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.

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.

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.

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.

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.

Acute-phase serum superoxide dismutase level as a predictive biomarker for stroke-associated infection.

Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.

Clinical Heterogeneity in Patients with Glutamate Decarboxylase Antibody.

OBJECTIVE: To explore the diversity and clinical features of anti-glutamate decarboxylase (GAD) antibody-associated neurological diseases. METHODS: Clinical data of a series of 5 patients positive for anti-GAD antibodies were retrospectively analyzed. RESULTS: All 5 patients were female, with a median age of 41.5 years (range 19-60 years). Their neurological symptoms included stiff-person syndrome (SPS), encephalitis, myelitis, cramp, visual loss, and paresthesia. Three patients (60%) were diagnosed with tumors, 2 cases of thymic tumor and 1 of breast cancer. On immunohistochemistry for tumor pathology, expression of GAD65 was found only in 1 patient. Four patients (80%) had abnormal brain MRI findings. All patients received immunotherapy and improved significantly after treatment, but 4 (80%) then experienced a relapse. CONCLUSIONS: Neurological manifestations in anti-GAD-positive patients are diverse and include SPS, encephalitis, myelitis, cramp, visual loss, and paresthesia.

Patients with suspected benign tumors and glial fibrillary acidic protein autoantibody: an analysis of five cases.

Aim: To investigate the clinical features of five glial fibrillary acidic protein (GFAP) antibody positive patients with suspected benign tumors and explore its underlying pathogenesis. Materials and methods: Overall, 1018 serum and cerebrospinal fluid (CSF) samples were tested by indirect immunofluorescence assay and data from five patients with suspected tumors and positive for GFAP autoantibody in the CSF were analyzed retrospectively. Results: The positive rate of GFAP antibody in the serum and CSF was 3.93% by indirect immunofluorescence assay. Tumors were diagnosed before or after neurologic onset in 5 of 40 patients (12.5%) and no deterioration of the tumors was found during the long-term follow-up. Of the five patients, one patient suffered a thyroid nodule, one patient had a small nodule in the left lung, two patients suffered meningiomas, and one patient had a suspicious eosinophilic granuloma. Conclusion: GFAP autoimmunity may be a paraneoplastic immune response with a low frequency of tumor in Chinese patients with GFAP astrocytopathy.

Glutamic Acid Decarboxylase Antibody in a Patient with Myelitis: A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the positive rate of serum glutamic acid decarboxylase (GAD) autoantibody in patients with myelitis and to describe the clinical findings in patients with positive GAD antibody. METHODS: Serum samples were collected from 390 patients with myelitis, including 210 patients positive for aquaporin 4 (AQP4) antibody and 180 patients negative for AQP4. GAD65 antibody was measured by an indirect immunofluorescence assay. RESULTS: Only 1 serum and cerebral spinal fluid sample from 390 patients (0.26%) was positive for anti-GAD antibodies. The patient was a female with relapsing myelitis and a thymic mass. Thymic resection was undertaken, and pathological examination revealed a benign thymic cyst. Extensive infiltration of lymphocytes positive for CD3, CD4, CD8 and CD20 was found. Immunohistochemistry showed positive expression of GAD65 in the cyst. CONCLUSIONS: Although serum GAD65 antibodies were present in a patient, it is not recommended to routinely screen for GAD65 antibodies in patients with myelitis because of their rare occurrence. However, screening for GAD65 antibodies should be considered in patients who have been diagnosed with cancer or a thymic abnormality.

