Autoimmune glial fibrillary acidic protein astrocytopathy, presenting as encephalomyelitis: A Case report 

Autoimmune glial fibrillary acidic protein astrocytopathy, presenting as encephalomyelitis: A Case report | 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 Case Report Autoimmune glial fibrillary acidic protein astrocytopathy, presenting as encephalomyelitis: A Case report Jiawei Jiang, Jiating Bao, Yu Guo, Yue mao, Hongmei Gao, Shuying Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6880809/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, a 40-year-old male patients with encephalomyelitis and GFAP-IgG positivity are described. Case presentation : This case report describes a patient with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, a 40-year-old male who presented with hiccups and lower limb weakness following a fever. Comprehensive neuroimaging and laboratory analyses, combined with clinical manifestations, ultimately led to a diagnosis of encephalomyelitis. The treatment regimen included high-dose steroids and immunosuppressants, resulting in slight improvement of the patient's clinical symptoms. Conclusions : This case highlights the diversity of autoimmune astrocytopathy with GFAP and the importance of early diagnosis, emphasizing the critical role of individualized treatment strategies in improving prognosis. The uniqueness of this case provides new insights for clinicians, suggesting that such rare diseases should be considered in patients with similar symptoms. Glial fibrillary acidic protein (GFAP) Encephalitis Central nervous system Case report Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy(GFAP-A)is an central nervous system(CNS)。In recent years, GFAP-A has gradually attracted widespread attention.The main characteristic of this disease is the production of antibodies against GFAP in the patient's body, which leads to damage and dysfunction of the nervous system. The onset is often subacute or insidious, making it easily misdiagnosed as an infection, degenerative disease, demyelination, tumor, or vascular disorder 1 。As the number of cases increases, the medical community's understanding of this disease deepens, highlighting its importance and complexity in clinical practice. The clinical manifestations of GFAP-A are diverse, with patients potentially experiencing various neurological symptoms such as headaches, seizures, and psychiatric symptoms, often accompanied by an increase in lymphocytes in the cerebrospinal fluid and a positive response to GFAP antibodies. The immunoglobulin (IgG) of GFAP is produced by infiltrating lymphocytes from the peripheral and central nervous systems and is considered a biomarker for autoimmune GFAP astrocytopathy. Its positivity in serum or cerebrospinal fluid (CSF) can help distinguish GFAP-A from other diseases that require differential diagnosis 2 。This case report describes a patient with GFAP-A, whose clinical presentation is encephalomyelitis. By providing a detailed description of the case, etiology, clinical manifestations, and diagnostic methods, it helps enhance physicians' ability to recognize such rare conditions, promoting timely and accurate diagnosis and treatment. Such reports play a crucial role in expanding physicians' knowledge base and increasing awareness of rare diseases. 2. Case presentation A 40-year-old male patient presented with a 10-day history of febrile illness. His medical history included coronary atherosclerotic heart disease diagnosed 9 years prior, managed with dual coronary artery stenting and maintenance antiplatelet therapy (clopidogrel), and hypertension diagnosed 3 years earlier, with suboptimal blood pressure control due to intermittent adherence to sustained-release nifedipine. Notably, the patient reported remote methamphetamine use for a 6-month period 20 years prior. The current episode was characterized by persistent fever with a maximum recorded temperature of 38.5°C, unaccompanied by chills, respiratory symptoms, gastrointestinal disturbances, or peripheral edema. Initial self-administered empiric antiviral therapy resulted in temperature reduction to a fluctuating baseline of 37.4–38°C. Three days prior to admission, the patient developed neurological manifestations including recurrent hiccups, involuntary limb tremors, dysarthria, lethargy, and urinary retention. Cranial magnetic resonance imaging (MRI) performed externally demonstrated bilateral basal ganglia involvement, specifically a left thalamic softening lesion, subtle bilateral frontoparietal subcortical white matter hyperintensities suggestive of demyelination, and saddle-shaped sella turcica herniation. No therapeutic interventions were initiated at that time. One day preceding hospitalization, acute flaccid paraparesis necessitated emergency evaluation. Initial diagnostic considerations included pyrexia of unknown origin and electrolyte imbalance. Abdominopelvic computed tomography (CT) detected urinary retention, requiring transient catheterization. Admission laboratory investigations revealed: Hematology: Elevated leukocytosis (WBC 15.44×10^9/L) with neutrophilic predominance (86.1%, absolute count 13.29×10^9/L) and C-reactive protein elevation (7.29 mg/L). Biochemistry: Hyponatremia (129.80 mmol/L), normokalemia (3.89 mmol/L), hypochloremia (97.80 mmol/L), azotemia (urea 14.07 mmol/L; creatinine 202.60 µmol/L), and reduced glomerular filtration rate (34.39 mL/min/1.73m²). Urinalysis: Hematuria (217 RBCs/µL, homogeneous morphology; occult blood 3+), trace leukocyte esterase (+-), proteinuria (+-), and microalbuminuria (urine protein/creatinine ratio 283.19 mg/g; microalbumin/creatinine ratio 166.17 mg/g). Clinical progression encompassed recurrent pyrexia with neuropsychiatric deterioration, including altered mentation. Supportive management involving fluid resuscitation, empirical antimicrobial therapy, and antipyretic measures yielded limited clinical improvement, ultimately necessitating intensive care unit(ICU) admission for advanced monitoring and therapeutic escalation. Upon ICU admission, the patient presented with acute encephalopathy characterized by confusion (Glasgow Coma Scale E3V4M5), symmetrical brainstem reflexes (pupils 2.5 mm bilaterally with intact photomotor responses), and meningismus. Neuromuscular evaluation revealed asymmetric paresis (Medical Research Council [MRC] scale: upper extremities 4/5, lower extremities 2/5) with absent pyramidal tract signs (bilateral Babinski negative). Cerebrospinal fluid (CSF) analysis demonstrated marked lymphocytic pleocytosis (65 cells/µL; 98% mononuclear) accompanied by blood-brain barrier disruption (protein 249.8 mg/dL) and hypoglycorrhachia (3.37 mmol/L vs serum 7.8 mmol/L). Microbiological evaluation excluded bacterial/fungal pathogens through negative acid-fast staining, India ink preparation, and Mycobacterium tuberculosis PCR. Comprehensive autoimmune profiling showed pan-negative results for neuronal surface antibodies (anti-NMDAR, LGI1, CASPR2) and systemic autoimmunity markers, though low-titer reactivity against influenza A/B and atypical respiratory pathogens (Chlamydia pneumoniae, Legionella pneumophila) was observed. Viral metagenomic sequencing identified Epstein-Barr virus DNA (3 sequence reads) in CSF, suggesting possible viral reactivation. Empirical neurotropic antiviral therapy with intravenous acyclovir (10 mg/kg q8h) and osmotherapy (mannitol 20% 1 g/kg q6h) was initiated for presumed viral encephalitis, guided by the triad of encephalopathy, CSF inflammation, and EBV detection. Seven days post-treatment initiation, the patient demonstrated partial clinical response with defervescence and resolved