulated by a specific genetically-encoded program. In the search for new players involved in muscle mass regulation, in the past years we identified Fbxo30/MUSA1, a previously uncharacterized E3 ubiquitin ligase that sits at the crossroads of two fundamental pathways controlling muscle mass; indeed, MUSA1 expression is driven by FoxO3 during catabolic conditions, while it is suppressed by the BMP signaling. Methods: To better characterize MUSA1 role in skeletal muscle physiology, we generated muscle-specific knock-out mice. Results: MUSA1 deletion leads to progressive sarcomere disorganization in knock-out muscles. In particular, histological and electron microscope analyses revealed the presence of wide areas within aged knock-out muscle fibers characterized by the presence of indigested proteinaceous material completely disrupting sarcomeres architecture. Moreover, these aggregates appear as enlarged Z-line, resembling nemaline rods, a feature typical of nemaline myopathies. As a consequence, these ultrastructural alterations lead to muscle weakness in aged knock-out animals. In line with these evidences, aged knock-out muscles proteomes show progressive accumulation of proteins important for sarcomeres and cytoskeleton assembly and stabilization, together with Z-line components. For this reason, we speculate that MUSA1 could be involved in some of these proteins turnover. Indeed, we demonstrated by in vitro ubiquitination assay that MUSA1 is responsible for actinin 3 (ACTN3) poly-ubiquitination when coupled with the E2 conjugating enzyme UbcH2. Conclusion: Concluding, our data support MUSA1 as a novel critical player in controlling Z-line homeostasis together with muscle function. However, further investigations are needed to better characterize MUSA1 substrates and to precisely dissect the molecular pathogenic mechanisms involved in the perspective of therapeutic intervention.

Dr. Sadıka Özdemir , Dr. Ebru Özbezen Kızıltan, Dr. Sezin Alpaydın Baslo, Dr. Aysun Soysal Bakirkoy Prof. Dr. Mazhar Osman Training and Research Hospital for Mental Health and Neurological Diseases, University of Health Sciences, Istanbul, Turkey, istanbul, Turkey Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) shows a variable clinical course ranging from sustained remission to relapsing disease. Although electrophysiological studies are essential for diagnosis, their longitudinal evolution and prognostic value in long-term follow-up are not fully established. Methods: We retrospectively analyzed clinical and electrophysiological data of CIDP patients followed between 2000 and 2024. Patients with available baseline and follow-up nerve conduction studies were included. Functional outcomes were assessed using the Medical Research Council (MRC) sum score, modified Rankin Scale (mRS), and INCAT disability score. Remission, stable disease, and relapse were defined using standardized clinical criteria. Longitudinal electrophysiological changes were analyzed using repeated-measures general linear models, and correlations with clinical outcomes were assessed using appropriate statistical tests. Results: Forty-two CIDP patients were included, with a median follow-up of 57.6 months (range: 3–240). The overall remission rate was 71.1%. Patients achieving remission showed significant longitudinal improvement in CMAP amplitudes, whereas relapsing patients demonstrated persistent electrophysiological abnormalities. Conduction blocks detected at baseline largely resolved or evolved into temporal dispersion on follow-up, consistent with remyelination under treatment. Importantly, baseline axonal involvement—particularly reduced lower-limb CMAP amplitudes—was significantly associated with higher long-term disability scores (higher INCAT and mRS, lower MRC scores). The presence of diabetes mellitus was associated with a reduced likelihood of remission. Conclusion: Longitudinal electrophysiological changes in CIDP closely reflect clinical course and functional outcome. While demyelinating features may improve with treatment, baseline axonal damage is a strong predictor of long-term disability. Serial nerve conduction studies provide clinically meaningful prognostic information and should be considered an integral part of long-term disease monitoring in CIDP.

Prof. Nalini Atchayaram , Miss Suravi Dash, Mr. Prashanth Vashishta, Assoc. Prof. Gautham Arunachal, Assoc. Prof. Seena Vengalil, Mr. Chetan Ghati, Prof. Yogananda Markandeya National Institute of mental Health and Neurosciences, Bangalore, India Background: Congenital myasthenic syndromes (CMS) represent a heterogeneous group of inherited neuromuscular disorders characterized by impaired signal transmission at the neuromuscular junction (NMJ). These conditions arise from pathogenic variants in single or multiple proteins critical for synaptic function. The advent of next-generation sequencing technologies has markedly advanced the discovery of novel CMS-associated genes, surpassing the limitations of earlier candidate gene and linkage-based approaches. Importantly, the genetic diversity underlying CMS translates into distinct pathogenic mechanisms, variable clinical phenotypes, and differing prognostic outcomes, thereby necessitating individualized therapeutic strategies. A treatment effective for one CMS subtype may be ineffective or even deleterious in another, underscoring the need for precision medicine. Although certain clinical features may appear gene-specific, considerable phenotypic overlap exists across mutations, and intrafamilial variability suggests the influence of genetic modifiers. Consequently, accurate molecular diagnosis is essential to guide tailored interventions. Methods: In this study, we investigated an Indian cohort of CMS patients, clinically examined 128 individuals, and sequenced 75 patient samples to date. Analysis using GNOMAD and Varsome databases revealed 35 novel variants spanning 10 genes. Here, we present detailed findings from a single Indian-origin patient exhibiting fluctuating limb-girdle muscle weakness, ptosis, and fatigability. Results: Family history excluded consanguinity, though her elder brother displayed similar symptoms. Electrophysiological evaluation through repetitive nerve stimulation demonstrated a decremental response in the deltoid muscle. Whole-exome sequencing identified a homozygous MUSK variant c.1742T>A (p.Ile581Asn), consistent with autosomal recessive inheritance and associated acetylcholine receptor deficiency. In silico analysis further revealed that variant p.Ile581Asn leads to substitution of a conserved hydrophobic isoleucine with a larger, polar asparagine and is predicted to disrupt hydrophobic interactions. Conservation analysis confirmed Ile581 as highly conserved across species, and structural modeling classified the variant as likely pathogenic with high confidence (score 0.957). Protein stability predictions using DDMut and MUPro indicated destabilization (ΔΔG −0.34 kcal/mol and −1.7 kcal/mol, respectively). Molecular dynamics simulations performed with GROMACS v2023.3 demonstrated increased RMSD in the MUSK p.Ile581Asn variant compared to wild type, suggesting significant structural perturbation. To establish a personalized NMJ model, patient-specific induced pluripotent stem cells (iPSCs) were generated and validated. These iPSCs exhibited compact morphology, expression of pluripotency markers (OCT4, NANOG, TRA-1-60), normal karyotype, and trilineage differentiation potential confirmed by germ layer markers (Nestin, Troponin-I, Alpha-fetoprotein). Differentiation yielded mature motor neurons expressing OLIG2, ChAT, and β3-tubulin, with patch-clamp recordings confirming neuronal maturity. Parallel differentiation produced myotubes expressing MYOD and MYHC, indicative of successful myogenesis. Future work will involve co-culturing patient-derived motor neurons and myotubes in NMJ microfluidic chambers to further dissect disease mechanisms and therapeutic responses. Conclusion: Overall, this integrative approach—combining clinical evaluation, genetic analysis, computational modeling, and patient-specific iPSC-derived NMJ models—demonstrates the feasibility of personalized in vitro platforms for mechanistic studies and therapeutic development in CMS.

Asst. Prof. Milos Brkusanin , Mr. Nemanja Garai, Mr. Nemanja Radovanović, Asst. Prof. Jovan Pešović, Dr. Lana Radenković, Mrs Suzana Matijašević Joković, Miss Vanja Obadović, Miss Sanja Madić, Miss Ksenija Obadović, Prof. Goran Brajušković, Prof. Dušanka Savić Pavićević University of Belgrade - Faculty of Biology, Centre for Human Molecular Genetics, Belgrade, Serbia Background: Spinal muscular atrophy (SMA) is among the most severe inherited neuromuscular disorders and, in the absence of timely intervention, a leading genetic cause of infant mortality. The availability of disease-modifying therapies has fundamentally changed the natural history of SMA, with the greatest clinical benefit achieved when treatment is initiated presymptomatically. This has positioned newborn screening (NBS) for SMA as both a medical necessity and a public health priority. Methods: In 2021, Serbia initiated its first genetic newborn screening program for SMA, centralized at the Faculty of Biology, University of Belgrade, a national reference center for SMA diagnostics and research since 1997. During a 17-month pilot phase, 12,000 newborns from two maternity hospitals were screened using dried blood spots and real-time PCR to detect SMN1 exon 7 absence, with confirmatory MLPA analysis and SMN2 copy number determination. Results: Following the successful pilot, a nationwide SMA NBS program was launched on September 15, 2023. The program currently covers 52 public and 6 private maternity hospitals across Serbia. By January 16, 2025, a total of 141,101 newborns had been screened, identifying 22 infants with SMA. Of these, 20 received immediate disease-modifying therapy: 8 infants with 2 SMN2 copies, 8 with 3 copies, and 4 with 4 copies. Two infants with 5 SMN2 copies are under active clinical surveillance. To date, treated infants remain predominantly asymptomatic. Clinical decision-making is coordinated by a national multidisciplinary Expert SMA Commission, ensuring individualized treatment strategies based on genetic findings, clinical assessment, and laboratory parameters. The program has enabled the first reliable estimate of SMA incidence in Serbia (1:6,414 live births) and demonstrates the feasibility and clinical impact of presymptomatic diagnosis within a middle-income healthcare system. Conclusion: The Serbian experience highlights how structured newborn screening workflows, centralized diagnostics, and personalized therapeutic approaches can transform SMA from a devastating, life-limiting disease into a manageable condition. This program serves as a practical model for integrating precision medicine into national public health systems through close collaboration between academia, patient organizations, industry partners, and governmental institutions.

Ms. Eline Cuveele 1,2 , Dr. Sam Geuens 1,2 , Ms. Kim Wittebols 1 , Ms. Joanna Willen 1 , Prof. Céline Gillebert 2 , Prof. Liesbeth De Waele 1,2 1 University Hospitals Leuven, Leuven, Belgium. 2 KU Leuven, Leuven, Belgium Background: Boys with Duchenne muscular dystrophy (DMD) are at increased risk for cognitive, behavioral and emotional difficulties that can substantially affect daily functioning, social participation and family life. Currently available behavioral questionnaires are largely generic and insufficiently capture neurobehavioral characteristics specific to DMD. The DuMAND (Duchenne Muscular Dystrophy-Associated Neurobehavioral Difficulties) Checklist was developed as a disease-specific instrument to systematically measure neurobehavioral functioning in boys with DMD across five categories: (1) cognition and learning , (2) social responsiveness , (3) externalizing behavior , (4) emotion regulation and (5) eating and sleeping . Methods: This ongoing psychometric validation study uses a longitudinal design with three measurement timepoints at six-month intervals, aligned with routine clinical follow-up visits. Boys aged between 3 and 20 years with genetically confirmed DMD are recruited at the University Hospitals Leuven in Belgium. Parents or primary caregivers complete the DuMAND Checklist together with a battery of standardized questionnaires, including the Child Behavior Checklist (CBCL), the Behavior Rating Inventory of Executive Function (BRIEF), the Social Responsiveness Scale-Second Edition (SRS-2) and a social-emotional functioning questionnaire (SEV). Results: Planned analyses include assessment of internal consistency using Cronbach’s alpha and inter-rater reliability using Cohen’s kappa. Convergent validity will be examined through correlations between DuMAND categories and conceptually related subscales of established instruments, while divergent validity will be explored using correlations with theoretically unrelated subscales. Exploratory factor analysis (EFA) will be conducted to investigate the underlying factor structure of the DuMAND Checklist. Conclusion: This study aims to provide a methodologically robust evaluation of the psychometric properties of the DuMAND Checklist in a Belgian DMD cohort.   Data collection is currently ongoing. Results from the cross-sectional and interim longitudinal analyses are anticipated to be available for presentation at the time of the 2026 ICNMD Congress. Completion of recruitment and longitudinal follow-up is expected to allow full psychometric evaluation, and final conclusions regarding reliability, validity and clinical applicability will be drawn once data collection and analyses are complete.

Dr. Nurit Birman Har-Noy 1 , Dr. Omer Bouzaglo 1 , Prof. Vivian Drory 1,2 , Dr. David Kravitz 1 , Dr. Tahani Sheikh Saker 1 , Assoc. Prof. Alon Abraham 1,2 1 Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 2 Tel-Aviv University, Tel-Aviv, Israel Background: Facioscapulohumeral muscular dystrophy (FSHD) requires reliable and accessible objective biomarkers for clinical monitoring and therapeutic trials. Current quantitative ultrasound (US) methods often rely on echogenicity, which frequently requires specialized software. This study aimed to validate a rapid, generic protocol focusing on muscle thickness as a clinical correlate in FSHD. Methods: Twenty-seven genetically confirmed adult FSHD patients (mean age 45.3 ± 12.8 years) were recruited between September 2023 and April 2024. A standardized US protocol was used to measure muscle thickness in eight relaxed muscles (biceps brachii, APB, FDI, ADM, quadriceps, tibialis anterior, EDB, and AHB) on the right side. For the biceps, quadriceps, and tibialis anterior, measurements were also taken during full contraction. Hyperechogenic muscles (Heckmatt 3-4) were assigned a thickness of zero. Sum scores of relaxed and contracted thicknesses were correlated with the FSHD Clinical Score (FSHD-CS), Clinical Severity Score (FSHD-CSS), 6-minute walk test (6-MWT), and manual muscle testing. Results: Relaxed and contracted sum muscle thickness showed strong to very strong correlations with most clinical outcomes (r = 0.61 to 0.86, p < 0.01). Specifically, relaxed sum muscle thickness demonstrated a correlation of r = -0.86 with both FSHD-CS and FSHD-CSS. Correlation with the 6-MWT was r = 0.74 for relaxed sum muscle thickness and r = 0.61 for contracted sum muscle thickness. Muscle thickness measurements did not correlate with age, BMI, or symptom duration. The entire US evaluation was completed in less than ten minutes. Conclusion: This rapid and reproducible ultrasound protocol demonstrates a strong correlation with disease burden in FSHD across multiple clinical scales. Unlike software-dependent echogenicity methods, muscle thickness measurement is easily implementable across routine US systems and diverse clinical settings. These findings suggest that muscle thickness sum scores can serve as an objective biomarker for monitoring disease progression and assessing treatment effects in clinical trials.

Prof. Shanshan MAO Children‘s hospital, Zhejiang university school of medicine, HANGZHOU, China Background: Children with ocular myasthenia gravis (OMG) often suffer from relapse under traditional treatment with corticosteroid-related side effects. The biologic agent telitacicept, recently approved for adult patients with generalized MG, has shown good efficacy. This study aims to evaluate the efficacy and safety of telitacicept in children with OMG. Methods: This is a case series of four children with OMG who were treated with telitacicept in Children's Hospital, Zhejiang University School of Medicine from April 2024 to December 2025. Clinical data were retrospectively collected before and after treatment, including patient demographics, clinical characteristics, scores of quantitative MG scale and MG-activity of daily living scale, as well as laboratory tests. Adverse events were also evaluated. Results: Among the four patients, two were males and two were females. The median age at onset was 3.2 years (range 1.7 to 10.5 years), and the median course of disease before telitacicept treatment was 8.2 years (range 2.7 to 12.2 years). These children were previously received pyridostigmine bromide, corticosteroids, and nonsteroidal immunosuppressants such as azathioprine and mycophenolate mofetil. However, their symptoms of ptosis, diplopia, and ocular duction limitation did not improve, and adverse effects related to long-term corticosteroid use were observed. Following treatment with telitacicept, the ocular symptoms of these children showed improvement within one month. Subsequently, corticosteroids and other immunosuppressants treatment were successfully discontinued in all children after 5 to 16 months. At the last follow-up, both scores of quantitative MG scale and MG-activity of daily living scale decreased from baseline, indicating a reduction in the severity of the disease and an improvement in quality of life. No adverse drug reactions were reported during treatment period. Conclusion: Telitacicept demonstrates significant efficacy in improving clinical symptoms of children with OMG and exhibits a relatively good safety profile, which is beneficial in reducing the reliance on corticosteroids and immunosuppressants.

Dr. Omar Keritam 1,2 , Dr. Gudrun Zulehner 1,2 , Dr. Raphael Wurm 1,2 , Mr. Felix Gruber 3 , Dr. Jakob Rath 1,2 , Dr. Martin Krenn 1,2 , Dr. Daniel Bormann 1,2 , Dr. Marcus Erdler 4 , Dr. Simone Mahal 5 , Dr. Anna Wiesenhofer 5 , Dr. Magdalena Gosk-Tomek 5 , Dr. Mika Rappold 6 , Dr. Anna Hüpper 5 , Dr. Katia Vettori 5 , Dr. Theresa Antonia Griedl 7 , Dr. Christian Kiss 7 , Dr. Valeriu Gold 7 , Prof. Julia Wanschitz 8 , Dr. Anna Hotter 8 , Dr. Vera Kleinveld 8 , Dr. Corinne Horlings 8 , Dr. Michael Gräßl 9 , Dr. Anette Schwerin-Nagl 9 , Dr. Johannes Troger 10 , Dr. Susanne Grinzinger 11 , Dr. Eva Stögmann 12 , Dr. Petra Müller 13 , Dr. Dieter Langenscheidt 14 , Prof. Barbara Plecko 9 , Prof. Fritz Zimprich 1,2 , Dr. Raffi Topakian 13,15 , Dr. Christian Eggers 16 , Prof. Stefan Quasthoff 7 , Dr. Florian Knipp 5 , Prof. Günther Bernert 17 , Dr. Matthias Baumann 18 , Prof. Wolfgang Löscher 8 , Prof. Hakan Cetin 1,2 1 Department of Neurology, Medical University of Vienna, Vienna, Austria. 2 Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria. 3 Austrian Federation of Social Insurances, Vienna, Austria. 4 Department of Neurology, Klinik Donaustadt, Vienna, Austria. 5 Department of Paediatrics, Klinik Favoriten, Vienna, Austria. 6 Primary Care Centre Nepomuk, Vienna, Austria. 7 Department of Neurology, Medical University of Graz, Graz, Austria. 8 Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 9 Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria. 10 Department of Neurology, Klinikum Klagenfurt, Klagenfurt, Austria. 11 Department of Neurology, Paracelsus Medical University, Salzburg, Austria. 12 Department of Paediatrics, Landesklinikum Mödling, Mödling, Austria. 13 Department of Neurology, Academic Teaching Hospital Wels-Grieskirchen, Wels, Austria. 14 Department of Neurology, Landeskrankenhaus Rankweil, Rankweil, Austria. 15 Clinical Research Institute for Neurosciences, Johannes Kepler University, Linz, Austria. 16 Department of Neurology, Johannes Kepler University, Linz, Austria. 17 Department of Paediatrics, Medical University of Vienna, Vienna, Austria. 18 Division of Paediatric Neurology, Department of Paediatrics I, Medical University Innsbruck, Innsbruck, Austria Background: Spinal muscular atrophy (SMA) is a genetic motor neuron disease caused by homozygous deletions or other pathogenic variants in the SMN1 gene, resulting in the degeneration of lower motor neurons associated with progressive weakness and muscle wasting. The development and approval of disease-modifying therapies (DMT) in recent years has fundamentally transformed the management, as well as the clinical and epidemiological landscape of patients with SMA. Methods: In this study, hospitalisation and prescription databases together with the capture-recapture method are utilised to estimate the prevalence of SMA in Austria and to identify co-morbidities associated with SMA. Patients were matched to healthy controls (1:10) by sex, age and district of residence. Results: We estimated a total population of 236 patients (95% CI 231-241) with SMA in Austria and a corrected prevalence of 2.5/100,000 persons in the year 2023. Patients with SMA showed significantly higher use of several medication classes, particularly therapies related to respiratory and infectious conditions. Healthy controls, by contrast, exhibited higher prescribing rates of cardiovascular medications, including beta-blockers and ACE inhibitors, as well as lipid-lowering agents and muscle relaxants. Conclusion: Our findings provide a robust nationwide estimate of SMA prevalence in Austria and highlight a distinct pattern of co-morbidities in the era of disease-modifying therapies, supporting informed healthcare planning and long-term management of patients with SMA.

Dr. Rui Shimazaki 1,2 , Dr. Satoru Noguchi 2 , Dr. Shinichiro Hayashi 2 , Prof. Kazuma Sugie 1 , Prof. Ichizo Nishino 2 1 Nara Medical University, Kashihara, Japan. 2 National Center of Neurology and Psychiatry, Kodaira, Japan Background: Variants in the FHL1 gene cause FHL1-related myopathies (FHL1-RMs), a group of neuromuscular disorders with diverse clinical presentations. The pattern of fatty replacement in leg muscle of patients with FHL-RMs have been previously described. This study aimed to comprehensively characterize the spatial and temporal patterns of skeletal muscle fat replacement throughout the whole body in FHL1-RMs, to examine disease progression over time, and to evaluate the relationship between imaging findings and clinical symptoms. Methods: We retrospectively analyzed 21 whole-body imaging studies from 10 patients with genetically confirmed FHL1-RMs. Fatty replacement was scored in 47 muscles using the modified Mercuri score (mMS). Longitudinal data were used to stratify patients into slow, moderate, and rapid progression groups. K-means clustering was applied to classify muscles based on their chronological patterns of fatty infiltration. Hierarchical clustering and violin plots were used to explore inter-muscle and inter-patient variations. Results: Despite notable variability in the rate of disease progression, a consistent pattern of muscle involvement was observed across patients. Muscles were classified into three progression clusters: early-onset and early attainment of the maximal mMS (e.g., paraspinal and posterior thigh muscles), steadily progressive (e.g., trunk and lower leg muscles), and late-onset with slow changes (e.g., shoulder and anterior thigh muscles). Initial symptoms appeared in the legs or trunk, followed later by symptoms in the arms in almost all patients. This order appeared to be consistent with the pattern of muscle fatty replacement. Additionally, joint contractures, spinal rigidity, and winged scapula were observed in one to three out of ten individuals, which would be related to fat replacement in the paraspinal spinal muscles and trapezius. These patterns paralleled the clinical symptom progression. In early-stage patients, STIR imaging revealed muscle signal abnormalities preceding fat replacement detectable on T1-weighted images. Conclusion: This study demonstrates that longitudinal muscle imaging assessments in FHL1-RMs reveal consistent spatial patterns of muscle fat replacement despite marked inter-individual variability in age of onset and progression rates. Fat replacement typically begins in the posterior thigh, lower leg, and paraspinal muscles, later involving the arms and shoulders, with continuous progression in trunk muscles. STIR imaging detected early muscle involvement before overt fat replacement. These findings support longitudinal imaging as a sensitive biomarker for disease staging, early diagnosis, and evaluation of therapeutic efficacy in future clinical trials.

Prof. Paola Sandroni Mayo Clinic, Rochester, United States Background: As symptoms referable to autonomic dysfunction are relatively common, it is a frequent occurrence to diagnose patients as having a primary autonomic failure or dysfunction when the actual pathology may be elsewhere. Particularly conditions affecting cardiovascular and gastrointestinal systems could be extremely difficult to differentiate from a primary autonomic problem. One of the most common mimickers that we encounter these days is probably persistent postural perceptual dizziness as well as pervasive conditions such as myalgic encephalomyelitis. Rheumatologic and immune mediated conditions can also contribute to the patient is suffering from autonomic symptoms and other conditions such as pelvic floor dyssynergia could mimic gastrointestinal dysmotility. There is certainly a subset of patients that appears to suffer from a constellation of symptoms characterized by orthostatic intolerance, pain, fatigue, cognitive dysfunction (“brain fog”), functional dyspepsia, interstitial cystitis, sleep disturbances, widespread pain and other symptoms such as difficulty thermoregulating, which may suggest predisposition to electrical instability at the level of autonomic pathways resulting in dysregulation across central and peripheral autonomic networks generating multiple symptoms that Individually are non‑dangerous; however, their cumulative effect can be profoundly disabling. There is little value in addressing these symptoms separately. Multiple studies have indicated that a more global strategy with a multidisciplinary team approach yields a much better outcome than when care is fragmented among different specialists that do not coordinate care in a cohesive manner. But there is still a lot of discussion on what these strategies should be. Addressing symptoms in isolation has limited clinical value. Fragmented care commonly results in conflicting treatment recommendations, redundant diagnostic testing, poor symptom control, patients’ disengagement and providers’ dissatisfaction. Many physicians report discomfort managing these patients due to diagnostic ambiguity, lack of standardized care pathways, resource and coordination challenges. Unified diagnostic formulation, patient education focused on symptom coherence and coordinated therapeutic interventions are likely to be the best strategy to improve functional status, reduce symptom burden and enhance patient and provider confidence.

