Unmet Needs in the Care of Patients with Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease: Insights from Germany

Unmet Needs in the Care of Patients with Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease: Insights from Germany | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Unmet Needs in the Care of Patients with Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease: Insights from Germany Katrin Giglhuber, Alix Bertrand, Clarissa Zappe, Ingo Kleiter, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9209675/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare autoimmune disorders. Their true prevalence in Germany is unknown and can only be estimated from heterogeneous international data. Assuming 1–3 cases per 100,000 people for each disease suggests several thousand affected individuals nationwide, yet the German Neuromyelitis Optica Study Group (NEMOS) registry currently holds records of only about 1,000 patients seen in specialised centres. Numbers and care structures outside such facilities remain largely unknown. This survey aimed to assess the current state of NMOSD and MOGAD care in Germany, identify gaps, and inform future care strategies. Methods An online questionnaire was distributed via NEMOS, the German Neurological Society (DGN), the Professional Association of German Neurologists (BVDN), and the German Network for Research on Autoimmune Encephalitis (GENERATE) from March to May 2025. Questions addressed care structures, diagnostics, coding, treatment, guideline use, and practitioners’ needs. Results A total of 104 physicians from all German federal states participated. Half worked in university hospitals, the remainder in other clinics and outpatient settings. Most were specialised in neuroimmunology (70.2%). Many reported an increase in patient numbers for NMOSD (55.8%) and MOGAD (77.4%). Diagnostic practices revealed significant inconsistencies: almost half of the respondents were unaware of their referral laboratory’s antibody assays, and ELISA remained in use despite clear recommendations for cell-based assays. ICD-10 coding varied widely. For first-line therapy of AQP4-antibody-positive NMOSD, off-label rituximab was most frequently used (69.6%), followed by satralizumab (57.1%), ravulizumab (55.4%) and inebilizumab (50.0%). AQP4-antibody-negative NMOSD was mainly treated with rituximab (87.0%). Also in MOGAD, rituximab was frequently used (by 58.9%), yet paediatricians preferred glucocorticoids and intravenous immunoglobulins. 69.9% initiated treatment for MOGAD after the first attack. Notably, 41.8% of physicians reported untreated NMOSD and 64.6% untreated MOGAD patients. Most respondents relied on national guidelines; 43.2% expressed a need for further education and patient information. Conclusions Our findings highlight substantial heterogeneity in the diagnosis and treatment of NMOSD and MOGAD in Germany with potential implications for patient outcomes. This underscores the need for harmonised procedures and targeted educational resources to improve diagnostic reliability, treatment equity, and overall quality of care. NMOSD MOGAD Healthcare Provider Survey Patient Care Real-World Setting. Figures Figure 1 Figure 2 Figure 3 Background Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are two rare autoimmune conditions of the central nervous system, classified as orphan diseases [ 1 ]. The prevalence in Germany is unknown. Estimates based on heterogeneous international data suggest a prevalence of one to three cases per 100,000 people for each condition [ 2 – 4 ], thus affecting 2,000–5,000 individuals in Germany. The German Neuromyelitis Optica Study Group (NEMOS) registry currently holds records of approximately 1,000 NMOSD and MOGAD patients (as of Dezember 2025). This would indicate that fewer than half of the estimated patient population are managed in specialised centres. The care structures for the remaining patients, who are probably treated in general neurological practices or non-specialised clinics, remain largely unknown. Confirming or refuting these estimates is particularly difficult due to inconsistent reporting, a lack of harmonised records and epidemiological data in Germany, and uneven awareness. Unlike other countries, Germany's dual specialist system means care for rare diseases is provided in both hospital-affiliated and community outpatient settings. Consequently, practice-based neurologists can prescribe disease-specific therapies, rather than patients being referred exclusively to specialist centres. In this dual-track system, specialist networks play a crucial role in pooling expertise and raising awareness of rare diseases. One such network in Germany is NEMOS, which comprises more than 60 single centres, primarily university hospitals and centres with a neuroimmunological focus, that have joined due to their specific interest in the care of patients with NMOSD and MOGAD. These conditions present multifaceted challenges for treating physicians. Beyond their rarity, both NMOSD and MOGAD require thorough laboratory and imaging diagnostics, present with unpredictable relapse patterns and the potential for severe disability, and necessitate highly individualised treatment decisions [ 5 – 7 ]. The current NMOSD diagnostic criteria were published ten years ago [ 8 ]. Nevertheless, a recent Latin American survey revealed considerable variation in the application of these criteria among neurologists [ 9 ]. Regarding the diagnosis of MOGAD, the currently recommended criteria were proposed only three years ago and are therefore still very new [ 5 ]. This underscores the evolving nature of these nosological entities and the challenges clinicians face in keeping pace with diagnostic advances. Both aquaporin-4 (AQP4)-antibody-positive NMOSD and MOG-antibody-associated disease are antibody-mediated, and antibody detection plays a crucial role in the diagnostic algorithm. Current international recommendations emphasise the use of cell-based assays (CBAs) for detecting AQP4-IgG and MOG-IgG, as these are more sensitive and specific than other methods, such as ELISA, western blot, or radioimmunoassay [ 10 , 11 ]. For AQP4-IgG, fixed CBAs currently represent the most widely recognised and recommended assay, although live CBAs may further increase sensitivity and are likely to be incorporated into future diagnostic criteria [ 8 , 12 , 13 ]. For MOG-IgG, live CBAs are recommended and widely accepted as the reference standard [ 5 , 14 ]. However, the extent to which these standards are implemented in routine care remains unclear. The therapeutic landscape has also become increasingly complex. Since 2019, four monoclonal antibodies have received approval for the treatment of AQP4-antibody-positive NMOSD: eculizumab, satralizumab, inebilizumab, and ravulizumab [ 15 – 19 ]. While these offer targeted options, they also introduce significant cost disparities compared to the previously standard off-label agent, rituximab. In contrast to AQP4-antibody-positive NMOSD, no therapies are currently approved for AQP4-antibody-negative NMOSD and MOGAD, resulting in treatment strategies that are even more heterogeneous [ 20 , 21 ]. Attempts to analyse shifts in treatment regimens or the general disease burden using statutory health insurance data are hindered substantially by inconsistent and suboptimal ICD-10 coding practices. Although the ICD-10 code G36.0: Neuromyelitis optica [Devic syndrome] is specific to NMOSD, it still might be underused in AQP4-antibody-negative NMOSD or misused in MOGAD due to its direct impact on treatment decisions and drug reimbursement. This non-specificity has significant implications for epidemiological research and clinical practice, potentially leading to patient misidentification or exclusion, an underestimation of disease prevalence, and an inability to accurately assess treatment patterns and effectiveness [ 22 , 23 ]. In view of these uncertainties, there is an unmet need to better understand the "real-world" management of patients with NMOSD and MOGAD. The primary goal of this survey was to evaluate the current state of care in Germany across different institutional settings, to identify diagnostic and therapeutic gaps, and to inform future educational and healthcare strategies. Methods Ethics The survey was done within the framework of the project “NUTSEN: New therapies for rare diseases like NMOSD”, which has been approved by the Ethics Committee of the Technical University of Munich, Germany (Reference 2024-599-S-NP). Questionnaire Design The questionnaire was designed and implemented using the online platform LamaPoll [ 24 ]. Depending on the individual response path, participants were presented with between 8 and 55 items across four main domains: General care structures – place of work, neuroimmunological expertise and patient numbers, Diagnosis – diagnostic procedures, antibody testing and ICD-10 coding, Therapy – treatment approaches and monitoring, and Resources – applied guidelines, training, patient support services and practitioners’ needs. In addition, two case examples were included to explore expertise in diagnostic procedures. Several items allowed multiple responses, and some were conditionally displayed depending on prior answers. The full questionnaire can be found in the supplementary material (Suppl. 1). Data acquisition The survey was conducted between March and May 2025. A link to the questionnaire was disseminated to physicians via NEMOS, the German Neurological Society (DGN), the Professional Association of German Neurologists (BVDN) and the German Network for Research on Autoimmune Encephalitis (GENERATE), with recipients encouraged to further share the invitation with colleagues. Responses were collected anonymously, and no personally identifiable information was obtained. Data analysis Participants who indicated that they were a neurologist or neuro-paediatrician and who had completed the initial two survey questions (concerning the federal state and place of work) were included in the analysis. Participants who did not complete the survey were identified at each question and excluded from subsequent analyses stepwise; the respective sample size is reported for each question. Analyses were based on the remaining valid sample size. Descriptive statistics were used to summarise participants’ demographics and survey responses, including mean, median, and range where appropriate. Free-text comments were reviewed, and relevant content was abstracted for analysis. Figures were generated using R (version 4.4.3). Results Study cohort Between March and July 2025, a total of 127 participants initiated the survey, of whom 104 were included in the analysis. They represented all 16 German federal states, with the highest proportions from North Rhine-Westphalia (21/104, 20.2%) and Bavaria (20/104, 19.2%), reflecting the number of inhabitants. Half of the respondents (54/104, 51.9%) were affiliated with university hospitals, 17.3% (18/104) with other clinics, and 30.8% (32/104) with individual or group practices and medical care centres (Fig. 1 ). A neuroimmunological focus was reported by 70.2% (73/104), half of which (39/73, 53.4%) were working at a NEMOS centre. General Care Structures Of the respondents, 78.6% (77/98) reported treating NMOSD patients, of whom 88.3% (68/77) primarily managed adults and 11.4% (9/77) primarily children. Caseload varied considerably, with approximately one third (28/77, 36.4%) serving as primary physician for only 1–3 patients, while 18.2% (14/77) managed twenty patients or more. Most respondents (58/77, 75.9%) had been treating NMOSD patients throughout their clinical careers, while 24.7% (19/77) reported starting only after the emergence of treatment options. 55.8% (43/77) observed increasing NMOSD case numbers, primarily attributable to enhanced referrals and diagnostic awareness. 