hiccups, yet exhibited progressive paraparesis (lower extremity MRC grade 2-). Neurological examination revealed persistent meningeal irritation (Kernig's sign positive, nuchal rigidity) and equivocal bilateral extensor plantar responses. Repeat cerebrospinal fluid (CSF) analysis confirmed persistent lymphocytic pleocytosis (92 cells/µL, 97% small lymphocytes) with resolving albuminocytologic dissociation (protein 166.7 mg/dL vs initial 249.8 mg/dL) and stable CSF-to-serum glucose discordance (3.17 vs 7.8 mmol/L). Epstein-Barr virus (EBV) DNA was identified via metagenomic sequencing (3 sequence reads). The results of the CSF autoimmune encephalitis antibody tests indicated a positive GFAP antibody IgG at 1:10+, while AQP4, MOG, and MBP antibodies were negative. The serum autoimmune encephalitis antibody tests also showed a positive GFAP antibody IgG at 1:10+, with negative results for AQP4, MOG, and MBP antibodies, (Fig. 1 ). The CSF GFAP-IgG antibody screening using an indirect immunofluorescence method based on animal brain tissue sections (tissue-based assay, TBA) was positive for the cerebellum, hippocampus, and cerebral cortex, (Fig. 2 ). Quantitative immunoglobulin analysis revealed sustained intrathecal synthesis (IgG index 1.26; 76.02 mg/dL/24h) with CSF-restricted oligoclonal bands, corroborated by Reiber diagram analysis indicating concurrent blood-brain barrier dysfunction (31% intrathecal IgG fraction).Contrast-enhanced MRI of the neuraxis revealed multi-level inflammatory involvement: bilateral basal ganglia and periventricular linear enhancement, accompanied by leptomeningeal thickening and enhancement extending from the medulla oblongata to the cervical spinal cord (Fig. 3 ). Disseminated punctate parenchymal lesions with associated leptomeningeal inflammation were observed throughout the cervical and thoracic spinal segments, while lumbosacral imaging demonstrated cauda equina involvement with characteristic dural enhancement (Fig. 4 ).Therapeutic intervention comprised high-dose methylprednisolone (1,000 mg/day IV for 72 hours, subsequently tapered to 500 mg/day) combined with intravenous immunoglobulin (4mg/kg/day ×5 days). This regimen achieved measurable biochemical improvement, with CSF pressure declining to 205 mmH2O and protein levels demonstrating a 17.3% reduction from baseline (refer to Table 1 ). Partial motor recovery was evidenced by improved lower extremity strength (MRC grade improvement from 2- to 2), though electrophysiological studies confirmed residual axonal-predominant sensorimotor polyneuropathy. Somatosensory evoked potentials revealed conduction delays localized to dorsal root entry zones and spinal cord afferent pathway.Following transfer to a specialized rehabilitation facility due to patient preference, one-month telephone follow-up documented persistent neurological deficits including MRC grade 2 + paraparesis and chronic lower limb dysesthesia. The clinical trajectory underscores the characteristic refractoriness of neuromuscular complications in GFAP-associated autoimmunity, despite aggressive immunomodulatory therapy. Table 1 Routine test results of CSF Day 1 Day 7 Day 13 Day 22 Pressure (cmH2O) > 330 240 205 265 character Colorless and transparent Colorless and transparent Colorless and transparent Colorless and transparent Small lymphocyte % 97 94 99 Percentage of multiple nuclear cells (%) 2 - - - Percentage of mononuclear cells (%) 98 2 6 1 CSF white blood cell count (×10^6/L) 65 92 275 75 CSF Number of red blood cells (×10^6/L) 20 15 1 4 Chloride (CL, mmol/L) 118.8 117.1 121 119.1 Lactate dehydrogenase (LDH, U/L 98.9 64.4 - - CSF Protein (csfPro, mg/dL) 249.8 166.7 229.7 119.7 CSF Glucose (GLU) (mmol/L) 3.37 3.17 5.97 4.98 Adenosine deaminase (ADA, U/L 14.8 15.1 - - Blood glucose (mmol/L) 7.4 7.8 10.8 7.1 3. Discussion Neuroimmune antigen-specific autoimmune encephalitis generally presents with subacute onset clinical manifestations, which can easily be misdiagnosed as infections, degenerative diseases, demyelination, tumors, or vascular diseases. Fever, headache, and meningeal symptoms are often reported as initial symptoms, and some patients experience prodromal flu-like symptoms. This raises speculation that certain cases of GFAP-A may be triggered by prior viral or bacterial infections. The clinical features of GFAP-A vary widely as it affects different regions of the CNS. The initial stage of GFAP-A is characterized by fever 3 。The initial stage of GFAP-A is characterized by fever, headache, fatigue, nausea, and neck pain. In the largest study conducted by Kunchok et al.55% of patients had syndromic meningoencephalitis, and 40% had meningoencephalomyelitis 1 .Symptoms of meningitis include delirium, headache, neck stiffness, vomiting, tremors, blurred vision, seizures, and psychiatric symptoms, while symptoms of myelitis include sensory and motor dysfunction 4 .Visual symptoms are also common manifestations of GFAP-A, with heterogeneity including optic neuritis, papilledema, and intervertebral disc inflammation. Cerebrospinal fluid shows clinical features of hypoglycorrhachia, elevated protein, and increased WBC, making it difficult to distinguish from infectious causes, especially tuberculous meningitis. Other less common diseases include chronic relapsing course, Parkinson's syndrome, and rapidly progressive dementia 5 .The patient in this case was initially diagnosed with infection-related meningitis. After antiviral and antibacterial treatment, there was no significant improvement in symptoms, and neurological symptoms progressively worsened. Overall, the clinical presentation is highly similar to infectious diseases, psychological disorders, and other neurological diseases, making differential diagnosis challenging. However, based on neuroimaging characteristics and the disease's characteristic rapid response to immunosuppressive treatment, clinical attention should be given to the screening of such cases. GFAP is an intermediate filament (IF) III protein uniquely present in astrocytes of the CNS, non-myelinating Schwann cells of the peripheral nervous system (PNS), and enteric glial cells. The expression of GFAP is crucial for the normal structure of white matter and the integrity of the blood-brain barrier, as astrocytes provide structural and functional support to neurons 6 .The pathophysiological mechanism of GFAP-A has not been fully elucidated. Although autoantibodies against GFAP can be detected in the central nervous system, the exact cause of this phenomenon remains unclear. Considering that the GFAP protein is located in the cytoplasm of astrocytes, and because antibodies cannot bind to intracellular antigens, GFAP antibodies in cerebrospinal fluid and/or serum merely reflects a biomarker of a cytotoxic T cell-mediated immune response. This also suggests that there must be a potential trigger that exposes GFAP in the cytoplasm to the immune system, thereby leading to the production of autoantibodies 5 。