Dr. Brigida Boccanegra 1 , Dr. Lisamaura Tulimiero 1 , Dr. Raffaella Quarta 1 , Assoc. Prof. Elena Conte 1 , Dr. Simonetta Andrea Licandro 2 , Dr. Alessandra Decio 2 , Dr. Roberta Lenti 1 , Dr. Alberto Ladisa 1 , Dr. Giorgia Dinoi 1 , Dr. Letizia Claudione 1 , Assoc. Prof. Sabata Pierno 1 , Assoc. Prof. Paola Mantuano 1 , Assoc. Prof. Ornella Cappellari 1 , Dr. Gianluca Fossati 2 , Dr. Christian Steinkühler 2 , Prof. Annamaria De Luca 1 1 Department of Pharmacy – Drug Sciences, University of Bari “Aldo Moro”, Bari, Italy. 2 Preclinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, Milan, Italy Background: Efficient skeletal muscle contraction relies on tight mechano-metabolic coupling regulated by AMP-activated protein kinase (AMPK). Duchenne muscular dystrophy (DMD) is characterized by aberrant AMPK activation and altered metabolic signalling. Here, we investigated the expression and regulation of liver kinase B1 (LKB1), the main upstream activator of AMPK. LKB1 activation occurs with the formation of a heterotrimeric complex with two accessory proteins, the pseudokinase STE20-related adaptor α (STRADα) and the scaffolding mouse protein 25 (MO25). We previously provided the first evidence that LKB1 and its partners are severely downregulated, at gene and protein level, in gastrocnemius muscle (GC) of 6-months-old BL10 mdx and D2 mdx mice, the new murine model with a more severe dystrophic phenotype (Boccanegra et al, DMM 2023). Methods: With the aim to assess if the impairment of LKB1 expression is a neuromuscular disease-specific feature, we analysed the expression of LKB1-STRADA-MO25 genes in tibialis anterior (TA) muscles of 15-week-old SOD1G93A mice, the primary mouse model for amyotrophic lateral sclerosis. Then, we investigated the dynamics of LKB1-STRADA-MO25 expression in early and in chronic DMD pathology phase, by qRT-PCR analyses in GC, diaphragm (DIA) and heart of the two murine dystrophic models throughout lifespan (4,8,28,52 weeks of age). Strain-matched WT mice were used as controls. Furthermore, we evaluated the gene expression profile of the complex in patient-derived immortalized cells (hDMD, deletion in exon 48-50) compared to WT human cells, throughout myogenesis (0,4,6,11 days of differentiation). Moreover, with the aim of detecting the precise localization of the kinase, we performed immunofluorescence analyses (IF) for LKB1 in human WT and dystrophic cells (11 days of differentiation). Results: qRT-PCR analysis showed that the expression of LKB1-STRADA-MO25 genes was similar SOD1G93A mice in comparison with WT controls. In contrast, the expression of all three genes was severely downregulated in GC and DIA of both dystrophic mouse models, at all ages, with an overall reduction of more than 50% vs. background-related WT mice. Furthermore, heart muscles of both mdx mice models, as well as D2 WT mice, displayed a downregulation of LKB1 only at a late stage of disease (52 weeks). Notably, an 8-week treatment with the pan-HDAC inhibitor vorinostat (5 mg/kg, 5 times a week, i.p.) restored LKB1 gene and protein expression in D2 mdx mice (5 weeks of age), with recovery scores (RS) of 197% and 204%, respectively. This effect correlated with significant downregulation of miR-451, miR-195 and miR-17, known post-transcriptional repressors of LKB1. In contrast, the selective HDAC1/2 inhibitor Rodin-A (4 mg/kg, i.p.) increased LKB1 mRNA (RS 138%) but did not restore protein levels or modify miRNA expression (Fig.1). Studies in patient-derived myoblasts (HDMD, deletion 48-50; AB1098) showed impaired LKB1 expression during differentiation (0, 6, 11 day). Moreover, LKB1 fluorescence was widespread in healthy cells but reduced and mainly nuclear in HDMD. Conclusion: Overall, these findings identify the LKB1–STRADα–MO25 axis as a regulatory node disrupted in DMD and responsive to epigenetic modulation, highlighting its therapeutic potential. (supported by NL_DPP number 22.004, ERC SEEDS UNIBA 2023-UNBACLE-0245439, PRIN MUR 2020 Prot. 2020ELYA32)

Prof. Simon Rinaldi 1 , Prof. Thomas H. Brannagan 2 , Dr. Pietro Emiliano Doneddu 3,4 , Dr. Karissa L. Gable 5 , Dr. Luis Querol 6 , Prof. Mark Stettner 7 , Dr. Kevin Budding 8 , Dr. Susan Ellor 8 , Dr. Hafedh Haddad 8 , Dr. Martin Markov 8 , Dr. Reena Patel 8 , Dr. Olivier Van de Steen 8 , Dr. Inge Van de Walle 8 , Prof. Jeffrey A. Allen 9 1 University of Oxford, Oxford, United Kingdom. 2 Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, Columbia University, New York, United States. 3 Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy. 4 Humanitas University, 20072 Pieve Emanuele, Milan, Italy. 5 Duke University Medical Center, Duke University, Durham, United States. 6 Neuromuscular Diseases Unit, Hospital de La Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. 7 University Medicine Essen, Essen, Germany. 8 argenx, Ghent, Belgium. 9 University of Minnesota, Minneapolis, United States Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy involving complement-driven macrophage-mediated demyelination. Empasiprubart binds complement C2, blocking activation of the classical and lectin complement pathways. Two phase 3, randomized, double-blinded studies in participants with CIDP will compare intravenous (IV) empasiprubart versus placebo (EMNERGIZE, NCT07091630 ) and IV empasiprubart versus IV immunoglobulin (IVIg) (EMVIGORATE, NCT06920004 ). Methods: EMNERGIZE (placebo-controlled) will randomize ∼160 adults with CIDP 2:1 to receive either empasiprubart or placebo on Days 1 and 8, then once every 4 weeks in a 24-week double-blind treatment period (Part A) ( Figure 1 ). EMVIGORATE (double-dummy) will randomize ∼218 adults with CIDP 1:1 on stable maintenance IVIg to receive either empasiprubart or continue the stable IVIg dose in a 24-week double-blind treatment period (Part A) ( Figure 2 ). Both studies are followed by a 4-week double-blind rollover, 23-month open-label period (Part B) and 15-month safety follow-up. Results: The primary endpoint for both studies is a reduction of >=1 point versus baseline in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score at Week 24. Key secondary endpoints (Week 24) include changes from baseline in Inflammatory Rasch-built Overall Disability Scale score, Medical Research Council sum score, dominant hand grip strength, Timed Up and Go, and time to reduction of >=1 point versus baseline in aINCAT score. The EMVIGORATE study commenced on August 22, 2025, while EMNERGIZE commenced on September 16, 2025. Enrollment site information from both studies will be presented. Conclusion: These two global phase 3 studies will evaluate the efficacy and safety of empasiprubart in participants with CIDP. Similar designs and endpoints with complementary study populations support the potential role of empasiprubart as a reference treatment across patients with CIDP, regardless of treatment status.

Dr. Malin Petersson , Dr. Jing Wu, Prof. Fredrik Piehl, Prof. Lars Alfredsson, Assoc. Prof. Susanna Brauner Karolinska Institutet, Stockholm, Sweden Background: Thymoma-associated myasthenia gravis (TAMG), which accounts for approximately 10% of all MG cases, represents a distinct clinical subgroup characterized by more severe disease. Conversely, among patients diagnosed with thymoma, around a third will develop MG. We and others have reported increased MG risk associated with obesity (mainly aged men) and smoking (early-onset MG; EOMG), as well as an inverse association with alcohol consumption. In thymoma, both smoking and alcohol use have also been linked to increased risk. However, to date, no environmental risk factors have been identified specifically for TAMG. Methods: The Genes and Environment in Myasthenia Gravis study (GEMG) is a cross-sectional questionnaire study, conducted nationwide in Sweden 2018 to 2019. TAMG patients included in the GEMG study were identified by linkage to the nationwide MG registry and selection of cases based on reports of thymectomy pathology outcomes. Population-based controls without MG were matched to cases (15:1), based on year of birth and sex. Possible risk factors were evaluated by conditional logistic regression. Results: Ninety-one TAMG patients were matched to 1,364 controls. The mean age at onset was 49 (SD 16) years, with 54% females. In a multivariable regression analysis, we found that ever smoking compared to never-smokers was associated with an increased risk of TAMG (OR 1.90, 95% CI 1.14-3.18, p=0.015). Patients who were current smokers at disease had almost twice the risk of developing MG compared to never smokers (OR 2.03, 95% CI 1.08-3.84, p=0.029). Similarly, those who quit smoking compared to never-smokers displayed an OR of 1.82, 95% CI 0.99-3.36, p=0.054. Alcohol consumption was negatively associated with TAMG (drinker compared to non-drinkers OR 0.32, 95% CI 0.18-0.55, p<0.001). Furthermore, fish consumption at least once weekly was also inversely associated with TAMG (OR 0.57, 95% CI 0.33-0.98, p=0.043). Neither body mass index (BMI) at age 20, physical activity nor oral tobacco use was associated with TAMG. Conclusion: We examined risk factors for TAMG and observed that smoking, particularly smoking at onset, was associated with an increased risk of TAMG. In contrast, alcohol consumption was associated with a reduced risk, opposite to what has been reported for thymoma, suggesting that alcohol may modulate pathways critical for the development of autoimmunity.

Dr. Patricia Garay-Albízuri 1,2,3 , Dr. Roberto Fernández-Torrón 1,2,3 , Dr. Pablo Iruzubieta 1,2,3,4 , Dr. Juan José Poza 1,2,3 , Dr. María José Iñarra Velasco 5 , Dr. María Lure-Berregi 5 , Dr. Loreto Martorell 6,7 1 Department of Neurology, Donostialdea Integrated Health Organisation, Osakidetza, San Sebastián, Spain. 2 Neuromuscular Diseases Group, Neurosciences Area, Biogipuzkoa Health Research Institute, San Sebastián, Spain. 3 CIBERNED, CIBER, Spanish Ministry of Science & Innovation, Carlos III Health Institute, Madrid, Spain. 4 Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Canada. 5 Department of Gynecology, Donostialdea Integrated Health Organization, Osakidetza, San Sebastián, Spain. 6 Department of Genetic and Molecular Medicine-IPER, Hospital Sant Joan de Déu and Institut de Recerca Sant Joan de Déu, Barcelona, Spain. 7 Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Madrid, Spain Background: Gynecological disorders are highly prevalent among women with myotonic dystrophy type 1 and have a significant impact on women’s health and quality of life. However, the prevalence of individual gynecological comorbidities in this population has not been systematically assessed. Methods: We conducted a single-center retrospective study including women with myotonic dystrophy type 1 followed at a tertiary care hospital between January 2011 and November 2025. Data on major gynecological disorders were collected, including the presence of uterine myomas, polyps, gynecological neoplasms and/or history of gynecological surgery, together with other clinical and demographic variables. Results: A total of 176 women were included, with a median follow-up time of 14.95 years (IQR 14,75–14.95). Ninety-four women (53.9%) presented gynecological disorders, the most frequent being uterine fibroids (47%), followed by endometriosis and endometrial polyps (13.6% each). The presence of gynecological disorders was significantly associated with age using the U Mann-Whitney test. Fifteen patients developed gynecological malignancies, with ovarian cancer being the most common (n = 7). During follow-up, 27,8% of women (N=49) underwent hysterectomy, with multiple uterus fibroids as the leading indication (45% of all hysterectomies); all women with this condition underwent hysterectomy. Twenty-two women of this group (44,9%) had additionally a double anexectomy. Conclusion: Gynecological disorders are common in women with myotonic dystrophy and represent a relevant source of morbidity in a substantial proportion of patients. These findings highlight the need for a multidisciplinary management approach in this population.

Prof. Sunyoung Kim Ulsan University Hospital, Ulsan, Korea, Republic of Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal lymphoma characterized by proliferation of malignant B cells within small vessel lumina. Neurologic manifestations may mimic immune-mediated neuropathies, leading to diagnostic delay. Methods: A 62-year-old woman with a history of hypertension and seropositive rheumatoid arthritis initially presented with anal and left posterior thigh pain, followed by fever and a diagnosis of influenza A. Two days later, she developed abrupt bilateral leg weakness, sensory impairment below the L1 dermatome, and bowel and bladder dysfunction. Initial neurologic examination showed Medical Research Council (MRC) grade 2 weakness in the lower extremities, decreased anal tone, intact cranial nerve function, and preserved deep tendon reflexes (DTRs). Cerebrospinal fluid (CSF) analysis demonstrated albuminocytologic dissociation but with decreased glucose and markedly elevated LDH. Nerve conduction studies (NCS) revealed reduced bilateral tibial and peroneal CMAP amplitudes, prolonged left median distal latency, and absent F and H reflexes. Spine MRI showed enhancement of the cauda equina from L1 to S3 and inflammatory changes in the epidural space from C7 to S1. On hospital day (HD) 3, as the patient’s bilateral lower-extremity strength deteriorated to MRC grade 1 and the knee and ankle DTRs progressed to areflexia, a 5-day course of intravenous immunoglobulin (IVIG) was initiated. Despite IVIG, further deterioration occurred on HD 6, including limitation of extraocular movements, bilateral upper-extremity weakness (MRC grade 3), impaired cheek puffing, and a confusional state. Repeat NCS on HD 6 revealed further decreased CMAP amplitudes in the tibial and peroneal nerves, suggestive of acute motor axonal polyradiculoneuropathy. On HD 7, she developed respiratory difficulty and a drowsy mental state and was transferred to the intensive care unit. Arterial blood gas analysis revealed a pO₂ of 67 mmHg, a lactate level of 11.6 mmol/L, and a SaO₂ of 93.3% despite supplemental oxygen. Chest CT and abdominal–pelvic CT were performed due to worsening pneumonia. Abdominal–pelvic CT revealed infiltrative involvement of the cervix, vagina, adnexa, adrenal glands, and kidneys, with mild splenomegaly—findings strongly suggestive of systemic lymphoma Results: A cervical biopsy performed on HD 12 showed CD20-positive squeezed cells within vascular lumina, with limited diagnostic interpretability, but raising suspicion for IVLBCL. Despite broad-spectrum antibiotics and corticosteroid treatment, multiorgan failure progressed, and the patient expired on HD 15. Conclusion: This case demonstrates that IVLBCL may initially present as a Guillain-Barré syndrome. Markedly elevated LDH, reflecting tumor-related tissue destruction, along with atypical CSF findings (elevated protein, low glucose, high LDH) and poor response to IVIG should raise suspicion for IVLBCL. Early systemic imaging and tissue biopsy are essential for timely diagnosis and treatment in patients with rapidly progressive neuropathy and unexplained systemic abnormalities.

Dr. Otto Hernandez Fustes 1,2 , Miss Thalita Aparecida dos Santos 1 , Mr. Webert Alex Santos Benetti 1 , Mr. Edson Hideki Kawamura Junior 1 , Dr. Paulo Jose Lorenzoni 1,2 , Dr. Cláudia Suemi Kamoi Kay 2 , Dr. Renata Dal-Pra Ducci Cirino 1,2 , Dr. Paula Raquel do Vale Pascoal Rodrigues 2 , Dr. Rosana Herminia Scola 1 1 Federal University of Paraná,, Curitiba, Brazil. 2 Clinics Complex Hospital at Federal University of Paran, Curitiba, Brazil Background: The skin wrinkling test (SWT) is a noninvasive clinical method used to assess sympathetic small fibers associated with vasomodulation, pain, and temperature regulation. Amyotrophic lateral sclerosis (ALS), a condition recently described as not only motor―but also sensory―in nature, has been evaluated using SWT. Studies have revealed that the SWT index reflects the density of intraepithelial fibers in skin biopsy. Methods: This observational, cross-sectional study was conducted at a tertiary care hospital and included 27 patients diagnosed with ALS and 109 volunteers. All participants underwent the SWT, involving immersion of the right hand in water (temperature, 40°C) for 30 min. Skin wrinkling was assessed by 3 observers using 2 distinct scales. All were undergoing drug treatment with riluzole. The time of disease evolution and ALSFRS-R functional scale were recorded. Results: In relation to the study samples, regarding age, the ALS group was statistically different from the control group (p<0.001) but with no statistical difference in relation to the paired group (p=0.403), indicating that the ALS group was homogeneous in relation to the paired. Interobserver agreement was excellent (p<0.001) across all 3 groups; significant agreement was also found between the scales. Quantitative analysis revealed that the ALS group exhibited significantly lower mean scores on Scale 1 (8.23 versus [vs.] 12.78; p=0.001) than controls, and on Scale 2 (0.52 vs. 0.86, and 0.84; p<0.002) than both controls and matched controls. Qualitatively, patients diagnosed with ALS exhibited a higher frequency of negative results (p=0.001 and p=0.013 for Scales 1 and 2, respectively). Disease severity was not associated with a greater probability of the test having a positive or negative result on scale 1 (p=0.329) or 2 (p=0.914). Similarly, the test results were not associated with the length of ALS progression (p=0.283 and p=0.779, respectively) Conclusion: A relevant result of our study was the pilot investigation on the level of agreement between different SWT evaluators for the same individual. Our evaluators, comprising 2 initial evaluators and 1 tiebreaker evaluator, qualitatively and quantitatively graded the results produced by the SWT in each study participant. Using the ICC for interobserver reliability, we found excellent agreement between the 2 initial evaluators, with p<0.001 for the control, paired, and ALS groups. SWT demonstrated excellent inter-rater agreement. Significant differences were observed between patients with ALS and controls, indicating the involvement of sympathetic fine fibers in patients with ALS. These findings highlight the utility of the SWT as a tool for assessing the sensory components of ALS.

Assoc. Prof. Özgü İNAL ÖZÜN 1 , Prof. Emre ADIGÜZEL 2 , Assoc. Prof. Çağlar SOYLU 1 , Assoc. Prof. Duygu TÜRKER 1 , Assoc. Prof. Didem ARDIÇLI 2 , Miss Ceren Şevval KARATAŞ 3 , Miss Merve ÖZTÜRK 3 , Mrs Buse BİRBİR 1 , Prof. Deniz YÜKSEL 4 1 University of Health Sciences Turkey, Gülhane Faculty of Physiotherapy and Rehabilitation, Ankara, Turkey. 2 University of Health Sciences Turkey, Ankara Bilkent City Hospital, Ankara, Turkey. 3 University of Health Sciences Turkey, Gulhane Institute of Health Sciences, Ankara, Turkey. 4 University of Health Sciences Turkey, Ankara Etlik City Hospital, Ankara, Turkey Background: SMA patients frequently report problems such as impaired jaw function, fatigue during chewing, difficulty swallowing solid foods, and choking. Feeding difficulties such as swallowing problems and aspiration, and chewing problems are frequently reported in SMA Type I, less frequently in SMA Type II, and occasionally in SMA Type III. More than half of SMA Type II patients have been reported to experience dysphagia, which can result in severe complications, including aspiration pneumonia and death. Patients with SMA Type II are now included in the scope of drug treatment, and the drugs used have shown positive effects on SMA Type II patients. With these new developments, problems other than motor level decline (e.g., swallowing dysfunction) have become more important in children with SMA. However, the risk of dysphagia and chewing functions in children with SMA Type II have been addressed in a limited number of studies in the literature. In this context, this study was planned to investigate the risk of dysphagia and chewing function in children with SMA Type II. Methods: Eighteen orally fed children with SMA Type II, aged between 6.4 and 13.4 (months), were included in the study. All children were receiving Nusinersen treatment. Descriptive information and feeding information of the participants were recorded using a socio-demographic form. The Pediatric Eating Assessment Tool (PEDI-EAT-10) was used to assess dysphagia and the Karaduman Chewing Performance Scale (KÇPS) was used to assess chewing function (0-4; 0: normal chewing). The child was given a standard biscuit, and their biting and chewing behaviors during feeding were video recorded for 3-5 minutes. The videos were then reviewed and analyzed. Results: The study evaluated 10 girls and 8 boys. The prevalence of scoliosis was 77.8% (n=14). Sucking ability was present at birth in 83.3% (n=15), and all participants were fed in a sitting position (100%, n=18). 88.9% (n=16) of participants were able to tolerate all consistencies. The average feeding time per meal was determined to be 28.06 minutes. A history of lung infection in the last year was reported in 22.2% (n=4), and a history of intensive care in 38.9% (n=7). Daytime drooling problems were observed in 55.6% (n=10) and nighttime drooling problems in 22.2% (n=4). The distribution of the KÇPS was as follows: Level 0:50% (n=9), Level 1:33.3% (n=6), Level 2:11.1% (n=2), and Level 4:5.6% (n=1). The PEDI-EAT-10 score ranged from 0 to 27, with an average of 3.17 ± 6.39. Conclusion: In the current study, feeding problems in children with SMA Type II can manifest in different ways. During the evaluation, families reported that their children did not experience any problems with chewing or swallowing. The assessments revealed that 33.3% of participants were at risk for dysphagia, and 50% experienced chewing problems. Another notable finding of the study was the evaluation of nighttime drooling problems in addition to daytime drooling problems in children with SMA Type II.

Dr. Audrey Cambier 1 , Dr. Beatrice Labella 2 , Dr. Paula Panos-Basterra 1 , Dr. Marion Masingue 1 , Dr. Anthony Behin 1 , Dr. Juliette Nectoux 3,4 , Dr. Camille Verebi 3,4 , Dr. Pauline Gaignard 5 , Dr. Corinne Metay 6 , Dr. Tanya Stojkovic 1 1 Centre de Référence des maladies Neuromusculaires Nord/Est/Ile-de-France, Institut de Myologie, Hôpital Pitié-Salpêtrière, APHP, Paris, France. 2 Functional Unit of Neuromuscular Pathology, Neuropathology Department, Pitié-Salpêtrière Hospital, APHP, Paris, France. 3 Service de Médecine Génomique Des Maladies de Système Et d'Organe, Hôpital Cochin, APHP. Centre Université de Paris Cité, Paris, France. 4 Laboratoire SeqOIA, Paris, France. 5 Service de Biochimie, UF Maladies héréditaires du métabolisme, CRMR Carammel, Filnemus, CHU Bicêtre AP-HP, Paris, France. 6 Molecular and Cellular Cardiogenetics and Myogenetics UF, Chromosomic and Molecular Genetic Center and INSERM UMRS 974, Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Paris, France Background: Biallelic pathogenic variants in the MICU1 gene, a key regulator of mitochondrial calcium uptake, cause a rare mitochondrial myopathy that often mimics limb-girdle muscular dystrophy (LGMD), resulting in diagnostic delay. Methods: We analysed five adult patients from three unrelated consanguineous families carrying biallelic MICU1 gene variants. Clinical, biochemical, electrophysiological, imaging, histopathological and whole-genome sequencing data were collected. Results: Five patients (two males) of Tunisian, Pakistani and Moroccan origin were included. Mean age at onset was 81 months (range 10–300), with a mean age at diagnosis of 34 years, corresponding to a mean diagnostic delay of 27 years. Weakness was predominantly proximal with a limb-girdle distribution, except for one scapuloperoneal phenotype. Scapular winging and calf hypertrophy were present in three patients each. At last follow-up, three patients were ambulant, one required unilateral support and one was wheelchair dependent. Creatine kinase levels were markedly elevated in all patients (mean peak 5,257 U/L), and muscle biopsies showed dystrophic or myopathic changes compatible with LGMD. Extra-muscular features included cognitive impairment, short stature, ganglionopathy and thyroid dysfunction. Whole-genome sequencing identified pathogenic biallelic variants in the MICU1 gene in all patients. Conclusion: Variants in the MICU1 gene cause an LGMD-like myopathy with prominent extra-muscular features suggestive of mitochondrial disease. Systematic inclusion of the MICU1 gene in LGMD diagnostic panels may reduce diagnostic delay and improve disease classification.

Dr. Ahwon Kim 1 , Dr. Do-Yeon Lee 2 , Dr. Sue young Ha 2 , Prof. Jung-Joon Sung 2 1 Myongji Hospital, Goyang, Korea, Republic of. 2 Seoul National University Hopsital, Seoul, Korea, Republic of Background: Phosphaturic mesenchymal tumors (PMTs) are very rare soft tissue tumors that present with pain, bone fracture, and weakness attributed to hypophosphatemia. To our knowledge, biopsy-confirmed cases of myopathy in PMT have not been previously documented, and the pathophysiology of myopathy in PMT is unknown. Methods: We reviewed the clinical and pathological characteristics of PMT and investigated the pathophysiology of PMT-induced myopathy. From retrospective chart reviews, 15 patients with biopsy-confirmed PMT were identified from 2004 to 2020 in two tertiary hospitals. In order to investigate the mitochondrial dysfunction in PMT-induced myopathy, the muscle tissues from two patients with or without myopathy, who had limb weakness, were compared with normal muscle tissues on the basis of mitochondrial protein expression. Results: Most of the patients had osteomalacia or hypophosphatemia. Thirteen of the 15 PMT cases occurred on the left. Nine patients were overweight or obese. One patient had PMT-induced myopathy while the other had intracranial hemorrhage. Immunohistochemistry revealed that the expression of mitofusin 2, which is related to mitochondrial fusion, and ATP5B, mitochondrial ATP synthase subunit, were significantly decreased while the expression of mitochondrial fission factor and dynamin-related protein 1, which is related to mitochondrial fission, were significantly increased in the PMT-induced myopathy compared to the patient who had no myopathy but limb weakness, and the normal controls. PMT-induced hypophosphatemia leads to mitochondrial dysfunction resulting in decreased ATP synthesis. Conclusion: Clinicians should be aware of various clinical manifestations of PMT, risk of weight gain, and reversibility of symptoms by tumor removal.