Brain Immunohistopathology in a Patient with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel meningoencephalomyelitis. However, the pathogenesis of this disease is unclear. We therefore examined a brain biopsy from a patient with autoimmune GFAP astrocytopathy by immunohistopathology. METHODS: We examined brain biopsy sections from a patient with autoimmune GFAP astrocytopathy using hematoxylin and eosin (HE) and Luxol fast blue (LFB) staining, and immunostaining with antibodies for CD4, CD8, CD3, CD20, CD68, CD138, Neu-N, GFAP, myelin oligodendrocyte glycoprotein (MOG), and aquaporin-4 (AQP4). RESULTS: HE staining revealed extensive inflammatory cells (marked lymphocytes) around brain vessels, and LFB showed no signs of demyelination or axon loss. Immunohistochemical analysis showed CD3+ and CD4+ T cells cuffing around brain vessels, accompanied by CD8+ T cells, CD20+ B cells, and CD138+ plasma cells, while some macrophages (CD68+) were scattered throughout the brain parenchyma. There was no loss of AQP4 or MOG expression in this patient, while GFAP was abundantly expressed. CONCLUSIONS: These findings suggest that inflammatory cells, including T cells, B cells, plasma cells, and macrophages, are involved in autoimmune GFAP astrocytopathy. Demyelination and astrocyte loss may not necessarily occur in this disease.

Treatment of Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: Follow-Up in 7 Cases.

OBJECTIVE: The aim of this work was to report an autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy with long-term follow-up in 7 patients. METHODS: Antibodies were detected by indirect immunofluorescence assay and patient data were analyzed retrospectively. RESULTS: Seven patients (4 female, 3 male) with ≥1 year follow-up were included. All patients had positive GFAP antibodies in their cerebral spinal fluid (CSF). Their median age at disease onset was 56 years (range 27-69) and the median disease duration was 1 year (range 1-4). In the initial attack, all patients received intravenous methylprednisolone (IVMP) followed by oral steroids, which were tapered. Six patients received intravenous immunoglobulin (IVIg). One patient had no response to IVIg and IVMP. Four patients received immunosuppressive agents. Five patients underwent the second lumbar puncture after treatment. CSF white blood cell counts, protein levels, and antibody titers were significantly decreased. CSF protein levels correlated positively with the Expanded Disability Status Scale score, which was elevated at each lumbar puncture. Four patients experienced relapse. To date, 6 patients had a bad prognosis, of which 2 died. CONCLUSIONS: Some patients with GFAP astrocytopathy experienced a poor response to treatment although they received steroids and immunosuppressive agents.

STAF score is a new simple approach for diagnosing cardioembolic stroke.

BACKGROUND AND PURPOSE: Detecting cardioembolic stroke soon after acute cerebral ischemia has a major impact on secondary stroke prevention. Recently, the Score for the Targeting of Atrial Fibrillation (STAF) was introduced to identify stroke patients at risk of atrial fibrillation. However, whether the STAF score could be a useful approach to differentiate cardioembolic stroke from other stroke subtypes is unclear. METHODS: Consecutive patients with acute ischemic stroke that were admitted to our stroke center were enrolled. Each patient was assessed (age, baseline National Institutes of Health Stroke Scale, left atrial dilatation and absence of vascular etiology) to calculate the STAF score. A follow-up visit was conducted for each patient during hospitalization to determine the diagnosed stroke etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: The median and interquartile range of the STAF score was significantly higher in the cardioembolic than in the non-cardioembolic group [6 (2) vs. 2 (3), p < 0.001]. The discriminating ability of the STAF score model was good as demonstrated by the receiver operating characteristic curve. The area under the curve (AUC) of STAF score (AUC = 0.98; 95% CI, 0.96-0.99) was significantly greater than B-type natriuretic peptide (AUC = 0.87; 95% CI, 0.83-0.91) (p < 0.05). The optimal STAF cut-off value was ≥ 5, which diagnosed cardioembolic stroke with a sensitivity of 90% and specificity of 95%. CONCLUSIONS: The STAF score is a simple and accurate tool that can discriminate the cardioembolic stroke from other types during hospitalization for acute ischemic stroke.

Aquaporin-4 antibody in neuromyelitis optica: re-testing study in a large population from China.