Various potential triggers have been identified in the literature, including Epstein-Barr virus (EBV) infection, traumatic brain injury, other autoimmune diseases, herpes simplex virus encephalitis, dengue fever, syphilis, and COVID-19 infection 7 .GFAP astrocytopathy caused by viral encephalitis typically presents a biphasic pattern, with the first peak resulting from direct viral invasion and the second peak driven by the production of autoantibodies 8 .In addition, cancer has also been identified as a possible triggering factor, as it may lead to paraneoplastic syndromes. Studies have shown that approximately 20–34% of patients have tumors present simultaneously, with ovarian teratomas being the most common type, accounting for about 34% of all tumors 4 .In addition, about 20% of patients with GFAP-positive astrocytopathy also have other autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease, and rheumatoid arthritis. The tumor markers tested in this patient were all negative, and no evidence of tumors was found, which may be related to the short duration of the disease and requires long-term follow-up. GFAP-A cerebrospinal fluid examination often shows inflammatory changes, with 90% of patients exhibiting an increase in white blood cell count predominantly consisting of lymphocytes, which may be related to enhanced immune system activity. At the same time, protein levels are elevated (in severe cases, >1g/L), while glucose levels are usually normal 9 .GFAP antibodies testing is an important basis for diagnosing this disease, with a serum positive rate of 45% and a cerebrospinal fluid positive rate as high as 94% 10 .Cerebrospinal fluid testing has a higher diagnostic value than serum testing 11 .In addition, GFAP antibody positivity may overlap with antibodies related to other autoimmune diseases, particularly anti-N-methyl-D-aspartate receptor(NMDA) antibodies and AQP4 antibodies, which can increase the complexity of diagnosis. 5 In this case, the patient's cerebrospinal fluid protein sharply increased in a short period, which may be related to the specific action of GFAP antibodies. In terms of imaging, MRI of patients with autoimmune GFAP astrocytopathy shows multiple lesions, primarily affecting the white matter of the brain, basal ganglia, hypothalamus, brainstem, cerebellum, and ventricles 5 .The enhanced MRI of the patient's head shows abnormal enhancement in the bilateral basal ganglia and bilateral periventricular areas; the enhanced MRI of the spinal cord shows diffuse punctate and linear abnormal enhancement in the medulla, cervical, and thoracic spinal cord, indicating involvement of the brain and spinal cord. GFAP is expressed most highly in the perivascular regions of the brain and around the central canal of the spinal cord, with autoantibodies in GFAP astrocytopathy leading to lymphocytic inflammation in these areas, corresponding to the enhancement seen on MR imaging. The characteristic imaging findings of GFAP astrocytopathy include linear perivascular and periventricular enhancement radiating outward, accompanied by associated white matter T2/FLAIR hyperintensities; punctate and nodular enhancement patterns can also be observed in the supratentorial and infratentorial brain, as well as in the enhancement of the pia mater and ependyma 12 .The most common clinical manifestation is meningitis (with or without myelitis), and it rarely presents as isolated myelitis 3 .Radial vascular periventricular line-like enhancement perpendicular to the ventricles is considered a highly specific change for this disease, and some studies suggest that this phenomenon may be related to small venulitis 13 .However, these imaging findings are not specific, so it is essential to comprehensively analyze the patient's clinical manifestations and laboratory test results during the diagnostic process. For the treatment of this disease, the Mayo Clinic in the United States recommends high-dose hormone and immunoglobulin pulse therapy during the acute phase, followed by immunosuppressive therapy during the maintenance phase, which has a significant control effect on the disease. The author reviewed relevant studies on autoimmune GFAP astrocytopathy, summarizing its treatment and prognosis, and concluded that the disease shows significant improvement under acute phase treatment, but is prone to relapse and residual sequelae in the later stages. Early immunotherapy can be administered in cases of irreversible damage, and careful withdrawal of hormones while monitoring patient symptoms and CSF findings can help avoid sequelae and relapses. Additionally, plasma exchange has shown some therapeutic effect in patients who are insensitive to hormones 1 .After adding hormone pulse and immunoglobulin treatment, the patient's lower limb weakness symptoms did not improve significantly, but two subsequent CSF examinations showed a significant decrease in protein levels. 4. Conclusion In the study of GFAP-A, the complexity of the disease and its profound impact on patients' quality of life are gradually being recognized. A detailed case analysis and literature review reveal the diversity and challenges of GFAP-A. These challenges pertain to its clinical features, etiology, diagnosis, and treatment. Notably, most patients are relatively sensitive to immunotherapy and recover well, but our patient with long-segment spinal cord injury and peripheral nerve damage has a poor prognosis. Overall, research on GFAP-A is advancing rapidly. While existing studies offer preliminary insights, further exploration and validation are necessary in many areas.Future research should prioritize early diagnostic strategies, in-depth analysis of etiological mechanisms, and the creation of personalized treatment plans to enhance patients' quality of life and prognosis. Abbreviations GFAP Autoimmune glial fibrillary acidic protein GFAP-A Autoimmune glial fibrillary acidic protein astrocytopathy CNS central nervous system IgG immunoglobulin CSF cerebrospinal fluid MRI magnetic resonance imaging CT computed tomography WBC leukocytosis TBA tissue-based assay ICU intensive care unit MRC Medical Research Council IF intermediate filament PNS peripheral nervous system EBV Epstein-Barr virus NMDA N-methyl-D-aspartate receptor Declarations Ethics approval and consent to participate We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. As this is a case report describing clinical observations, ethics approval was waived. Consent for publication Written informed consent for publication of clinical details and any accompanying images were obtained from the patient himself . Availability of data and material Not applicable. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This study is supported by National Key Clinical Specialty Construction Project of China (2011-873) and Tianjin Medical Construction of Key Discipline (Specialty) Funded Project (TJYXZDXK-013A). Authors' contributions JWJ Writing original draft, Data curation and Conceptualization. JTB and YG: Data curation. YM and HMG: Writing review ; SYY:editing, Funding acquisition. All authors read and approved the final manuscript. Acknowledgements The authors would like to thank the patient for letting us publish his case and all the contributors for their input and work. Clinical trial number Not applicable. References Kunchok A, Zekeridou A, McKeon A. Autoimmune glial fibrillary acidic protein astrocytopathy. Curr Opin Neurol Jun. 2019;32(3):452–8. 10.1097/wco.0000000000000676 . Bien CG, Büttner T, Reichen IC, et al. Glial Fibrillary Acidic Protein Autoimmunity After Aseptic Meningitis: A Report of 2 Cases. Neurol Neuroimmunol Neuroinflamm Jan. 2024;11(1). 10.1212/nxi.0000000000200180 . Shetty D, Brahmbhatt S, Desai A, et al. Glial Fibrillary Acidic Protein Astrocytopathy: Review of Pathogenesis, Imaging Features, and Radiographic Mimics. AJNR Am J Neuroradiol Oct. 2024;3(10):1394–402. 10.3174/ajnr.A8236 . Xiao J, Chen X, Shang K, et al. Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study. J Neuroimmunol Nov. 2021;15:360:577718. 10.1016/j.jneuroim.2021.577718 . Kimura A, Takekoshi A, Yoshikura N, Hayashi Y, Shimohata T. Clinical characteristics of autoimmune GFAP astrocytopathy. J Neuroimmunol Jul. 2019;15:332:91–8. 10.1016/j.jneuroim.2019.04.004 . Kimura A, Takemura M, Yamamoto Y, Hayashi Y, Saito K, Shimohata T. Cytokines and biological markers in autoimmune GFAP astrocytopathy: The potential role for pathogenesis and therapeutic implications. J Neuroimmunol Sep. 2019;15:334:576999. 