Dr. Corinna Preusse 1,2,3 , Miss Katharina Brokamp 1 , Prof. Andreas Meisel 1 , Assoc. Prof. Andreas Roos 4,5,6 , Dr. Paolo Doksani 1 , Dr. Andreas Hentschel 7 , Dr. Carsten Dittmayer 8 , Prof. Markus Schuelke 2 , Prof. Jens-Carsten Rueckert 9 , Prof. Matthias Pumberger 10 , Prof. Friederik Schömig 10 , Prof. Werner Stenzel 3 , Prof. Sarah Hoffmann 1 1 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neurology and Neuroscience Clinical Research Center, Charitéplatz 1, 10117 Berlin, Germany, Berlin, Germany. 2 Charité - Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), Department of Neuropediatrics and NeuroCure Cluster of Excellence, Augustenburger Platz 1, 13353 Berlin, Germany, Berlin, Germany. 3 Charité - Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Neuropathology, Charitéplatz 1, 10117 Berlin, Germany, Berlin, Germany. 4 Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology, University Duisburg-Essen, 45147 Essen, Germany, Essen, Germany. 5 Brain and Mind Research Institute, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada., Ottawa, Canada. 6 Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Bochum, Germany, Bochum, Germany. 7 Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V., 44139, Dortmund, Germany, Dortmund, Germany. 8 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Pathology, Charitéplatz 1, 10117 Berlin, Germany, Berlin, Germany. 9 Charité - Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Thoracic Surgery, Charitéplatz 1, 10117 Berlin, Germany, Berlin, Germany. 10 Charité - Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Center for Musculoskeletal Surgery, Charitéplatz 1, 10117 Berlin, Germany, Berlin, Germany Background: For over four decades, complement deposition at the neuromuscular junction (NMJ) in acetylcholine receptor antibody-positive myasthenia gravis (AChR-ab⁺-MG) has been recognized as a major contributor to motor endplate destruction. Nevertheless, comprehensive studies addressing the extent, variability, and molecular correlates of NMJ pathology in this condition remain scarce. Given the rapid clinical improvement observed with recent immunotherapies, suggesting that irreversible destruction of NMJ is unlikely, we examined the morphology and molecular profiles of NMJs in AChR-ab⁺-MG using multiple complementary approaches. Methods: Intercostal muscle (ICM) biopsy specimen from 58 patients with AChR-ab⁺-MG were analyzed and compared to non-disease controls (NDC, biopsy specimen obtained during scoliosis surgery; n=7) using histology, electron microscopy (EM) and transcriptomic and proteomic profiling. Results: The mean age at biopsy was 48.1 years (SD 16.5), and 64.9% were female. Mean disease duration at the time of biopsy was 4.4 years (SD 3.6). The mean MG-ADL score was 6.9 (SD 3.6), the mean QMG score 11.4 (SD 5.3), and the mean MG-QoL score was 19.2 (SD 9.7), 14% of patients had experienced myasthenic crisis. Regarding ongoing treatments, 91.2% of patients received acetylcholinesterase inhibitors, 50.9% were treated with glucocorticoids, and 52.6% with conventional immunosuppressants. Three patients (5.3%) had not received any MG specific therapy at time of biopsy. Thymic pathology included thymoma (10.5%), thymic hyperplasia (31.6%) and was normal in the remaining patients. Histological evaluation revealed prominent C5b-9 deposition on endplates in all samples, affecting on average 75% of detectable NMJs (range 33–100%), whereas no C5b-9-positive staining was detectable on the endplates of control intercostal muscle biopsies. Additionally, immune cell infiltration close to the NMJ was detectable, and immunohistochemistry demonstrated occasional CD8⁺ T cells and a more prominent CD68⁺ macrophage infiltration, while B cells were consistently absent. Transcriptomic analysis by qPCR revealed upregulation of immune-related genes such as IL1B and STAT3 , indicating a local pro-inflammatory milieu. Interestingly, this includes increased expression of the B cell chemoattractant BAFF , despite the absence of detectable B cells. Furthermore, proteomic profiling revealed two upregulated and nine downregulated proteins between MG compared to NDC, with many of the reduced proteins linked to extracellular matrix integrity or vesicular trafficking, suggesting impaired structural compensation and synaptic stress in the context of chronic immune-mediated NMJ damage. Ultrastructural analysis was performed in 44 NMJs and the pre- and post-synaptic morphology including individual fold length, branching and fold areas were assessed. AChR-ab⁺-MG patients muscles harbored NMJ with reduced numbers and short folds as well as a postsynaptic apparatus with small plump folds. Conclusion: Together, these findings reveal that complement-mediated affection of NMJ in skeletal muscle of AChR-ab⁺-MG is heterogeneous and that even in individual biopsies, not all NMJs demonstrate complement deposition and undergo consecutive structural disruption, and if so, that the destructive process may not be terminal. Hence, our combined histologic, ultrastructural, and molecular data highlight significant intra- and interindividual variability. These observations underscore the importance of examining the precise extent and nature of NMJ involvement in MG and may inform future therapeutic strategies targeting local immune mechanisms.

Miss Sanne Evers 1 , Miss Pinar Özkaynar 1 , Miss Renske Kamperman 1 , Dr. Filip Eftimov 1 , Prof. Eleonora Aronica 2 , Dr. Esther van Leeuwen 3 , Prof. Rohit Aggarwal 4 , Prof. Yves Allenbach 5 , Prof. Marianne de Visser 1 , Prof. Ivo van Schaik 1 , Prof. Patrick Bossuyt 6 , Dr. Camiel Verhamme 1 , Dr. Joost Raaphorst 1 , Dr. Anneke van der Kooi 1 1 Amsterdam UMC, department of neurology, Amsterdam, Netherlands. 2 Amsterdam UMC, department of pathologydepartment of neurology, Amsterdam, Netherlands. 3 Amsterdam UMC, department of laboratory medicine, Amsterdam, Netherlands. 4 university of Pittsburgh medical centre, pittsburg, United States. 5 Pitié-Salpêtrière University Hospital, Sorbonne Université, Paris, France. 6 Amsterdam UMC, Department of Epidemiology & Data Science, Amsterdam, Netherlands Background: Selecting a diagnostic strategy for Idiopathic Inflammatory Myopathy (IIM) is challenging due to the absence of strong evidence on the performance of potential tests. This prospective study evaluated multiple diagnostic strategies. Methods: We conducted a prospective diagnostic accuracy study with an over-complete study design. Patients with clinical suspicion of IIM, requiring immunosuppressive treatment, underwent autoantibody testing (Ab), muscle magnetic resonance imaging (MRI), muscle ultrasound (US), electromyography (EMG), and a muscle biopsy. The reference diagnosis (IIM or IIM mimic) was assigned by an expert panel, based on the complete clinical information, including six months of follow-up. Diagnostic strategies, combining these modalities, were evaluated for sensitivity, specificity, positive/negative predictive values, and patient-reported burden. Results: In total 100 patients were included, 67 IIM, 33 IIM mimics. Muscle MRI had the highest sensitivity 96% and the lowest specificity 42%. Muscle biopsy had the highest specificity of 97%, followed by Ab, with a specificity of 94%. Patients reported a higher burden from both EMG and muscle biopsy, compared to Ab, MRI, and US. The most optimal diagnostic strategy comprised Ab and MRI in all patients, followed by a biopsy in 34/100 patients. This yielded a sensitivity of 96% and a specificity of 94% and limited patient-reported burden. Replacing MRI by US or EMG resulted in a similar diagnostic accuracy. Conclusion: In patients suspected of IIM, individual diagnostic tests had either limited sensitivity or specificity. Diagnostic strategies including autoantibody testing, combined with either MRI, EMG or US, and a muscle biopsy only in selected cases, were found to yield the optimal combination of highest sensitivity and specificity with a moderate burden, reported by patients.

Dr. Roger Collet Vidiella 1 , Dr. Marta Caballero-Avila 1 , Dr. Tineke Casneuf 2 , Dr. Erik Hofman 2 , Dr. Geoffrey Istas 2 , Ms. Paula Llarch 1 , Dr. Lorena Martín-Aguilar 1 , Dr. Elba Pascual-Goñi 1 , Dr. Arne De Roeck 2 , Dr. Bianca Balbino 2 , Dr. Luis Querol 1 1 Neuromuscular Diseases Unit, Hospital de La Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. 2 argenx, Ghent, Belgium Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy causing proximal and distal weakness, sensory disturbance, and possible irreversible disability. Neurofilament light chain (NfL) levels indicate axonal damage and may potentially serve as a disease activity and prognostic biomarker in inflammatory disorders, including CIDP. NfL levels were analyzed in ADHERE ( NCT04281472 ), the largest CIDP cohort to date. Methods: Participants with probable/definite active CIDP (demonstrated by treatment withdrawal run-in phase) received open-label, weekly subcutaneous (SC) efgartigimod PH20 1000 mg (stage A) for ≤12 weeks. Responders entered stage B and were randomized (1:1) to weekly efgartigimod PH20 SC 1000 mg or placebo for ≤48 weeks. Serum NfL (sNfL) was measured longitudinally in 214 participants, from which NfL z-score (zNfL) was determined. Results: During stage A, sNfL levels remained stable in responders with baseline levels within healthy reference range (≤20 pg/mL, n=114); sNfL reduced by 18% over time in responders with elevated baseline levels (>20 pg/mL, n=36). In participants receiving continuous efgartigimod through stage B, sNfL reduced by 35% by week 24 (n=13). Mean (SD) sNfL levels at stage A baseline were 18.9 (22.6) pg/mL (n=214), corresponding to a mean (SD) zNfL of 0.64 (1.57). Elevated baseline zNfL levels were associated with a higher CIDP disease activity status (CDAS 5). zNfL scores at stage A baseline were the highest in samples fromCIDP-treatment-naïve participants versus those who had previously received CIDP treatment. Conclusion: ADHERE represents the broadest CIDP dataset evaluated for NfL. Baseline NfL levels correlated with CDAS scores, with higher levels indicating more active disease. Among efgartigimod-treated responders who had elevated baseline sNfL, we observed a reduction in sNfL in both stages A and B. NfL levels may serve as a contextual biomarker, alongside clinical assessment. Further analysis will determine whether NfL can inform on disease monitoring.

Dr. Nurul Fadli 1,2 , Dr. Adrian Ridski Harsono 1,2 , Asst. Prof. Winnugroho Wiratman 1,2,3 , Dr. Faisal Parlindungan 4 , Dr. Dinda Larastika Riyanto 2 , Asst. Prof. Luh Ari Indrawati 2,3 , Asst. Prof. Astri Budikayanti 2,3 , Assoc. Prof. Fitri Octaviana 2,3 , Asst. Prof. Manfaluthy Hakim 2,3 , Asst. Prof. Ahmad Yanuar Safri 2,3 1 Neurology Department Universitas Indonesia Hospital, Depok, Indonesia. 2 Neurology Department Faculty of Medicine Universitas Indonesia, Depok, Indonesia. 3 Neurology Department Cipto Mangunkusmo General Hospital, Jakarta, Indonesia. 4 Internal Medicine Department Universitas Indonesia Hospital, Depok, Indonesia Background: Connective tissue disease (CTD) is a group of systemic inflammatory diseases that attack connective tissue in various organs due to autoantibody processes. CTD can involve various organ systems, with one manifestation being the neuromuscular system, which can worsen morbidity and quality of life in patients. However, neuromuscular involvement in CTD is often underrecognized. This study aimed to determine the prevalence, clinical characteristics, and types of neuromuscular involvement in patients with CTD. Methods: A retrospective, descriptive, cross-sectional study was conducted using secondary data from patients diagnosed with CTD who had neuromuscular symptoms and underwent electrodiagnostic testing at the neurology clinic of the University of Indonesia Hospital. Data were collected from medical records during the period of May 2019 to July 2025. The data collected included demographics, clinical symptoms,neurological examination, nerve conduction study and electromyography, ancillary testing and final diagnosis of the patients. Results: A total of 44 patients with CTD underwent electrodiagnostic examinations during the study period. The majority were female (97.6%), with a mean age of 41.29 ± 1.908 years. The types of CTD included systemic lupus erythematosus (31.7%), Sjögren’s syndrome (26.8%), rheumatoid arthritis (26.8%), and overlap syndrome (14.6%). Neurological symptoms reported by patients included sensory impairment (61%), pain (61%), weakness (41.5%), tremor and disequilibrium. Neuromuscular involvement confirmed by abnormal electrodiagnostic findings were found in 21 patients (51.2%), including disorders of the peripheral nerves (neuropathies) in 15 patients, neuromuscular junction (myasthenia gravis) in 1 patient, and muscles (myositis) in 5 patients. Conclusion: Neuromuscular involvement is a common manifestation in patients with CTD. Neurological evaluation should be considered as part of routine assessment in patients with CTD for earlier detection and management.

Dr. Thaina Louise Rodrigues , Dr. Enzo Pellacani, Dr. Bruno Graziosi, Dr. Alessandra Tolentino, Dr. Ana Marina Silva, Dr. Roseli Corazzini, Dr. Alzira Carvalho Centro Universitário FMABC, Santo André, Brazil Background: Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of genetic myopathies characterized by progressive proximal muscle weakness. Among these, dystroglycanopathies result from defects in the glycosylation of alpha-dystroglycan 1,2. Variants in the ISPD gene acts in isoprenoid synthesis and plays a role in alpha-DG and are associated with milder phenotypes resulting from partial or complete impairment of alpha-DG, with a broad clinical spectrum ranging from severe congenital forms to late-onset limb-girdle presentations 3,4. Methods: We describe the case of two Brazilian siblings born to non-consanguineous parents. Patient 1, male, developed symptoms at 15 months of age, presenting with frequent falls, proximal muscle weakness, toe-walking (equine gait), winged scapula, and persistent CPK elevation (1,800–27,000 U/L). Patient 2, female, at 9 years of age, presented an oligosymptomatic phenotype, with mild proximal weakness, slight scoliosis, winged scapula, and increased CPK (2,000–5,000 U/L), muscle biopsy showed a dystrophic pattern, positive immunohistochemical for dystroglycan, and thigh MRI revealed muscle atrophy and fatty replacement. Neither patient showed cardiac or respiratory involvement. Initial genetic investigation was negative for MLPA for Duchenne Muscular Dystrophy in Patient 1 and inconclusive in the whole exome analysis via next-generation sequencing (NGS), as well as in the LGMD molecular panel for Patient 2. An expanded genetic panel for neuromuscular diseases identified two compound heterozygous variants in the ISPD gene (7p21): c.636A>C (p.Glu212Asp) and an exon 10 deletion, shared by both siblings. After parents segregation was observed, each parent carried one of the variants. These were at first classified as variants of uncertain significance (VUS) and later reclassified as likely-pathogenic and pathogenic, respectively. Results: This case highlights the phenotypic variability and intrafamilial heterogeneity associated with the ISPD gene. The heterozygous variants initially classified as VUS (c.636A>C and exon 10 deletion), later reclassified as likely-pathogenic and pathogenic, respectively, were associated for the first time with an LGMDR20 phenotype. These findings underscore the importance of accurate clinical phenotyping and systematic genetic reanalysis for establishing the correct diagnosis in hereditary myopathies. Conclusion: This report aims to present new variants associated with LGMD.

Prof. Paulo José Lorenzoni , Mr. Lucas Cesar Werneck, Mr. Igor Baroni Cardoso, Prof. Otto Jesus Hernandez Fustes, Dr. Paula Raquel do Vale Pascoal Rodrigues, Prof. Renata Dal-Pra Ducci, Dr. Claudia Suemi Kamoi Kay, Prof. Rosana Herminia Scola Universidade Federal do Paraná, Curitiba, Brazil Background: Hereditary neuropathies comprise a group of genetically determined disorders that primarily affect the peripheral nerves and exhibit marked clinical heterogeneity. Their genetic aetiology is highly diverse, with more than 100 genes described, and the prevalence of specific subtypes varies according to inheritance pattern and geographical origin. Methods: This study analysed a cohort of patients with hereditary neuropathies diagnosed at a single referral centre for neuromuscular diseases in Southern Brazil. The aim was to contribute to disease characterisation and to determine the distribution of neuropathy subtypes in this region, thereby defining the genetic profile of affected patients. Results: A total of 86 patients with suspected hereditary neuropathy were included. Next-generation sequencing panel analysis identified pathogenic or likely pathogenic variants in 48 patients; however, four individuals harbouring variants in genes associated with other disorders (SCN10A, ATP7A, MYH14, and SIGMAR1) were excluded. Among the remaining 44 patients, variants were identified in the following genes: PMP22 (n = 19), TTR (n = 9), GJB1 (n = 6), MORC2 (n = 3), SPTLC1 (n = 1), LRSAM1 (n = 1), ATP1A1 (n = 1), SH3TC2 (n = 1), MFN2 (n = 1), GDAP1 (n = 1), and POLG (n = 1). Distinct variants affecting different exons were observed across most genes. Recurrent findings included duplication of exons 1–5 in PMP22 , recurrent TTR variants (p.Val50Met, p.Val142Ile, and p.Val127Ile), and the GJB1 frameshift variant p.Trp132Valfs*14. Conclusion: This study provides a comprehensive phenotypic and genotypic characterisation of hereditary neuropathies in a Southern Brazilian cohort. The distribution of genetic subtypes was compared with national and international data, contributing to a better understanding of the regional genetic landscape of hereditary neuropathies.

Asst. Prof. Leila Tamaoui 1,2 , Assoc. Prof. Fatima Ouchkat 1,2 , Asst. Prof. Basma Marzouk 1,2 , Dr. Bouchra Kabli 1 , Prof. Nazha Birouk 1,2 1 Clinical Neurophysiology Department, Hôpital des Spécialités of Rabat, Ibn Sina University Hospital, Rabat, Morocco. 2 Medical school of Mohammed V University, Rabat, Morocco Background: Diagnosis of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) remains challenging in variants that do not meet standard EAN/PNS 2021 electrodiagnostic criteria. In these cases, nerve conduction studies (NCS) may fail to capture proximal demyelination in the roots or plexuses. This study evaluates the utility of Somatosensory Evoked Potentials (SSEP) as a complementary tool to identify proximal lesions and reclassify these atypical phenotypes. Methods: We conducted an observational study of seven patients presenting with clinical features of CIDP variants (including distal acquired demyelinating symmetric neuropathy [DADS], Lewis-Sumner syndrome, and pure motor variants) between April 2024 and October 2025. All patients underwent standard NCS and upper limb SSEP (median and/or ulnar nerve stimulation). SSEP parameters analyzed included distal latencies (N9), cervical latencies (N13), and N9-N13 interpeak intervals to assess proximal conduction . Results: The cohort included six males and one female, aged 20 to 69 years. Phenotypes included two pure motor CIDP, two motor-predominant demyelinating polyneuropathy, and three multifocal motor-predominant forms. All patients (7/7) exhibited SSEP abnormalities despite inconclusive sensory NCS. Three patients showed complete abolition of plexic and medullary responses, while four presented with significantly prolonged latencies, indicating proximal conduction blocks. Notably, in one patient initially presenting with complete response abolition, a one-year follow-up after corticosteroid pulse therapy demonstrated the reappearance of responses, reflecting the resolution of proximal blocks and correlating with clinical recovery. Conclusion: SSEP are essential for identifying proximal demyelination missed by distal sensory conduction studies. They provide critical evidence of sensory involvement in “pure motor” forms and help differentiate multifocal motor variants from Lewis-Sumner syndrome, which carries significant therapeutic implications. Furthermore, SSEP serve as an objective biomarker for monitoring treatment efficacy and remyelination.

Dr. Leslie Nelson 1 , Ms. Natalie Land 2 , Dr. Melissa Maravic 2 , Dr. Thomas Brown 3 , Dr. Christabella Cherubino 3 , Dr. Mouhamed Gueye 3 1 Department of Physical Therapy, University of Texas Southwestern Medical Center, Dallas, United States. 2 Precision AQ, New York, United States. 3 Scholar Rock, Inc., Cambridge, United States Background: SMA is a neuromuscular disorder marked by the irreversible degeneration of spinal motor neurons, resulting in progressive muscle atrophy, weakness, and loss of motor function. Although motor function scales such as the HFMSE are commonly used to evaluate treatment effectiveness in patients with SMA, it can be challenging to determine whether changes in motor function scores are clinically meaningful. As a result, individual insights from patients or their caregivers are often required to obtain a more accurate understanding of treatment impact. Methods: To gain deeper insights into how functional changes on the HFMSE are perceived in terms of clinical meaningfulness, we conducted 60-minute, web-based, semi-structured interviews among patients, their caregivers, and providers (neurologists/physical therapists) experienced with treating SMA and utilizing the HFMSE to monitor motor function. Here we report outcomes from interviews with neurologists (n=11), highlighting their interpretation of what constitutes clinically meaningful change for the HFMSE and functional tasks that may be the most meaningful. Results: For interviewed neurologists, the mean age (SD) was 50.8 (9.9) years, with most specializing in neuromuscular medicine (7/11; 63.6%), followed by pediatric neurology (3/11; 27.3%), clinical neurophysiology (2/11; 18.2%), epilepsy (1/11; 9.1%), and/or vascular neurology (1/11;9.1). The most common clinical settings of practice were universities/academic medical centers (4/11; 36.4%) and multi-specialty group practices (3/11; 27.3%). All 11 interviewed neurologists (100%) reported they spend at least 80% of their work week providing direct care to patients and indicated they were ‘very familiar’ with the HFMSE (100%), with 10 (90.9%) reporting they received specific training on its administration. When defining clinically meaningful change, neurologists frequently framed it from the patient’s perspective, generally characterizing it as a change that clearly enhances a patient’s functioning, independence, and capacity to perform everyday activities. They also noted that any point improvement on functional tasks within the HFMSE reflects a meaningful gain in independence and quality of life, with the most impact being noted for patients who were previously unable to perform those tasks. One neurologist highlighted this when discussing the lifting hands to head task, “They [patients] would have more autonomy…This means that they can do certain tasks better such as feeding themselves…” Another neurologist noted the importance of patients making small improvements in the standing task stating, “Standing alone, you can probably take a shower that way by yourself, dress by yourself. That's big.” A separate neurologist also noted the significance of any point improvement in the sitting to laying task, emphasizing the impact on quality of life, “[Improvement] makes a tremendous change in their quality of life…their motor functioning and their ability to perform the motor work.” Conclusion: According to neurologists’ responses, clinically meaningful change is best understood through a patient-centered lens, with improvements in daily functioning and independence being assessed in relation to each patient’s goals and lived experience. Neurologists generally agreed that any point improvement, regardless of functional task, can meaningfully affect a patient’s independence and quality of life, highlighting the clinical and patient-focused value of recognizing and tracking small changes.

Dr. Mathias Maisenbacher , Prof. Pariwat Thaisetthawatkul Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, United States Background: Andersen-Tawil Syndrome (ATS) is an extremely rare type of periodic paralysis (PP) (estimated prevalence 1:1,000,000). ATS classically presents as a triad of periodic paralysis, cardiac abnormalities, and characteristic facial and skeletal features. Approximately70% of cases are linked to autosomal dominant mutations in KCNJ2/Kir2.1 (ATS1). More frequent than dysmorphic features, cardiac manifestations of ATS1 have been found in about 90% of cases, and may include a U-wave, ventricular bigeminy, bidirectional ventricular tachycardia, and/or QT-interval prolongation. Here, we report a genetically confirmed case of ATS without cardiac conduction defect, the diagnosis of which required clinical recognition of facial and skeletal dysmorphism. Methods: Case Report Results: A 30-year-old male presented with a 16-year history of episodic limb weakness since adolescence. Attacks occurred nearly monthly and varied in severity, ranging from mild weakness to profound paralysis lasting several days. Common triggers included awakening after sleep and high-carbohydrate meals. There were no sensory, autonomic, or bulbar symptoms. During a prior hospitalization for severe weakness, he was found to be severely hypokalemic. The patient never suffered cardiac symptoms or syncopal episodes. There was no family history of recurrent paralysis, though a paternal relative had cardiac events. The neurologic exam was completely normal. The patient’s general appearance was notable for obesity with mild dysmorphic features, including a small chin, mild hypertelorism, low-set ears, and short fingers. Basic laboratory tests were normal. Routine nerve conduction and EMG studies were normal. The long exercise test demonstrated a post-exercise compound muscle action potential (CMAP) decrement of approximately 51%. An electrocardiogram (EKG) was normal. Genetic testing revealed a pathogenic variant of the KCNJ2 gene, confirming the diagnosis of ATS. The patient reported a reduction in attack frequency following lifestyle modifications and pharmacologic therapy with carbonic anhydrase inhibitors and potassium supplementation. Cardiology evaluation did not reveal any cardiac or rhythm abnormalities. The patient remains stable under multidisciplinary follow-up. Conclusion: ATS is an exceedingly rare condition that occurs along a spectrum of episodic weakness, dysmorphic features, and cardiac abnormalities. However, these cardiac abnormalities may not be present at initial presentation. Therefore, clinical recognition of the facial and finger dysmorphia is essential in case of a normal EKG and absence of cardiac symptoms. Mild facial dysmorphisms such as micrognathia are commonly idiopathic phenomena in adults and may easily be overlooked. Reduced penetrance, de novo mutations, and phenotypic ATS without KCNJ2 abnormalities (ATS2) further complicate the diagnosis, making attentive clinical and electrodiagnostic examination paired with a high index of suspicion essential in all cases of PP. Early diagnosis enables targeted management, improves quality of life, and reduces potential cardiac risks.