73.5% (72/98) reported treating MOGAD patients, with 84.7% (61/72) primarily managing adults and 15.3% (11/72) primarily children. Caseload distribution was comparable to NMOSD, with 41.7% (30/72) managing only 1–3 patients and 13.9% (10/72) managing twenty patients or more. (Neuro-)Paediatricians reported caring for proportionally higher numbers of MOGAD patients compared with adult neurologists. Regarding MOGAD patient numbers, a rising trend was reported by 76.4% (55/72). Among the respondents, 42.9% (42/98) reported transferring NMOSD and MOGAD patients to specialised centres for a second opinion or for an annual study visit as part of the NEMOS national cohort study. Most non-referrers were already based at NEMOS centres (35/56, 62.5%) and university hospitals (45/56, 80.4%). Diagnosis Laboratory testing The vast majority of respondents (77/84, 91.7%) reported diagnosing NMOSD and MOGAD patients themselves. Amongst these, 44.0% (33/75) reported testing patients with any first manifestation of an autoimmune disorder of the central nervous system for antibodies against AQP4 and MOG, whereas the others restricted testing to patients with clinical or imaging features typical of NMOSD or MOGAD. The majority (64/75, 85.3%) routinely tested for both antibodies in parallel. When asked about the referral laboratory used for antibody testing, 24.0% (18/75) of respondents were unaware which laboratory they used (“decision made by the routine laboratory”), and the other 76.0% (57/75) named a wide range of laboratories, ranging from major reference centres to in-house facilities (Table 1 ). Table 1 Antibody testing. Laboratory used for AQP4- and MOG-antibody testing % (n/N) Do not know; samples sent to routine laboratory Name a wide range of laboratories (free text) 24.0 (18/75) 76.0 (57/75) Know method used by referral laboratory for AQP4-antibody testing % (n/N) No 46.7 (35/75) Yes 53.3 (40/75) If yes, which method : % (n/N) Fixed CBA 67.5 (27/40) Live CBA 15.0 (6/40) ELISA 10.0 (4/40) Stepwise: ELISA / fixed CBA / live CBA 7.5 (3/40) Know method used by referral laboratory for MOG-antibody testing % (n/N) No 41.9 (31/74) Yes 58.1 (43/74) If yes, which method : % (n/N) Fixed CBA 51.2 (22/43) Live CBA 37.2 (16/43) ELISA 9.3 (4/43) Stepwise: ELISA / fixed CBA / live CBA 2.3 (1/43) Questions and response options concerning antibody testing. Responses reported as percentage (n/N) of total. Aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), cell-based assay (CBA). Regarding the assay used at their referral laboratory for AQP4-antibody detection, half of the respondents (40/75, 53.3%) reported knowing the method, whereas the other half (35/75, 46.7%) did not. Amongst those aware of the assay, the majority used the recommended CBAs (fixed: 27/40 (67.5%), live: 6/40 (15.0%)), but nevertheless, 17.5% (7/40) reported using an ELISA or stepwise approaches that started with ELISA. Notably, of those unaware of the method, 85.7% (30/35) still diagnosed and treated NMOSD patients, and only about half (19/35, 54.3%) referred their patients to specialised centres for a second opinion. For MOG-antibody testing, 58.1% (43/74) stated that they knew which assay was used. Among those practitioners, 51.2% (22/43) reported the use of a fixed CBA, 37.2% (16/43) a live CBA, and 11.6% (5/43) an ELISA or stepwise approach. Almost all respondents (68/73, 93.2%) indicated that they would re-test in cases of persisting clinical suspicion of NMOSD or MOGAD in patients with initially negative results. When re-testing, 66.2% (45/68) used the same assay, 51.5% (35/68) also employed alternative serum testing approaches, and 36.8% (25/68) included cerebrospinal fluid testing. Most commonly, re-testing was performed after 3–6 months (47/68, 69.1%) or following a second attack (35/68, 51.5%). ICD-10 Coding The majority of respondents (61/77, 79.2%, Fig. 2 ) coded AQP4-antibody-positive NMOSD as G36.0: Neuromyelitis optica [Devic syndrome] according to ICD-10. 18.2% (14/77) did not perform coding on their own. Coding practices for AQP4-antibody-negative NMOSD were more heterogeneous: fewer than two-thirds (44/77, 57.1%) used G36.0 , with many also applying G04.8: Other encephalitis, myelitis and encephalomyelitis , G35.-: Multiple sclerosis [Encephalomyelitis disseminata] , G36.8/G36.9: Other specified acute disseminated demyelination/Acute disseminated demyelination, unspecified , or G37.8/G37.9: Other specified demyelinating diseases of central nervous system/Demyelinating disease of central nervous system, unspecified . For MOGAD, the codes G04.8 and G37.8/G37.9 were used by around one third of respondents (26/77 and 29/77). Fewer applied G36.0, G35.- and G36.8/G36.9. Therapy Of 77 respondents, 58 (75.3%) reported initiating or switching therapies themselves, all of whom were able to administer intravenous treatments. AQP4-antibody-positive NMOSD For first-line treatment of AQP4-antibody-positive NMOSD, 69.6% (39/56) reported using rituximab, 57.1% (32/56) satralizumab, 55.4% (31/56) ravulizumab, 50.0% (28/56) inebilizumab, 30.4% (17/56) eculizumab and 23.2% (13/56) oral glucocorticoids (Fig. 3 A). When asked for their preferred therapy, 13 of 36 respondents (36.1%) named rituximab. For second-line therapy in AQP4-antibody-positive NMOSD, inebilizumab was preferred (31/52, 59.6%), followed by ravulizumab and satralizumab (each by 28/52, 51.9%, Fig. 3 B). Escalation of treatment was reported to be required in an average of 15.4% of cases. With respect to rituximab, 77.2% (44/57) reported using it off-label in AQP4-antibody-positive NMOSD when reimbursement was granted, with most of them applying for coverage themselves. Regarding complement inhibitors, most respondents (40/53, 75.5%) initiated therapy with ravulizumab as their routine first-line option. In addition, 28.1% (16/57) indicated switching all patients previously treated with eculizumab to ravulizumab. AQP4-antibody-negative NMOSD For the first-line treatment of AQP4-antibody-negative NMOSD, the majority reported using rituximab (47/54, 87.0%), followed by azathioprine (20/54, 37.0%) and oral glucocorticoids (13/54, 24.1%, Fig. 3 C). All respondents used rituximab off-label for AQP4-antibody-negative NMOSD when reimbursement was granted. Escalation therapy was reported to be required in an average of 16.9% of cases. For these patients, tocilizumab was the most used second-line agent (25/50, 50.0%), followed by rituximab (22/50, 44.0%, Fig. 3 D). While 58.2% (39/67) reported treating all their (AQP4-antibody-positive and -negative) NMOSD patients, 41.8% (28/67) also had untreated cases, of which one-third (10/28, 35.7%) reported exclusively AQP4-antibody-negative untreated patients. MOGAD Around two-thirds of respondents (39/56, 69.6%) initiated treatment for MOGAD after the first attack, regardless of whether they were primarily treating children (6/9, 66.7%) or adults (33/45, 73.3%). Several free-text responses reflected individualized treatment approaches depending on attack severity, recovery, and antibody titres. For MOGAD first-line treatment, rituximab (33/56, 58.9%) was most frequently used, followed by oral glucocorticoids (22/56, 39.3%), intravenous immunoglobulins (IVIG), and azathioprine (each by 21/56, 37.5%, Fig. 3 E). For MOGAD second-line therapy, practitioners applied rituximab (29/56, 51.8%), tocilizumab (27/56, 48.2%), and IVIG (26/56, 46.4%, Fig. 3 F). Among nine respondents who primarily treated paediatric MOGAD patients, oral glucocorticoids and IVIG were the preferred first-line treatments (applied each by 4/9, 44.4%), while IVIG (5/9, 55.6%) and rituximab (4/9, 44.4%) dominated second-line therapy. 64.6% of respondents (42/65) had MOGAD patients without current therapy, whereas the other 35.4% (23/65) treated all their patients. Monitoring The majority of respondents (66/75, 88.0%) used the Expanded Disability Status Scale (EDSS) for clinical monitoring. In addition, 64.0% (48/75) assessed visual function, and 53.3% (40/75) walking ability. Paediatricians reported using tests adapted to the child’s developmental stage. Regarding MR diagnostics, 18.1% (13/72) reported performing imaging only at diagnosis and during attacks, whereas 81.9% (59/72) indicated routine imaging, most commonly on an annual basis. Resources To guide treatment decisions for NMOSD and MOGAD, most respondents (48/56, 85.7%) indicated relying on the national guidelines of the DGN, followed by recommendations of NEMOS (46/56, 82.1%) and presentations or discussions at specialist conferences (44/56, 78.6%). Awareness of patient self-help organizations was limited, with only 41.9% (31/74) reporting knowledge of such resources. When asked about additional needs to support the diagnosis and management of NMOSD and MOGAD, 43.2% (38/88) expressed a demand for further resources. The most frequently mentioned priorities were education and training (particularly online formats, and content tailored to paediatric NMOSD/MOGAD), patient information materials, and structured guidance, including updated recommendations, improved networking, and greater laboratory transparency. Case examples Case #1 concerned a 39-year-old female patient with a medical history of optic neuritis and myelitis, who was now exhibiting signs of paraparesis and bowel dysfunction, with longitudinal, extensive spinal cord involvement on MRI (Table 2 ). Most respondents (63/67, 94.0%) correctly identified that this patient met dissemination in space criteria for NMOSD diagnosis and recognised that the patient met the IPND 2015 diagnostic criteria even in the case of negative antibody findings (62/65, 95.4%). However, divergent opinions emerged when respondents were asked to consider a modified scenario without a history of optic neuritis but with prolonged visual evoked potentials, in which case 40.3% (27/67) erroneously deemed this sufficient to meet the criteria. Table 2 Case #1 . CASE VIGNETTE (1 of 2) • 39-year-old woman • History of optic neuritis in the right eye (confirmed by ophthalmologist); history of myelitis with residual deficits • Current symptoms: paraparesis of the legs, bowel dysfunction • Brain MRI: unremarkable • Spinal cord MRI: T2-hyperintense lesion at level T1-T8 with contrast enhancement Does this patient meet dissemination in space criteria for NMOSD diagnosis (according to the IPND 2015 Criteria)? % (n/N) Yes 94.0 (63/67) No 6.0 (4/67) If the prior optic neuritis were absent, but visual evoked potentials of the right eye were prolonged (despite absence of clinical symptoms in that eye), would the NMOSD diagnostic criteria be met? % (n/N) Yes 40.3 (27/67) No 59.7 (40/67) Based on the above information, does this patient meet the criteria for NMOSD diagnosis (according to the IPND 2015 Criteria if she is AQP4-IgG-seronegative? % (n/N) No, this patient does not have a core clinical characteristic of NMOSD. 0 No, although this patient presents with a core clinical characteristic of NMOSD, since she is AQP4-IgG-seronegative. 3.1 (2/65) Yes, provided there is no better explanation, because she has a core clinical characteristic of NMOSD, a history of other core clinical characteristics, and the required supporting MRI findings. 95.4 (62/65) No, this patient presents with a core clinical characteristic of NMOSD, but meets neither dissemination in space nor dissemination in time criteria and therefore does not have NMOSD. 1.5 (1/65) Description of Case #1, questions and response options. Responses reported as percentage (n/N) of total. Correct response options are underlined. Case #2 involved a 28-year-old female patient with a history of bilateral optic neuritis without residuals (Table 3 ). The patient subsequently presented with new vision loss and pain in the right eye, accompanied by bilateral longitudinally extensive optic nerve involvement on MRI. Almost all respondents (63/65, 96.9%) correctly concluded that MOG antibody testing should be performed alongside AQP4 antibody testing for this clinical presentation. Given borderline-positive MOG-IgG serology (titre 1:32) and negative AQP4-IgG, the majority (51/64, 79.7%) of neurologists diagnosed the patient with MOGAD in line with the current criteria [ 5 ]. Table 3 Case #2. CASE VIGNETTE (2 of 2) • 28-year-old woman • History of bilateral optic neuritis without residual deficits • Current symptoms: recurrent visual deterioration in the right eye, pronounced pain with eye movement • Brain MRI: bilateral longitudinally extensive T2-hyperintense optic nerves, otherwise unremarkable • Spinal cord MRI: unremarkable Would you test this patient for MOG antibodies? % (n/N) Yes, because bilateral optic neuritis excludes the diagnosis of multiple sclerosis. 