10.1016/j.jneuroim.2019.576999 . Iorio R, Damato V, Evoli A, et al. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. J Neurol Neurosurg Psychiatry Feb. 2018;89(2):138–46. 10.1136/jnnp-2017-316583 . Cheng P, Huang W, Yang M, et al. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report of bimodal overlapping encephalitis. Front Immunol. 2023;14:1258048. 10.3389/fimmu.2023.1258048 . Kimura A, Takekoshi A, Shimohata T. Characteristics of Movement Disorders in Patients with Autoimmune GFAP Astrocytopathy. Brain Sci Mar. 2022;29(4). 10.3390/brainsci12040462 . Flanagan EP, Hinson SR, Lennon VA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol Feb. 2017;81(2):298–309. 10.1002/ana.24881 . Zhang YM, Liu S, Liu TT, Zhao HD, Shi JQ. GFAP antibody-negative myelitis with high similarity to autoimmune GFAP astrocytopathy: a case report. Neurol Sci Sep. 2022;43(9):5659–61. 10.1007/s10072-022-06127-3 . Hagbohm C, Ouellette R, Flanagan EP, et al. Clinical and neuroimaging phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy: A systematic review and meta-analysis. Eur J Neurol Jul. 2024;31(7):e16284. 10.1111/ene.16284 . Gravier-Dumonceau A, Ameli R, Rogemond V, et al. Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study. Neurology Feb. 2022;8(6):e653–68. 10.1212/wnl.0000000000013087 . Additional Declarations No competing interests reported. Supplementary Files CAREChecklistofinformationtoincludewhenwritingacasereport.pdf Cite Share Download PDF Status: Posted Version 1 posted 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-6880809","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":502208085,"identity":"16b8fbee-4538-4535-812d-26a20d375ef1","order_by":0,"name":"Jiawei Jiang","email":"","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiawei","middleName":"","lastName":"Jiang","suffix":""},{"id":502208086,"identity":"8f9f184e-772c-47db-94a1-80127cd53365","order_by":1,"name":"Jiating Bao","email":"","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jiating","middleName":"","lastName":"Bao","suffix":""},{"id":502208087,"identity":"a742a7e1-e0b4-40d0-98b5-8a3423bebba9","order_by":2,"name":"Yu Guo","email":"","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Guo","suffix":""},{"id":502208088,"identity":"01dbc3cf-a151-4d0c-8e97-90797a8a0ed8","order_by":3,"name":"Yue mao","email":"","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"mao","suffix":""},{"id":502208089,"identity":"e6b1d1a3-959d-44e1-b7f9-ca328a322f24","order_by":4,"name":"Hongmei Gao","email":"","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongmei","middleName":"","lastName":"Gao","suffix":""},{"id":502208090,"identity":"323b4f1a-a8aa-42b6-8c1b-430ecf97fa7f","order_by":5,"name":"Shuying Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYPACCQYG9sbGBx9I08JzuNlwBokWpbdJcxCj0OD42cMvf7ZZyBvcfNggzcBgJ6fbQEjLmbw0a942CcMNtxMbjAsYko3NDhDSciDHzJixTSLBAKgleQbDgcRtBLWcf2Nm+BOk5ebBhsM8RGm5kWP8gBek5QZjYzNRWiRvvDFj5jknYTjzTGIz4wwDIvzCdz7H+OOPsjp5vuPHn//4UGEnR1CLwgEGNglGNrg7CSgHAfkGBuYPDH+IUDkKRsEoGAUjFwAAy1hHZ0yu22cAAAAASUVORK5CYII=","orcid":"","institution":"Tianjin First Center Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shuying","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-06-12 13:23:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6880809/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6880809/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89464135,"identity":"fedf5c8b-9507-4e15-96eb-9e0c37030cfc","added_by":"auto","created_at":"2025-08-20 08:17:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":860669,"visible":true,"origin":"","legend":"\u003cp\u003eThe immunoreactivity of patient’s GFAP-IgG via cell-based assay (CBA) in CSF and serum.\u003c/p\u003e\n\u003cp\u003eThe red fluorescence represents the GFAP antibody in the sample.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/3cf0d7bf1b375c52a3f5cdb1.png"},{"id":89463037,"identity":"0cb2cdb6-d906-4279-9646-b040f6d77994","added_by":"auto","created_at":"2025-08-20 08:09:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":923708,"visible":true,"origin":"","legend":"\u003cp\u003eScreening results of GFAP IgG antibody detected by TBA in CSF.\u003c/p\u003e\n\u003cp\u003eCSF was used to detect GFAP IgG antibody by indirect immunofluorescence assay (TBA) based on animal brain tissue sections. Astrocyte staining of GFAP IgG was positive in cerebellum (panel a), hippocampus (panel b) and cerebral cortex (panel c). Panel d is the negative control and panel E is the positive control.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/6ddf8c63c16eb065493c3eea.png"},{"id":89463043,"identity":"d4c2aa3f-b586-46f0-800c-9b16ee01ce8b","added_by":"auto","created_at":"2025-08-20 08:09:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":732774,"visible":true,"origin":"","legend":"\u003cp\u003e\u003ca href=\"https://lib.plagh.cn/s/com/sciencedirect/www/G.https/topics/neuroscience/magnetic-resonance-imaging-of-brain\" title=\"Learn more about Brain MRI of from ScienceDirect's AI-generated Topic Pages\"\u003eBrain MRI of\u003c/a\u003e the patient.\u003c/p\u003e\n\u003cp\u003ea-b:Crescent-shaped long T2 signal shadows are visible around the bilateral lateral ventricles. c-d:Post-contrast T1-weighted MRI imaging showed linear perivascular radial gadolinium enhancement around the ventricle (arrow).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/449522d788e6f07dda12a5c3.png"},{"id":89464136,"identity":"b5de4a3e-5aab-40ac-8a61-df133b0c1277","added_by":"auto","created_at":"2025-08-20 08:17:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":323551,"visible":true,"origin":"","legend":"\u003cp\u003eSpinal cord MR\u003ca href=\"https://lib.plagh.cn/s/com/sciencedirect/www/G.https/topics/neuroscience/magnetic-resonance-imaging-of-brain\" title=\"Learn more about Brain MRI of from ScienceDirect's AI-generated Topic Pages\"\u003e of\u003c/a\u003e the patient.\u003c/p\u003e\n\u003cp\u003ea:There were no abnormal signals in the spinal cord on plain MRI\u003c/p\u003e\n\u003cp\u003eb-d:The sagittal post-contrast T1-weighted MRI imaging showed leptomeningeal enhancement around medulla, pons and spinal cord (arrow head). Longitudinal extensive punctate and linear abnormal enhancement lesions in the whole spinal cord also can be seen(arrow).\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/2b1571a97bc1d3cc869564d8.png"},{"id":99211849,"identity":"f095940b-cee7-4b0e-ad67-55db865d163b","added_by":"auto","created_at":"2025-12-30 08:10:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3451660,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/64574905-7b2c-4249-b381-9691b9388b0f.pdf"},{"id":89465276,"identity":"9204f70c-d82e-40bb-ae49-445694ec7105","added_by":"auto","created_at":"2025-08-20 08:25:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":83482,"visible":true,"origin":"","legend":"","description":"","filename":"CAREChecklistofinformationtoincludewhenwritingacasereport.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6880809/v1/a299cb53baa494847691b618.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Autoimmune glial fibrillary acidic protein astrocytopathy, presenting as encephalomyelitis: A Case report ","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy(GFAP-A)is an central nervous system(CNS)。In recent years, GFAP-A has gradually attracted widespread attention.The main characteristic of this disease is the production of antibodies against GFAP in the patient's body, which leads to damage and dysfunction of the nervous system. The onset is often subacute or insidious, making it easily misdiagnosed as an infection, degenerative disease, demyelination, tumor, or vascular disorder\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e。