Ms. Kaitey Guite 1 , Dr. Eric P. Hoffman 2 , Dr. Michela Guglieri 3 , Dr. Paula R. Clemens 4 , Dr. Utkarsh J. Dang 1 1 Carleton Univeristy, Ottawa, Canada. 2 Binghamton University, New York, United States. 3 Newcastle University, Newcastle Upon Tyne, United Kingdom. 4 University of Pittsburgh School of Medicine, Pittsburgh, United States Background: Duchenne Muscular Dystrophy (DMD) is an X-linked disease characterized by progressive muscle degeneration. Its rarity, heterogenous presentation, and progressive course highlight the need for innovative trial designs to better assess drug efficacy. Strategies based on sample enrichment and/or subgroup-based primary analyses are a promising alternative to an all-comers primary analysis, while still retaining wide inclusion criteria. However, which subgroup is the most suitable for assessing efficacy is unclear. Moreover, the perception of a “honeymoon period” for the first 7 years where absolute motor function may improve and affect statistical power of comparisons in trials remains widespread. Our objective was to assess change in young 4--7-year untreated boys to understand improvement, stability, or decline in DMD in a typical clinical trial timeframe. Define subgroups that could increase statistical power compared to an all-comers analysis. Methods: We used data from a randomized, double blinded, placebo-controlled registrational trial of vamorolone (VBP15-004), a dissociative steroid approved for DMD in boys over 2 years old, as well as data from the placebo arm of another published interventional study. A longitudinal analysis approach was employed to compare subgroup estimates to those from an all-comers analysis. Results: The VBP15-004 trial previously showed significant steroid-related improvements in primary and multiple secondary motor outcomes. Across these outcomes (time to stand from supine [TTSTAND], time to climb 4 steps, time to run/walk 10m, six-minute walk distance [6MWD], and Northstar Ambulatory Assessment), no significant honeymoon period (improvements in motor outcomes) was identified on placebo until age 7.5 years. A literature review identified common subgroups used for DMD, typically based on age at trial baseline, specific motor outcomes, or imaging measures (fat fraction). The ability of these subgroups to improve statistical power of corticosteroid treatment effect was assessed using VBP15-004 data. The ≥ 5-second TTSTAND and 300m-400m 6MWD subgroups demonstrated the best sensitivity for detecting treatment effect of corticosteroids. Sample size and power calculations further supported the use of the ≥ 5 seconds TTSTAND subgroup demonstrating a smaller sample size required: i.e., 4 to 5 sec TTSTAND subgroup to achieve 0.9 power. Conclusion: While some steroid-naïve boys with DMD may show a marginal improvement in some motor outcomes in early age bins, none of the motor outcomes showed consistent strength improvement until <7.5 yrs in this typical age range of interest for interventional trials.   The ≥ 5-second TTSTAND and 300m-400m subgroups were found to provide greater statistical power for a corticosteroid effect than an all-comers analysis. These findings may be important both for steroid-naïve interventional trial designs and steroid add-on trials. For the former, these provide guidance for potentially capturing a range of participants with higher sensitivity to drug effects, while for the latter, importantly, underscore the large effect size for corticosteroid treatment that should be considered in clinical trials that are add-ons to corticosteroid standard of care.

Dr. Yuebing Li 1 , Miss Kavita Gandhi 2 , Dr. Wisam Karmous 3 , Dr. Marie Fitzgibbon 2 , Dr. Ibrahim Turkoz 4 , Dr. I-Ching Tsai 5 , Dr. Zia Choudhry 6 , Dr. Wim Noel 7 , Dr. Louis Jackson 8 , Dr. Sindhu Ramchandren 6 , Dr. Hiroyuki Murai 9 1 Neuromuscular Center, Neurological Institute, Cleveland Clinic, Cleveland, OH,, United States. 2 Johnson & Johnson, Raritan, NJ, United States. 3 Johnson & Johnson, Issy-les-Moulineaux, France. 4 Johnson & Johnson, Titusville,, NJ, United States. 5 Johnson & Johnson, Singapore, Singapore. 6 Johnson & Johnson, Titusville, NJ, United States. 7 Johnson & Johnson, Beerse, Belgium. 8 Johnson & Johnson, Horsham, PA, United States. 9 Department of Neurology, International University of Health and Welfare, Narita, Japan Background: Nipocalimab demonstrated sustained disease control, with improvements in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) total scores during the 24-week double-blind phase (versus placebo) and through Week-60 of the open-label (OLE) phase of Vivacity-MG3. Corticosteroid dose adjustment was prohibited during the double-blind phase but permitted in the OLE, where all patients received nipocalimab. The objective of the present analysis was to characterize corticosteroid usage, patterns of corticosteroid dose reduction/ discontinuation, and symptom improvements among nipocalimab-treated patients with generalized myasthenia gravis (gMG) during the OLE phase of Vivacity-MG3 ( NCT04951622 ) study. Methods: Corticosteroid dose reductions to ≤20, ≤15, ≤7.5, ≤10, and ≤5 mg/day prednisone-equivalent were evaluated through OLE data cutoff. Among patients on a low corticosteroid dose ( ≤ 10 or ≤ 5 mg/day), the proportions achieving meaningful clinical improvement (MCI; ≥2-point MG-ADL), minimum symptoms expression (MSE; MG-ADL score=0 or 1), and sustaining these for ≥8-weeks were evaluated. Results: Of 89 patients receiving corticosteroids at OLE baseline (placebo/nipocalimab:44 [49%], nipocalimab/nipocalimab:45 [51%]), 45% reduced or discontinued corticosteroids by data cutoff; the mean steroid dose reduced from 23 mg/day to 10 mg/day prednisone-equivalent. By OLE data cut-off, 85.4%, 71.9%, 60.7%, 41.6%, and 33.7%, of patients were on ≤ 20, ≤ 15, ≤ 10, ≤7.5, ≤ 5 mg/day prednisone-equivalents, respectively. Among those on ≤ 10 mg/day (n=54), 98.1% (n=53) achieved MCI and 44.4% (n=24) achieved MSE; sustained MCI and MSE for ≥8-weeks was achieved by 94.4% (n=51) and 24.1% (n=13), respectively. For those on ≤ 5 mg/day (n=30), 100.0% (n=30) achieved MCI and 60.0% (n=18) achieved MSE, sustained MCI and MSE for ≥8-weeks was achieved by 93.3% (n=28) and 33.3% (n=10), respectively. Conclusion: By OLE data cutoff, nearly half of patients receiving corticosteroids at baseline, reduced or discontinued corticosteroids. A substantial proportion of patients who were on low dose corticosteroid ( ≤ 10 or ≤ 5 mg/day) during the OLE sustained MCI and/or MSE for ≥8-weeks. Results support the corticosteroid-sparing effect of nipocalimab and concurrent meaningful clinical improvement and sustained disease control in nipocalimab-treated patients with gMG.

Dr. Hyung Jun Park 1 , Dr. Yunjung Choi 1 , Dr. Young-Chul Choi 1 , Dr. Jeong Hee Cho 2 , Dr. Bum Chun Suh 3 , Dr. Sang Beom Kim 4 , Dr. Woo-Kyung Kim 5 , Dr. Yang-Ki Minn 6 1 Department of Neurology, Gangnam Severance Hospital, Younsei University College of Medicine, Seoul, Korea, Republic of. 2 Department of Neurology, National Health Insurance Service Ilsan Hospital, Goyang, Korea, Republic of. 3 Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of. 4 Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea, Republic of. 5 Department of Neurology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic of. 6 Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic of Background: Desmin-related myopathy (desminopathy) is a myofibrillar myopathy caused by pathogenic variants in the DES gene, typically affecting both skeletal and cardiac muscle. It often presents with progressive skeletal myopathy, cardiomyopathy, and arrhythmias, which can obscure the recognition of a unifying cardioskeletal disorder. In Korea, desminopathy has been reported mainly based on pathological findings, with few genetically confirmed cases. Here, we report a Korean patient with late-onset, distal-predominant myopathy and atrial fibrillation harboring a pathogenic DES variant. Methods: We reviewed clinical features, serum creatine kinase (CK), electromyography, and muscle computed tomography (CT) findings. Targeted sequencing was performed using the NextSeq550Dx/2000 System (Illumina). Results: A 65-year-old man presented with a 10-year history of progressive gait disturbance beginning in his mid-fifties. He had undergone catheter ablation for atrial fibrillation three years earlier and had been otherwise healthy and physically active. Neurological examination revealed asymmetric lower-limb weakness with distal predominance, impaired toe and heel walking, and steppage gait. There was no family history of neuromuscular disease. Serum CK was mildly elevated (549 U/L). Electromyography showed myopathic changes. Lower limb muscle CT demonstrated symmetric fatty atrophy of the peroneus longus and brevis bilaterally, with mild subcutaneous edema. Targeted sequencing identified a heterozygous missense DES variant, NM_001927.4 :c.35C>T (p.Ser12Phe), located in exon 1. DES encodes desmin, the major intermediate filament protein in cardiac, skeletal, and smooth muscle. Dysfunctional desmin disrupts cytoskeletal integrity and myofibrillar organization, contributing to both skeletal myopathy and cardiac dysfunction. Desminopathy exhibits wide phenotypic heterogeneity, influenced by inheritance patterns and the location of pathogenic variants within the desmin molecule. Most cases present in the third to fourth decade with progressive distal weakness and variable cardiac involvement. Our patient developed symptoms in his mid-fifties and had atrial fibrillation, highlighting an unusually late onset and expanding the phenotypic spectrum. The coexistence of distal myopathy and cardiac arrhythmia should raise suspicion for desminopathy and underscores the diagnostic value of targeted gene panel testing. Given that cardiac manifestations are common and may evolve over time, systematic cardiologic evaluation and longitudinal follow-up are warranted even in predominantly skeletal presentations. Conclusion: We report a genetically confirmed Korean case of desminopathy due to a pathogenic DES variant, broadening the clinicogenetic spectrum of this disease. This case emphasizes the importance of cardiac evaluation in patients presenting with distal myopathy.

Prof. Anders Oldfors 1 , Dr. Malin Nilsson 1 , Assoc. Prof. Carola Hedberg-Oldfors 2 1 Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden. 2 Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden Background: Mitochondrial disorders are diseases of the respiratory chain that lead to impaired energy production and tissue dysfunction. Virtually any organ may be affected, resulting in a broad clinical spectrum. Cardiomyopathy has been reported as an isolated and severe manifestation of mitochondrial disease but is rarely suspected based on heart failure alone. Moreover, mitochondrial cardiomyopathies are generally not detected using conventional routine staining of endomyocardial biopsies. Diagnosis of mitochondrial disorders typically relies on genetic, biochemical, and histopathological analyses of skeletal muscle biopsy. In contrast, the assessment of mitochondrial protein expression, enzymatic function, and ultrastructural morphology in myocardial tissue has not been extensively studied, despite its potential utility for identifying isolated mitochondrial cardiomyopathy—an entity that may be underdiagnosed among cardiomyopathies. Methods: Nine patients with a genetically confirmed diagnosis of mitochondrial cardiomyopathy and available cardiac muscle tissue were included. Genetic defects comprised mtDNA point mutations affecting tRNA and protein-coding genes, single large-scale mtDNA deletions, and nuclear gene mutations in AARS2 , PARS2 , and AGK (Sengers syndrome). Cardiac material included endomyocardial biopsies, heart explants, and post-mortem specimens. Immunohistochemistry was performed on fresh-frozen and formalin-fixed paraffin-embedded sections to assess the expression of selected subunits of respiratory chain complexes I–V. Enzyme histochemistry was applied to fresh-frozen tissue to evaluate the activity of complexes II and IV. Mitochondrial ultrastructure was examined by electron microscopy. All findings were compared with control myocardial tissue. Results: Enzyme histochemistry was available in seven cases; six demonstrated complex IV deficiency, while none showed complex II deficiency. Immunohistochemical analysis revealed complex I deficiency in seven of nine cases and complex IV deficiency in three cases. Respiratory chain deficiencies typically displayed a mosaic pattern among cardiomyocytes. Electron microscopy showed nonspecific mitochondrial abnormalities without distinctive ultrastructural features. Conclusion: Our findings support the concept that myocardial tissue can provide histopathological evidence of mitochondrial cardiomyopathy in the majority of cases. Immunohistochemistry and enzyme histochemistry targeting respiratory chain complexes I and IV appear particularly informative. Further studies are warranted to validate these methods and to determine their diagnostic value in the routine evaluation of endomyocardial biopsies.

Ms. Jin-Ah Kim 1,2 , Ms. Do-Yeon Lee 3 , Prof. Jung-Joon Sung 1 , Prof. Jong-Il Kim 1 1 Seoul National University Hospital, Seoul, Korea, Republic of. 2 Genomic medicine Institute, Seoul, Korea, Republic of. 3 Seoul National University, Seoul, Korea, Republic of Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Although accumulating evidence indicates that glial cell dysfunction plays a crucial role in ALS pathogenesis, neurofilament light chain, which reflects neuroaxonal damage, is predominantly used in ALS. Here, we aimed to identify novel glial biomarkers from activated microglia and astrocytes through single-nucleus RNA sequencing (snRNA-seq) and proteomics analysis of patient serum. Methods: We performed snRNA-seq of the spinal cord from hSOD1 G93A transgenic mice at pre-symptomatic (P60), peri-symptomatic (P90), and progressive (P120) stages. Differential gene expression (DEG) analyses were conducted for microglia and astrocytes, respectively, compared to littermate controls. Protein expression changes were identified using Western blot analysis. Human relevance was supported by analyzing publicly available snRNA-seq datasets from sporadic ALS patients. Results: In microglia, Apoe was the most significantly upregulated, evident from the pre-symptomatic stage. Western blot analysis demonstrated that APOE protein also rose prior to symptom onset and became markedly elevated according to disease progression. Apoe upregulation is assumed to be associated with enhanced lipid transport during the clearance of myelin debris resulting from oligodendrocyte degeneration. In astrocytes, Fn1 was significantly upregulated, consistent with its key role in reactive astrogliosis and glial scar formation. Importantly, both APOE and FN1 increases were confirmed in spinal cord tissues from sporadic ALS patients. Conclusion: By integrating snRNA-seq data from an ALS mouse model and human tissues, we identified candidate biomarkers reflecting active glial cells. While ApoE did not show significant changes in serum, its high systemic levels could potentially mask disease-related alterations, suggesting that additional validation in CSF is required.

Dr. Tanish Modi 1 , Dr. Brendan Putko 2 , Dr. Kamal Shouman 1 , Dr. Marcus Pinto 1 1 Mayo Clinic, Rochester, United States. 2 University of Alberta, Edmonton, Canada Background: Immunoglobulin light-chain (AL) amyloidosis is the most common cause of amyloid neuropathy, with peripheral nerve involvement occurring in up to one‑third of patients. The neuropathy is typically sensory predominant, and autonomic symptoms are frequent. Rarely it may mimic a motor neuron disorder. Methods: We describe a patient with AL amyloidosis presenting with progressive weakness resembling a lower motor neuron disorder. Results: A 69-year-old man presented with a 4-year history of slowly progressive weakness without sensory or autonomic symptoms. Initial manifestations included chewing fatigue, progressive dysphonia, and dysphagia. He later developed bilateral but asymmetric (right > left) hand weakness with atrophy. These findings were initially attributed to C8 radiculopathies and carpal tunnel syndrome. He also experienced bilateral rotator cuff injuries resulting in persistent shoulder girdle weakness. Carpal tunnel release and C7–T1 bilateral foraminotomies did not result in clinical improvement. Neurological examination demonstrated asymmetric mild-to-moderate distal-predominant weakness and atrophy in the upper limbs (right > left) and right lower limb with normal reflexes and normal sensory exam. Electromyography showed active and chronic denervation in the bulbar, cervical, thoracic, and lumbosacral segments, consistent with a diffuse anterior horn cell disorder, superimposed by a mild sensory neuropathy. Laboratory evaluation revealed markedly elevated kappa free light chains (131 mg/dL; normal 0.33–1.94) and an abnormal kappa/lambda ratio of 655 (normal 0.26-1.65). Serum mass spectrometry (mass-fix) identified a small IgG kappa monoclonal gammopathy. Subcutaneous fat aspirate was positive for amyloid, and mass spectrometry confirmed kappa AL amyloidosis. Bone marrow biopsy demonstrated 15–20% clonal plasma cells. There was no evidence of renal involvement, lytic bone lesions, or other systemic manifestations. The patient initiated treatment with daratumumab-CyBorD. Neurological function remained stable over six months, but only a partial hematologic response was achieved. Given the atypical presentation, a right vastus lateralis muscle biopsy and sural nerve biopsy were obtained. Muscle biopsy revealed prominent interstitial amyloid deposition with mild myopathic features, and mass spectrometry analysis confirmed kappa AL amyloidosis. The sural nerve biopsy identified small perivascular amyloid deposits and mild decreased density of myelinated fibers. With biopsy-confirmed neuromuscular amyloid infiltration, treatment was escalated to autologous hematopoietic stem cell transplantation. Due to persistent partial hematologic response, the patient subsequently underwent chimeric antigen receptor T-cell therapy, resulting in a complete hematologic response and mild improvement in bulbar and upper limb symptoms after 2 months. Conclusion: AL amyloidosis should be considered in the differential diagnosis of lower motor neuron syndromes, even in the absence of sensory or autonomic involvement. The mechanism underlying predominant motor involvement in this case remains uncertain. Tissue confirmation of amyloid deposition in both muscle and nerve guided escalation of therapy and contributed to improved clinical outcomes.

Prof. Edicson Ruiz-Ospina 1,2 , Prof. Sandra Milena Castellar-Leones 1,2,3 , Prof. Jorge Arturo Diaz-Ruiz 1,2 , Dr. Cristian Correa-Arrieta 2 , Dr. Diana Ramirez-Montaño 4 , Dr. Eduardo Echeverry 4 , Dr. Juan David Lopez 5 , Dr. Ana Laura Castro 6 , Dr. Juan Pablo Muñoz 7 , Dr. Diana Luzuriaga-Carpio 8 , Dr. Dario Zambrano-Vera 9 , Dr. Edison Vasquez 10 , Dr. Daniel Cesar Chávez 10 , Prof. Fernando Ortiz-Corredor 1,2,3 1 Universidad Nacional de Colombia, Bogota, Colombia. 2 CIFEL, Bogota, Colombia. 3 Hospital Universitario Nacional de Colombia, Bogota, Colombia. 4 Clinica Imbanaco, Cali, Colombia. 5 Fundacion Valle de Lili, Cali, Colombia. 6 Hospital Universal Cartago, Cartago, Costa Rica. 7 Caja Costarricense de Seguro Social, Alajuela, Costa Rica. 8 Hospital General Manuel Ygnacio Monteros-IESS, Loja, Ecuador. 9 Hospital de Especialidades Carlos Andrade Marín-IESS, Quito, Ecuador. 10 Hospital Teodoro Maldonado Carbo-IESS, Guayaquil, Ecuador Background: Hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) is characterized by marked clinical heterogeneity, which frequently delays diagnosis and complicates individualized management. In Latin America, detailed phenotypic characterization remains limited, partly due to unequal access to specialized functional assessments and regional genetic variability. This study aimed to identify clinical sub-phenotypes of hATTR-PN in a multi-country Latin American cohort, with particular emphasis on small-fiber dysfunction (cold detection threshold [CDT] and heat pain threshold [HPT]) as an infra-clinical marker of disease progression. Methods: We evaluated 105 patients from Colombia, Ecuador, and Costa Rica. Hierarchical cluster analysis using Ward’s D2 method was applied to a multidimensional dataset comprising 30 clinical, functional, sensory, and imaging variables. Clinical severity and symptoms were assessed using the Neuropathy Impairment Score (NIS), Norfolk Quality of Life–Diabetic Neuropathy (QOL-DN), COMPASS-31, and the Neuropathic Pain Scale (NPS). Functional performance was measured with the Nine-Hole Peg Test (NHP), monopodal static balance (MSB), Timed Up and Go (TUG), and the 5-item Sit-to-Stand test (SST5). Small-fiber function was assessed through CDT and HPT. High-resolution ultrasound was used to quantify the cross-sectional area (CSA) of the vagus nerve, brachial plexus, and peripheral nerves (median, ulnar, tibial, peroneal, and sural). Cluster stability was evaluated using bootstrap resampling (B = 100). Results: Four distinct phenotypic clusters were identified. Cluster 2 (n = 34) showed the highest stability (Bootmean = 0.91) and represented a sub-clinical profile, with a median NIS of 0.00 and preserved MSB and NHP performance. Cluster 4 (n = 29; Bootmean = 0.71) corresponded to a “small-fiber predominant” phenotype, characterized by a high prevalence of infra-clinical sensory abnormalities (abnormal foot CDT in 72.4% and abnormal foot HPT in 58.6%), despite a median NIS of 0.00. Cluster 1 (n = 24; Bootmean = 0.51) included the most severe cases, with the greatest impairment in functional tests (NHP median: 28.7 s; MSB median: 4.1 s), higher autonomic involvement (COMPASS-31 median: 17.0), and vagus nerve CSA enlargement. Cluster 3 (n = 18; Bootmean = 0.63) demonstrated a distinct, focal infra-clinical state characterized by isolated sensory dissociation, with predominant HPT involvement in the hands (88.9% abnormal) while cold detection and distal lower-limb thresholds remained largely preserved. Significant differences across clusters were observed for NIS, NPS, NHP, MSB, and most ultrasound measures (p < 0.001), except for brachial plexus diameter (p = 0.373). Conclusion: This analysis identifies clinically meaningful hATTR-PN phenotypes within a Latin American cohort. Comparison of Clusters 3 and 4 offers important insight into early disease stages: Cluster 3 reflects a localized infra-clinical state with predominant HPT involvement in the hands, whereas Cluster 4 represents a more advanced infra-clinical stage with widespread distal small-fiber dysfunction affecting both CDT and HPT. These findings support small-fiber impairment as the earliest marker preceding motor involvement, functional decline, and overt nerve enlargement, highlighting the importance of small-fiber assessment for early diagnosis in Colombian, Ecuadorian, and Costa Rican populations.

Asst. Prof. Stephan Wenninger Friedrich-Baur-Institute, Munich, Germany Background: Respiratory muscle weakness (RMW) is a major contributor to morbidity and mortality in many neuromuscular disorders (NMD). Progressive weakness of inspiratory and expiratory muscles leads to restrictive ventilatory insufficiency, impaired cough, sleep-disordered breathing, and ultimately chronic respiratory failure. Current respiratory management in NMD primarily focuses on supportive interventions such as non-invasive ventilation and airway clearance techniques. However, strategies aimed at directly improving respiratory muscle performance have received comparatively little attention in clinical practice. Respiratory muscle training (RMT), particularly inspiratory muscle training (IMT), has emerged as a potentially valuable and feasable therapeutic approach to enhance respiratory strength, ventilatory efficiency, and exercise tolerance. Small interventional studies in conditions such as Duchenne muscular dystrophy, late-onset Pompe disease, and myotonic dystrophy type 1 suggest that structured respiratory training programs may improve maximal inspiratory pressure and other pulmonary function parameters. Nevertheless, evidence remains heterogeneous with regard to training protocols, duration, and clinical endpoints. Methods: The presentation is based on a narrative literature review which was conducted to identify interventional studies evaluating respiratory muscle training in patients with neuromuscular disorders. Particular emphasis was placed on studies assessing inspiratory muscle training using threshold resistance devices, which represent the most widely applied and validated training modality. Outcome measures of interest included maximal inspiratory pressure (MIP), forced vital capacity (FVC), maximal voluntary ventilation (MVV), and patient-reported outcomes. Results: Across published studies as well as based on own experience in daily routine care, IMT demonstrated consistent improvements in respiratory muscle strength, most commonly reflected by increases in maximal inspiratory pressure. Improvements in ventilatory parameters such as FVC and MVV were less frequently reported in some cohorts, particularly when endurance-focused training protocols were applied. Evidence from randomized and controlled studies remains limited but suggests that structured respiratory training can lead to clinically meaningful physiological adaptations. Across different studies, IMT was well tolerated and no serious adverse events attributed to IMT were observed in any trial. Moreover, adherence rates were generally acceptable when training was performed in structured home-based programs with regular follow-up. Importantly, greater adherence to the training protocol was associated with larger improvements in respiratory muscle strength, highlighting the relevance of sustained patient engagement. Conclusion: IMT represents a feasible, safe, and potentially effective therapeutic strategy for patients with NMD and respiratory involvement. Available clinical evidence indicates that structured inspiratory training programs can improve respiratory muscle strength and may enhance ventilatory efficiency in selected patient populations. Both strength-oriented and endurance-oriented training protocols appear beneficial, although endurance-based approaches may provide broader physiological effects on ventilation. Despite these encouraging findings, the overall evidence base remains limited by small sample sizes, heterogeneous study designs, and variability in training protocols and outcome measures. Within multidisciplinary neuromuscular care, respiratory muscle training may represent a valuable proactive intervention, particularly in early stages of respiratory involvement before the development of advanced ventilatory insufficiency. Future research should focus on standardized training protocols, integration with telemedicine-supported care models, and the evaluation of clinically meaningful outcomes in neuromuscular disease cohorts.