0 No, the absence of residual deficits from prior optic neuritis suggests the diagnosis of multiple sclerosis. 0 No, this clinical presentation is more typical of NMOSD and I only test for AQP4 antibodies. 0 Yes, in combination with testing for AQP4 antibodies. 96.9 (63/65) No, because a diagnosis of MOGAD could not be made due to the absence of dissemination in space. 3.1 (2/65) Does this patient meet the current diagnostic criteria for MOGAD if the MOG-IgG titre is only borderline positive with 1:32? % (n/N) No, because she has only one core clinical event of MOGAD. 1.6 (1/64) No, although she has a core clinical event of MOGAD, since she lacks supporting clinical or radiologic features. 14.1 (9/64) Yes, provided she is AQP4-IgG-seronegative and alternative diagnoses have been excluded, because she has a core clinical characteristic of MOGAD with required supporting MRI findings. 79.7 (51/64) No, she demonstrates a core clinical event with supporting MRI findings of NMOSD, so MOGAD diagnostic criteria should not be applied. 4.7 (3/64) Description of Case #2, questions and response options. Responses reported as percentage (n/N) of total. Correct response options are underlined. Discussion The results of our survey on the current management of NMOSD and MOGAD in Germany exemplify the shortcomings in the handling of rare neurological diseases: Despite the availability of clear diagnostic criteria and the emergence of new medications, substantial disparities and unmet needs persist in routine clinical practice. Moreover, it emphasizes once again the challenges of accurately depicting the real world of rare disease management in the face of a paucity of rapport, consistency and knowledge. Responder characteristics reflecting Care Structures and Specialist Engagement There are around 6,700 ambulatory neurological practitioners in Germany and the number of DGN members exceeds 13,500 [ 25 , 26 ]. A total of 127 individuals responded to the survey advertisement. With approximately one-third of neurologists managing small patient cohorts and fewer than one-fifth regularly treating twenty patients or more, both inside and outside the university setting, this small cohort should be representative of German neurology, covering different experience levels based purely on caseload. Nevertheless, given that more than two thirds reported a neuroimmunological focus, we can assume that particularly engaged specialists were aware of and interested in participating at this survey. Only a small proportion of our respondents who practise outside reference centres did not refer their patients to specialised centres, yet many other practitioners without referral networks may not have been available for the survey or simply never heard about it. It is impossible to quantify the magnitude of this selection bias, but it is likely to be substantial. The Antibody-Testing Problem The most striking finding of our study was the low knowledge and precision regarding antibody testing. The NMOSD and MOGAD communities rigorously advocate for CBA, increasingly supported by studies suggesting even superior sensitivity with live versus fixed cells [ 11 , 13 , 14 ]. Whilst countries such as France maintain reference networks with centralised antibody testing, Germany so far lacks a standardised diagnostic infrastructure. Multiple laboratories offer AQP4- and MOG-IgG testing using heterogeneous assay methods without general standardisation or quality benchmarks. Consequently, guideline recommendations remain unevenly adopted across centres. Some respondents referred samples to their "routine laboratory" without knowing whether or where they were transferred onward or which method was used. Of those who were aware of their referral laboratory, only half could specify the assays used, and a concerning minority still reported using ELISA. As antibody status is crucial for diagnosis, treatment selection and prognosis in NMOSD and MOGAD, inaccurate results from suboptimal testing methods can compromise the entire therapeutic process, potentially from the very first step [ 27 ]. This raises another difficult-to-investigate question: How many patients with NMOSD and MOGAD may be misclassified and consequently receive incorrect treatment due to diagnostic error? Coding as the Blind Spot of Health Services Research The ICD-10 coding analysis revealed a differentiated, but ultimately problematic picture. In most cases, AQP4-antibody-positive NMOSD was coded accurately. However, AQP4-antibody-negative NMOSD was coded correctly far less frequently, and for MOGAD, for which there is no specific ICD-10 code yet, practitioners employed entirely heterogeneous coding strategies. This is more than just an administrative inconvenience. Claims-based analyses, increasingly used as the basis for health services research and cost-effectiveness evaluations, depend entirely on coding accuracy. If coding for these diseases is already so inconsistent, the epidemiological and economic analyses derived from such data will be systematically biased. Application of Diagnostic Criteria The short case examples showed that practitioners generally applied the current NMOSD diagnostic criteria correctly - although specific scenarios, such as subclinical latency delays in visually evoked potentials, can seemingly lead to misinterpretation, as was found in the aforementioned survey by the Latin American colleagues [ 9 ]. Diagnosing MOGAD with borderline antibody titres proved substantially more challenging. This is unsurprising, given that MOGAD is a more recent nosological entity than NMOSD, and the diagnostic criteria are less well established [ 5 ]. Rock-solid Rituximab Rituximab remains a solid rock in the therapy landscape in Germany across all three conditions, which is significant from both clinical and economic perspectives. In AQP4-antibody-negative NMOSD, rituximab is widely used. In AQP4-antibody-positive NMOSD, it remains a preferred treatment option despite the introduction of new medications. This is unsurprising and implicitly validates the efficacy and safety of this off-label drug over a period of around two decades [ 28 – 30 ]. For MOGAD, however, the situation is more nuanced, revealing an instructive gap between guideline recommendations and clinical practice. Recent data suggest that MOGAD patients treated with rituximab experience less favourable outcomes compared to those receiving IVIG [ 31 ], with rituximab showing similar efficacy to azathioprine [ 32 ], but this is not yet reflected in our real-world data. The persistent predominance of rituximab in clinical practice also highlights a critical question in the context of the orphan drug debate: if cost-effective, established off-label therapies are effective, then the added value of new, more expensive medications must be demonstrated not only in clinical trials but also under real-world conditions. However, prospective, randomized, head-to-head comparisons between new drugs and rituximab are still pending. Future implications and suggestions Taken together, our findings reveal a clear need for education, standardisation, and harmonisation of diagnostic and therapeutic procedures across the neurological community. Following our real-world insights from Germany, we suggest: building awareness of state-of-the-art antibody-testing in laboratories incorporating guidance on the relevance of correct ICD-10-coding into guidelines establishing educational and training programs, including open case discussion rounds, to keep practitioners up-to-date and encourage cooperation. Furthermore, our results indicate a systemic gap that extends far beyond NMOSD and MOGAD. Crucially, these issues cannot be resolved by medical disciplines alone; they require investment in systems, and a rethinking of 'innovation' in the management of rare diseases. Conclusions Our findings emphasise the urgent need for standardised laboratory procedures, harmonised ICD-10 coding, closer collaboration between specialist centres, general neurological practitioners and laboratories, and targeted educational initiatives to improve the consistency and quality of care for patients with NMOSD and MOGAD in Germany. Abbreviations Aquaporin-4 (AQP4) Cell-based assay (CBA) Expanded Disability Status Scale (EDSS) German Network for Research on Autoimmune Encephalitis (GENERATE) German Neurological Society (DGN) Intravenous immunoglobulin (IVIG) Myelin oligodendrocyte glycoprotein (MOG) Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) Neuromyelitis optica spectrum disorder (NMOSD) Neuromyelitis Optica Study Group (NEMOS) Professional Association of German Neurologists (BVDN) Declarations Ethics approval and consent to participate The survey was done within the framework of the project “NUTSEN: New therapies for rare diseases like NMOSD”, which has been approved by the Ethics Committee of the Technical University of Munich, Germany (Reference 2024-599-S-NP). The survey design did not necessitate informed consent procedures. Consent for publication Not applicable. Availability of data and materials The dataset generated and/or analysed during the current study are not publicly available due to local regulations concerning data protection but are available from the corresponding author on reasonable request. Competing interests KG received reimbursement of travelling expenses from UCB, Nexstim and Viatris. She has received personal fees for advisory boards from Viatris. AlB has nothing to declare. CZ received reimbursement of travelling expenses from UCB. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, GlaxoSmithKline, Hexal, Juvisé Pharmaceuticals, Merck, Neuraxpharm, Roche/Chugai, Sanofi, and Viatris. IA received research grants, speaking honoraria and travel support from Argenx, Alexion, Amgen, Roche, Sanofi and Merck. AcB receives funding from the Innovationsausschuss of the German Federal Joint Committee (G-BA; grant 01VSF23040) and from the German Federal Ministry of Research, Technology and Space (BMFTR; grant 01ZZ2505A). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, CSL Behring, Horizon/Amgen, Merck, Neuraxpharm, Novartis, and Roche, and his institution has received compensation for clinical trials from Ad Scientiam, Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. Funding This project was supported by a grant from the German Federal Joint Committee / Innovation Fund (G-BA; project NUTSEN, funding code 01VSF23040). Authors' contributions KG: conceptualization, methodology, software, investigation, validation, data curation, analysis, writing - original draft, writing - review & editing, visualisation AlB: investigation, validation, data curation, writing - review & editing CZ: investigation, validation, data curation, writing - review & editing IK: conceptualization, methodology, validation, writing - review & editing IA: conceptualization, methodology, validation, writing - review & editing AB: conceptualization, methodology, investigation, validation, data curation, analysis, writing - original draft, writing - review & editing, supervision, project administration Acknowledgements We thank all participants of our survey and the DGN, BVDN and GENERATE for their support. References Orphanet an online rare disease and orphan drug database. Copyright, INSERM 1999. https://orpha.net . Accessed 17 January 2026. Hor, J. Y., Asgari, N., Nakashima, I., Broadley, S. A., Leite, M. I., Kissani, N., et al. 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(2023). Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Annals Of Neurology , 93 (6), 1053–1068. 10.1002/ana.26626 Pittock, S. J., Berthele, A., Fujihara, K., Kim, H. J., Levy, M., Palace, J., et al. (2019). Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. New England Journal Of Medicine , 381 (7), 614–625. 10.1056/NEJMoa1900866 Traboulsee, A., Greenberg, B. M., Bennett, J. L., Szczechowski, L., Fox, E., Shkrobot, S., et al. (2020). Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. The Lancet Neurology , 19 (5), 402–412. 10.1016/s1474-4422(20)30078-8 Yamamura, T., Kleiter, I., Fujihara, K., Palace, J., Greenberg, B., Zakrzewska-Pniewska, B., et al. (2019). Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. New England Journal Of Medicine , 381 (22), 2114–2124. 10.1056/NEJMoa1901747 Kümpfel, T., Giglhuber, K., Aktas, O., Ayzenberg, I., Bellmann-Strobl, J., Haussler, V., et al. (2023). Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. Journal Of Neurology . 10.1007/s00415-023-11910-z Stögbauer, J., Schegerer, V., Klein, C., Pawlitzki, M., Meuth, S. G., Aktas, O., et al. (2025). Therapeutic approaches in adults with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A review of current evidence. Autoimmun Rev , 103970. 10.1016/j.autrev.2025.103970 Gmuca, S., Hardy, D. I., Narula, S., Stoll, S., Harris, J., Zhao, Y., et al. (2020). Validation of claims-based diagnoses of adult and pediatric neuromyelitis optica spectrum disorder and variations in diagnostic evaluation and treatment initiation. Mult Scler Relat Disord , 37 , 101488. 10.1016/j.msard.2019.101488 Knapp, R. K., Hardtstock, F., Wilke, T., Maywald, U., Deiters, B., Schneider, S., et al. (2022). Evaluating the Economic Burden of Relapses in Neuromyelitis Optica Spectrum Disorder: A Real-World Analysis Using German Claims Data. Neurol Ther , 11 (1), 247–263. 10.1007/s40120-021-00311-x 2007–2026 LIBL LamaPoll [Internet]. Berlin: LamaPoll; © 2007–2026. https://www.lamapoll.de . Accessed 15 January 2025. DGN German Neurological Society. https://www.dgn.org . Accessed 15 December 2025. National Association of Statutory Health Insurance Physicians - Facts and Figures. https://www.kbv.de/infothek/zahlen-und-fakten . Accessed 15 December 2025. Kister, I., & Paul, F. (2015). Pushing the boundaries of neuromyelitis optica: does antibody make the disease? Neurology , 85 (2), 118–119. 10.1212/wnl.0000000000001749 Damato, V., Evoli, A., & Iorio, R. (2016). Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-analysis. JAMA Neurol , 73 (11), 1342–1348. 10.1001/jamaneurol.2016.1637 Dong, G. Y., Meng, Y. H., & Xiao, X. J. (2022). A meta-analysis on efficacy and safety of rituximab for neuromyelitis optica spectrum disorders. Medicine (Baltimore) , 101 (36), e30347. 10.1097/md.0000000000030347 Zéphir, H., Bernard-Valnet, R., Lebrun, C., Outteryck, O., Audoin, B., Bourre, B., et al. (2015). Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. Journal Of Neurology , 262 (10), 2329–2335. 10.1007/s00415-015-7852-y Bilodeau, P. A., Vishnevetsky, A., Molazadeh, N., Lotan, I., Anderson, M., Romanow, G., et al. (2024). Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. Multiple sclerosis (Houndmills Basingstoke England) , 30 (3), 357–368. 10.1177/13524585241226830 Şen, S., Kürtüncü, M., Demir, S., Gündüz, T., Demirel, E., Tütüncü, M., et al. (2025). Comparative efficacy of rituximab versus azathioprine in the treatment of MOG antibody-associated disease (MOGAD). Journal Of Neuroimmunology , 407 , 578686. 10.1016/j.jneuroim.2025.578686 Additional Declarations Competing interest reported. KG received reimbursement of travelling expenses from UCB, Nexstim and Viatris. She has received personal fees for advisory boards from Viatris. AlB has nothing to declare. CZ received reimbursement of travelling expenses from UCB. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, GlaxoSmithKline, Hexal, Juvisé Pharmaceuticals, Merck, Neuraxpharm, Roche/Chugai, Sanofi, and Viatris. IA received research grants, speaking honoraria and travel support from Argenx, Alexion, Amgen, Roche, Sanofi and Merck. AcB receives funding from the Innovationsausschuss of the German Federal Joint Committee (G-BA; grant 01VSF23040) and from the German Federal Ministry of Research, Technology and Space (BMFTR; grant 01ZZ2505A). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, CSL Behring, Horizon/Amgen, Merck, Neuraxpharm, Novartis, and Roche, and his institution has received compensation for clinical trials from Ad Scientiam, Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. Supplementary Files wantednmosdandmogadsupplementary20260314.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 28 Apr, 2026 Reviews received at journal 28 Apr, 2026 Reviews received at journal 26 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 25 Mar, 2026 Submission checks completed at journal 25 Mar, 2026 First submitted to journal 24 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9209675","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614778391,"identity":"caaaa60c-a452-4244-9b32-7d4d1995b379","order_by":0,"name":"Katrin Giglhuber","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIie3PsWrDMBCA4RMGTTFazwTaVxCYBgrGeRUZgddunlMKlyW0a5YOfYNOwWOKQZNJVm8leC5k7ZTGdgPpcG3HQvWDBBL6kATg8/3BsJvMcUgICMQMQPX78jsSnIgYSES/IUOfRLsfSDTfuv2uhPRePVEblslN/Lq4eoYiYcl4ZINlVoMl3M3jsM6vV240aWCTs+QCbAAZgZX4QuOQKj3piKCKJ6r9Qg46pp4c+IfhcEsq1W1H1lrLnqz57y/b+EjQSBQUPdZWo8uLxmwsS3CbteKdkunlQ+XwrUy1uqtWzb5IWXKS2QzN2dow586bguJf7/P5fP+8D6d7To/nruEjAAAAAElFTkSuQmCC","orcid":"","institution":"TUM University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Katrin","middleName":"","lastName":"Giglhuber","suffix":""},{"id":614778392,"identity":"f2ab4e63-fa36-487a-9fcf-906272202517","order_by":1,"name":"Alix Bertrand","email":"","orcid":"","institution":"TUM University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alix","middleName":"","lastName":"Bertrand","suffix":""},{"id":614778393,"identity":"4dc24405-4899-47ef-8c54-28b649c12ef3","order_by":2,"name":"Clarissa Zappe","email":"","orcid":"","institution":"TUM University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Clarissa","middleName":"","lastName":"Zappe","suffix":""},{"id":614778395,"identity":"a6da2f00-f757-4307-b0d9-76787bca4382","order_by":3,"name":"Ingo Kleiter","email":"","orcid":"","institution":"Marianne-Strauss-Klinik","correspondingAuthor":false,"prefix":"","firstName":"Ingo","middleName":"","lastName":"Kleiter","suffix":""},{"id":614778398,"identity":"99718cbf-bdf5-446e-b2bb-595d6f497b29","order_by":4,"name":"Ilya Ayzenberg","email":"","orcid":"","institution":"Ruhr University Bochum, St. Josef Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ilya","middleName":"","lastName":"Ayzenberg","suffix":""},{"id":614778401,"identity":"3f6fddc7-9552-4a80-90fe-5b7bfa54fc9d","order_by":5,"name":"Achim Berthele","email":"","orcid":"","institution":"TUM University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Achim","middleName":"","lastName":"Berthele","suffix":""}],"badges":[],"createdAt":"2026-03-24 09:23:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9209675/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9209675/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105984193,"identity":"466552c7-e00f-4497-8325-1648acd97ff2","added_by":"auto","created_at":"2026-04-02 07:13:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114206,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParticipants’ affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDonut chart showing the distribution of participants across different affiliations (% of total; N=104).\u003c/strong\u003e Each colour represents a different institution type: University Hospital, Other Clinic, Medical Care/Neuro Centre, Group Practice, and Private Practice (see legend).\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9209675/v1/68c22d819122a68736e2d10c.png"},{"id":105984194,"identity":"332e2acb-0209-4b92-ad6e-3aa44bc2d979","added_by":"auto","created_at":"2026-04-02 07:13:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":35017,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eICD-10 coding practices\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICD-10 code selections for AQP4-antibody-positive NMOSD (A), AQP4-antibody-negative NMOSD (B), and MOGAD (C). \u003c/strong\u003eBars indicate the absolute number of responses (of N=77 respondents) with each colour representing a different ICD-10 code (see legend). G04.8: Other encephalitis, myelitis and encephalomyelitis, G35.-: Multiple sclerosis [Encephalomyelitis disseminata], G36.0: Neuromyelitis optica [Devic syndrome], G36.8/G36.9: Other specified acute disseminated demyelination/Acute disseminated demyelination, unspecified, G37.8/G37.9: Other specified demyelinating diseases of central nervous system/Demyelinating disease of central nervous system, unspecified. Multiple selections per participant were permitted. For AQP4-antibody-positive NMOSD no respondent selected G36.8/G36.9 (A, zero-height bar).\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9209675/v1/e2ac61b3fab39a20bb808a01.png"},{"id":105984192,"identity":"371cfc38-e86a-46b8-a4df-9468eb5fef77","added_by":"auto","created_at":"2026-04-02 07:13:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":88427,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImmunotherapy choices\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrug selections for first-line and second-line treatment in AQP4-antibody-positive NMOSD (A, B), AQP4-antibody-negative NMOSD (C, D), and MOGAD (E, F).\u003c/strong\u003e Bars represent absolute numbers of responses (of N=56 respondents), with each colour representing a different drug: Cortisone, Azathioprine, Mycophenolate Mofetil, IVIG, Rituximab, Inebilizumab, Eculizumab, Ravulizumab, Tocilizumab, and Satralizumab (see legend). Multiple selections per participant were permitted. Zero-height bars represent drugs with no reported use.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9209675/v1/43bc57fb150c5300297784d2.png"},{"id":106094821,"identity":"1e71b46a-aae2-4308-9f6c-730f92de0af1","added_by":"auto","created_at":"2026-04-03 11:43:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1863772,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9209675/v1/f4d3c25b-3ab6-44d3-a25f-7209daef2d19.pdf"},{"id":105984191,"identity":"112f9cc9-faf4-43bb-b88f-11d07f4d738d","added_by":"auto","created_at":"2026-04-02 07:13:24","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25790,"visible":true,"origin":"","legend":"","description":"","filename":"wantednmosdandmogadsupplementary20260314.docx","url":"https://assets-eu.researchsquare.com/files/rs-9209675/v1/889aa713da4c1049bf2cc9c1.docx"}],"financialInterests":"Competing interest reported. KG received reimbursement of travelling expenses from UCB, Nexstim and Viatris. She has received personal fees for advisory boards from Viatris.\n\nAlB has nothing to declare.\n\nCZ received reimbursement of travelling expenses from UCB.\n\nIK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, GlaxoSmithKline, Hexal, Juvisé Pharmaceuticals, Merck, Neuraxpharm, Roche/Chugai, Sanofi, and Viatris.\n\nIA received research grants, speaking honoraria and travel support from Argenx, Alexion, Amgen, Roche, Sanofi and Merck.\n\nAcB receives funding from the Innovationsausschuss of the German Federal Joint Committee (G-BA; grant 01VSF23040) and from the German Federal Ministry of Research, Technology and Space (BMFTR; grant 01ZZ2505A). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, CSL Behring, Horizon/Amgen, Merck, Neuraxpharm, Novartis, and Roche, and his institution has received compensation for clinical trials from Ad Scientiam, Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme.","formattedTitle":"Unmet Needs in the Care of Patients with Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease: Insights from Germany","fulltext":[{"header":"Background","content":"\u003cp\u003eNeuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are two rare autoimmune conditions of the central nervous system, classified as orphan diseases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence in Germany is unknown. Estimates based on heterogeneous international data suggest a prevalence of one to three cases per 100,000 people for each condition [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], thus affecting 2,000\u0026ndash;5,000 individuals in Germany. The German Neuromyelitis Optica Study Group (NEMOS) registry currently holds records of approximately 1,000 NMOSD and MOGAD patients (as of Dezember 2025). This would indicate that fewer than half of the estimated patient population are managed in specialised centres. The care structures for the remaining patients, who are probably treated in general neurological practices or non-specialised clinics, remain largely unknown. Confirming or refuting these estimates is particularly difficult due to inconsistent reporting, a lack of harmonised records and epidemiological data in Germany, and uneven awareness.\u003c/p\u003e \u003cp\u003eUnlike other countries, Germany's dual specialist system means care for rare diseases is provided in both hospital-affiliated and community outpatient settings. Consequently, practice-based neurologists can prescribe disease-specific therapies, rather than patients being referred exclusively to specialist centres. In this dual-track system, specialist networks play a crucial role in pooling expertise and raising awareness of rare diseases. One such network in Germany is NEMOS, which comprises more than 60 single centres, primarily university hospitals and centres with a neuroimmunological focus, that have joined due to their specific interest in the care of patients with NMOSD and MOGAD.\u003c/p\u003e \u003cp\u003eThese conditions present multifaceted challenges for treating physicians. Beyond their rarity, both NMOSD and MOGAD require thorough laboratory and imaging diagnostics, present with unpredictable relapse patterns and the potential for severe disability, and necessitate highly individualised treatment decisions [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe current NMOSD diagnostic criteria were published ten years ago [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Nevertheless, a recent Latin American survey revealed considerable variation in the application of these criteria among neurologists [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Regarding the diagnosis of MOGAD, the currently recommended criteria were proposed only three years ago and are therefore still very new [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This underscores the evolving nature of these nosological entities and the challenges clinicians face in keeping pace with diagnostic advances.\u003c/p\u003e \u003cp\u003eBoth aquaporin-4 (AQP4)-antibody-positive NMOSD and MOG-antibody-associated disease are antibody-mediated, and antibody detection plays a crucial role in the diagnostic algorithm. Current international recommendations emphasise the use of cell-based assays (CBAs) for detecting AQP4-IgG and MOG-IgG, as these are more sensitive and specific than other methods, such as ELISA, western blot, or radioimmunoassay [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. For AQP4-IgG, fixed CBAs currently represent the most widely recognised and recommended assay, although live CBAs may further increase sensitivity and are likely to be incorporated into future diagnostic criteria [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For MOG-IgG, live CBAs are recommended and widely accepted as the reference standard [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the extent to which these standards are implemented in routine care remains unclear.\u003c/p\u003e \u003cp\u003eThe therapeutic landscape has also become increasingly complex. Since 2019, four monoclonal antibodies have received approval for the treatment of AQP4-antibody-positive NMOSD: eculizumab, satralizumab, inebilizumab, and ravulizumab [\u003cspan additionalcitationids=\"CR16 CR17 CR18\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. While these offer targeted options, they also introduce significant cost disparities compared to the previously standard off-label agent, rituximab. In contrast to AQP4-antibody-positive NMOSD, no therapies are currently approved for AQP4-antibody-negative NMOSD and MOGAD, resulting in treatment strategies that are even more heterogeneous [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAttempts to analyse shifts in treatment regimens or the general disease burden using statutory health insurance data are hindered substantially by inconsistent and suboptimal ICD-10 coding practices. Although the ICD-10 code \u003cem\u003eG36.0: Neuromyelitis optica [Devic syndrome]\u003c/em\u003e is specific to NMOSD, it still might be underused in AQP4-antibody-negative NMOSD or misused in MOGAD due to its direct impact on treatment decisions and drug reimbursement. This non-specificity has significant implications for epidemiological research and clinical practice, potentially leading to patient misidentification or exclusion, an underestimation of disease prevalence, and an inability to accurately assess treatment patterns and effectiveness [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn view of these uncertainties, there is an unmet need to better understand the \"real-world\" management of patients with NMOSD and MOGAD. The primary goal of this survey was to evaluate the current state of care in Germany across different institutional settings, to identify diagnostic and therapeutic gaps, and to inform future educational and healthcare strategies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e The survey was done within the framework of the project \u0026ldquo;NUTSEN: New therapies for rare diseases like NMOSD\u0026rdquo;, which has been approved by the Ethics Committee of the Technical University of Munich, Germany (Reference 2024-599-S-NP).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eQuestionnaire Design\u003c/h3\u003e\n\u003cp\u003eThe questionnaire was designed and implemented using the online platform \u003cem\u003eLamaPoll\u003c/em\u003e [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Depending on the individual response path, participants were presented with between 8 and 55 items across four main domains:\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eGeneral care structures \u0026ndash; place of work, neuroimmunological expertise and patient numbers,\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eDiagnosis \u0026ndash; diagnostic procedures, antibody testing and ICD-10 coding,\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTherapy \u0026ndash; treatment approaches and monitoring, and\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eResources \u0026ndash; applied guidelines, training, patient support services and practitioners\u0026rsquo; needs.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003cp\u003eIn addition, two case examples were included to explore expertise in diagnostic procedures. Several items allowed multiple responses, and some were conditionally displayed depending on prior answers. The full questionnaire can be found in the supplementary material (Suppl. 1).\u003c/p\u003e\n\u003ch3\u003eData acquisition\u003c/h3\u003e\n\u003cp\u003eThe survey was conducted between March and May 2025. A link to the questionnaire was disseminated to physicians via NEMOS, the German Neurological Society (DGN), the Professional Association of German Neurologists (BVDN) and the German Network for Research on Autoimmune Encephalitis (GENERATE), with recipients encouraged to further share the invitation with colleagues. Responses were collected anonymously, and no personally identifiable information was obtained.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eParticipants who indicated that they were a neurologist or neuro-paediatrician and who had completed the initial two survey questions (concerning the federal state and place of work) were included in the analysis. Participants who did not complete the survey were identified at each question and excluded from subsequent analyses stepwise; the respective sample size is reported for each question. Analyses were based on the remaining valid sample size. Descriptive statistics were used to summarise participants\u0026rsquo; demographics and survey responses, including mean, median, and range where appropriate. Free-text comments were reviewed, and relevant content was abstracted for analysis. Figures were generated using R (version 4.4.3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy cohort\u003c/h2\u003e \u003cp\u003eBetween March and July 2025, a total of 127 participants initiated the survey, of whom 104 were included in the analysis. They represented all 16 German federal states, with the highest proportions from North Rhine-Westphalia (21/104, 20.2%) and Bavaria (20/104, 19.2%), reflecting the number of inhabitants. Half of the respondents (54/104, 51.9%) were affiliated with university hospitals, 17.3% (18/104) with other clinics, and 30.8% (32/104) with individual or group practices and medical care centres (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A neuroimmunological focus was reported by 70.2% (73/104), half of which (39/73, 53.4%) were working at a NEMOS centre.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eGeneral Care Structures\u003c/h3\u003e\n\u003cp\u003eOf the respondents, 78.6% (77/98) reported treating NMOSD patients, of whom 88.3% (68/77) primarily managed adults and 11.4% (9/77) primarily children. Caseload varied considerably, with approximately one third (28/77, 36.4%) serving as primary physician for only 1\u0026ndash;3 patients, while 18.2% (14/77) managed twenty patients or more. Most respondents (58/77, 75.9%) had been treating NMOSD patients throughout their clinical careers, while 24.7% (19/77) reported starting only after the emergence of treatment options. 55.8% (43/77) observed increasing NMOSD case numbers, primarily attributable to enhanced referrals and diagnostic awareness.\u003c/p\u003e \u003cp\u003e73.5% (72/98) reported treating MOGAD patients, with 84.7% (61/72) primarily managing adults and 15.3% (11/72) primarily children. Caseload distribution was comparable to NMOSD, with 41.7% (30/72) managing only 1\u0026ndash;3 patients and 13.9% (10/72) managing twenty patients or more. (Neuro-)Paediatricians reported caring for proportionally higher numbers of MOGAD patients compared with adult neurologists. Regarding MOGAD patient numbers, a rising trend was reported by 76.4% (55/72).\u003c/p\u003e \u003cp\u003eAmong the respondents, 42.9% (42/98) reported transferring NMOSD and MOGAD patients to specialised centres for a second opinion or for an annual study visit as part of the NEMOS national cohort study. Most non-referrers were already based at NEMOS centres (35/56, 62.5%) and university hospitals (45/56, 80.4%).\u003c/p\u003e\n\u003ch3\u003eDiagnosis\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory testing\u003c/h2\u003e \u003cp\u003eThe vast majority of respondents (77/84, 91.7%) reported diagnosing NMOSD and MOGAD patients themselves. Amongst these, 44.0% (33/75) reported testing patients with any first manifestation of an autoimmune disorder of the central nervous system for antibodies against AQP4 and MOG, whereas the others restricted testing to patients with clinical or imaging features typical of NMOSD or MOGAD. The majority (64/75, 85.3%) routinely tested for both antibodies in parallel.\u003c/p\u003e \u003cp\u003eWhen asked about the referral laboratory used for antibody testing, 24.0% (18/75) of respondents were unaware which laboratory they used (\u0026ldquo;decision made by the routine laboratory\u0026rdquo;), and the other 76.0% (57/75) named a wide range of laboratories, ranging from major reference centres to in-house facilities (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibody testing.