As the number of cases increases, the medical community's understanding of this disease deepens, highlighting its importance and complexity in clinical practice. The clinical manifestations of GFAP-A are diverse, with patients potentially experiencing various neurological symptoms such as headaches, seizures, and psychiatric symptoms, often accompanied by an increase in lymphocytes in the cerebrospinal fluid and a positive response to GFAP antibodies. The immunoglobulin (IgG) of GFAP is produced by infiltrating lymphocytes from the peripheral and central nervous systems and is considered a biomarker for autoimmune GFAP astrocytopathy. Its positivity in serum or cerebrospinal fluid (CSF) can help distinguish GFAP-A from other diseases that require differential diagnosis\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e。This case report describes a patient with GFAP-A, whose clinical presentation is encephalomyelitis. By providing a detailed description of the case, etiology, clinical manifestations, and diagnostic methods, it helps enhance physicians' ability to recognize such rare conditions, promoting timely and accurate diagnosis and treatment. Such reports play a crucial role in expanding physicians' knowledge base and increasing awareness of rare diseases.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eA 40-year-old male patient presented with a 10-day history of febrile illness. His medical history included coronary atherosclerotic heart disease diagnosed 9 years prior, managed with dual coronary artery stenting and maintenance antiplatelet therapy (clopidogrel), and hypertension diagnosed 3 years earlier, with suboptimal blood pressure control due to intermittent adherence to sustained-release nifedipine. Notably, the patient reported remote methamphetamine use for a 6-month period 20 years prior. The current episode was characterized by persistent fever with a maximum recorded temperature of 38.5\u0026deg;C, unaccompanied by chills, respiratory symptoms, gastrointestinal disturbances, or peripheral edema. Initial self-administered empiric antiviral therapy resulted in temperature reduction to a fluctuating baseline of 37.4\u0026ndash;38\u0026deg;C. Three days prior to admission, the patient developed neurological manifestations including recurrent hiccups, involuntary limb tremors, dysarthria, lethargy, and urinary retention. Cranial magnetic resonance imaging (MRI) performed externally demonstrated bilateral basal ganglia involvement, specifically a left thalamic softening lesion, subtle bilateral frontoparietal subcortical white matter hyperintensities suggestive of demyelination, and saddle-shaped sella turcica herniation. No therapeutic interventions were initiated at that time.\u003c/p\u003e\u003cp\u003eOne day preceding hospitalization, acute flaccid paraparesis necessitated emergency evaluation. Initial diagnostic considerations included pyrexia of unknown origin and electrolyte imbalance. Abdominopelvic computed tomography (CT) detected urinary retention, requiring transient catheterization. Admission laboratory investigations revealed: Hematology: Elevated leukocytosis (WBC 15.44\u0026times;10^9/L) with neutrophilic predominance (86.1%, absolute count 13.29\u0026times;10^9/L) and C-reactive protein elevation (7.29 mg/L). Biochemistry: Hyponatremia (129.80 mmol/L), normokalemia (3.89 mmol/L), hypochloremia (97.80 mmol/L), azotemia (urea 14.07 mmol/L; creatinine 202.60 \u0026micro;mol/L), and reduced glomerular filtration rate (34.39 mL/min/1.73m\u0026sup2;). Urinalysis: Hematuria (217 RBCs/\u0026micro;L, homogeneous morphology; occult blood 3+), trace leukocyte esterase (+-), proteinuria (+-), and microalbuminuria (urine protein/creatinine ratio 283.19 mg/g; microalbumin/creatinine ratio 166.17 mg/g). Clinical progression encompassed recurrent pyrexia with neuropsychiatric deterioration, including altered mentation. Supportive management involving fluid resuscitation, empirical antimicrobial therapy, and antipyretic measures yielded limited clinical improvement, ultimately necessitating intensive care unit(ICU) admission for advanced monitoring and therapeutic escalation.\u003c/p\u003e\u003cp\u003eUpon ICU admission, the patient presented with acute encephalopathy characterized by confusion (Glasgow Coma Scale E3V4M5), symmetrical brainstem reflexes (pupils 2.5 mm bilaterally with intact photomotor responses), and meningismus. Neuromuscular evaluation revealed asymmetric paresis (Medical Research Council [MRC] scale: upper extremities 4/5, lower extremities 2/5) with absent pyramidal tract signs (bilateral Babinski negative). Cerebrospinal fluid (CSF) analysis demonstrated marked lymphocytic pleocytosis (65 cells/\u0026micro;L; 98% mononuclear) accompanied by blood-brain barrier disruption (protein 249.8 mg/dL) and hypoglycorrhachia (3.37 mmol/L vs serum 7.8 mmol/L). Microbiological evaluation excluded bacterial/fungal pathogens through negative acid-fast staining, India ink preparation, and Mycobacterium tuberculosis PCR. Comprehensive autoimmune profiling showed pan-negative results for neuronal surface antibodies (anti-NMDAR, LGI1, CASPR2) and systemic autoimmunity markers, though low-titer reactivity against influenza A/B and atypical respiratory pathogens (Chlamydia pneumoniae, Legionella pneumophila) was observed. Viral metagenomic sequencing identified Epstein-Barr virus DNA (3 sequence reads) in CSF, suggesting possible viral reactivation. Empirical neurotropic antiviral therapy with intravenous acyclovir (10 mg/kg q8h) and osmotherapy (mannitol 20% 1 g/kg q6h) was initiated for presumed viral encephalitis, guided by the triad of encephalopathy, CSF inflammation, and EBV detection.\u003c/p\u003e\u003cp\u003eSeven days post-treatment initiation, the patient demonstrated partial clinical response with defervescence and resolved hiccups, yet exhibited progressive paraparesis (lower extremity MRC grade 2-). Neurological examination revealed persistent meningeal irritation (Kernig's sign positive, nuchal rigidity) and equivocal bilateral extensor plantar responses. Repeat cerebrospinal fluid (CSF) analysis confirmed persistent lymphocytic pleocytosis (92 cells/\u0026micro;L, 97% small lymphocytes) with resolving albuminocytologic dissociation (protein 166.7 mg/dL vs initial 249.8 mg/dL) and stable CSF-to-serum glucose discordance (3.17 vs 7.8 mmol/L). Epstein-Barr virus (EBV) DNA was identified via metagenomic sequencing (3 sequence reads). The results of the CSF autoimmune encephalitis antibody tests indicated a positive GFAP antibody IgG at 1:10+, while AQP4, MOG, and MBP antibodies were negative. The serum autoimmune encephalitis antibody tests also showed a positive GFAP antibody IgG at 1:10+, with negative results for AQP4, MOG, and MBP antibodies, (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The CSF GFAP-IgG antibody screening using an indirect immunofluorescence method based on animal brain tissue sections (tissue-based assay, TBA) was positive for the cerebellum, hippocampus, and cerebral cortex, (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Quantitative immunoglobulin analysis revealed sustained intrathecal synthesis (IgG index 1.26; 76.02 mg/dL/24h) with CSF-restricted oligoclonal bands, corroborated by Reiber diagram analysis indicating concurrent blood-brain barrier dysfunction (31% intrathecal IgG fraction).Contrast-enhanced MRI of the neuraxis revealed multi-level inflammatory involvement: bilateral basal ganglia and periventricular linear