BACKGROUND: Aquaporin-4 (AQP4) antibody sero-positivity is critically important in neuromyelitis optica (NMO). However, the sensitivity of different assays is highly variable. Repeating detection with a highly sensitive assay in a large population is necessary in the case of so-called negative NMO. METHODS: Retrospective analysis where AQP4 antibodies were detected by commercial cell-based assay (CBA), in-house M23-CBA and in-house M1-CBA. RESULTS: Of the 1011 serum samples, 206 (20.4%) were sero-positive by primary commercial CBA. In the retest, all 206 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA again, but only 124 positive in in-house M1-CBA. Among the 805 participants negative by primary commercial CBA, 71 participants were positive for in-house M23-CBA, of which 20 participants were positive for the second commercial CBA, and none were positive by in-house M1-CBA. Of the 171 cerebral spinal fluid samples, 75 (43.9%) were positive by primary commercial CBA. All 75 participants positive by primary commercial CBA also yielded positive results by in-house M23-CBA and the second commercial CBA. Forty-nine (65.3%) of these 75 participants were positive by in-house M1-CBA. Among the 96 participants negative by primary commercial CBA, 15 participants were positive for in-house M23-CBA and none were positive by in-house M1-CBA and the second commercial CBA. CONCLUSIONS: Different AQP4 isoforms in CBA result in different detection effects, and in-house M23-CBA is the most sensitive method. Some AQP4 antibody-negative NMO may be subject to diagnostic uncertainty due to limitations of the assays.

Circular RNA expression alterations are involved in OGD/R-induced neuron injury.

Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen-glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.

Anti-KIR4.1 Antibodies in Chinese Patients with Central Nervous System Inflammatory Demyelinating Disorders.

OBJECTIVES: The aim of this study was to explore the frequency of KIR4.1 antibodies in patients with multiple sclerosis (MS) and in control groups using a cell-based assay. MATERIALS AND METHODS: A transfected HEK-293A cell line expressing KIR4.1 was established to test for the presence of KIR4.1 antibodies in blood serum. We tested 904 subjects, including 188 patients with MS, 264 patients with neuromyelitis optica spectrum disorders (NMOSD), 209 patients with other inflammatory neurologic disease (OIND), 203 patients with other noninflammatory neurological disease (OND), and 40 healthy controls. RESULTS: KIR4.1 antibodies were present in 23 of the 188 (12.2%) MS patients, 42 of the 264 (15.9%) NMOSD patients, 32 of the 209 (15.3%) OIND patients, 24 of the 203 (11.8%) OND patients, and 2 of the 40 (5%) healthy controls. There were no significant differences among the MS and control groups (p = 0.279). CONCLUSIONS: Anti-KIR4.1 antibody, as determined by a cell-based assay, is not a specific biomarker for MS.

Neuromyelitis optica spectrum disorders may be misdiagnosed as Wernicke's encephalopathy.

PURPOSE: To raise doctors' attention to the differential diagnosis of neuromyelitis optica spectrum disorders (NMOSD) and Wernicke's encephalopathy (WE). PATIENTS AND METHODS: We extensively reviewed the medical records of 136 patients who had visited our hospital since 2008 and were suspected of having central nervous system demyelinating diseases. Four of those patients had somnolence, electrolyte imbalance and brain lesions around the third ventricle and were included in the study. We tested the serum of the four patients for the presence of aquaporin-4 (AQP4) M23 antibody. RESULTS: All the four patients had positive AQP4 antibody in their serum. Two of the patients were misdiagnosed as WE before AQP4 antibody detection occurred. CONCLUSIONS: NMOSD and WE have similar brain lesion locations, histopathological changes and clinical manifestations. It is important to distinguish NMOSD from WE by detecting AQP4 antibody in serum or cerebral spinal fluid. Vitamin B1 should also be administered to the patients who have a history of thiamine deficiency.

Hypothalamic abnormality in patients with inflammatory demyelinating disorders.