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLaboratory used for AQP4- and MOG-antibody testing\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e% (n/N)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDo not know; samples sent to routine laboratory\u003c/p\u003e \u003cp\u003eName a wide range of laboratories (free text)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.0 (18/75)\u003c/p\u003e \u003cp\u003e76.0 (57/75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKnow method used by referral laboratory for AQP4-antibody testing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.7 (35/75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.3 (40/75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eIf yes, which method\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFixed CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.5 (27/40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLive CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.0 (6/40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eELISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0 (4/40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStepwise: ELISA / fixed CBA / live CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.5 (3/40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKnow method used by referral laboratory for MOG-antibody testing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.9 (31/74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.1 (43/74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eIf yes, which method\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFixed CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.2 (22/43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLive CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.2 (16/43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eELISA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3 (4/43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStepwise: ELISA / fixed CBA / live CBA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3 (1/43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eQuestions and response options concerning antibody testing.\u003c/b\u003e Responses reported as percentage (n/N) of total. Aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), cell-based assay (CBA).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding the assay used at their referral laboratory for AQP4-antibody detection, half of the respondents (40/75, 53.3%) reported knowing the method, whereas the other half (35/75, 46.7%) did not. Amongst those aware of the assay, the majority used the recommended CBAs (fixed: 27/40 (67.5%), live: 6/40 (15.0%)), but nevertheless, 17.5% (7/40) reported using an ELISA or stepwise approaches that started with ELISA. Notably, of those unaware of the method, 85.7% (30/35) still diagnosed and treated NMOSD patients, and only about half (19/35, 54.3%) referred their patients to specialised centres for a second opinion.\u003c/p\u003e \u003cp\u003eFor MOG-antibody testing, 58.1% (43/74) stated that they knew which assay was used. Among those practitioners, 51.2% (22/43) reported the use of a fixed CBA, 37.2% (16/43) a live CBA, and 11.6% (5/43) an ELISA or stepwise approach.\u003c/p\u003e \u003cp\u003eAlmost all respondents (68/73, 93.2%) indicated that they would re-test in cases of persisting clinical suspicion of NMOSD or MOGAD in patients with initially negative results. When re-testing, 66.2% (45/68) used the same assay, 51.5% (35/68) also employed alternative serum testing approaches, and 36.8% (25/68) included cerebrospinal fluid testing. Most commonly, re-testing was performed after 3\u0026ndash;6 months (47/68, 69.1%) or following a second attack (35/68, 51.5%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eICD-10 Coding\u003c/h2\u003e \u003cp\u003eThe majority of respondents (61/77, 79.2%, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) coded AQP4-antibody-positive NMOSD as \u003cem\u003eG36.0: Neuromyelitis optica [Devic syndrome]\u003c/em\u003e according to ICD-10. 18.2% (14/77) did not perform coding on their own.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCoding practices for AQP4-antibody-negative NMOSD were more heterogeneous: fewer than two-thirds (44/77, 57.1%) used \u003cem\u003eG36.0\u003c/em\u003e, with many also applying\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eG04.8: Other encephalitis, myelitis and encephalomyelitis\u003c/em\u003e,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eG35.-: Multiple sclerosis [Encephalomyelitis disseminata]\u003c/em\u003e,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eG36.8/G36.9: Other specified acute disseminated demyelination/Acute disseminated demyelination, unspecified\u003c/em\u003e, or\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cem\u003eG37.8/G37.9: Other specified demyelinating diseases of central nervous system/Demyelinating disease of central nervous system, unspecified\u003c/em\u003e.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFor MOGAD, the codes \u003cem\u003eG04.8\u003c/em\u003e and \u003cem\u003eG37.8/G37.9\u003c/em\u003e were used by around one third of respondents (26/77 and 29/77). Fewer applied \u003cem\u003eG36.0, G35.- and G36.8/G36.9.\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTherapy\u003c/h2\u003e \u003cp\u003eOf 77 respondents, 58 (75.3%) reported initiating or switching therapies themselves, all of whom were able to administer intravenous treatments.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAQP4-antibody-positive NMOSD\u003c/h2\u003e \u003cp\u003eFor first-line treatment of AQP4-antibody-positive NMOSD, 69.6% (39/56) reported using rituximab, 57.1% (32/56) satralizumab, 55.4% (31/56) ravulizumab, 50.0% (28/56) inebilizumab, 30.4% (17/56) eculizumab and 23.2% (13/56) oral glucocorticoids (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). When asked for their preferred therapy, 13 of 36 respondents (36.1%) named rituximab.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor second-line therapy in AQP4-antibody-positive NMOSD, inebilizumab was preferred (31/52, 59.6%), followed by ravulizumab and satralizumab (each by 28/52, 51.9%, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Escalation of treatment was reported to be required in an average of 15.4% of cases.\u003c/p\u003e \u003cp\u003eWith respect to rituximab, 77.2% (44/57) reported using it off-label in AQP4-antibody-positive NMOSD when reimbursement was granted, with most of them applying for coverage themselves.\u003c/p\u003e \u003cp\u003eRegarding complement inhibitors, most respondents (40/53, 75.5%) initiated therapy with ravulizumab as their routine first-line option. In addition, 28.1% (16/57) indicated switching all patients previously treated with eculizumab to ravulizumab.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eAQP4-antibody-negative NMOSD\u003c/h2\u003e \u003cp\u003eFor the first-line treatment of AQP4-antibody-negative NMOSD, the majority reported using rituximab (47/54, 87.0%), followed by azathioprine (20/54, 37.0%) and oral glucocorticoids (13/54, 24.1%, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). All respondents used rituximab off-label for AQP4-antibody-negative NMOSD when reimbursement was granted.\u003c/p\u003e \u003cp\u003eEscalation therapy was reported to be required in an average of 16.9% of cases. For these patients, tocilizumab was the most used second-line agent (25/50, 50.0%), followed by rituximab (22/50, 44.0%, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003eWhile 58.2% (39/67) reported treating all their (AQP4-antibody-positive and -negative) NMOSD patients, 41.8% (28/67) also had untreated cases, of which one-third (10/28, 35.7%) reported exclusively AQP4-antibody-negative untreated patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMOGAD\u003c/h2\u003e \u003cp\u003eAround two-thirds of respondents (39/56, 69.6%) initiated treatment for MOGAD after the first attack, regardless of whether they were primarily treating children (6/9, 66.7%) or adults (33/45, 73.3%). Several free-text responses reflected individualized treatment approaches depending on attack severity, recovery, and antibody titres.\u003c/p\u003e \u003cp\u003eFor MOGAD first-line treatment, rituximab (33/56, 58.9%) was most frequently used, followed by oral glucocorticoids (22/56, 39.3%), intravenous immunoglobulins (IVIG), and azathioprine (each by 21/56, 37.5%, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE). For MOGAD second-line therapy, practitioners applied rituximab (29/56, 51.8%), tocilizumab (27/56, 48.2%), and IVIG (26/56, 46.4%, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003eAmong nine respondents who primarily treated paediatric MOGAD patients, oral glucocorticoids and IVIG were the preferred first-line treatments (applied each by 4/9, 44.4%), while IVIG (5/9, 55.6%) and rituximab (4/9, 44.4%) dominated second-line therapy.\u003c/p\u003e \u003cp\u003e64.6% of respondents (42/65) had MOGAD patients without current therapy, whereas the other 35.4% (23/65) treated all their patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMonitoring\u003c/h2\u003e \u003cp\u003eThe majority of respondents (66/75, 88.0%) used the Expanded Disability Status Scale (EDSS) for clinical monitoring. In addition, 64.0% (48/75) assessed visual function, and 53.3% (40/75) walking ability. Paediatricians reported using tests adapted to the child\u0026rsquo;s developmental stage.\u003c/p\u003e \u003cp\u003eRegarding MR diagnostics, 18.1% (13/72) reported performing imaging only at diagnosis and during attacks, whereas 81.9% (59/72) indicated routine imaging, most commonly on an annual basis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eResources\u003c/h2\u003e \u003cp\u003e To guide treatment decisions for NMOSD and MOGAD, most respondents (48/56, 85.7%) indicated relying on the national guidelines of the DGN, followed by recommendations of NEMOS (46/56, 82.1%) and presentations or discussions at specialist conferences (44/56, 78.6%).\u003c/p\u003e \u003cp\u003eAwareness of patient self-help organizations was limited, with only 41.9% (31/74) reporting knowledge of such resources.\u003c/p\u003e \u003cp\u003eWhen asked about additional needs to support the diagnosis and management of NMOSD and MOGAD, 43.2% (38/88) expressed a demand for further resources. The most frequently mentioned priorities were education and training (particularly online formats, and content tailored to paediatric NMOSD/MOGAD), patient information materials, and structured guidance, including updated recommendations, improved networking, and greater laboratory transparency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eCase examples\u003c/h2\u003e \u003cp\u003eCase #1 concerned a 39-year-old female patient with a medical history of optic neuritis and myelitis, who was now exhibiting signs of paraparesis and bowel dysfunction, with longitudinal, extensive spinal cord involvement on MRI (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Most respondents (63/67, 94.0%) correctly identified that this patient met dissemination in space criteria for NMOSD diagnosis and recognised that the patient met the IPND 2015 diagnostic criteria even in the case of negative antibody findings (62/65, 95.4%). However, divergent opinions emerged when respondents were asked to consider a modified scenario without a history of optic neuritis but with prolonged visual evoked potentials, in which case 40.3% (27/67) erroneously deemed this sufficient to meet the criteria.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eCase #1\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCASE VIGNETTE (1 of 2)\u003c/p\u003e \u003cp\u003e\u0026bull; 39-year-old woman\u003c/p\u003e \u003cp\u003e\u0026bull; History of optic neuritis in the right eye (confirmed by ophthalmologist); history of myelitis with residual deficits\u003c/p\u003e \u003cp\u003e\u0026bull; Current symptoms: paraparesis of the legs, bowel dysfunction\u003c/p\u003e \u003cp\u003e\u0026bull; Brain MRI: unremarkable\u003c/p\u003e \u003cp\u003e\u0026bull; Spinal cord MRI: T2-hyperintense lesion at level T1-T8 with contrast enhancement\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoes this patient meet dissemination in space criteria for NMOSD diagnosis (according to the IPND 2015 Criteria)?