Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus.

Cognitive dysfunction is a feature in multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. A notable aspect of MS brains is hippocampal demyelination, which is closely associated with cognitive decline. However, the mechanisms underlying this phenomenon remain unclear. Chitinase-3-like (CHI3L1), secreted by activated astrocytes, has been identified as a biomarker for MS progression. Our study investigates CHI3L1's function within the demyelinating hippocampus and demonstrates a correlation between CHI3L1 expression and cognitive impairment in patients with MS. Activated astrocytes release CHI3L1 in reaction to induced demyelination, which adversely affects the proliferation and differentiation of neural stem cells and impairs dendritic growth, complexity, and spine formation in neurons. Our findings indicate that the astrocytic deletion of CHI3L1 can mitigate neurogenic deficits and cognitive dysfunction. We showed that CHI3L1 interacts with CRTH2/receptor for advanced glycation end (RAGE) by attenuating ß-catenin signaling. The reactivation of ß-catenin signaling can revitalize neurogenesis, which holds promise for therapy of inflammatory demyelination.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.

Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study.

Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism. Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques. Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients. Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions.

Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.

Chitinase-3-like protein 1 (CHI3L1) is primarily secreted by activated astrocytes in the brain and is known as a reliable biomarker for inflammatory central nervous system (CNS) conditions such as neurodegeneration and autoimmune disorders like neuromyelitis optica (NMO). NMO is an astrocyte disease caused by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4) and leads to vision loss, motor deficits, and cognitive decline. In this study examining CHI3L1's biological function in neuroinflammation, we found that CHI3L1 expression correlates with cognitive impairment in our NMO patient cohort. Activated astrocytes secrete CHI3L1 in response to AQP4 autoantibodies, and this inhibits the proliferation and neuronal differentiation of neural stem cells. Mouse models showed decreased hippocampal neurogenesis and impaired learning behaviors, which could be rescued by depleting CHI3L1 in astrocytes. The molecular mechanism involves CHI3L1 engaging the CRTH2 receptor and dampening ß-catenin signaling for neurogenesis. Blocking this CHI3L1/CRTH2/ß-catenin cascade restores neurogenesis and improves cognitive deficits, suggesting the potential for therapeutic development in neuroinflammatory disorders.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Detection and significance of glial fibrillary acidic protein antibody in autoimmune astocytopathy and related diseases.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an antibody-related astrocytic disease for which a specific GFAP antibody serves as a biological marker. Indeed, cerebral spinal fluid positive and/or seropositivity for GFAP is an important basis for its diagnosis. However, because patients with autoimmune encephalitis or demyelinating diseases can have a similar antibody profile, termed overlapping autoimmune syndrome, it remains a challenge for clinicians to diagnose and suitably classify autoimmune GFAP-A. To further understand the significance of GFAP antibody detection in neuroimmune diseases, this article discusses GFAP antibodies in autoimmune GFAP-A, progress for detection of GFAP antibodies, diagnostic significance of GFAP antibodies in prototypical disease, as well as overlapping syndrome.

Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.

BACKGROUND: Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD. METHODS: Through questionnaires in four medical centres in 2016-2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted. RESULTS: The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues. CONCLUSION: Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD.

Prevalence of multiple sclerosis in Guangzhou, China: A population-based case-finding prospective study.

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: To Identify Its Diagnosis, Management and Prognosis (GFAP-AID) Registry: Study Protocol for an Ambispective, Multicenter Registry in China.