enhancement, accompanied by leptomeningeal thickening and enhancement extending from the medulla oblongata to the cervical spinal cord (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Disseminated punctate parenchymal lesions with associated leptomeningeal inflammation were observed throughout the cervical and thoracic spinal segments, while lumbosacral imaging demonstrated cauda equina involvement with characteristic dural enhancement (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e).Therapeutic intervention comprised high-dose methylprednisolone (1,000 mg/day IV for 72 hours, subsequently tapered to 500 mg/day) combined with intravenous immunoglobulin (4mg/kg/day \u0026times;5 days). This regimen achieved measurable biochemical improvement, with CSF pressure declining to 205 mmH2O and protein levels demonstrating a 17.3% reduction from baseline (refer to Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Partial motor recovery was evidenced by improved lower extremity strength (MRC grade improvement from 2- to 2), though electrophysiological studies confirmed residual axonal-predominant sensorimotor polyneuropathy. Somatosensory evoked potentials revealed conduction delays localized to dorsal root entry zones and spinal cord afferent pathway.Following transfer to a specialized rehabilitation facility due to patient preference, one-month telephone follow-up documented persistent neurological deficits including MRC grade 2\u0026thinsp;+\u0026thinsp;paraparesis and chronic lower limb dysesthesia. The clinical trajectory underscores the characteristic refractoriness of neuromuscular complications in GFAP-associated autoimmunity, despite aggressive immunomodulatory therapy.\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\u003eRoutine test results of CSF\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDay 1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDay 7\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDay 13\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDay 22\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePressure (cmH2O)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;330\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e205\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e265\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003echaracter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorless and transparent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eColorless and transparent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eColorless and transparent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eColorless and transparent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmall lymphocyte %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage of multiple nuclear cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage of mononuclear cells (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF white blood cell count (\u0026times;10^6/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e275\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF Number of red blood cells (\u0026times;10^6/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChloride (CL, mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e118.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e117.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e121\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e119.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLactate dehydrogenase (LDH, U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF Protein (csfPro, mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e249.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e166.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e229.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e119.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSF Glucose (GLU) (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdenosine deaminase (ADA, U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood glucose (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eNeuroimmune antigen-specific autoimmune encephalitis generally presents with subacute onset clinical manifestations, which can easily be misdiagnosed as infections, degenerative diseases, demyelination, tumors, or vascular diseases. Fever, headache, and meningeal symptoms are often reported as initial symptoms, and some patients experience prodromal flu-like symptoms. This raises speculation that certain cases of GFAP-A may be triggered by prior viral or bacterial infections. The clinical features of GFAP-A vary widely as it affects different regions of the CNS. The initial stage of GFAP-A is characterized by fever\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e。The initial stage of GFAP-A is characterized by fever, headache, fatigue, nausea, and neck pain. In the largest study conducted by Kunchok et al.55% of patients had syndromic meningoencephalitis, and 40% had meningoencephalomyelitis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.Symptoms of meningitis include delirium, headache, neck stiffness, vomiting, tremors, blurred vision, seizures, and psychiatric symptoms, while symptoms of myelitis include sensory and motor dysfunction\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.Visual symptoms are also common manifestations of GFAP-A, with heterogeneity including optic neuritis, papilledema, and intervertebral disc inflammation. Cerebrospinal fluid shows clinical features of hypoglycorrhachia, elevated protein, and increased WBC, making it difficult to distinguish from infectious causes, especially tuberculous meningitis. Other less common diseases include chronic relapsing course, Parkinson's syndrome, and rapidly progressive dementia\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.The patient in this case was initially diagnosed with infection-related meningitis. After antiviral and antibacterial treatment, there was no significant improvement in symptoms, and neurological symptoms progressively worsened. Overall, the clinical presentation is highly similar to infectious diseases, psychological disorders, and other neurological diseases, making differential diagnosis challenging. However, based on neuroimaging characteristics and the disease's characteristic rapid response to immunosuppressive treatment, clinical attention should be given to the screening of such cases.\u003c/p\u003e\u003cp\u003eGFAP is an intermediate filament (IF) III protein uniquely present in astrocytes of the CNS, non-myelinating Schwann cells of the peripheral nervous system (PNS), and enteric glial cells. The expression of GFAP is crucial for the normal structure of white matter and the integrity of the blood-brain barrier, as astrocytes provide structural and functional support to neurons\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.The pathophysiological mechanism of GFAP-A has not been fully elucidated. Although autoantibodies against GFAP can be detected in the central nervous system, the exact cause of this phenomenon remains unclear. Considering that the GFAP protein is located in the cytoplasm of astrocytes, and because antibodies cannot bind to intracellular antigens, GFAP antibodies in cerebrospinal fluid and/or serum merely reflects a biomarker of a cytotoxic T cell-mediated immune response. This also suggests that there must be a potential trigger that exposes GFAP in the cytoplasm to the immune system, thereby leading to the production of autoantibodies\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e。