\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e% (n/N)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eYes\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94.0 (63/67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.0 (4/67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIf the prior optic neuritis were absent, but visual evoked potentials of the right eye were prolonged (despite absence of clinical symptoms in that eye), would the NMOSD diagnostic criteria be met?\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.3 (27/67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNo\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.7 (40/67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBased on the above information, does this patient meet the criteria for NMOSD diagnosis (according to the IPND 2015 Criteria if she is AQP4-IgG-seronegative?\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, this patient does not have a core clinical characteristic of NMOSD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, although this patient presents with a core clinical characteristic of NMOSD, since she is AQP4-IgG-seronegative.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1 (2/65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eYes, provided there is no better explanation, because she has a core clinical characteristic of NMOSD, a history of other core clinical characteristics, and the required supporting MRI findings.\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.4 (62/65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, this patient presents with a core clinical characteristic of NMOSD, but meets neither dissemination in space nor dissemination in time criteria and therefore does not have NMOSD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5 (1/65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cb\u003eDescription of Case #1, questions and response options.\u003c/b\u003e Responses reported as percentage (n/N) of total. Correct response options are underlined.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCase #2 involved a 28-year-old female patient with a history of bilateral optic neuritis without residuals (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The patient subsequently presented with new vision loss and pain in the right eye, accompanied by bilateral longitudinally extensive optic nerve involvement on MRI. Almost all respondents (63/65, 96.9%) correctly concluded that MOG antibody testing should be performed alongside AQP4 antibody testing for this clinical presentation. Given borderline-positive MOG-IgG serology (titre 1:32) and negative AQP4-IgG, the majority (51/64, 79.7%) of neurologists diagnosed the patient with MOGAD in line with the current criteria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCase #2.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCASE VIGNETTE (2 of 2)\u003c/p\u003e \u003cp\u003e\u0026bull; 28-year-old woman\u003c/p\u003e \u003cp\u003e\u0026bull; History of bilateral optic neuritis without residual deficits\u003c/p\u003e \u003cp\u003e\u0026bull; Current symptoms: recurrent visual deterioration in the right eye, pronounced pain with eye movement\u003c/p\u003e \u003cp\u003e\u0026bull; Brain MRI: bilateral longitudinally extensive T2-hyperintense optic nerves, otherwise unremarkable\u003c/p\u003e \u003cp\u003e\u0026bull; Spinal cord MRI: unremarkable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWould you test this patient for MOG antibodies?\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e% (n/N)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, because bilateral optic neuritis excludes the diagnosis of multiple sclerosis.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, the absence of residual deficits from prior optic neuritis suggests the diagnosis of multiple sclerosis.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, this clinical presentation is more typical of NMOSD and I only test for AQP4 antibodies.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eYes, in combination with testing for AQP4 antibodies.\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.9 (63/65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, because a diagnosis of MOGAD could not be made due to the absence of dissemination in space.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1 (2/65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDoes this patient meet the current diagnostic criteria for MOGAD if the MOG-IgG titre is only borderline positive with 1:32?\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e% (n/N)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, because she has only one core clinical event of MOGAD.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6 (1/64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, although she has a core clinical event of MOGAD, since she lacks supporting clinical or radiologic features.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.1 (9/64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eYes, provided she is AQP4-IgG-seronegative and alternative diagnoses have been excluded, because she has a core clinical characteristic of MOGAD with required supporting MRI findings.\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.7 (51/64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, she demonstrates a core clinical event with supporting MRI findings of NMOSD, so MOGAD diagnostic criteria should not be applied.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (3/64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cb\u003eDescription of Case #2, questions and response options.\u003c/b\u003e Responses reported as percentage (n/N) of total. Correct response options are underlined.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of our survey on the current management of NMOSD and MOGAD in Germany exemplify the shortcomings in the handling of rare neurological diseases: Despite the availability of clear diagnostic criteria and the emergence of new medications, substantial disparities and unmet needs persist in routine clinical practice. Moreover, it emphasizes once again the challenges of accurately depicting the real world of rare disease management in the face of a paucity of rapport, consistency and knowledge.\u003c/p\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eResponder characteristics reflecting Care Structures and Specialist Engagement\u003c/h2\u003e \u003cp\u003eThere are around 6,700 ambulatory neurological practitioners in Germany and the number of DGN members exceeds 13,500 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. A total of 127 individuals responded to the survey advertisement. With approximately one-third of neurologists managing small patient cohorts and fewer than one-fifth regularly treating twenty patients or more, both inside and outside the university setting, this small cohort should be representative of German neurology, covering different experience levels based purely on caseload. Nevertheless, given that more than two thirds reported a neuroimmunological focus, we can assume that particularly engaged specialists were aware of and interested in participating at this survey. Only a small proportion of our respondents who practise outside reference centres did not refer their patients to specialised centres, yet many other practitioners without referral networks may not have been available for the survey or simply never heard about it. It is impossible to quantify the magnitude of this selection bias, but it is likely to be substantial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eThe Antibody-Testing Problem\u003c/h2\u003e \u003cp\u003eThe most striking finding of our study was the low knowledge and precision regarding antibody testing. The NMOSD and MOGAD communities rigorously advocate for CBA, increasingly supported by studies suggesting even superior sensitivity with live versus fixed cells [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Whilst countries such as France maintain reference networks with centralised antibody testing, Germany so far lacks a standardised diagnostic infrastructure. Multiple laboratories offer AQP4- and MOG-IgG testing using heterogeneous assay methods without general standardisation or quality benchmarks. Consequently, guideline recommendations remain unevenly adopted across centres. Some respondents referred samples to their \"routine laboratory\" without knowing whether or where they were transferred onward or which method was used. Of those who were aware of their referral laboratory, only half could specify the assays used, and a concerning minority still reported using ELISA. As antibody status is crucial for diagnosis, treatment selection and prognosis in NMOSD and MOGAD, inaccurate results from suboptimal testing methods can compromise the entire therapeutic process, potentially from the very first step [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This raises another difficult-to-investigate question: How many patients with NMOSD and MOGAD may be misclassified and consequently receive incorrect treatment due to diagnostic error?\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eCoding as the Blind Spot of Health Services Research\u003c/h2\u003e \u003cp\u003eThe ICD-10 coding analysis revealed a differentiated, but ultimately problematic picture. In most cases, AQP4-antibody-positive NMOSD was coded accurately. However, AQP4-antibody-negative NMOSD was coded correctly far less frequently, and for MOGAD, for which there is no specific ICD-10 code yet, practitioners employed entirely heterogeneous coding strategies. This is more than just an administrative inconvenience. Claims-based analyses, increasingly used as the basis for health services research and cost-effectiveness evaluations, depend entirely on coding accuracy. If coding for these diseases is already so inconsistent, the epidemiological and economic analyses derived from such data will be systematically biased.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eApplication of Diagnostic Criteria\u003c/h2\u003e \u003cp\u003eThe short case examples showed that practitioners generally applied the current NMOSD diagnostic criteria correctly - although specific scenarios, such as subclinical latency delays in visually evoked potentials, can seemingly lead to misinterpretation, as was found in the aforementioned survey by the Latin American colleagues [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Diagnosing MOGAD with borderline antibody titres proved substantially more challenging. This is unsurprising, given that MOGAD is a more recent nosological entity than NMOSD, and the diagnostic criteria are less well established [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eRock-solid Rituximab\u003c/h2\u003e \u003cp\u003eRituximab remains a solid rock in the therapy landscape in Germany across all three conditions, which is significant from both clinical and economic perspectives. In AQP4-antibody-negative NMOSD, rituximab is widely used. In AQP4-antibody-positive NMOSD, it remains a preferred treatment option despite the introduction of new medications. This is unsurprising and implicitly validates the efficacy and safety of this off-label drug over a period of around two decades [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. For MOGAD, however, the situation is more nuanced, revealing an instructive gap between guideline recommendations and clinical practice. Recent data suggest that MOGAD patients treated with rituximab experience less favourable outcomes compared to those receiving IVIG [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], with rituximab showing similar efficacy to azathioprine [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], but this is not yet reflected in our real-world data. The persistent predominance of rituximab in clinical practice also highlights a critical question in the context of the orphan drug debate: if cost-effective, established off-label therapies are effective, then the added value of new, more expensive medications must be demonstrated not only in clinical trials but also under real-world conditions. However, prospective, randomized, head-to-head comparisons between new drugs and rituximab are still pending.