Dr. Cristina Muntean Firanescu 1 , Dr. Sebastian Thams 1 , Dr. Kristin Samuelsson 1 , Dr. Malin Kvarnung 2 , Dr. Maria Mannila 3 , Dr. Rayomand Press 1 1 Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. 2 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 3 Department of Cardiology and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden Background: MYBPC1-related congenital myopathy with tremor (MYOTREM) is a rare autosomal dominant neuromuscular disorder characterized by neonatal hypotonia, muscle weakness without evidence of neuropathy, and a myogenic tremor. While primarily considered a skeletal muscle disorder, the full clinical spectrum remains incompletely defined. Only a limited number of patients with MYBPC1-related congenital myopathy have been reported, and long-term follow-up data are scarce. Methods: We present a 26-year-old man with a previously reported heterozygous pathogenic MYBPC1 variant (p.Leu233Arg), occurring de novo, with no other affected family members. He was born at term with normal birth weight and was admitted to the neonatal unit due to involuntary movements consistent with tremor and a spontaneous pneumothorax, which resolved without intervention. Shortly after birth, hypotonia affecting both axial and limb musculature was noted. Early motor development was delayed. Independent ambulation was achieved at 14 months and was characterized by gait instability and recurrent falls. During childhood, proximal muscle weakness predominantly involving the lower extremities developed, together with reduced muscular endurance and impaired balance. These findings persisted into adulthood. Excessive sweating developed during adolescence and has remained present. Tremor was a prominent and persistent feature, affecting the upper and lower extremities as well as the tongue. The tremor was postural and kinetic, clinically characterized as a fine, high-frequency tremor of approximately 20 Hz. Results: Nerve conduction studies showed no evidence of polyneuropathy. Muscle biopsy performed in childhood, including immunohistochemistry and electron microscopy, did not demonstrate any pathological abnormalities. Brain MRI demonstrated slowly progressive cerebellar vermis atrophy, first noted at 16 years of age and confirmed on follow-up imaging in adulthood. No additional structural brain abnormalities were identified. Blood workup did not reveal any alternative explanation for the cerebellar atrophy. Cardiac evaluation performed at 26 years of age revealed mildly reduced left ventricular systolic function with an ejection fraction of approximately 45%. Long-term ECG monitoring and cardiac biomarkers were normal, and no alternative cardiac etiology was identified. Extensive evaluation of the hyperhidrosis, including assessment for endocrine, autonomic, and secondary causes, did not reveal an alternative explanation. Conclusion: This case describes a patient with MYBPC1-related congenital myopathy and tremor, in whom cerebellar atrophy and adult-onset cardiac findings were also observed. A causal relationship between the MYBPC1 variant and the cerebellar and cardiac findings cannot be established. These findings may be coincidental or reflect an additional, as yet unidentified etiology; nevertheless, they underscore the importance of careful longitudinal neurological and cardiac follow-up. Systematic collection of long-term clinical data may help further delineate the clinical spectrum of MYBPC1-related disease.

Dr. Per Widholm , Dr. Markus Karlsson, Dr. Mary Folz AMRA Medical AB, Linköping, Sweden Background: To facilitate detection of treatment effects in heterogenous and slowly progressing muscle diseases, there is a need for more objective and responsive biomarkers that can accurately describe the small changes in muscle composition anticipated during the timespan of a clinical trial. Changes that often are too small to be captured by functional tests such as time-up-and-go (TUG). Utilizing whole-body MRI, a framework consisting of standardized scan-protocols and image analysis pipeline including new composite biomarkers has previously been developed. By utilizing the innate high reproducibility of MRI together with an enrichment strategy where muscles with a high probability of near-term progression is identified and combined into composite scores, the aim is to provide more responsive biomarkers that can be used as endpoints in multi-site clinical trials in neuromuscular disorders. These biomarkers were included as secondary endpoints in a 48-week phase 2b study of Losmapimod (ReDUX4) in FSHD with an optional open label extension (OLE) study. Methods: Whole-body quantitative MRI were acquired using fat-water separated imaging (Dixon). Lean Muscle Volume (LMV), Muscle Fat Fraction (MFF), and Muscle Fat Infiltration (MFI) were quantified in 36 muscles covering arms, shoulder girdles, thorax, and legs. The muscles were divided in three different categories (A, B, C) reflecting the probability of near-term progression based on the baseline fat content where B-muscles are anticipated to have the highest progression. Whole-body composite scores for LMV, MFF, MFI were generated for both A- and B-muscles. The mean change from baseline at weeks 48, 96, and 120 were calculated using paired t-tests and reported as percent change for LMV and absolute change in percentage points (pp) for MFF and MFI. The responsiveness of the biomarkers were assessed using standardized response mean (SRM). Results: The change from baseline in B-muscle whole-body composite LMV/MFF/MFI (mean±SE [SRM]) were -5.37%±0.60% [1.1], p<0.001 / 1.38pp±0.25pp [0.67], p<0.001 / 0.27pp±0.09pp [0.38], p<0.003 at week 48; -8.85%±0.80% [1.34 ], p<0.001 / 3.11pp±0.42pp [0.89], p<0.001 / 0.80pp±0.13pp [0.73], p<0.001 at week 96; and -10.93%±0.94% [1.46], p<0.001 / 4.57pp±0.55pp [1.04], p<0.001 / 1.13pp±0.18pp [0.8], p<0.001 at week 120. The corresponding changes observed in A-muscles were -0.84%±0.49% [0.21], p=0.09 / 0.06pp±0.14pp [0.05], p=0.6 / 0.07pp±0.06pp [0.14], p=0.2; -2.23%±0.55% [0.48], p<0.001 / 0.57pp±0.16pp [0.41], p<0.001 / 0.37pp±0.07pp [0.63], p<0.001; -3.27%±0.62% [0.66], p<0.001 / 0.92pp±0.19pp [0.6], p<0.001 / 0.50pp±0.08pp [0.82], p<0.001. Conclusion: Describing progression in heterogenous and slowly progressing diseases such as neuromuscular disorders is challenging and increases both cost and complexity in drug development. By utilizing whole-body MRI to identify muscles with an increased likelihood of near-term progression, the responsiveness of the biomarkers can increase significantly, potentially enabling earlier detection of disease progression or treatment response.

Dr. Miriam Hiebeler 1 , Dr. Simone Thiele 1 , Mrs Eva Malm 1 , Mrs Caterina Wendel 1 , Prof. Angela Abicht 2 , Prof. Maggie Walter 1 1 Friedrich-Baur-Institute, LMU, Munich, Germany. 2 MGZ München, Munich, Germany Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder caused by mutations in the DMD gene. While mainly affecting males, female heterozygous carriers may also exhibit clinical symptoms ranging from elevated creatine kinase levels to muscle weakness, cardiomyopathy, or overt myopathy. The variability in clinical expression among female carriers is thought to be largely influenced by patterns of X-chromosome inactivation (XCI), an epigenetic mechanism that silences one of the two X chromosomes in somatic cells. Methods: Our study aims to characterize the XCI patterns in both peripheral blood and skeletal muscle tissue of genetically confirmed symptomatic female DMD carriers and to investigate potential correlations with clinical manifestations. We will conduct a cross-sectional observational study including about 30 symptomatic female DMD carriers with a confirmed heterozygous mutation in the DMD gene. XCI analysis is performed using DNA extracted from peripheral blood and muscle biopsy samples. Skewing patterns are classified based on established thresholds. Intraindividual comparison between blood and muscle XCI patterns will be conducted, results will be correlated with clinical and cardiac data of the participants. Results: The study will assess the degree to which blood-based XCI analysis reflects the situation in muscle tissue and how XCI skewing correlates with clinical symptoms. Conclusion: Results are expected to improve the understanding of the molecular pathophysiology in symptomatic carriers and may contribute to more accurate diagnostic and prognostic evaluation in symptomatic female DMD carriers.

Dr. Diana Chitimus 1,2,3 , Assoc. Prof. Szatmari Szabolcs 4,5 , Assoc. Prof. Laura Florea 6 , Dr. Marian Feticu 7 , Prof. Pascal Laforet 8,9,2 , Prof. Carmen Adella Sirbu 3,10 1 Doctoral School, Faculty of Medicine, ‘’Carol Davila’’ University of Medicine and Pharmacy, 050474, Bucharest, Romania. 2 INSERM U 1179, Handicap Neuromusculaire, UVSQ Paris-Saclay, Paris, France. 3 Department of Neurology, “Carol Davila” Central Military Emergency University Hospital, 1010242, Bucharest, Romania. 4 2nd Clinic of Neurology, Târgu Mures County Emergency Clinical Hospital, 540136, Targu Mures, Romania. 5 George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mures, 540142, Targu Mures, Romania. 6 . Department of Nephrology-Internal Medicine, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania. 7 Department of Neurology, “Regina Maria” Military Emergency University Hospital, Brasov, Romania. 8 Neurology Department, Raymond Poincaré University Hospital, Garches, France. 9 Nord-Est-Ile-de-France Neuromuscular Reference Center, FHU PHENIX, Paris, France. 10 Department 6-Clinical neurosciences Carol Davila” University of Medicine and Pharmacy, 050474, Bucharest, Romania Background: Late-Onset Pompe disease (LOPD) is a clinically heterogeneous neuromuscular disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the GAA gene. Phenotypic and genotypic data from Eastern Europe remain scarce in the published literature, hence the aim of this study is to characterize the population of LOPD patients in Romania. Methods: This is a retrospective, multi-center cohort study that included all the genetically confirmed LOPD patients in Romania. Data was extracted from three regional centers, and included demographic, clinical, functional, and molecular characteristics. Results are expressed as median and interquartile (IQR) range. Results: We identified nine patients diagnosed with Pompe disease, in seven different families. The median age of diagnosis was 35 years-old, while the median age of symptom onset was 28. The common mutation c.-32-13T>G was identified in six patients, two siblings had the c.569G>A mutation, while one patient was heterozygous for the c.2297A>C mutation. At the time of inclusion, three patients needed walking assistance. The median of the 6-minutes-walkin-test(6MWT) was 375 meters [286.75 m-480 m], while the median FVC(%) was 81% [66.4% - 86.9%]. None of the patients are under ventilatory support. The creatine kinase (CK) median was 579 [2091-1542.5]. Eight patients received enzyme-replacing treatment (ERT) with alglucosidase alfa, and one had a positive anti-enzyme antibody titer, however without reported adverse reactions. Regarding the systemic manifestations in our cohort, two patients had history of recurrent ischemic strokes, and one patient has aortic ectasia. No history of dysphagia or macroglossia was noted in our cohort. Conclusion: To our knowledge, this is the first study investigating the Romanian LOPD population. Our findings suggest that while the most prevalent genotype is consistent with previously reported studies in Caucasian population, the phenotypic variability remains important. In most patients the respiratory function was largely preserved, however with an important motor impairment. Despite the increasing awareness of neuromuscular disorders, LOPD remains largely underdiagnosed in the Romanian population, however with an increasing number of centers committed to monitor and treat these patients.

Mrs Shivi Gunawardane , Dr. David Saxon, Dr. Anastassia Kerasidis, Dr. Oluwaseyi Olulana, Dr. Hassan Khuram, Dr. Nicholas Streicher, Dr. Yasir Al-Khalili Georgetown University, Washington DC, United States Background: Autoimmune nodopathies associated with Neurofascin antibodies can resemble CIDP but lack demyelination and respond poorly to IVIG. In contrast, patients with anti-FGFR3 antibodies present with painful sensory neuropathy, frequently non-length dependent with dorsal root ganglion or small fiber predominance. We present an unusual case of seropositivity for anti-NF186 and anti-FGFR3. Methods: A 71-year-old woman with Hashimoto’s thyroiditis and lumbar radiculopathy developed progressive, predominantly left-sided lower-extremity spasticity with painful paresthesias and thoracolumbar numbness radiating to the legs (“hot knife”) with intermittent cold sensations. Symptoms worsened with weight bearing, stairs, and cold weather. She remained independently ambulatory but was limited by pain, gait instability, and intermittent urinary urgency with incontinence. She reported intermittent, self-limited episodes of abrupt generalized weakness with transient blurry vision/diplopia and falls; one episode occurred during use of an external neuromodulator and resolved after deactivation. Visual hallucinations were also reported. Exam showed intact cranial nerves; strength 5/5 except ankle dorsiflexion 4/5; intact pain/temperature; diffuse areflexia, 1+ brachioradialis; and normal Romberg. CSF protein was markedly elevated (352 mg/dL). EMG/NCS showed an axonal sensorimotor neuropathy without demyelination, with mildly reduced sensory amplitudes, mildly slowed median/ulnar velocities, absent right fibular F-waves, limited needle testing due to hypertonicity. Workup was unrevealing (no M-spike; negative LGI1, CASPR2, NMDA-R, GAD65; mildly elevated B6). INCAT remained 0 despite 10 IVIG infusions and pulse steroids, though sensory symptoms partially improved. WashU testing identified anti-NF186 and anti-FGFR3 IgG, prompting IVIG discontinuation and planned rituximab. Results: Discussion: This case highlights dual seropositivity for anti–neurofascin-186 (NF186) and anti-FGFR3 antibodies—an association that, to our knowledge, has not been previously reported. These antibody-mediated neuropathies share overlapping features including limb weakness, painful paresthesias, sensory ataxia, and gait instability, and the patient’s phenotype likely reflects contributions from both immune targets. Markedly elevated CSF protein, episodic diplopia suggesting cranial nerve involvement, and diffuse areflexia align with an anti-NF186–associated nodopathy, while autonomic symptoms (notably bladder dysfunction) and fatigue have been described in anti-FGFR3–associated polyneuropathy. Electrodiagnostic testing demonstrated a sensorimotor axonal neuropathy without clear demyelinating features, a pattern reported in both entities. IVIG is often less effective in autoimmune nodopathies, though anti-NF186 cases show variable responses. In anti-FGFR3 polyneuropathy, symptomatic benefit has been reported, but consistent functional improvement remains unestablished. In contrast, B-cell–depleting therapy, most notably rituximab, has shown favorable outcomes in both conditions. Given this patient’s lack of meaningful improvement with corticosteroids and IVIG, escalation to rituximab is next therapeutic step. Conclusion: This case shows how antibody testing can reframe an “atypical CIDP.” The patient’s painful paresthesias, gait instability, diffuse areflexia, autonomic/bladder symptoms, episodic cranial/visual complaints, markedly elevated CSF protein, and axonal sensorimotor neuropathy without demyelination—plus dual anti-NF186 and anti-FGFR3 seropositivity and poor response to IVIG/steroids—support an antibody-associated immune neuropathy/nodopathy rather than classic CIDP. These antibodies are clinical tools, not standalone diagnoses: interpret them in context, and if discordant, confirm with repeat/alternative testing, reassess EDX/CSF, exclude mimics, and follow longitudinally. Staying current with evolving literature guides timely, targeted therapy.

Dr. Evgeniya Melnik 1 , Prof. Vladimir Kenis 2 , Dr. Kseniya Zabudskaya 1 , Dr. Vadim Tsargush 3 , Prof. Sergei Nikitin 1 , Prof. Elena Dadali 1 1 Research Centre for Medical Genetics, Moscow, Russia. 2 H. Turner National Medical Research Centre for Children's Orthopedics and Trauma Surgery of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia. 3 Limited Liability Company “My Medical Center Advanced Technologies”, Krasnodar region, Sirius, Russia Background: Dyneinopathies are a group of DYNC1H1 -related disorders caused by dysfunction of lower motor neurons in the anterior horns of the spinal cord and/or motor structures of the brain. The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a key motor protein required for retrograde axonal transport along microtubules and normal neurodevelopment. Pathogenic variants in DYNC1H1 lead to a broad phenotypic spectrum ranging from neurodevelopmental disorders with central nervous system involvement to predominantly peripheral motor neuron disease resembling spinal muscular atrophy (SMA), typically with lower limb predominance, and combined senso-motor neuropathies such as Charcot–Marie–Tooth disease type 20. Increasing evidence indicates that DYNC1H1 -related disease may also include significant neuro-orthopedic manifestations, including congenital long-bone fractures, hip dysplasia/dislocation, arthrogryposis, and spinal deformities. However, the combination of SMA-like motor neuron disease with congenital multiple arthrogryposis and congenital fractures remains rare and insufficiently characterized, highlighting the need for further clinical and genetic characterization of these presentations. Methods: We report three unrelated male patients aged 6 months to 13 years presenting with a rare phenotype of DYNC1H1 -related disease. All patients underwent comprehensive clinical evaluation, neurophysiological testing, and neuroimaging. Muscle MRI was performed to assess muscle involvement patterns and fatty replacement. Electromyography (EMG) was used to evaluate the type and distribution of neuromuscular impairment. Genetic testing included whole-exome sequencing (WES) in all cases. Identified variants were confirmed by Sanger sequencing, and their de novo origin was established through parental testing. Results: Two patients carried a previously reported pathogenic variant in the tail domain of DYNC1H1 : NM_001376.5 :c.791G>A, p.(Arg264Gln). The third patient harbored a novel variant, NM_001376.5 :c.1822C>A, p.(Leu608Met), located in the stalk domain. Clinically, all patients demonstrated generalized hypotonia and predominant lower limb weakness, multiple joint contractures from birth, hip dislocations, foot deformities, and congenital fractures of long bones. Muscle MRI revealed marked and early fatty infiltration of the lower limb muscles, detectable already in infancy. EMG showed features consistent with a generalized neurogenic process, supporting motor neuron involvement. The combination of SMA-like weakness, congenital multiple arthrogryposis, and fractures represents a distinctive and rare DYNC1H1 -related phenotype. Conclusion: These three cases expand the phenotypic spectrum of DYNC1H1 -related disease and broaden the known variant landscape, including identification of a novel DYNC1H1 variant. Our observations highlight the importance of including DYNC1H1 in NGS diagnostic panels when SMA-like presentations are accompanied by arthrogryposis and congenital fractures. Additionally, early and extensive fatty infiltration of lower limb muscles on MRI should be considered during orthopedic decision-making and long-term management planning in affected patients.

Dr. Laurent Servais 1,2 , Dr. Nicolas Deconinck 3,4 , Dr. Liesbeth De Waele 5,6 , Dr. David Gómez-Andrés 7 , Dr. Kalina Dimova 8 , Dr. Jenny Li 8 , Ms. Nanjun Liu 8 , Dr. Nick Long 8 , Ms. Meghan MacNally 8 , Dr. Ridhi Parasrampuria 8 , Dr. Kiran Patki 8 , Ms. Dania M.D. Porco 8 , Dr. Divya Reddy 8 , Ms. Marie Rosenfeld 8 , Dr. Natarajan Sethuraman 8 1 Department of Paediatrics, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom. 2 Department of Paediatrics, Neuromuscular Reference Centers, University Hospital of Liège, Liège, Belgium. 3 Neuromuscular Reference Center, UZ Gent, Ghent, Belgium. 4 Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium. 5 Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium. 6 Department of Development and Regeneration, KU Leuven, Leuven, Belgium. 7 Child Neurology, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain. 8 Entrada Therapeutics, Boston, United States Background: Approximately 8% of individuals with Duchenne muscular dystrophy (DMD) have exon 44 skip-amenable dystrophin gene mutations. ENTR-601-44 is under investigation for the potential treatment of individuals with DMD who have confirmed exon 44 skip-amenable dystrophin gene mutations. ENTR-601-44 is an Endosomal Escape Vehicle peptide-phosphorodiamidate morpholino oligomer (PMO) conjugate intended to target dystrophin pre-mRNA and induce exon 44 skipping, thereby restoring expression of near full-length and functional dystrophin protein. ENTR-601-44 has demonstrated exon skipping and dystrophin restoration in skeletal muscle cells derived from individuals with DMD who have an exon 44 skip-amenable mutation. In the gastrocnemius muscle of mice with an exon 44 skip-amenable dystrophin mutation (del45hDMD. mdx ), one 30-mg/kg intravenous dose of ENTR-601-44 increased dystrophin protein from <1% to 46% of wild-type levels. In nonhuman primates, 4 doses of ENTR-601-44 produced 29% DMD exon 44 skipping, indicating target engagement. Furthermore, in the first-in-human phase 1 ENTR-601-101 study in healthy adult male volunteers, ENTR-601-44 dosed at 6 mg/kg was well tolerated and showed dose-dependent increases in urinary excretion of the final metabolite (PMO-44) and exon 44 skipping. Together, these findings support further study of ENTR-601-44 in individuals with exon 44 skip-amenable DMD. Herein, we present Cohort 1 data from participants in Part A (double-blind period) of the ENTR-601-44-201 study. Methods: ENTR-601-44-201 is a first-in-patient global 2-part phase 1/2 study of ENTR-601-44 in participants with a confirmed mutation in the dystrophin gene that is amenable to exon 44 skipping. Part A is a randomized, double-blind, placebo-controlled, multiple ascending dose design, focusing on safety/tolerability, pharmacokinetics, and pharmacodynamics (exon 44 skipping and dystrophin expression). Approximately 24 participants are planned, divided into 3 cohorts of 8 participants, each to receive ENTR-601-44 (6, ≤12, or ≤18 mg/kg) or placebo. Key study eligibility criteria include males assigned at birth aged 4–20 years, inclusive, with a confirmed genetic diagnosis of exon 44 skip-amenable DMD, and who are ambulatory with a Performance of the Upper Limb v2.0 (PUL 2.0) entry item A of at least 3 at screening. If on glucocorticoid therapy, participants must be on a stable dose and regimen for at least 3 months before dosing. No prior treatment with any exon-skipping therapy or gene therapy is allowed. All participants in Part A are eligible for continued treatment in an open-label extension period. Results: Eight males with genetically confirmed DMD amenable to exon 44 skipping were randomized 3:1 to receive 3 doses of ENTR-601-44 (6 mg/kg) or placebo as an intravenous infusion over 6-week intervals. Participants underwent baseline muscle biopsy before the first dose of treatment during the screening period, and then again at the end of the treatment period at week 19 (6 weeks after the final dose). At baseline, mean age was 10 (range, 6–17) years and mean body mass index was 19.5 (range, 15.6–25.2) kg/m 2 . Mean age at DMD diagnosis was 3 (range, 0–7) years. Conclusion: Topline data, including assessments of safety and tolerability, change in dystrophin and exon 44 skipping levels, and pharmacokinetics of ENTR-601-44 will be presented.

Prof. Valentina Damato Department of Neuroscience, University of Florence, Florence, Italy. SOD Neurologia d'urgenza, Careggi University Hospital, Florence, Italy Background: Myasthenia gravis (MG) is a rare autoimmune neuromuscular junction disorder with marked heterogeneity in clinical phenotype and immunopathogenesis. Over recent decades, its epidemiology has evolved substantially, offering insights into disease mechanisms and healthcare needs. Contemporary population-based studies report an annual incidence of approximately 10–30 per million person-years and a prevalence ranging from 10 to over 30 per 100,000 population, with consistent evidence of increasing disease frequency worldwide. This rise is attributed to population ageing, improved diagnostic accuracy, and reduced mortality. Notably, shifts in MG subtypes, particularly the growing predominance of late-onset and very-late-onset MG, suggest changing interactions between genetic susceptibility, environmental exposures, and immune ageing. Methods: This presentation synthesizes data from recent population-based epidemiological studies, systematic reviews, and longitudinal cohort analyses spanning the past five decades. Key metrics include incidence, prevalence, demographic distribution, and subtype-specific trends. Special emphasis is placed on large registry-based studies and retrospective cohort analyses examining temporal changes in age at onset, antibody status, and clinical outcomes. Comparative evaluation of methodological approaches (registry-based vs clinical cohorts) and subgroup stratification (AChR, MuSK, seronegative MG; early vs late onset) is performed to contextualize observed epidemiological variability. Results: Global MG incidence ranges from approximately 2.7 to 61 cases per million person-years, with more robust estimates clustering between 10 and 30 per million, while prevalence has increased up to 25–50 per 100,000 in recent large-scale studies . A consistent temporal increase in prevalence is driven by improved survival and ageing populations. Demographically, MG shows a bimodal age distribution, with early-onset predominance in females and increasing incidence in older males . Recent longitudinal data demonstrate a marked shift toward very-late-onset MG (≥65 years), with median age at onset increasing from ∼35 years in the 1970s to ∼65 years in recent decades. This shift is accompanied by a higher proportion of AChR-antibody-positive disease and increased comorbidities. Subtype variation remains geographically distinct: MuSK-MG is more prevalent in Mediterranean and African populations, whereas juvenile MG is more common in East Asia . Despite increasing prevalence, mortality has declined, with only modestly elevated standardized mortality ratios in treated populations. Conclusion: The epidemiology of MG is undergoing a significant transition characterized by increasing prevalence, ageing patient populations, and evolving subtype distribution. The rise of late- and very-late-onset MG has important implications for disease management, given higher comorbidity burden and treatment-related risks in older patients. These trends likely reflect both improved healthcare systems and true biological changes, including immunosenescence and environmental influences. Future epidemiological research should prioritize standardized methodologies and detailed subgroup analyses to better elucidate etiological mechanisms and guide precision medicine strategies.