Various potential triggers have been identified in the literature, including Epstein-Barr virus (EBV) infection, traumatic brain injury, other autoimmune diseases, herpes simplex virus encephalitis, dengue fever, syphilis, and COVID-19 infection\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.GFAP astrocytopathy caused by viral encephalitis typically presents a biphasic pattern, with the first peak resulting from direct viral invasion and the second peak driven by the production of autoantibodies\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.In addition, cancer has also been identified as a possible triggering factor, as it may lead to paraneoplastic syndromes. Studies have shown that approximately 20\u0026ndash;34% of patients have tumors present simultaneously, with ovarian teratomas being the most common type, accounting for about 34% of all tumors\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.In addition, about 20% of patients with GFAP-positive astrocytopathy also have other autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease, and rheumatoid arthritis. The tumor markers tested in this patient were all negative, and no evidence of tumors was found, which may be related to the short duration of the disease and requires long-term follow-up.\u003c/p\u003e\u003cp\u003eGFAP-A cerebrospinal fluid examination often shows inflammatory changes, with 90% of patients exhibiting an increase in white blood cell count predominantly consisting of lymphocytes, which may be related to enhanced immune system activity. At the same time, protein levels are elevated (in severe cases, \u0026gt;1g/L), while glucose levels are usually normal\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.GFAP antibodies testing is an important basis for diagnosing this disease, with a serum positive rate of 45% and a cerebrospinal fluid positive rate as high as 94%\u003csup\u003e10\u003c/sup\u003e.Cerebrospinal fluid testing has a higher diagnostic value than serum testing\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.In addition, GFAP antibody positivity may overlap with antibodies related to other autoimmune diseases, particularly anti-N-methyl-D-aspartate receptor(NMDA) antibodies and AQP4 antibodies, which can increase the complexity of diagnosis.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003eIn this case, the patient's cerebrospinal fluid protein sharply increased in a short period, which may be related to the specific action of GFAP antibodies.\u003c/p\u003e\u003cp\u003eIn terms of imaging, MRI of patients with autoimmune GFAP astrocytopathy shows multiple lesions, primarily affecting the white matter of the brain, basal ganglia, hypothalamus, brainstem, cerebellum, and ventricles\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.The enhanced MRI of the patient's head shows abnormal enhancement in the bilateral basal ganglia and bilateral periventricular areas; the enhanced MRI of the spinal cord shows diffuse punctate and linear abnormal enhancement in the medulla, cervical, and thoracic spinal cord, indicating involvement of the brain and spinal cord. GFAP is expressed most highly in the perivascular regions of the brain and around the central canal of the spinal cord, with autoantibodies in GFAP astrocytopathy leading to lymphocytic inflammation in these areas, corresponding to the enhancement seen on MR imaging. The characteristic imaging findings of GFAP astrocytopathy include linear perivascular and periventricular enhancement radiating outward, accompanied by associated white matter T2/FLAIR hyperintensities; punctate and nodular enhancement patterns can also be observed in the supratentorial and infratentorial brain, as well as in the enhancement of the pia mater and ependyma\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.The most common clinical manifestation is meningitis (with or without myelitis), and it rarely presents as isolated myelitis\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.Radial vascular periventricular line-like enhancement perpendicular to the ventricles is considered a highly specific change for this disease, and some studies suggest that this phenomenon may be related to small venulitis\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.However, these imaging findings are not specific, so it is essential to comprehensively analyze the patient's clinical manifestations and laboratory test results during the diagnostic process.\u003c/p\u003e\u003cp\u003eFor the treatment of this disease, the Mayo Clinic in the United States recommends high-dose hormone and immunoglobulin pulse therapy during the acute phase, followed by immunosuppressive therapy during the maintenance phase, which has a significant control effect on the disease. The author reviewed relevant studies on autoimmune GFAP astrocytopathy, summarizing its treatment and prognosis, and concluded that the disease shows significant improvement under acute phase treatment, but is prone to relapse and residual sequelae in the later stages. Early immunotherapy can be administered in cases of irreversible damage, and careful withdrawal of hormones while monitoring patient symptoms and CSF findings can help avoid sequelae and relapses. Additionally, plasma exchange has shown some therapeutic effect in patients who are insensitive to hormones\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.After adding hormone pulse and immunoglobulin treatment, the patient's lower limb weakness symptoms did not improve significantly, but two subsequent CSF examinations showed a significant decrease in protein levels.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn the study of GFAP-A, the complexity of the disease and its profound impact on patients' quality of life are gradually being recognized. A detailed case analysis and literature review reveal the diversity and challenges of GFAP-A. These challenges pertain to its clinical features, etiology, diagnosis, and treatment. Notably, most patients are relatively sensitive to immunotherapy and recover well, but our patient with long-segment spinal cord injury and peripheral nerve damage has a poor prognosis. Overall, research on GFAP-A is advancing rapidly. While existing studies offer preliminary insights, further exploration and validation are necessary in many areas.Future research should prioritize early diagnostic strategies, in-depth analysis of etiological mechanisms, and the creation of personalized treatment plans to enhance patients' quality of life and prognosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGFAP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAutoimmune glial fibrillary acidic protein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGFAP-A\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAutoimmune glial fibrillary acidic protein astrocytopathy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecentral nervous system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIgG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eimmunoglobulin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecerebrospinal fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emagnetic resonance imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecomputed tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eleukocytosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTBA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etissue-based assay\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMedical Research Council\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintermediate filament\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eperipheral nervous system\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEBV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEpstein-Barr virus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNMDA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eN-methyl-D-aspartate receptor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that we have read the journal\u0026rsquo;s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. As this is a case report describing clinical observations, ethics approval was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and any accompanying images were obtained from the patient himself . \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is supported by National Key Clinical Specialty Construction Project of China (2011-873) and Tianjin Medical Construction of Key Discipline (Specialty) Funded Project\u0026nbsp;(TJYXZDXK-013A).