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eFuture implications and suggestions\u003c/h2\u003e \u003cp\u003eTaken together, our findings reveal a clear need for education, standardisation, and harmonisation of diagnostic and therapeutic procedures across the neurological community. Following our real-world insights from Germany, we suggest:\u003c/p\u003e \u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003ebuilding awareness of state-of-the-art antibody-testing in laboratories\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eincorporating guidance on the relevance of correct ICD-10-coding into guidelines\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eestablishing educational and training programs, including open case discussion rounds, to keep practitioners up-to-date and encourage cooperation.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e \u003cp\u003eFurthermore, our results indicate a systemic gap that extends far beyond NMOSD and MOGAD. Crucially, these issues cannot be resolved by medical disciplines alone; they require investment in systems, and a rethinking of 'innovation' in the management of rare diseases.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003e Our findings emphasise the urgent need for standardised laboratory procedures, harmonised ICD-10 coding, closer collaboration between specialist centres, general neurological practitioners and laboratories, and targeted educational initiatives to improve the consistency and quality of care for patients with NMOSD and MOGAD in Germany.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAquaporin-4 (AQP4)\u003c/p\u003e\n\u003cp\u003eCell-based assay (CBA)\u003c/p\u003e\n\u003cp\u003eExpanded Disability Status Scale (EDSS)\u003c/p\u003e\n\u003cp\u003eGerman Network for Research on Autoimmune Encephalitis (GENERATE)\u003c/p\u003e\n\u003cp\u003eGerman Neurological Society (DGN)\u003c/p\u003e\n\u003cp\u003eIntravenous immunoglobulin (IVIG)\u003c/p\u003e\n\u003cp\u003eMyelin oligodendrocyte glycoprotein (MOG)\u003c/p\u003e\n\u003cp\u003eMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)\u003c/p\u003e\n\u003cp\u003eNeuromyelitis optica spectrum disorder (NMOSD)\u003c/p\u003e\n\u003cp\u003eNeuromyelitis Optica Study Group (NEMOS)\u003c/p\u003e\n\u003cp\u003eProfessional Association of German Neurologists (BVDN)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe survey was done within the framework of the project “NUTSEN: New therapies for rare diseases like NMOSD”, which has been approved by the Ethics Committee of the Technical University of Munich, Germany (Reference 2024-599-S-NP). The survey design did not necessitate informed consent procedures.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset generated and/or analysed during the current study are not publicly available due to local regulations concerning data protection but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eKG received reimbursement of travelling expenses from UCB, Nexstim and Viatris. She has received personal fees for advisory boards from Viatris.\u003c/p\u003e\n\u003cp\u003eAlB has nothing to declare.\u003c/p\u003e\n\u003cp\u003eCZ received reimbursement of travelling expenses from UCB.\u003c/p\u003e\n\u003cp\u003eIK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, GlaxoSmithKline, Hexal, Juvisé Pharmaceuticals, Merck, Neuraxpharm, Roche/Chugai, Sanofi, and Viatris.\u003c/p\u003e\n\u003cp\u003eIA received research grants, speaking honoraria and travel support from Argenx, Alexion, Amgen, Roche, Sanofi and Merck.\u003c/p\u003e\n\u003cp\u003eAcB receives funding from the Innovationsausschuss of the German Federal Joint Committee (G-BA; grant 01VSF23040) and from the German Federal Ministry of Research, Technology and Space (BMFTR; grant 01ZZ2505A). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, CSL Behring, Horizon/Amgen, Merck, Neuraxpharm, Novartis, and Roche, and his institution has received compensation for clinical trials from Ad Scientiam, Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis project was supported by a grant from the German Federal Joint Committee / Innovation Fund (G-BA; project NUTSEN, funding code 01VSF23040).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eKG: conceptualization, methodology, software, investigation, validation, data curation, analysis, writing - original draft, writing - review \u0026amp; editing, visualisation\u003c/p\u003e\n\u003cp\u003eAlB: investigation, validation, data curation, writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eCZ: investigation, validation, data curation, writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eIK: conceptualization, methodology, validation, writing - review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eIA: conceptualization, methodology, validation, writing - review \u0026amp; editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAB: conceptualization, methodology, investigation, validation, data curation, analysis, writing - original draft, writing - review \u0026amp; editing, supervision, project administration\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all participants of our survey and the DGN, BVDN and GENERATE for their support.\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOrphanet an online rare disease and orphan drug database. 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Part II: Attack therapy and long-term management. \u003cem\u003eJournal Of Neurology\u003c/em\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00415-023-11910-z\u003c/span\u003e\u003cspan address=\"10.1007/s00415-023-11910-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSt\u0026ouml;gbauer, J., Schegerer, V., Klein, C., Pawlitzki, M., Meuth, S. G., Aktas, O., et al. (2025). 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Pushing the boundaries of neuromyelitis optica: does antibody make the disease? \u003cem\u003eNeurology\u003c/em\u003e, \u003cem\u003e85\u003c/em\u003e(2), 118\u0026ndash;119. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.0000000000001749\u003c/span\u003e\u003cspan address=\"10.1212/wnl.0000000000001749\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDamato, V., Evoli, A., \u0026amp; Iorio, R. (2016). 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Comparative efficacy of rituximab versus azathioprine in the treatment of MOG antibody-associated disease (MOGAD). \u003cem\u003eJournal Of Neuroimmunology\u003c/em\u003e, \u003cem\u003e407\u003c/em\u003e, 578686. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2025.578686\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2025.578686\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurological-research-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Neurological Research and Practice](https://link.springer.com/journal/42466)","snPcode":"42466","submissionUrl":"https://submission.springernature.com/new-submission/42466/3","title":"Neurological Research and Practice","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"NMOSD, MOGAD, Healthcare Provider Survey, Patient Care, Real-World Setting.","lastPublishedDoi":"10.21203/rs.3.rs-9209675/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9209675/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNeuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare autoimmune disorders. Their true prevalence in Germany is unknown and can only be estimated from heterogeneous international data. Assuming 1\u0026ndash;3 cases per 100,000 people for each disease suggests several thousand affected individuals nationwide, yet the German Neuromyelitis Optica Study Group (NEMOS) registry currently holds records of only about 1,000 patients seen in specialised centres. Numbers and care structures outside such facilities remain largely unknown. This survey aimed to assess the current state of NMOSD and MOGAD care in Germany, identify gaps, and inform future care strategies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn online questionnaire was distributed via NEMOS, the German Neurological Society (DGN), the Professional Association of German Neurologists (BVDN), and the German Network for Research on Autoimmune Encephalitis (GENERATE) from March to May 2025. Questions addressed care structures, diagnostics, coding, treatment, guideline use, and practitioners\u0026rsquo; needs.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 104 physicians from all German federal states participated. Half worked in university hospitals, the remainder in other clinics and outpatient settings. Most were specialised in neuroimmunology (70.2%). Many reported an increase in patient numbers for NMOSD (55.8%) and MOGAD (77.4%). Diagnostic practices revealed significant inconsistencies: almost half of the respondents were unaware of their referral laboratory\u0026rsquo;s antibody assays, and ELISA remained in use despite clear recommendations for cell-based assays. ICD-10 coding varied widely. For first-line therapy of AQP4-antibody-positive NMOSD, off-label rituximab was most frequently used (69.6%), followed by satralizumab (57.1%), ravulizumab (55.4%) and inebilizumab (50.0%). AQP4-antibody-negative NMOSD was mainly treated with rituximab (87.0%). Also in MOGAD, rituximab was frequently used (by 58.9%), yet paediatricians preferred glucocorticoids and intravenous immunoglobulins. 69.9% initiated treatment for MOGAD after the first attack. Notably, 41.8% of physicians reported untreated NMOSD and 64.6% untreated MOGAD patients. Most respondents relied on national guidelines; 43.2% expressed a need for further education and patient information.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings highlight substantial heterogeneity in the diagnosis and treatment of NMOSD and MOGAD in Germany with potential implications for patient outcomes. This underscores the need for harmonised procedures and targeted educational resources to improve diagnostic reliability, treatment equity, and overall quality of care.\u003c/p\u003e","manuscriptTitle":"Unmet Needs in the Care of Patients with Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease: Insights from Germany","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:12:03","doi":"10.21203/rs.3.rs-9209675/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-28T21:23:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T21:14:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-26T17:31:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29237082930155686198345041699437028023","date":"2026-04-17T06:07:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"95621875157002807023396472563717532413","date":"2026-04-01T15:17:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-30T12:03:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-26T00:41:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T00:40:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurological Research and Practice","date":"2026-03-24T09:12:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurological-research-and-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Neurological Research and Practice](https://link.springer.com/journal/42466)","snPcode":"42466","submissionUrl":"https://submission.springernature.com/new-submission/42466/3","title":"Neurological Research and Practice","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6408febb-f355-4576-a899-6597185c9a71","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-19T09:55:10+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:12:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9209675","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9209675","identity":"rs-9209675","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}