Dr. Max Hahn , Dr. Alex Addinsall, Dr. Nicolas Eskesen, Dr. Anitta Kinga Sárvári, Dr. Kasper Andersen, Dr. Alexander Hamilton, Dr. Estrid Pedersen, Dr. Marco Tozzi, Dr. Henrik Hansen, Dr. Urmas Roostalu Gubra, Hørsholm, Denmark Dr. Max Hahn Background: Anatomically precise and quantitative assessment of skeletal muscle volume and morphology remains a major challenge in preclinical research of sarcopenia and related muscle disorders. Conventional readouts, such as the extrapolation of 2D stereological data originating from a single section, as well as whole-body lean mass lack spatial resolution and fail to capture changes in muscle architecture that critically determine muscle function. Rodent models of conditions involving muscle remodelling induced by pharmacological intervention (e.g.,Dexamethasone, Formoterol) aging or obesity (DIO) provide complementary and clinically relevant contexts to evaluate advanced muscle imaging approaches. Here, we characterized a scalable, AI-enabled high-resolution imaging platform based on light-sheet fluorescence microscopy (LSFM) for holistic 3D quantitative assessment of muscle volume, vascularization, innervation, and fibrosis of individual skeletal muscles in the intact mouse hindlimb. Methods: A fully automated pipeline combining optical tissue clearing, autofluorescence- and immunofluorescence-based LSFM, and AI-driven image analysis was established for intact mouse hindlimbs. In pharmacological studies, 12-week-old C57BL/6J mice were treated for 21 days with vehicle, Dexamethasone (IP, QD), or Formoterol (IP, QD). In aged-sarcopenia models, male C57BL/6J mice included young (4 months), aged (13 months), and old (23 months) lean controls, as well as aged DIO mice fed high-fat diet for 13 months. Whole hindlimbs were scanned ex vivo at micrometer resolution and downsampled for analysis. A 2D U-Net–based segmentation approach enabled volumetric quantification of individual muscles. Multidimensional LSFM readouts included muscle volume, fiber-type composition, capillary density, innervation, and fibrosis, complemented by echoMRI, muscle weights, ex vivo contractile function, and conventional histology. Results: The LSFM pipeline enabled reproducible alignment and high-throughput, anatomically precise quantification of individual hindlimb muscles across diverse models. In pharmacological studies, Dexamethasone induced reductions in whole-body lean mass and gastrocnemius weight, whereas Formoterol increased lean mass and gastrocnemius weight, with corresponding changes in 3D muscle volume detectable at micrometer resolution. Aged DIO mice exhibited substantial increases in fat mass with only marginal lean mass gains compared with aged-matched lean controls, accompanied by pronounced alterations in muscle architecture. LSFM-derived 3D metrics bridged the gap between whole-body composition data and histological endpoints, revealing spatially resolved muscle phenotypes not captured by traditional methods. Conclusion: We present a scalable LSFM-based platform for high-resolution, multidimensional 3D assessment of skeletal muscle remodelling across pharmacological, aging, and obesity models. This approach effectively captures dynamic changes in muscle mass, integrates structural and quality-related endpoints, and provides a mesoscopic bridge between in vivo MRI and ex vivo histology. The platform holds strong potential for preclinical drug development, mechanistic studies of muscle biology, and future translational and cross-species applications in sarcopenia and related muscle disorders.

Dr. Tania Garrido-Hernández 1 , Dr. María del Mar Martínez-Salmerón 1 , Dr. Marta Rodríguez-Camacho 1 , Mr. Javier Del-Águila-Mejía 2,3 , Dr. Beatriz Vélez-Gómez 1 1 Torrecárdenas University Hospital, Almería, Spain. 2 2National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain. 3 Epidemiology and Public Health Biomedical Network Research Consortium (CIBERESP), Madrid, Spain Background: Myasthenia gravis (MG) is a chronic autoimmune disorder increasingly affecting older adults, with rising prevalence and comorbidity burden across Europe. However, contemporary nationwide data describing MG-related hospital utilisation in European healthcare systems remain limited. This study examined temporal trends and severity-related hospital outcomes in Spain between 2016 and 2022. Methods: We conducted a retrospective, population-based analysis using the Spanish Minimum Basic Data Set, including all adult hospital episodes with a primary diagnosis of MG (ICD-10-ES G70.00, G70.01). Hospital admissions, day-hospital visits and emergency department (ED) encounters were evaluated. Variables included demographics, markers of disease severity (intensive care unit [ICU] admission and myasthenic crisis), in-hospital mortality and comorbidities. Temporal trends were analysed using Poisson regression. Results: A total of 20,251 MG-related episodes corresponding to 6,308 unique patients were identified. Hospital admissions declined by 2.3% annually, whereas day-hospital and ED utilisation increased markedly from 2018 onwards, particularly among older adults. Despite this shift toward ambulatory management, in-hospital mortality remained low and stable (mean 2.6%). ICU admissions increased from 8.2% to 13.7% of hospitalised patients. Myasthenic crisis accounted for 4.5% of admissions and was strongly associated with ICU utilisation, representing 39% of all ICU stays. Conclusion: MG care in Spain is undergoing a sustained transition toward ambulatory management without evidence of worsening short-term hospital outcomes. Despite an ageing patient population and rising ICU utilisation, in-hospital mortality remained stable, supporting the safety of outpatient-based MG care models. These findings highlight the need for integrated clinical data to inform future healthcare planning in MG.

Dr. Eunbyol Hwang 1 , Assoc. Prof. Jung Hwang Lee 2 1 Department of Neurology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of. 2 2Department of Neurology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of Background: Immune-mediated polyradiculoneuropathies can present with subacute, ascending sensory disturbances that clinically mimic spinal cord disorders. Early recognition is critical to avoid misdiagnosis and delay in appropriate immunomodulatory treatment. We report a case of immune-mediated sensory-predominant polyradiculoneuropathy that initially presented with features suggestive of myelopathy, including ascending sensory loss and spinal root enhancement on magnetic resonance imaging (MRI). Methods: A 36-year-old woman presented with a 2-month history of gradually progressive sensory loss in the right leg, more prominent on the lateral aspect, which had been treated as lumbar disc disease at a local clinic with epidural injection, without improvement. Half a day later, similar sensory loss developed in the left leg. The next day, sensory disturbance ascended to the level of the umbilicus, and shortly thereafter, she developed numbness and tingling in both hands. On admission, she reported hypoesthesia below the upper abdomen and all four limbs, with sensory loss, neuropathic pain, and gait instability. Neurological examination revealed reduced light touch sensation below C6∼C8 dermatomes, with preserved muscle strength and deep tendon reflexes. Spinal MRI demonstrated diffuse enhancement of the rootlets and nerve roots below the T7 level, without evidence of cord compression or intrinsic cord lesion. Cerebrospinal fluid (CSF) analysis revealed normal cell counts (WBC 0, RBC 0) and mildly elevated protein (80.3 mg/dL). Nerve conduction studies (NCS) demonstrated sensory polyneuropathy with relatively preserved motor conduction. The patient was treated with a 5-day course of high-dose intravenous methylprednisolone, followed by outpatient follow-up with oral steroid taper (prednisolone 5 mg) and repeat NCS. Results: After high-dose steroid therapy, her sensory symptoms and gait instability improved significantly, and she was discharged. During outpatient follow-up, clinical symptoms continued to improve, with gradual recovery of sensation in the limbs and trunk. Repeat NCS demonstrated improvement in sensory nerve action potentials compared to the initial study, supporting a favorable response to immunomodulatory treatment. The pattern of ascending sensory loss, spinal root enhancement, and CSF protein elevation without pleocytosis, along with clinical and electrophysiological improvement after steroids, was consistent with an immune-mediated sensory-predominant polyradiculoneuropathy. Conclusion: This case illustrates an immune-mediated, sensory-predominant polyradiculoneuropathy that initially mimicked myelopathy due to ascending sensory loss and spinal root enhancement on MRI. The clinical response to high-dose steroids and improvement on follow-up NCS support an immune-mediated mechanism. In patients presenting with subacute, ascending sensory disturbances, immune-mediated polyradiculoneuropathy should be considered in the differential diagnosis, even when the initial presentation suggests a spinal cord disorder. Early neuroimaging, CSF analysis, and NCS are essential to differentiate between myelopathy and immune-mediated polyradiculoneuropathy and to guide timely immunotherapy.

Dr. Sara Liguori 1 , Dr. Marco Paoletta 2 , Assoc. Prof. Antimo Moretti 1 , Prof. Giovanni Iolascon 1 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy. 2 Department of Mental and Physical Health and Preventive Medicine, University of Campania : “Luigi Vanvitelli”, Naples, Italy Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with an estimated incidence of 1 in 3,000 live births. It is mainly characterized by neurocutaneous manifestations and an increased risk of benign and malignant tumors, but it is a multisystem disorder involving several organs and tissues. NF1 is caused by loss-of-function mutations in the NF1 gene on chromosome 17q11, which encodes neurofibromin, a protein regulating cell proliferation and differentiation through multiple intracellular signaling pathways.¹ Recent evidence indicates that neurofibromin also plays a role in muscle cell growth, bone extracellular matrix formation, and bone metabolism regulation.² Consequently, its dysfunction may contribute to musculoskeletal abnormalities in NF1, including bone dysplasia, hypotonia, and muscle weakness, potentially promoting physical inactivity and reducing quality of life.³ Despite their clinical relevance, musculoskeletal manifestations in NF1 remain poorly investigated. This study aimed to characterize musculoskeletal impairment iin a cohort of adult NF1 patients Methods: This observational study included patients with NF1. Data collected included age, body mass index (BMI), and history of fragility fractures. Muscle strength was assessed using a portable dynamometer, physical performance with the Short Physical Performance Battery (SPPB), and gait parameters with a BTS G-Walk® inertial sensor. Quality of life was assessed using the SF-36, and physical activity using the IPAQ, expressed as weekly metabolic equivalent of task (MET) minutes. Physical activity was classified as “inactive” (2520 MET/week), corresponding to groups 0–2. Bone metabolism was assessed through laboratory tests and DXA (GE Lunar), measuring bone mineral density (BMD) at the lumbar spine (L1–L4), left femoral neck, and total body less head. Results: We recruited 83 patients (37 M; 46 F) with an average age of 40.61 ± 15.45 years and an average BMI of 24.34 ± 4.31 kg/ m2. The mean handgrip strength was 27.94 ± 10.17 kg. On analysis of the level of PA, 17 patients (20.5%) were found to be inactive, 38 patients (45.8%) sufficiently active, and 28 patients (33.7%) active or very active. On comparing the patients stratified by PA, statistically significant differences were found between Group 0 and Group 2 for the three sub-items of the SPPB (p < 0.05). Thirty patients completed the densitometric examination (14 M; 16 F); of these, 19 (63.3%) showed normal mean values for sex and age, 7 had values consistent with a diagnosis of osteopenia (23.3%), while 4 had a diagnosis of osteoporosis/reduced values for sex and age. When comparing the densitometric parameters by level of PA, no statistically significant differences were found between the three groups (p >0.05). Conclusion: Our data provided a musculoskeletal characterization of a cohort of adults with NF1. Although many patients were physically active, muscle strength remained below that of the general population, and bone health was compromised in one-third of the cohort. Promoting regular physical activity is crucial for improving musculoskeletal health in NF1 patients. Future research should focus on long-term effects of physical activity on bone strength in this population.

Dr. Rei Takada 1 , Dr. Taro Matsuoka 1 , Dr. Yosuke Kimura 1 , Dr. Amane Matsuura 1 , Dr. Yosuke Miyamoto 1 , Prof. Masafumi Morimoto 1 , Assoc. Prof. Tomohiro Chiyonobu 2 , Assoc. Prof. Hideki Yoshida 3 , Asst. Prof. Takenori Tozawa 1 1 Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. 2 Department of Molecular Diagnostics and Therapeutics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. 3 Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan Background: Disease-modifying therapies and newborn screening have led to improved survival outcomes in Spinal Muscular Atrophy (SMA). However, a key challenge remains that Survival Motor Neuron (SMN) replacement therapies alone are insufficient for recovering neuromuscular junction (NMJ) dysfunction, which precedes neurodegeneration. Consequently, SMN-independent therapies combined with SMN replacement therapy are gaining attention. We focus on low-density lipoprotein receptor-related protein 4 (Lrp4) as a therapeutic target molecule for restoring NMJ formation abnormalities. Using a Drosophila SMA model, we will verify the ameliorative effect of enhancing Bone Morphogenetic Proteins (BMP) signaling through forced Lrp4 expression on NMJ formation abnormalities. Methods: We utilized a neuron-specific Smn knockdown line by using elav-GAL4 and a compound heterozygous line by crossing two heterozygous mutant alleles, Smn 73Ao which contains a point mutation in YG box and Smn f01109 which is predicted to introduce a premature stop codon. Furthermore, we achieved neuron-specific overexpression of Lrp4 in this Smn compound heterozygote using the GAL4-UAS system. The motor function was evaluated using a crawling assay for larvae and a climbing assay for adults. The immunostaining analysis is performed to assess the morphological abnormalities in NMJ. To assess BMP signaling activity, we measured the fluorescence intensity of phosphorylated Mad (pMad), a downstream effector of the signaling pathway, at the NMJ, the anterior Corner Cell (aCC) motor neuron nuclei and muscle nuclei. Results: In similar to Smn knockdown lines, the Smn compound heterozygotes exhibited loss of motor function in both larvae and adults, morphological abnormalities at the NMJ and reduced expression of pMad suggesting decreased BMP activity. Neuron-specific overexpression of Lrp4 in the Smn compound heterozygotes restored NMJ morphology and BMP activity, although it did not improve motor function. Besides, we found that the expression of pMad was reduced at the aCC motor neuron nuclei and muscle nuclei in the Smn compound heterozygotes. Notably, this reduction was also restored by neuronal-specific Lrp4 overexpression. Conclusion: Our study showed that neuron-specific Lrp4 overexpression can partially rescue the SMA pathology by restoring NMJ morphology through the recovery of impaired BMP signaling in Drosophila SMA model. These results suggest that Lrp4 may be one of the candidate molecules for SMN-independent therapies in SMA and the therapeutic target for other neuromuscular disorders impaired BMP signaling.

Prof. Hyunjin Ju 1 , Prof. Sookin Moon 2 1 Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea, Republic of. 2 Department of Laboratory Medicine, Nowon Eulji Medical Center, Eulji University, Daejeon, Korea, Daejeon, Korea, Republic of Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset neuromuscular disorder caused by short polyalanine expansions in the PABPN1 gene. Although OPMD has been well characterized in certain ethnic populations, genetically confirmed cases in Koreans remain extremely rare, and familial cases have scarcely been reported. Methods: A 68-year-old woman presented with about five years of progressive proximal weakness, mainly difficulty climbing stairs. On neurological examination, bilateral ptosis, dysphagia, and dysarthria with nasal speech were noted. Her accompanying older brother in his 70s exhibited similar symptoms. Detailed family history taking revealed multiple affected individuals across successive generations involving both sexes, suggesting an autosomal dominant inheritance pattern [Figure 1]. Results: Laboratory studies showed normal thyroid function and serum creatine kinase levels (132 U/L). Anti-acetylcholine receptor antibodies and repetitive nerve stimulation were negative. Needle electromyography did not show abnormal denervation potentials or pathological neurogenic/myogenic motor unit potentials. Thigh MRI revealed diffuse fatty replacement predominantly affecting the posterior compartment muscles bilaterally. Targeted next-generation sequencing identified a heterozygous pathogenic duplication in the PABPN1 gene ( NM_004643.3 : c.15_23dup, p.Ala9_Ala11dup) in the proband, confirming the diagnosis of OPMD. Additional genetic analysis was performed on the asymptomatic 41-year-old daughter of the affected brother; the absence of the mutation in this individual was confirmed. Conclusion: This case highlights the critical role of careful neurological examination and deep family history assessment in identifying inherited neuromuscular disorders that may otherwise be misattributed to normal aging. This report expands the clinical and genetic spectrum of OPMD in the Korean population.

Assoc. Prof. Ornella Cappellari 1 , Dr. Raffaella Quarta 1 , Dr. Mitchell Han 2 , Dr. Enrica Cristiano 1 , Dr. Manuel Marinelli 1 , Dr. Vincent Mouly 3 , Dr. Nikolas Gaio 2 , Prof. Annamaria De Luca 1 1 Department of Pharmacy – Drug Sciences, University of Bari “Aldo Moro”, Bari, Italy. 2 BIOND Solutions B.V., Delft, Netherlands. 3 Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France Background: Duchenne muscular dystrophy (DMD) is an X‑linked recessive, muscle‑wasting neuromuscular disorder caused by mutations in the dystrophin gene, leading to progressive muscle degeneration, loss of function, and premature death, with no resolutive cure currently available 1,2 . Preclinical research has traditionally relied on 2D cell cultures and animal models, which partially reproduce human disease complexity and raise important issues in terms of time and ethics. Three‑dimensional, patient‑derived skeletal muscle organoids and muscle‑on‑chip systems have emerged as promising platforms for disease modelling and drug screening, with the high potential in developing patient‑specific models, enabling personalized medicine, and implementing the 3Rs policy by reducing animal use. Methods: In this study, we developed hydrogel‑based skeletal muscle‑on‑chip constructs using three immortalized human myogenic cell lines obtained from the biobank MyoLine: a healthy control line (HWT), a DMD line (HDMD1) from a patient with a stop codon mutation in exon 59, and a DMD line (HDMD2) from a patient carrying an exon 48–50 deletion. Bundles were generated in microchips (BIOND Solutions) using a Matrigel/Geltrex and fibrin hydrogel, seeded at day 0, and cultured under differentiation conditions. Results: Within 24 hours, bundles showed evident compaction, and a progressively organized 3D structure up to day 9 of differentiation. After 9 days of differentiation, HWT, HDMD1, and HDMD2 bundles displayed organized structures capable of eliciting a contractile response to electrical stimulation. Immunostaining for actin and sarcomeric α‑actinin demonstrated the presence of aligned, multinucleated myofibers and revealed the structural complexity and maturation state of the engineered tissues. In a larger series of experiments, fibrin‑based skeletal muscle organoids has been used to independently validate the platform for phenotypic profiling and preclinical applications. This analysis highlighted clear differences in muscle calcium-competent contractility between healthy and dystrophic organoids, particularly in force generation and resistance to fatigue over time. Interestingly, these functional differences tended to attenuate with prolonged culture in a stable physiological environment and in the absence of continuous nerve‑like stimulation, suggesting that a major component of the phenotype may be related to delayed myogenic maturation rather than fixed structural defects alone. This delay in differentiation program was also supported by expression of key myogenesis genes in the three cell-lines derived organoids. Conclusion: Future work will refine the further characterization of the role of genetic background in phenotype and differentiation status and will explore how contraction‑induced stress and/or inflammation can unmask dystrophin‑related alterations in structure and function. Overall, this patient‑derived skeletal muscle‑on‑chip platform represents a feasible tool for disease modelling and preclinical studies in DMD and other rare neuromuscular disorders (supported by PNRR-Mnesys PE_00000006 project). REFERENCES 1 Aartsma‐Rus et al. 2006 2 Mercuri et al. 2019

Assoc. Prof. Utkarsh Dang 1 , Assoc. Prof. Roula Tsonaka 2 , Ms. Chiara Degan 2 , Ms. Rebecca Tobin 1 , Prof. Cristina Al-Khalili Szigyarto 3 , Assoc. Prof. Yuri van der Burgt 2 , Prof. Jordi Diaz Manera 4 , Prof. Michela Guglieri 4 , Assoc. Prof. Pietro Spitali 2 , Prof. Yetrib Hathout 5 1 Carleton University, Ottawa, Canada. 2 Leiden University Medical Center, Leiden, Netherlands. 3 KTH Royal Institute of Technology, Stockholm, Sweden. 4 Newcastle University, Newcastle, United Kingdom. 5 Binghamton University, Binghamton, United States Background: Although newer drugs are gaining approval, steroids remain the most widely available standard of care for Duchenne muscular dystrophy (DMD). Moreover, most newer therapies are used in combination with steroids (prednisone, deflazacort, and vamorolone). Although steroids have proven clinical efficacy, well-known side effects (growth stunting, weight gain, adrenal suppression, bone health, puberty delay, etc.) affect adherence to recommended treatment dosage. In this context, existing literature has established some preliminary serum protein responses to steroids, but there is a paucity of large-scale, untargeted studies. Previous studies of biomarker response to steroids in DMD utilized patient samples from natural history studies, in which age range (and DMD progression) and treatment (type, regimen, lifetime exposure, etc.) may have confounded estimates. With most newer therapies used on a steroidal backbone, and the use of combination therapies likely to increase with time, it’s important to establish how biomarker levels change in response to steroids alone in a previously steroid-naïve population, to better understand response to other therapies (gene therapy, exon skipping therapy, etc.) and synergistic interaction with steroids. Our objectives were to investigate the a) longitudinal response of serum proteins, b) the dose-response between intermittent and daily prednisone, and c) the differential response to daily prednisone vs deflazacort over a shorter (1 year) and longer (up to 3 years) term using serum samples from a well-controlled clinical trial of prednisone and deflazacort in young boys with DMD. Methods: Proteomics profiles were obtained from a Somascan panel of ∼1500 protein targets using sera from 56 boys (4 to <11 years; <8 years at steroid-naïve baseline) with DMD from the FOR-DMD (Clinicaltrials.gov: NCT01603407 ) study. Following pre-processing, longitudinal analysis allowing non-linear response was conducted, analysing both 1-year (appropriate for typical clinical trials) and 2/3 years (appropriate for long-term follow-up) contrasts of within-group and between-group change to establish biomarker response to drug regimens. Results: Biosamples were from 14, 19, and 23 participants from the daily deflazacort, daily prednisone, and intermittent prednisone groups, respectively. Approximately 23%, 14%, and 5% of the protein abundances changed with daily deflazacort, prednisone, and intermittent prednisone, respectively, at year 1 (based on FDR-adjusted p<0.05), capturing proteins reflecting both efficacy and safety aspects. These proportions were all higher at the years 2/3 mark, given longer cumulative steroid exposure. Out of the subset of proteins previously identified as different between pre-treatment and healthy control samples, 22.8% responded to deflazacort at year 1, 16.6% responded to prednisone, and 6.3% responded to intermittent prednisone. Conclusion: We studied the dose-response of serum proteins between intermittent and daily prednisone, and differential response to daily prednisone vs deflazacort in a large-scale, untargeted fashion. We validated some serum proteins previously reported as differentially responsive to prednisone vs deflazacort, but also identified newer differentially responsive biomarkers. Our work may help to better understand the mechanism of action of steroids, the predictive potential of these biomarkers and their importance to accelerated regulatory pathways, help refine therapies, define synergistic interactions between novel treatments and steroids, and potentially use as surrogate/secondary outcomes in trials.