Purpose: Currently, no uniform diagnostic criteria or treatment consensus is available for patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). The aim of this registry is to develop diagnostic and therapeutic recommendations for GFAP-A based on clinical features, neuroimaging, neuroelectrophysiological examinations, laboratory tests, specific antibody tests, immunotherapy, and prognosis. Patients and methods: This multicenter, nationwide ambispective registry includes twenty-seven hospitals in China. From January 2020 to December 2022, consecutive hospitalized patients with symptoms of meningoencephalitis, as well as GFAP-IgG positive cerebrospinal fluid (CSF) or serum will be invited to join this study. It is conservatively estimated that over 300 patients will join the study. Data on demographics, medical history, treatment details and imaging features will be collected after discharge. Outcome events of interest will include modified Rankin Scale (mRS) and Expanded Disability Status Scale (EDSS), readmission with relapsed meningoencephalomyelitis, all-cause mortality, and mortality resulting from complications of GFAP-A. The follow-up will be conducted at six months and twelve months after discharge. Univariate and multivariate regression models will be used to calculate identify independent predictors of outcomes. Stratification analysis will be used to test whether results are similar between key subgroups. Discussion: This study will describe the risk factors, disease course, response to immunotherapy, and long-term prognosis of a large cohort of GFAP-A patients. By using these data, a relatively rational recommendation process for the diagnosis and treatment of GFAP-A will be developed. Trial Registration Number: ChiCTR2000041291.

Development of a Nomogram for Predicting Asymptomatic Coronary Artery Disease in Patients with Ischemic Stroke.

BACKGROUND: Coronary artery stenosis (CAS) ≥50% often coexists in patients with ischemic stroke, which leads to a significant increase in the occurrence of major vascular events after stroke. This study aimed to develop a nomogram for diagnosing the presence of ≥50% asymptomatic CAS in patients with ischemic stroke. METHODS: A primary cohort was established that included 275 non-cardioembolic ischemic stroke patients who were admitted from January 2011 to April 2013 to a teaching hospital in southern China. The preoperative data were used to construct two models by the best subset regression and the forward stepwise regression methods, and a nomogram between these models was established. The assessment of the nomogram was carried out by discrimination and calibration in an internal cohort. RESULTS: Out of the two models, model 1 contained eight clinical-related variables and exhibited the lowest Akaike Information Criterion value (322.26) and highest concordance index 0.716 (95% CI, 0.654-0.778). The nomogram showed good calibration and significant clinical benefit according to calibration curves and the decision curve analysis. CONCLUSION: The nomogram, composed of age, sex, NIHSS score on admission, hypertension history, fast glucose level, HDL cholesterol level, LDL cholesterol level, and presence of ≥50% cervicocephalic artery stenosis, can be used for prediction of ≥50% asymptomatic coronary artery disease (CAD). Further studies are needed to validate the effectiveness of this nomogram in other populations.

Serum molecular biomarkers in neuromyelitis optica and multiple sclerosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory demyelinating disorder of the central nervous system (CNS), which mainly affects the optic nerves and spinal cord. The aims of this study were to determine whether the expression levels of serological cytokines could distinguish 1) NMOSD from healthy controls (HCs); and 2) NMOSD patients with and without the aquaporin-4 (AQP4) antibody biomarker from each other; and 3) NMOSD patients without the antibody to AQP4 from MS patients. METHODS: The expression levels of 200 proteins in serum from 41 NMOSD (32 with antibodies to AQP4, 9 without antibodies to AQP4), 12 MS patients, and 34 HCs were measured using glass-based antibody arrays. None of the patients received any immunosuppressive treatment. In parallel, the correlation between protein expression in NMOSD/MS patients and clinical traits was determined with Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Thirty-nine serological proteins were differentially expressed in NMOSD patients compared to HCs, with 29 of these proteins not observed in MS patients. In addition, the data reveal 15 differentially-expression proteins (DEPs) between AQP4-IgG seronegative and AQP4-IgG seropositive NMOSD patients, and 9 DEPs between NMOSD and MS patients who did not have AQP4-IgG. CONCLUSION: Serological IL-17B is significantly upregulated in both NMOSD and MS patients compared to HCs, and could be a key biomarker of NMOSD and MS. Serological VEGF, MPIF-1 and NrCAM were positively associated with AQP4-IgG titer. We also demonstrate that EGF may be involved in the breakdown of the BBB by downregulating Claudin-5.