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJWJ Writing original draft, Data curation and Conceptualization.\u0026nbsp;JTB and YG:\u0026nbsp;Data curation.\u0026nbsp;YM and HMG: Writing review ; SYY:editing, Funding acquisition. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the patient for letting us publish his case and all the contributors for their input and work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKunchok A, Zekeridou A, McKeon A. Autoimmune glial fibrillary acidic protein astrocytopathy. Curr Opin Neurol Jun. 2019;32(3):452\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/wco.0000000000000676\u003c/span\u003e\u003cspan address=\"10.1097/wco.0000000000000676\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBien CG, B\u0026uuml;ttner T, Reichen IC, et al. Glial Fibrillary Acidic Protein Autoimmunity After Aseptic Meningitis: A Report of 2 Cases. Neurol Neuroimmunol Neuroinflamm Jan. 2024;11(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/nxi.0000000000200180\u003c/span\u003e\u003cspan address=\"10.1212/nxi.0000000000200180\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShetty D, Brahmbhatt S, Desai A, et al. Glial Fibrillary Acidic Protein Astrocytopathy: Review of Pathogenesis, Imaging Features, and Radiographic Mimics. AJNR Am J Neuroradiol Oct. 2024;3(10):1394\u0026ndash;402. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3174/ajnr.A8236\u003c/span\u003e\u003cspan address=\"10.3174/ajnr.A8236\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXiao J, Chen X, Shang K, et al. Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study. J Neuroimmunol Nov. 2021;15:360:577718. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2021.577718\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2021.577718\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKimura A, Takekoshi A, Yoshikura N, Hayashi Y, Shimohata T. Clinical characteristics of autoimmune GFAP astrocytopathy. J Neuroimmunol Jul. 2019;15:332:91\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2019.04.004\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2019.04.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKimura A, Takemura M, Yamamoto Y, Hayashi Y, Saito K, Shimohata T. Cytokines and biological markers in autoimmune GFAP astrocytopathy: The potential role for pathogenesis and therapeutic implications. J Neuroimmunol Sep. 2019;15:334:576999. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2019.576999\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2019.576999\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIorio R, Damato V, Evoli A, et al. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. J Neurol Neurosurg Psychiatry Feb. 2018;89(2):138\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/jnnp-2017-316583\u003c/span\u003e\u003cspan address=\"10.1136/jnnp-2017-316583\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCheng P, Huang W, Yang M, et al. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report of bimodal overlapping encephalitis. Front Immunol. 2023;14:1258048. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2023.1258048\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2023.1258048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKimura A, Takekoshi A, Shimohata T. Characteristics of Movement Disorders in Patients with Autoimmune GFAP Astrocytopathy. Brain Sci Mar. 2022;29(4). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/brainsci12040462\u003c/span\u003e\u003cspan address=\"10.3390/brainsci12040462\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlanagan EP, Hinson SR, Lennon VA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol Feb. 2017;81(2):298\u0026ndash;309. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.24881\u003c/span\u003e\u003cspan address=\"10.1002/ana.24881\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang YM, Liu S, Liu TT, Zhao HD, Shi JQ. GFAP antibody-negative myelitis with high similarity to autoimmune GFAP astrocytopathy: a case report. Neurol Sci Sep. 2022;43(9):5659\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10072-022-06127-3\u003c/span\u003e\u003cspan address=\"10.1007/s10072-022-06127-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagbohm C, Ouellette R, Flanagan EP, et al. Clinical and neuroimaging phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy: A systematic review and meta-analysis. Eur J Neurol Jul. 2024;31(7):e16284. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ene.16284\u003c/span\u003e\u003cspan address=\"10.1111/ene.16284\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGravier-Dumonceau A, Ameli R, Rogemond V, et al. Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study. Neurology Feb. 2022;8(6):e653\u0026ndash;68. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.0000000000013087\u003c/span\u003e\u003cspan address=\"10.1212/wnl.0000000000013087\" 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":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Glial fibrillary acidic protein (GFAP), Encephalitis, Central nervous system, Case report","lastPublishedDoi":"10.21203/rs.3.rs-6880809/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6880809/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, a 40-year-old male patients with encephalomyelitis and GFAP-IgG positivity are described.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e: This case report describes a patient with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, a 40-year-old male who presented with hiccups and lower limb weakness following a fever. Comprehensive neuroimaging and laboratory analyses, combined with clinical manifestations, ultimately led to a diagnosis of encephalomyelitis. The treatment regimen included high-dose steroids and immunosuppressants, resulting in slight improvement of the patient's clinical symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This case highlights the diversity of autoimmune astrocytopathy with GFAP and the importance of early diagnosis, emphasizing the critical role of individualized treatment strategies in improving prognosis. The uniqueness of this case provides new insights for clinicians, suggesting that such rare diseases should be considered in patients with similar symptoms.\u003c/p\u003e","manuscriptTitle":"Autoimmune glial fibrillary acidic protein astrocytopathy, presenting as encephalomyelitis: A Case report ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-20 08:09:11","doi":"10.21203/rs.3.rs-6880809/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"275381c3-cf99-4708-ae17-fa18d7e4aada","owner":[],"postedDate":"August 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-30T08:09:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-20 08:09:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6880809","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6880809","identity":"rs-6880809","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}