Dr. Karen M. Lynch 1 , Dr. Karissa L. Gable 2 , Dr. Matthew P. Mavor 3 , Dr. Mohammad H. Akhavanfar 3,4 , Dr. Kristen H.E. Beange 4 , Dr. Ryan B. Graham 3 , Dr. Jan C. Schuller 5 , Dr. Alex Seluzhytsky 1 1 Sanofi, Cambridge, MA, United States. 2 Neuromuscular Division, Department of Neurology, Duke University Medical Center, Durham, NC 27710, United States. 3 School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa K1N 6N5, Ontario, Canada. 4 Celestra Health Systems, Ottawa K2K 0G7, Ontario, Canada. 5 Enovalife, Cœur Défense A – 110 Esplanade du Général de Gaulle – 92931 Paris La Défense Cedex, France Background: Biomechanical gait assessments offer an objective alternative to clinical gait evaluations. However, they rely on non-transportable technology, requiring patients to travel and providing infrequent snapshots of walking ability. Using wearable technology, such as insoles, continuous monitoring in free-living conditions becomes possible, enabling development of digital biomarkers that comprehensively describe gait quality. This study aims to develop a digital biomarker that passively assesses gait quality in people with Chronic Inflammatory Demyelinating polyradiculoneuropathy (pwCIDP) using instrumented shoe insoles. Methods: Up to two-hundred mobile pwCIDP will perform 5- to 15-minute walks 3-times per week for 12-months under free-living conditions while wearing insoles (pressure, accelerometer, gyroscope) streaming to a smartphone app; to date, 107 participants have been recruited. First, insole data will undergo human activity recognition; classified ‘walk’ data are segmented into standardized lengths and analyzed for spatiotemporal and sensor waveform features. Participants will undergo remote Inflammatory Neuropathy Cause and Treatment score and Inflammatory Rasch-built Overall Disability scale assessments at six- and three-month intervals, respectively. Meaningful gait features will be derived by correlating with assessment scores and t-tests to identify significant differences from previously collected controls. By training a support vector machine to classify controls vs pwCIDP, a gait composite index score (gCI; 0-100%) will be developed and benchmarked against the most informative features and assessment scores. Locally estimated scatterplot smoothing regressions will be used to identify meaningful trends in gCI scores over time. Results: Data collection is ongoing. Trend analysis for all participants with ≥6 months of walking will be presented; a preliminary gCI will be developed and benchmarked using all recruited participants. Conclusion: Establishing a gCI for pwCIDP will enable longitudinal monitoring of disease progression from free-living walking bouts, reshaping how neurologists may understand and evaluate disease progression (i.e., improvement, worsening, maintenance) and treatment response (i.e., exercise, pharmacological, assistive devices).

Dr. Maria Kovalchuk 1 , Assoc. Prof. Eugenia Druzhinina 2 , Miss Sofya Vorobeva 3 , Miss Evgeniya Anatolyevna Tikhomirova 3 1 Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. 2 Pirogov Russian National Research Medical University, Moscow, Russia. 3 Scientific and Practical Psychoneurological Center named after Z. P. Solovyov, Moscow, Russia Background: Diabetic and chemotherapy-induced polyneuropathies (CIPN) are examples of length-dependent sensory axonal polyneuropathy (PNP). A classic early clinical manifestation of this type of PNP is distal sensory loss in the lower extremities. For instrumental confirmation of this complication, electrodiagnostic testing (nerve conduction studies (NCS)) is performed; the findings typically include a reduction in sensory nerve action potential (SNAP) amplitude. It was previously believed that a decreased sural-to-radial amplitude ratio (SRAR)—i.e., the ratio of sural SNAP amplitude to superficial radial SNAP amplitude—of <0.21 could serve as an early sign of this sensory length-dependent PNP. Methods: We retrospectively analyzed clinical and electrophysiological data from 29 pediatric patients with diabetes mellitus (DM) (16 females and 13 males; median age 16 years, interquartile range [IQR] 13.5–17), 56 adult patients with DM (42 females and 14 males; mean age 60 ± 13.8 years), and 21 pediatric patients receiving chemotherapy (CT). In each group, sensory nerve conduction parameters of the sural and superficial radial nerves were assessed, the sural-to-radial amplitude ratio (SRAR) was calculated, and groups were compared statistically. Patients with a sural sensory nerve action potential (SNAP) amplitude of 0 μV were excluded from the study. Results: In the pediatric DM group, the mean (M) sural sensory nerve action potential (SNAP) amplitude was 14.36 μV (SD ± 5.9), and the mean superficial radial SNAP amplitude was 24.44 μV (SD ± 8); the mean SRAR was 0.64 (SD ± 0.29). Nineteen patients had a DM duration of <10 years, and ten patients had a duration of ≥10 years. No statistically significant differences in SRAR were observed between these subgroups according to disease duration. In the pediatric CT group, the mean sural SNAP amplitude was 12.3 μV (SD ± 4.1), the mean superficial radial SNAP amplitude was 26.6 μV (SD ± 7), and the mean SRAR was 0.59 (SD ± 0.22). The difference in SRAR between pediatric patients with DM and those receiving CT was not statistically significant. In the adult DM group, the mean sural SNAP amplitude was 7.81 μV (SD ± 4.68), the mean superficial radial SNAP amplitude was 20.04 μV (SD ± 9.26), and the mean SRAR was 0.38 (SD ± 0.21). A statistically significant difference in SRAR was found between children and adults with DM. Conclusion: The sural-to-radial amplitude ratio (SRAR) did not differ significantly between pediatric patients with diabetes mellitus (DM) according to disease duration, nor between children with DM and those receiving chemotherapy (CT). It can be hypothesized that, when the sural sensory response (SNAP) is preserved, SRAR does not provide an advantage for detecting early signs of axonal polyneuropathy.

Dr. Diego Lopergolo 1 , Dr. Gianna Berti 1 , Dr. Robert Goodwin 2 , Dr. Francesco Michelassi 3 , Dr. Barbara Risi 4 , Prof. Marina Grandis 5 , Prof. Roberto Massa 6 , Dr. Filippo Maria Santorelli 7 , Dr. Gian Nicola Gallus 1 , Dr. Maria Lucia Valentino 8 , Dr. Flavia Palombo 9 , Dr. Dario Zoppi 10 , Dr. Lucia Ruggiero 10 , Prof. Gabriella Esposito 11 , Dr. Aleksandra Kawka 12 , Dr. Krzysztof Szczałuba 12 , Prof. Francesca Magri 13 , Prof. Stefania Corti 14 , Dr. Marco Savarese 15 , Prof. Massimiliano Filosto 4 , Prof. Alessandro Malandrini 1 , Prof. Nicola De Stefano 1 1 Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. 2 Medical College of Wisconsin, Milwaukee, United States. 3 Department of Neurology, Columbia University Medical Center, New York, United States. 4 NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy. 5 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy. 6 Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy. 7 IRCCS Fondazione Stella Maris, Pisa, Italy. 8 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 9 IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy. 10 Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy. 11 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy. 12 Centre of Excellence for Rare and Undiagnosed Diseases, Medical University of Warsaw, Warsaw, Poland. 13 Neuromuscular Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 14 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 15 Folkhälsan Research Center, Helsinki, Finland Background: The CCDC78 gene was identified approximately ten years ago as a novel candidate gene for autosomal dominant centronuclear myopathy type 4 (CNM4) (Majczenko et al., 2012). Clinical features described in the first reported family included neonatal hypotonia, muscle weakness, myalgias, mild-to-moderate motor impairment, and mild cognitive involvement. More recently, we reported a second family harboring a nonsense CCDC78 variant, providing the first insights into CCDC78 interactors and its putative role in skeletal muscle, with localization of the protein to the sarcoplasmic reticulum (Lopergolo et al., 2024). To date, however, no systematic genotype–phenotype correlation studies have been performed, and this ultrarare muscle disease remains poorly characterized. Methods: To establish genotype–phenotype correlations, we collected clinical, molecular, and histopathological data from 14 patients carrying CCDC78 point mutations. Patients were recruited from nine neuromuscular centers in Italy, Finland, Poland, and the United States. Results: We identified 11 families harboring ten different likely pathogenic germline CCDC78 variants. Age at symptom onset was highly variable. Recurrent clinical features included dropped head syndrome, bilateral scapular winging, and calf hypertrophy. Common histopathological findings on light microscopy were increased internal nuclei, predominance of type I fibers, and core-like areas. Transmission electron microscopy revealed sarcoplasmic reticulum dilatation and mitochondrial abnormalities in several patients. Additional extramuscular findings included atrial structural defects and osteoarticular abnormalities. Conclusion: This study represents the first comprehensive cohort of patients with CCDC78 mutations and significantly expands the clinical and pathological spectrum of CCDC78-related centronuclear myopathy. Our data provide robust support for the pathogenicity of germline CCDC78 variants. Despite marked phenotypic variability, consistent sarcoplasmic reticulum abnormalities on electron microscopy emerge as a potential disease hallmark, offering a valuable diagnostic clue in patients with congenital unresolved neuromuscular disorders.

Dr. Thaïs Tarancón 1 , Dr. Paolo Emilio Alboini 2 , Dr. Silvia Falso 3 , Dr. Rita Frangiamore 4 , Dr. Matteo Gastaldi 5 , Dr. Melania Guida 6 , Dr. Solange Kapetanovic Garcia 7,8 , Dr. Nicasio Rini 9 , Dr. Carmelo Rodolico 10 , Dr. Elena Rossini 11 , Prof. Sabrina Sacconi 12 , Dr. Guilhem Solé 13 , Dr. Karin Annoni 14 , Dr. Kerina Bonar 15 , Dr. Grégory Chollet 16 , Dr. Cristina Lopez 17 , Dr. Patrik Ohagen 18 , Dr. Cassandra Slader 19 1 UCB, Madrid, Spain. 2 Neurology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. 3 Department of Neuroscience, Catholic University of the Sacred Heart, Rome, Italy. 4 Neuroimmunology and Muscle Pathology Unit, IRCCS Carlo Besta Neurological Institute, Milan, Italy. 5 IRCCS Mondino Foundation, Neuroimmunology Research Unit, Pavia, Italy. 6 Neurology Unit, Department of Neurosciences, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 7 ALS and Neuromuscular Unit, Hospital Universitario Basurto, Bilbao, Spain. 8 NAT-RD Research Group, IIS Biobizkaia, Barakaldo, Spain. 9 Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy. 10 Department of Clinical and Experimental Medicine (DIMED), University of Messina, Sicily, Italy. 11 Department of Neurology, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. 12 Université Côte d’Azur, Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France. 13 Centre de Référence des Maladies Neuromusculaires AOC CHU de Bordeaux, Bordeaux, France. 14 UCB, Milan, Italy. 15 UCB, Slough, United Kingdom. 16 UCB, Colombes, France. 17 UCB, Barcelona, Spain. 18 UCB, Uppsala, Sweden. 19 UCB, Brussels, Belgium Background: Generalised myasthenia gravis (gMG) is a rare, chronic, autoimmune disease, characterised by fluctuating muscle weakness. MycarinG (Phase 3, NCT03971422 ) and its open-label extension studies (MG0004 [ NCT04124965 ] and MG0007 [ NCT04650854 ]), showed that the efficacy of rozanolixizumab, a neonatal Fc receptor blocker, was maintained over repeated treatment cycles across multiple myasthenia gravis (MG)-specific outcomes in patients with gMG. Managed Access Programmes (MAPs) enable the use of treatments prior to authorisation for patients with a severe/debilitating/life-threatening condition, where available treatments are deemed inadequate by patients and physicians, and there is no available clinical trial. Here, we describe rozanolixizumab utilisation patterns and patient characteristics in MAPs, initiated under protocolised compassionate use in France, Italy and Spain. Methods: This was an observational, retrospective, longitudinal cohort study of adults with gMG initiating rozanolixizumab treatment in MAPs in France, Italy and Spain between November 2022 and May 2025. The primary objective was to describe baseline demographics and disease characteristics of patients at treatment initiation. Change from baseline in MG Activities of Daily Living (MG-ADL), Garches and MG Quality of Life 15-Item Revised scores were also assessed when available. All analyses were descriptive. Results: Overall, 12 patients from France, 16 from Italy and <5 from Spain were included. Mean (standard deviation [SD]) age was 73.7 (14.6), 53.8 (14.0) and 61.5 (16.5) years, respectively. Most patients were female (58.3%, 87.5% and 50.0%, respectively). Additional data were available for Italy: mean (SD) number of years since initial MG diagnosis was 10.8 (10.6); 43.8% of patients had an MG diagnosis <5 years and baseline (mean [SD]) MG-ADL score was 7.4 (2.6). In the 2 years prior to enrolment, MG crises occurred in 6.3% of patients and MG-related hospitalisations occurred in 43.8%. Prior to enrolment, 56.3% of patients had received pyridostigmine and all patients had received corticosteroids. Treatment outcomes data will be presented in the poster. Conclusion: The baseline characteristics of the patients who entered the rozanolixizumab MAPs were indicative of a population with moderate-to-severe gMG. Funding: UCB.

Dr. Fumiaki Saito 1 , Dr. Masato Inoue 1 , Ms. Miki Ikada 1 , Dr. Shunsuke Kobayashi 1 , Dr. Genta Ito 2 , Dr. Hidetoshi Sakurai 3 , Dr. Yuko Miyagoe-Suzuki 1 1 Department of Neurology, School of Medicine, Teikyo University, Tokyo, Japan. 2 Department of Biomolecular Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan. 3 Department of Clinical Application, Center for iPS Research and Application, Kyoto University, Kyoto, Japan Background: Mutations in the valosin-containing protein ( VCP ) gene cause multisystem proteinopathy (MSP), manifesting as inclusion body myopathy (90%), frontotemporal dementia (30%), ALS (15%), and Paget’s disease of bone (50%). VCP is an AAA-type molecular chaperone that forms a homohexamer and collaborates with many adapter proteins to maintain proteostasis under normal, stress, and disease conditions. To clarify whether there are differences in the types and affinities of VCP-interacting proteins between normal cells and patient cells, we generated VCP-iPS cells and differentiated them into skeletal muscle cells. Methods: We generated iPS cells from a patient carrying c.572G>A (R191Q) missense mutation in the VCP gene. Isogenic control iPS cells were generated by genome editing using homology directed repair. These iPS cells were differentiated into skeletal muscle either by overexpression of MyoD or by an improved EZ-sphere method. Stress granules were induced with sodium arsenite and detected using a G3BP1 antibody. We, further, generated iPS cells with a spot-tag inserted at the C-terminus of the endogenous VCP gene by genome editing. The tagged VCP was pulled-down by Spot-Trap magnetic agarose (Chromotek) after cross-linking with DSP, then analyzed for its interacting proteins by LC-MS. Results: R191Q mutation did not affect the formation of stress granules induced by sodium arsenite in myoblasts differentiated from iPS cells. However, it delayed the stress granules disassembly after removal of arsenite. Spot-Tag pull-down assay identified several VCP-interacting proteins that had not been reported previously, in addition to known VCP adapters. Conclusion: Skeletal muscle cells induced from VCP- iPS cells provide an experimental model suitable for elucidating the molecular pathogenesis of VCP-myopathy, which has been conducted mostly using non-muscle cells or over-expression systems. In fact, using VCP- iPS cells with tagged endogenous VCP, we have successfully identified VCP-interacting proteins in skeletal muscle. We aim to further analyze interacting partners of VCP in patient cells to develop therapeutic strategies.

Dr. Sara Liguori 1 , Dr. Francesca D'Andrea 1 , Dr. Marco Paoletta 2 , Assoc. Prof. Antimo Moretti 1 , Prof. Giovanni Iolascon 1 , Prof. Anna Grandone 3 1 Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples, Italy. 2 Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy. 3 Department of Woman, Child and of General and Specialized Surgery, University of Campania, Naples, Italy Background: X-linked hypophosphatemic rickets (XLH; RC0170) is a rare genetic disorder affecting approximately 1 in 47,000 individuals. It results from inactivating mutations in the PHEX gene on the X chromosome, causing elevated blood level of fibroblast growth factor 23 (FGF23), which increases renal phosphate excretion and reduces 25-hydroxyvitamin D₃ activation. Chronic hypophosphatemia impairs bone mineralization, leading to rickets in childhood and osteomalacia in adulthood. Clinically, XLH is characterized by short stature, skeletal deformities, dental dysplasia, chronic musculoskeletal pain, enthesopathies, and reduced functional mobility. In 2019, the Italian Medicines Agency (AIFA) approved burosumab, an anti-FGF23 monoclonal antibody, demonstrating higher efficacy and improved tolerability than conventional therapy.¹ However, data on muscle strength and functional performance in pediatric patients treated with burosumab remain limited. The present study aimed to characterize this patient cohort using a standardized rehabilitative assessment protocol to guide personalized rehabilitation and monitor long-term treatment response. Methods: Pediatric patients with XLH receiving burosumab were enrolled and underwent a comprehensive clinical and instrumental evaluation. Isometric handgrip strength was measured with a portable Jamar dynamometer, and upper limb manual dexterity assessed with the Nine Hole Peg Test. Spatiotemporal gait parameters were evaluated through the 10-Meter Walking Test, while lower limb power with the Jump test, using the BTS BAIOBIT® wireless inertial sensor. Static balance was examined via the IPODO baropodometric platform and Pediatric Balance Scale (PBS). Body composition was assessed with iDEXA and bioelectrical impedance analysis (BIA), and bone mineral density determined through standard iDEXA densitometry. Fatigue was evaluated with the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™ MFS), including general, sleep/rest, and cognitive domains. Results: Twelve pediatric patients affected by XLH were enrolled (3 males, 9 females; mean age 7.58 ± 3.84 years; mean BMI 18.14 ± 2.33 kg/m²). Ten patients were within normal height ranges, though all fell below expected means for age. Handgrip strength, adjusted for sex and height, was within reference ranges in eight of ten patients. Manual dexterity was preserved in seven of eleven patients, while static balance was maintained in eleven of twelve. In the 10-meter walking test, right and left step cycle quality indexes averaged 90.0 ± 9.55% and 89.5 ± 11.51%. Jump test results showed mean maximum force 0.48 ± 0.22 kN and mean total power 619.72 ± 306.31 W. Baropodometric assessment revealed asymmetrical weight distribution in 50% of patients, with predominant forefoot loading in all (mean right forefoot 78.78 ± 18.15%). Height-adjusted DXA Z-scores were positive. iDEXA revealed appendicular muscle mass below age-adjusted means in seven of nine patients, although within normal limits; BIA showed reduced lean mass in seven of ten. Parent-reported fatigue was clinically significant in two of eleven patients for general fatigue and three of eleven for sleep/rest fatigue, while children reported milder subjective fatigue. Conclusion: Paediatric XLH patients treated with burosumab demonstrated preserved muscle strength, and static balance, with residual deficits in manual dexterity, body composition, and gait parameters. These results support the need for a multidimensional evaluation to devolp personalised rehabilitation programs and monitor treatment efficacy.

Mr. Jonathan Street 1,2 , Dr. Tecla Bonci 3,4 , Dr. Alexander Jakubiec 3,4 , Mr. Adrien Juraver 5 , Dr. Laura Castillo 6 , Dr. Óscar Reyes 6 , Dr. Shibeshish Belachew 5 , Dr. Channa Hewamadduma 7,8 , Dr. Claudia Mazzà 5 1 Academic Unit of Neuromuscular Disorders, Sheffield Teaching Hospitals, Sheffield, United Kingdom. 2 Sheffield Institute of Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom. 3 School of Mechanical, Aerospace and Civil Engineering, Sheffield, United Kingdom. 4 Insigneo Institute, Sheffield, United Kingdom. 5 Indivi AG, Basel, Switzerland. 6 Indivi AG, Córdoba, Spain. 7 Sheffield Teaching Hospitals Foundation Trust, Sheffield, United Kingdom. 8 Sheffield Institute for Translational Neurosciences (SITRAN), University of Sheffield, Sheffield, United Kingdom Background: Facioscapulohumeral muscular dystrophy (FSHD) affects the face, shoulders, trunk, and upper and lower limb muscles with symptoms varying in severity and rate of progression. Despite the increasing number of candidate therapeutics for FSHD from pre-clinical studies, heterogeneity of muscle involvement, shortage of robust FSHD biomarkers, and a lack of responsiveness to change seen in traditional outcome measures challenge the implementation of informative FSHD clinical trials. Wearable sensors are increasingly adopted in neurological and neuromuscular diseases to augment the accuracy of measures recorded during established tests of upper and lower limb motion. This is achieved by transforming sensor data into objective numerical outcomes, called sensor-derived measures (SDMs), which comprehensively quantify the loss of ability and the response to treatment. In this study, we evaluated the feasibility and accuracy of applying such an approach to the data collected with the motion sensors included in a smartphone to assess the shoulders range of motion and muscles fatigability during the execution of an upper limb motor task, designed specifically for capturing relevant aspects of FSHD related functional limitations. Methods: Twelve participants (Sex: 4 female, and 8 male; Age: Mean 48yr (SD 14.9); FSHD Clinical Score (FCS): Mean 7.4 (SD 2.6)) were asked to perform a test called “Traffic Controller”, during which they had to first separately explore their maximum ranges of shoulder flexion and abduction, and then stably hold their arm in front of them at shoulder level for 30s. Tests were repeated twice per side. While performing the motion, participants were asked to hold a phone (iPhone 16e) in their hand. The phone was used to record the sensor motion data (linear accelerations, angular velocities and orientation, sampling rate 50Hz). Besides recording the movement data, the phone provided detailed audio guidance on when and how to perform the various phases of the test. Instructions also included asking participants to keep their arm straight and the phone orientation constant, to ensure consistency between tests. As a preliminary analysis, the maximum angles during the flexion and lateral abduction phases were extracted as SDMs (Figure 1). Their values were compared against those obtained from a marker-based motion capture system (Vicon). Furthermore, the correlation of the SDMs with the FCS was investigated. Results: All participants completed the test without significant burdens. Results supported the feasibility of reliably estimating shoulder maximum flexion (ICC(2,1)=0.95) and abduction angles (ICC(2,1)=0.96) from the phone data. Comparison between the phone and the marker-based systems showed a correlation of 0.76 and 0.83 for the flexion and abduction angles, respectively. The data from both movements appeared to be strongly correlated with the FCS (flexion: right: r=0,79; left r=0.79; abduction: right: r=0,68; left r=0.70). Conclusion: The Traffic Controller proved to be a feasible structured test to estimate shoulder mobility in patients with FSHD using a Smartphone. While the study is still ongoing and further validation is needed to prove their generalisability, these pilot results pave the way for remotely monitoring treatment effects within a clinical trial setting involving patients with FSHD.

Prof. Jae-Young An Department of Neurology, St. Vincent’s hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea, Republic of Background: Ulnar neuropathy is primarily evaluated using nerve conduction studies (NCS). However, patients may continue to experience characteristic clinical symptoms despite normal or only minimally abnormal electrophysiological findings. In such nonlocalizing cases, accurate lesion localization and etiological assessment remain challenging. High-resolution ultrasonography enables direct visualization of peripheral nerve morphology and may provide diagnostic information beyond conventional electrophysiology. Methods: We retrospectively analyzed five patients with clinical features consistent with ulnar neuropathy whose routine NCS were either normal or demonstrated only an isolated reduction in distal ulnar sensory nerve action potential (SNAP) amplitude. Short-segment nerve conduction studies were nonlocalizing in some patients. All patients underwent ultrasonographic evaluation of the ulnar nerve, and one patient was followed longitudinally over a 2.4-year period. Results: Despite persistent ulnar neuropathic symptoms, none of the patients showed consistent lesion localization on NCS. In contrast, ultrasonography identified definite focal structural abnormalities of the ulnar nerve in all cases. Although ultrasonographic abnormalities were consistently detected within the elbow region, the site of maximal cross sectional area (CSA) enlargement varied among patients. Maximal nerve enlargement was observed at different locations along the ulnar nerve within the elbow, including the retrocondylar groove, the medial epicondyle, and the region between the humeral and ulnar heads of the flexor carpi ulnaris, indicating heterogeneity in the location of structural involvement rather than a single predominant site of compression. CSA values ranged from 14 to 36 mm². In one patient with only minimal NCS abnormalities, marked focal nerve enlargement was detected and subsequently confirmed surgically as a schwannoma. In the longitudinally followed patient, a previously observed conduction block resolved spontaneously over time without intervention, whereas ultrasonography demonstrated persistent focal nerve enlargement corresponding to ongoing clinical symptoms. Conclusion: This case series highlights a clear discordance among clinical symptoms, electrophysiological findings, and ultrasonographic localization in ulnar neuropathy. Although limited by the small number of cases, our findings suggest that the inability of NCS to localize pathology, together with the variable distribution of maximal structural abnormalities within the elbow, underscores the essential role of ultrasonography as a complementary diagnostic tool in patients with ulnar symptoms and nonlocalizing or electrophysiologically equivocal NCS.

Prof. Yi-Hua Qiu Nantong University, Nantong, China Background: Parkinson’ s disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN). Our research has demonstrated that the levels of interleukin (IL)-17A are elevated in the SN of rodent models of PD, and that IL-17A accelerates neurodegeneration in PD depending on microglial activation. Furthermore, existing studies indicate that exosomes released by activated microglia may play a significant role as mediators of neurodegeneration in PD. Methods: Herein, we demonstrated that BV-2-derived exosomes were taken up by ventral mesencephalic (VM) dopaminergic neurons, and mediated IL-17A effect of promoting dopaminergic neuronal injury. Results: IL-17A-treated BV-2-derived exosomes altered neuronal miR-7 and SNCA expression and promoted dopaminergic neuronal injury in vitro. Inhibiting BV-2 exosome formation and secretion by GW4869 alleviated dopaminergic neuronal injury. Silencing ciRS-7 in BV-2 altered neuronal miR-7 and SNCA expression and mitigated dopaminergic neuronal injury. Overexpression of ciRS-7 in VM neurons altered neuronal miR-7 and SNCA expression and promoted dopaminergic neuronal injury. Injection with exosomes derived from IL-17A-treated BV-2 altered ciRS-7, miR-7 and SNCA expression in SN in MPTP-intoxicated mice and promoted nigrostriatal dopaminergic neurodegeneration and motor impairment. However, injection with exosomes derived from IL-17A and ciRS-7-shRNA treated BV-2 attenuates the manifestations mentioned above. Conclusion: These findings suggest that microglia-derived exosomal ciRS-7 mediates IL-17A effect of promoting neurodegeneration via miR-7 and SNCA targets and may provide a new paradigm to study the pathology of PD.