Purkinje cell (PC) antibody positivity in a patient with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

PURPOSE: This case report is the first to describe the detection of antibodies against inositol 1,4,5-trisphosphate receptor 1 (ITPR1, I3PR) in a patient diagnosed with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. ITPR1 is known as one of the Purkinje cell antibodies present in autoimmune cerebellar ataxia (ACA). Here, we described the association between autoimmune GFAP astrocytopathy and autoimmune cerebellar disease (ACD). MATERIALS AND METHODS: Demographic features, clinical characteristics, cerebrospinal fluid (CSF) parameters and neuroimaging findings were collected from this patient. Specifically, antibodies against GFAP and other proteins associated with neurological disorders were measured by immunofluorescence staining in both serum and CSF samples. RESULTS: A 52-year-old woman was diagnosed with autoimmune inflammatory meningoencephalitis. She presented with cognitive dysfunction, psychiatric/behavioral abnormalities and serious insomnia with subacute onset. Brain magnetic resonance imaging (MRI) showed bilateral hyperintensity in the semioval centers on axial images and perivascular linear enhancement oriented radially to the ventricles on sagittal images. GFAP-IgG, oligoclonal bands (OBs), N-methyl-D-aspartate receptor (NMDAR)-IgG and ITPR1-IgG co-existed in her CSF. She responded well to immunoglobulin and steroid treatments. CONCLUSION: Here, we describe the case of a patient with autoimmune GFAP astrocytopathy whose CSF was positive for ITPR1-IgG; however, she did not show typical ataxia manifestations or cerebellar lesions on her MRI scan. This suggests that ITPR1-IgG is not pathogenic, and the positivity of this antibody in CSF is probably associated with the presence of autoimmune inflammation.

Comparing the efficacy and safety of the Skyflow device with those of the Solitaire FR stent in patients with acute ischemic stroke: a prospective, multicenter, randomized, non-inferiority clinical trial.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS. METHODS: This study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation. RESULTS: A total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups. CONCLUSION: Endovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study.

Objective: To explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity. Method: Patients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage. Results: One hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with apheresis (8%), IVMP combined with intravenous immunoglobulin (18%) and other therapies (3%). EDSS scores decreased significantly from a medium of 4 (interquartile range 3.0-5.5) at attack to 3.5 (3.0-4.5) at discharge, 3.5 (2.0-4.0) at the 1-month visit and 3.0 (2.0-4.0) at the 3-month visit (p<0.01 in all comparisons). The remission rate was 38.0% at discharge and 63.3% at the 1-month visit. Notably, relapse occurred in 12.2% of 74 patients by the 6-month follow-up. Higher levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-10, IL-13, and IL-1 receptor antagonist, predicted remission at the 1-month visit (OR=9.33, p=0.04). Serum NfL levels correlated positively with onset EDSS scores in acute-phase NMOSD (p<0.001, R2 = 0.487). Conclusions: Outcomes of NMOSD attacks were generally moderate. A high level of serum Th2-related cytokines predicted remission at the 1-month visit, and serum NfL may serve as a biomarker of disease severity at attack. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04101058, identifier NCT04101058.

Status of Immunotherapy Acceptance in Chinese Patients With Multiple Sclerosis: Analysis of Multiple Sclerosis Patient Survival Report 2018.

Objective: The prevalence of multiple sclerosis (MS) in China is low, although it has been increasing recently. Owing to the paucity of data on immunotherapy acceptance in the Chinese population, we conducted this study to analyze factors affecting the acceptance of immunotherapy and selection of disease-modifying therapies (DMTs) based on personal and clinical data of patients with MS. Methods: In this study, data were obtained from the Multiple Sclerosis Patient Survival Report 2018, which was the first national survey of patients with MS in China. There were 1,212 patients with MS from 31 provinces who were treated at 49 Chinese hospitals over a 4-month period from May 2018 to August 2018, and the patients were asked to complete online questionnaires to assess their understanding of the disease. Results: In general, highly educated patients with frequent relapses were more willing to receive treatment regardless of DMTs or other immunotherapy, and patients with more understanding of the disease opted to be treated. Younger patient population, patients with severe disease course, and those with more symptoms were likely to choose the treatment. Moreover, a higher proportion of women chose to be treated with DMTs than with other immunotherapies. Conclusions: Education status and patient awareness of the disease impact the treatment acceptance in Chinese patients with MS. Therefore, we call for improving the awareness of MS disease and social security to help patients to improve their quality of life.