Dr. Mehmet Bal 1 , Assoc. Prof. Dilek Agircan 1 , Assoc. Prof. Seyhan Taskin 2 1 Harran University Faculty of Medicine, Department of Neurology, Sanliurfa, Turkey. 2 Harran University Faculty of Medicine, Department of Physiology, Sanliurfa, Turkey Background: Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder characterized by chronic, fluctuating weakness of ocular and skeletal muscles. Oxidative stress has been implicated in MG pathogenesis through damage to acetylcholine receptors (AChRs), which are essential for neuromuscular transmission. Thiol–disulfide homeostasis (TDH) is a dynamic biochemical marker of oxidative stress and has been shown to shift toward oxidation in various neurological disorders, sometimes correlating with disease activity. This study aimed to compare TDH parameters between MG patients and healthy controls and to investigate their association with disease severity and fatigue. Methods: Patients diagnosed with MG and age- and sex-matched healthy controls were enrolled. Serum native thiol (NT) and total thiol (TT) levels (µmol/L) were measured, and disulfide (SS) levels were calculated using the formula SS = (TT − NT) / 2. The ratios SS/NT, SS/TT, and NT/TT were derived. Clinical assessment of MG patients included the MG Activities of Daily Living (MG-ADL) score, MGFA clinical classification, Fatigue Severity Scale (FSS), and Myasthenia Gravis Quality of Life-15 (MG-QoL15). MG phenotype (ocular or generalized), serological status (AChR or MuSK antibodies), disease duration, and current treatments were recorded. Associations between TDH parameters, disease severity, and fatigue were analyzed. Results: A total of 30 MG patients and 27 healthy controls were included. Compared with controls, MG patients exhibited significantly lower NT and TT levels, while SS levels were similar between groups. TDH parameters did not differ significantly according to MG phenotype, serological status, treatment modality, or predefined thresholds for fatigue (FSS ≥36) and quality of life (MG-QoL15 ≥20). However, patients with MG-ADL ≥6 showed significantly lower SS, SS/NT, and SS/TT ratios, along with a significantly higher NT/TT ratio. Correlation analysis demonstrated negative correlations between MG-ADL scores and SS, SS/NT, and SS/TT ratios, and a positive correlation between MG-ADL scores and the NT/TT ratio. No significant correlations were found between TDH parameters and FSS or MG-QoL15 scores, whereas FSS and MG-QoL15 were strongly and positively correlated. Conclusion: MG patients exhibit an altered thiol–disulfide balance characterized by reduced thiol reserves without increased disulfide accumulation, suggesting that oxidative imbalance in MG is primarily driven by thiol depletion. The association between TDH parameters and MG-ADL scores indicates a potential link between oxidative stress and clinical disease severity, independent of MG subtype, serological status, or treatment. In contrast, oxidative stress markers were not associated with fatigue or quality of life. These findings support the role of oxidative stress in MG pathogenesis and suggest that thiol–disulfide homeostasis may serve as a potential biomarker for disease severity, warranting further investigation in larger, longitudinal studies.

Dr. Pietro Emiliano Doneddu 1,2 , Dr. Mazen M. Dimachkie 3 , Dr. Karissa Gable 4 , Dr. Arjun Seth 5 , Dr. Yuyao Sun 6 , Mr. Brien Hawley 7 , Dr. Federico Bonofiglio 8 , Dr. Karen Lynch 9 1 Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele (MI), Italy. 2 Neuromuscular and Neuroimmunology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy. 3 The University of Kansas Hospital, Kansas City, KS, United States. 4 Division of Neuromuscular Medicine, Duke University, Durham, NC, United States. 5 Northwestern Medicine, Chicago, IL, United States. 6 University of Kentucky, Lexington, KY, United States. 7 Clinical Innovation Strategy Implementation, Sanofi, Morristown, NJ, United States. 8 DCVM and EGDS, Sanofi, Cambridge, MA, United States. 9 Sanofi, Cambridge, MA, United States Background: The Inflammatory Neuropathy Cause and Treatment (INCAT) scale is a widely implemented disability measure in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Recent advances in telemedicine, combined with patient-centric care approaches addressing geographic, mobility, and logistical challenges, have driven demand for virtual INCAT assessment to facilitate remote monitoring across clinical trials, registry studies, and routine clinical practice. We aim to evaluate inter-rater reliability of virtual INCAT assessments among multiple assessors and examine systematic agreement between registered nurse (RN)-administered assessments and neuromuscular experts’ evaluations to establish if RN-assessments can reliably replicate expert findings. Methods: As part of the ORBIT-CIDP study ( O bservational, R eal-world, Digital B iomarker, and I ntegrated T reatment Outcomes in CIDP; NCT06968975 ), we conducted a virtual INCAT validation sub-study. ORBIT-CIDP planned to enroll 200 participants with ≥3 months of therapy and residual disability for virtual INCAT assessments by RNs using a telehealth platform. 20 participants were randomly selected at the time of evaluation. These virtual sessions were video recorded with consent and de-identified videos underwent independent INCAT scoring by 7 neuromuscular specialists. Outcomes included 1) general agreement among all experts and scoring reliability, 2) targeted agreement and reliability between RNs and any other expert. Interobserver agreement was measured by Kendall W coefficient, Fleiss kappa, and mean absolute deviation. Interobserver reliability was measured by intraclass correlation coefficients. Pairwise agreement/reliability (RN vs expert) was measured similarly. Results: To be presented during the congress. Conclusion: The ORBIT-CIDP study will provide important evidence on the reliability of virtual INCAT assessments by establishing inter-rater concordance between clinical experts and RNs. If validated, telehealth-based INCAT assessment could transform CIDP patient evaluation by enabling remote monitoring in clinical trials, expanding access in resource-limited settings, and reducing patient burden. This study will lay the groundwork for future studies comparing virtual and in-person assessments to establish virtual INCAT as a reliable and accessible standard of care.

Dr. Gil Wolfe University at Buffalo/SUNY, Buffalo, United States Background: Although relatively rare, thymomas are associated with a variety of autoimmune and paraneoplastic phenomena, with the neuromuscular transmission disorder myasthenia gravis (MG) being the most common. However, a variety of other peripheral and central nervous system disorders have been described in the context of thymoma. Methods: Case series literature was reviewed based on a PubMed search that merged autoimmune and paraneoplastic neurologic disorders with thymoma. Autoantibody associations and therapeutic approaches beyond thymoma resection and systemic tumor management were also reviewed. Results: From the standpoint of neurologic disorders linked to thymoma, MG predominates, representing one-third to one-half of all associations. B2 thymomas are the most common histologic type, and autoantibodies to the acetylcholine receptor are present in nearly all these MG cases. The second most common association is most likely the central nervous system disorder of limbic encephalitis/ encephalomyelitis, associated with autoantibodies to ANNA-1 and Ma2. Cognitive, neuropsychiatric, spinal cord and even peripheral nerve involvement can occur with this syndrome, with immunosuppressive therapy (IST), plasma exchange (PE), intravenous immunoglobulin (IVIg), and B-cell depletion representing the avenues of therapy. Other central nervous system disorders include brainstem encephalitis (ANNA-2 and Ma2 autoantibodies), opsoclonus-myoclonus (ANNA-1 or 2, Ma1 or 2, or Yo autoantibodies), cerebellar degeneration (Yo or ANNA-1 autoantibodies), and neuromyelitis optica (NMO; AQPR, MOG, or ANNA-1 autoantibodies). Management of these disorders is similar to the approach for limbic encephalitis with the exception that C5 complement inhibitors, and anti-IL6 receptor and anti-CD19 agents are approved for NMO. The spectrum of peripheral nervous system disorders associated with thymoma is wide. In addition, to MG, Lambert Eaton myasthenic syndrome (LEMS) associated with the typical autoantibodies to the P/Q voltage-gated calcium channel has been reported with thymoma. Other conditions include cranial and polyneuropathies (GAD, amphiphysin, glycine receptor autoantibodies), autonomic neuropathy (neuronal acetylcholine receptor and CRMP5 autoantibodies), rippling muscle disease (neuronal acetylcholine receptor autoantibodies if thymomatous MG also present), neuromyotonia in the form of either Isaacs’ or Morvan’s syndrome (LGI1/CASPR2 autoantibodies), and inflammatory myopathies including granulomatous myositis. Of note, rippling muscle disease can also be inherited, with caveolin-3 gene mutations, and both stiff person and Morvan’s syndromes do cross over to involve the central nervous system. Beyond the specialized symptomatic and immunotherapy used for MG and LEMS, management of these other disorders typically involves IST, PE and IVIg. Stiff person syndrome can respond to benzodiazepines and anti-spasticity agents such as baclofen, while acetylcholinesterase inhibitors and agents used for orthostatic hypotension such as midodrine can help with autonomic neuropathies. Anti-epileptic agents such as phenytoin and carbamazepine have been used for many years to ameliorate symptoms of muscle stiffness in neuromyotonia. Conclusion: Although thymomas are an uncommon form of neoplasia, they are frequently associated with a wide variety of autoimmune disorders and paraneoplastic syndromes, with the peripheral and central nervous systems often involved. It is important for clinicians to be aware of these disorders so that appropriate chest imaging can be ordered. Although the data on prognosis remains mixed, earlier diagnosis and management of thymoma in general can positively influence survival.

Prof. Hyung-Soo Lee 1 , Assoc. Prof. Jungmin So 2 1 National Medical Center, Seoul, Korea, Republic of. 2 Ansan Hospital, Korea University, Ansan, Korea, Republic of Background: Early detection of diabetic polyneuropathy (DPN) is essential for the prevention and management of complications in type 1 diabetes mellitus (T1DM), as it is in type 2 diabetes mellitus (T2DM). However, the electrophysiologic characteristics of DPN in T1DM—particularly during the subclinical stage—remain less well characterized than those in T2DM. Methods: We retrospectively reviewed the medical records of patients aged 10–19 years with type 1 diabetes mellitus (T1DM) who underwent screening for diabetic polyneuropathy (DPN) in our electrodiagnostic laboratory between January 2022 and February 2024. Patients were excluded if they had a history of hereditary or otherwise known polyneuropathy, conditions associated with an increased risk of polyneuropathy (e.g., specific infections, systemic vasculitis, malignancy, or exposure to chemotherapy), or self-reported sensory or motor symptoms identified through a questionnaire. Motor nerve conduction studies (NCSs) were performed in the median, ulnar, peroneal, and posterior tibial nerves, while sensory NCSs were conducted in the median, ulnar, superficial peroneal, and sural nerves. Diabetic polyneuropathy was diagnosed when two or more independent electrophysiologic parameters exceeded the established reference values. Results: A total of 107 patients were included in the analysis, with a mean age of 17.02 years (range, 10.5–19.3 years); 51 were male, and 56 were female. Of these, 56 patients were diagnosed with diabetic polyneuropathy (DPN), while 51 did not meet the diagnostic criteria. There was no significant difference in mean age between the DPN and non-DPN groups (17.51 vs. 16.12 years, p = 0.648). Although the duration of diabetes tended to be longer in the DPN group, this difference did not reach statistical significance (8.47 vs. 6.98 years, p = 0.176). All patients in the DPN group demonstrated prolonged terminal latency in the ulnar nerve. The next most frequent abnormalities were reduced motor conduction velocity in the distal segment of the ulnar nerve (38.1%), followed by reduced motor conduction velocity in the posterior tibial nerve (23.9%). Additional common abnormalities included reduced sensory conduction velocity and decreased sensory nerve action potential amplitudes in the superficial peroneal and sural nerves, reduced motor conduction velocity in the posterior tibial and peroneal nerves, and prolonged terminal latency in the median nerve, each observed in 19.0% of patients. No abnormal nerve conduction study findings were observed in the non-DPN group. Conclusion: These findings suggest that subclinical DPN in T1DM represents a distinct electrophysiological feature, differing from both overt DPN and subclinical DPN observed in type 2 diabetes mellitus. Therefore, further investigation is warranted to better characterize the electrophysiological features of subclinical diabetic polyneuropathy in this population.

Dr. Ahmet Akpınar 1 , Prof. Eren Gozke 2 1 Kulu State Hospital, Konya, Turkey. 2 University of Health Sciences FSM Training and Research Hospital, Istanbul, Turkey Background: Facioscapulohumeral dystrophy (FSHD) is the third most common muscular dystrophy. It is inherited as autosomal dominant (AD) and affects skeletal muscles. Noonan syndrome (NS) is a genetic disorder characterized by facial dysmorphism, cardiac conduction abnormalities, skeletal anomalies, and clinically variable cognitive deficits, which are inherited as AD. Methods: A 30-year-old male patient was admitted to the neurology clinic with progressive weakness in both arms for several years. The patient had no known chronic disease history. In family history, her older brother had similar symptoms but had no diagnosis. There was no consanguinity between the patient’s parents, and they were completely healthy. Results: In the neurologic examination, he could not squeeze his eyes fully; his lips were prominently protruding forward. His shoulder and arm muscles were atrophic. His bilateral shoulder abduction was 4/5, and forearm flexion was 3/5, other muscle strengths were normal. Scapula alata was seen on the left side. There was no pyramidal sign, cerebellar findings and sensory deficit. In addition, the patient had scoliosis and thoracic deformities. Creatine kinase (CK) was slightly increased (396 U/L). EMG showed widespread myopathic involvement. As a result of the genetic examination of the patient, in the PTPN11 gene, an NM_002834.5 c.781>T(p.L261F) (p.Leu261Phe) (heterozygous) change was detected and evaluated as pathological. This change is a variant associated with NS in the Human Gene Mutation Database. Conclusion: Although neurologic involvement is rare in NS, it is associated with retinitis pigmentosa, neurofibromatosis type 1, and Charcot–Marie–Tooth disease. In addition, Chiari type 2 malformation and Dandy–Walker syndrome reported. Although myopathic involvement has been reported in NS cases, the coexistence of FSHD and NS is revealed for the first time with this case.

Dr. Giorgia Riolo 1,2 , Mr. Franco Salerno 1 , Dr. Alex Vicino 3 , Dr. Marta Cheli 1 , Dr. Sara Gibertini 1 , Dr. Alessandra Ruggieri 1 , Dr. Giada Giunta 1 , Dr. Eliana Iannibelli 1 , Dr. Alessandra Carnazzi 1 , Dr. Lucia Nicolini De Gaetano 1 , Dr. Massimo Costanza 1 , Dr. Silvia Bonanno 1 , Dr. Stefania Marcuzzo 1,4 , Dr. Paola Cavalcante 1 , Dr. Lorenzo Maggi 1 1 Neurology 4 - Neuroimmunology and Neuromuscular Diseases Unit – Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. 2 Ph.D. program in Pharmacological Biomolecular Sciences, Experimental and Clinical, University of Milan, Milano, Italy. 3 Nerve-Muscle Unit – Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 4 Brain-targeted Nanotechnologies (BraiNs) Lab, Joint Research Platform – Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy Background: Inclusion body myositis (IBM) is the most common acquired muscle disease affecting individuals over 45 years of age. Clinically, the disease manifests as a slowly progressive and asymmetric pattern of muscle weakness, predominantly affecting the quadriceps and deep finger flexors. To date, no therapies are available, and most patients ultimately develop severe disability, becoming wheelchair-dependent. Although IBM pathogenesis remains unclear, accumulating evidence supports a role for persistent immune activation in driving muscle fiber damage, and chronic viral infections have been suggested as potential modulators of this process. Among viruses, Hepatitis C virus (HCV) has been associated with several extrahepatic inflammatory and autoimmune manifestations. Of note, higher prevalence of HCV infection has been reported in IBM patients, although the HCV-IBM relationship remains poorly defined. Herein, we explored the inflammatory landscape of IBM muscle, focusing on cytokine/chemokine patterns, immune cell infiltration, and the potential pathogenetic link between viral infections, anti-viral response pathways and muscle degeneration. Methods: This study included treatment-naïve IBM (n=30), non-IBM myopathic patients (immune-mediated necrotizing myopathies, n=15; hereditary myopathies, n=22) and age- and sex-matched healthy controls (HC, n=18). Serum cytokine/chemokine profiling was performed by multiplex immunoassays. Gene expression of eotaxins, their receptor CCR3 and antiviral response mediators was assessed by qPCR in muscles, myoblasts and peripheral blood cells (PBMCs; eotaxins and CCR3 only). Immunofluorescence was used to evaluate immune cell infiltration and localize CCR3 in IBM and control tissues. HCV RNA presence in muscle biopsies from serologically HCV-positive (n=4) and -negative (n=3) IBM patients was analysed by droplet digital PCR (ddPCR) and RNAscope. Results: We revealed a significant increase of eotaxin-1 (CCL11), eotaxin-2 (CCL24) and eotaxin-3 (CCL26) levels in serum of IBM compared to non-IBM myopathic patients and HC, thus delineating an IBM-associated inflammatory chemokine signature. Accordingly, qPCR analysis showed a significant overexpression of CCL24 , CCL26 and CCR3 in muscle tissue and myoblasts, but not in PBMCs, of IBM compared to non-myopathic and non-IBM myopathic subjects. Increased CCR3 expression in IBM muscles was confirmed by immunofluorescence, and the protein mainly co-localized with macrophages and macrophage-enriched regions, thus linking the eotaxin increase with immune system cell infiltration into the muscle. By ddPCR and RNAscope, HCV RNA was detected in 3 out of 4 serologically HCV-positive IBM patients’ muscle, where it was found to co-localize with CCR3-positive infiltrating macrophages, thus suggesting that eotaxins can mediate viral genome entry into the muscle via CCR3. A viral contribution was further supported by qPCR data showing a significant increase in antiviral response genes, including MX1 , Granzyme , TLR3 , TLR7 and interferons, in IBM compared to control muscles. Conclusion: Our findings reveal a previously unknown mechanistic framework through which HCV, or other viral components/nucleic acids, may access muscle tissue, offering a new perspective on the crosstalk between viral infections and muscle chronic inflammation in IBM. Moreover, we highlight a role for the eotaxin-CCR3 axis in mediating immune system cell infiltration and chronic inflammatory pathways contributing to muscle fiber degeneration. These insights improve our understanding of IBM pathogenesis, promising to guide the development of novel, targeted, disease-modifying therapies.

Dr. Sofie Sunebo 1,2 , Dr. Emil Nilsson 3 , Dr. Martin Engvall 3,4 , Dr. Carola Oldfors 5,6,7 , Dr. Yan Shen 8 , Dr. Inger Nennesmo 9 , Dr. Olof Danielsson 2 , Prof. Anders Oldfors 5,6 , Dr. Hanna Appelqvist 1,2 , Dr. Ulrika Lindgren 5,6,10 1 Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. 2 Clinical Department of Neurology in Linköping, Region Östergötland, Linköping, Sweden. 3 Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden. 4 Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. 5 Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. 6 Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden. 7 Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden. 8 Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden. 9 Department of Pathology and Cancer Diagnostics, Karolinska University Hospital Solna, Stockholm, Sweden. 10 Neuromuscular Center, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden Background: Multiple acyl coenzyme A dehydrogenase deficiency (MADD) is a rare disorder of fatty acid metabolism causing a lipid storage myopathy, previously considered solely a genetic disorder, caused by recessive pathogenic variants mainly in the ETFDH gene. In 2024 we reported a strong association between MADD and the antidepressant medicine sertraline (Sunebo et al, Ann. Neurol . 2024). This association has thereafter been corroborated by other reports from different geographical areas. The number of reported patients is still low and more knowledge about sertraline-associated MADD is needed. Methods: A nationwide population-based registry search was conducted to identify adult patients with sertraline-associated MADD in Sweden 2014-2024. Patients with muscle biopsy reports of lipid storage myopathy or biochemical investigations showing acylcarnitine profile suggesting MADD were included. Medical records were retrospectively reviewed. The aim was to increase knowledge of incidence, clinical characteristics, diagnostics and treatment effect in sertraline-associated MADD. Results: We identified 40 (30/10 female/male) patients with sertraline-associated MADD. Median age at symptom onset was 42 years and muscle weakness the most common first symptom. All patients reported muscle symptoms during the disease course. Extra-muscular symptoms, including sensory disturbance (29 patients) and fatigue (18 patients), were common. Most patients had lipid accumulation in muscle fibers, abnormal acylcarnitine profile, myopathic electromyography pattern and elevated creatine kinase. Increased neurofilament light chain was found in six of 13 investigated patients. The length of treatment with sertraline before symptom onset varied between 0.3-20 years and the median dosage of sertraline at diagnosis was 150 mg (range 50-300 mg). Cyanocobalamin, folic acid and proton-pump inhibitors were the most frequent other medications at diagnosis. Five patients carried a heterozygous ETFDH  variant. All patients were treated with riboflavin (median dose 300mg/day). Almost all (38/39) experienced clinical improvement. Acylcarnitine profile improved in all patients (31/31) with available data. The mean incidence of sertraline-associated MADD was 1.24 patients per 100 000 adults receiving sertraline treatment per year. The mean incidence of genetic adult-onset MADD was 0.0077 per 100 000 adult inhabitants per year during the same period. Conclusion: This is the largest cohort of sertraline-associated MADD described so far, expanding the knowledge of clinical characteristics of this disease. Sertraline-associated MADD is an important differential diagnosis in patients with an initial suspicion of for example myasthenia gravis and inflammatory myopathies. New knowledge of first symptoms increases the chances of early detection and treatment, hopefully preventing severe, permanent, iatrogenic damage. No investigational method has a 100% sensitivity, and it is important that patients presenting with muscle symptoms during sertraline therapy undergo adequate evaluation to exclude MADD. Sertraline-associated MADD is much more common than genetic MADD with adult-onset in Sweden. The true incidence of sertraline-associated MADD might be higher since sertraline is a very common medication, used by 3.9% of the adult population in Sweden, and probably only the most severely affected patients undergo sufficient investigation for diagnosis.

Dr. Jakkrit Amornvit 1,2 , Mr. Tharadon Deepracha 3 , Ms. Phuettha Sangrut 3 , Mr. Peerakan Inkhao 3 , Ms. Wanicha Boonyuen 3 , Ms. Benjamat Pensrisirikul 3 , Ms. Supaporn Krittanupong 3 1 Division of Neurology, Department of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. 2 Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3 Chula Neuroscience Center, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand Background: Despite recommendations for annual neuropathy and foot screening, early detection of diabetic distal symmetric polyneuropathy (DSPN) remains inconsistent in routine practice, particularly in high-volume outpatient settings. A key barrier is not the availability of bedside tools, but limited time and a shortage of trained examiners to apply standardized assessments at scale. A workflow-ready screening approach that can be reliably delivered by non-physician healthcare professionals may help close this implementation gap. Methods: We conducted a cross-sectional diagnostic accuracy study at a Thai tertiary hospital. Adults with type 1 or 2 diabetes (n=78, age 30–65) without previously documented neuropathy were enrolled. The Neuropathy Symptom Score (NSS; 15-item symptom questionnaire) and Neuropathy Disability Score (NDS; brief bedside exam of distal sensation and ankle reflexes) were translated into Thai using forward–backward procedures and administered by trained nurses/health staff. A blinded reference standard was performed independently by a neurologist, including standardized neurological examination and nerve conduction studies to determine DSPN. Feasibility (administration time), internal consistency (Cronbach’s α), test–retest and inter-rater reliability, and criterion validity against the reference standard were assessed. Diagnostic performance (sensitivity, specificity, predictive values, AUC) was evaluated for NSS, NDS, and prespecified combined screening rules. Results: The Thai NSS/NDS instruments demonstrated excellent content validity and reliability. NSS showed high internal consistency (α=0.93) and strong 4-week test–retest stability (r=0.84). NDS inter-rater reliability was high (ICC=0.83). DSPN was confirmed in 45% of participants (35/78) by the reference standard; none had been previously diagnosed. Approximately 50% of newly identified DSPN cases were asymptomatic by symptom screening (NSS <3) despite objective distal sensory/reflex deficits on examination and/or nerve conduction studies. NSS and NDS scores were significantly higher in participants with DSPN than those without (mean NDS 5.0 vs 1.8, p90% but missed mild cases. Discrimination was good for both tools (AUC 0.80 for NSS, 0.84 for NDS). Nurses completed NSS/NDS assessments in under 10 minutes. Conclusion: Task-shifted implementation of NSS and NDS by non-physician staff was feasible and showed good diagnostic performance against a blinded neurologist and nerve conduction reference standard for DSPN. The Thai-translated NSS/NDS are reliable and valid, and their use in routine diabetes visits may expand screening coverage, support earlier risk stratification, and facilitate timely preventive care and referral pathways in settings where specialist time is limited.