CD8+ T-cell predominance in autoimmune glial fibrillary acidic protein astrocytopathy.

BACKGROUND AND OBJECTIVE: We aimed to report the pathological features of T lymphocytes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). METHODS: A retrospective pathological analysis of patients with GFAP-A was performed. RESULTS: Eight patients with GFAP-immunoglobulin G (IgG) and pathological data were included. Their biopsy findings were similar, and all showed marked lymphocytic infiltration in the white matter, with perivascular predominance. The lymphocytic infiltration was predominantly composed of CD8+ T lymphocytes rather than CD4+ T lymphocytes, except in one patient who had overlapping positive myelin oligodendrocyte glycoprotein-IgG. Unlike CD4+ T cells, CD8+ T cells were frequently observed adjacent to dystrophic neurons and astrocytes. There was also diffuse infiltration by CD68+ and CD163+ macrophages. CD8+ astrocytes were identified in two samples, but no CD4+ astrocytes were observed. CONCLUSIONS: A predominance of CD8+ T cells may be an important pathological and diagnostic feature in GFAP-A.

Autoimmune glial fibrillary acidic protein astrocytopathy mimics infectious meningitis: Two case reports.

BACKGROUND: Autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) has been recently characterized as a novel autoimmune central nervous system (CNS) disorder with GFAP antibody as the biomarker. However, nonspecific symptoms of A-GFAP-A contribute to misdiagnosis. CASE PRESENTATION: The patients presented with initial symptoms of fever, headache, and nuchal rigidity. Case 1 exhibited mild signs of irritability, active tendon reflexes, and dysuria; case 2 had transient loss of consciousness. Cerebrospinal fluid (CSF) revealed lymphocytosis, elevated protein level, and decreased glucose level. Magnetic resonance imaging (MRI) revealed radial gadolinium enhancement perpendicular to the lateral ventricle. Viral meningitis or tubercular meningitis was suspected. However, their inflammatory and pathogenic indicators showed no abnormal changes, and empirical antibiotic and antiviral drugs did not result in remarkable recovery. Subsequently, cases were detected with a strongly positive expression of GFAP antibody in CSF and the symptoms improved dramatically after high-dose methylprednisolone pulse treatment. CONCLUSION: A-GFAP-A with meningitis-like symptoms could initially masquerade as intracranial infection, and prompt detection of GFAP antibody is essential for differentiation.

Autoimmune glial fibrillary acidic protein astrocytopathy with lesions distributed predominantly in the entire spinal cord.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been considered a novel central nervous system autoimmune disease characterized by relapse and responsiveness to corticosteroid with a specific GFAP-Immunoglobulin G (IgG) being noted in cerebrospinal fluid. We report the case of a 21-year-old girl presenting with dysuria and weariness, who subsequently developed blurry vision, slight dysphagia, slurred speech, and sensory abnormality. GFAP-IgG was detected in her cerebrospinal fluid. Magnetic resonance imaging using both T2-weighted and contrast-enhanced T1-weighted images revealed a rare finding of lesions distributed mainly in the entire spinal cord rather than typical brain lesions. After treating with corticosteroids, her clinical symptoms were alleviated, and the spinal cord lesion enhancement was reduced. Our observations extend the clinical spectrum of autoimmune GFAP astrocytopathy. We suggest that rare distributed lesions in the entire spinal cord in patients with autoimmune GFAP astrocytopathy cannot be ignored by neurologists. The identification of potential atypical lesions broadens the understanding of autoimmune GFAP astrocytopathy.