BACKGROUND: Hypothalamic lesions in neuromyelitis optica (NMO) patients might be more specific for NMO than multiple sclerosis (MS). However, this is controversial. OBJECTIVE: To characterize clinical features of patients with inflammatory demyelinating disorders (IDDs) with visible hypothalamic lesions using magnetic resonance imaging (MRI). METHODS: Patients with IDDs (n = 429) were recruited retrospectively. RESULTS: Of 52 patients with hypothalamic images enrolled, 42 were positive for aquaporin-4 (AQP4) antibodies, including 28 patients with NMO, 6 with recurrent transverse myelitis, 3 with recurrent optic neuritis, and 5 with brainstem and brain syndrome. The remaining 10 patients were anti-AQP4-negative, including 3 with MS, 3 with acute disseminated encephalomyelitis, and 4 with other disorders. In the AQP4-positive group, manifestations, including ataxia, intractable hiccup and nausea, syndrome of inappropriate antidiuretic hormone secretion and encephalopathy were more frequent in those with hypothalamic lesions than those without. Cell counts of cerebrospinal fluid in patients with hypothalamic lesions differed from patients without lesions. Brain MRI abnormalities were more frequent in brainstem and hemisphere of the hypothalamic lesion group. CONCLUSIONS: Hypothalamic lesions were observed frequently in patients with AQP4 antibodies. Clinical manifestations and paraclinical features in AQP4-positive patients with hypothalamic lesions differed from those without lesions.

Dynamic change in magnetic resonance imaging of patients with neuromyelitis optica.

OBJECTIVE: To analyze changes in magnetic resonance imaging (MRI) of spinal cord lesions in neuromyelitis optica (NMO) and the correlation between segmental length of spinal cord lesions and expanded disability status scale (EDSS) scores. METHODS: Twenty-five patients with confirmed NMO were examined from the Second Affiliated Hospital of Guangzhou Medical University, China. The information collected included their treatment, MRI, laboratory tests, and EDSS scores at different stages. RESULTS: All cases exhibited spinal cord lesions, with 23 (92%) having longitudinally extensive transverse myelitis (extending ≥3 vertebral segments). There was a positive correlation between segmental length of spinal cord lesions and EDSS scores: during the acute phase, r = 0.430 (P = 0.032); during remission, r = 0.605 (P = 0.002). Enlarged spinal cord lesions and swelling were found in 18 cases (72%) during the acute phase, and 4 cases (16%, P = 0.000) after 6 months of treatment. Lesion enhancements were found in 17 cases (68%) during the acute phase, and 8 cases (32%, P = 0.023) after 6 months of treatment. Leptomeningeal enhancement was found in three cases during the acute phase, which disappeared after treatment. Atrophy of spinal cord lesions occurred in two cases. Change in lesions was statistically significant (P = 0.006) after 12 months of treatment. CONCLUSION: Positive correlation was found between segmental length of spinal cord lesions and EDSS scores, which was more significant during remission. After 6 months of regular treatment, restorative changes compared with the acute phase were found by MRI.

No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: To evaluate whether serum glutamic acid decarboxylase (GAD), N-methyl-D-aspartate-receptor (NMDAR), and aquaporin-4 (AQP4) autoantibodies coexist in patients with neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD). METHODS: Serum samples were collected from 98 patients with NMO/NMOSD. Serum GAD65, NMDAR and AQP4 antibodies were measured using a cell-based assay. RESULTS: A total of 63 patients (64.3%) had myelitis and optic neuritis and satisfied the revised diagnostic criteria for NMO. Longitudinally extensive transverse myelitis was seen on spinal cord magnetic resonance imaging, showing continuous T2-weighted signal abnormalities in at least three vertebral segments in 26 patients (26.5%); 5 patients (5.1%) had recurrent optic neuritis, and 4 patients (4.1%) had brain syndromes with optic neuritis and myelitis. None of the 98 patients had diabetes, stiff-man syndrome, or epilepsy. All 98 patients tested positive for AQP4 antibody. No patients tested positive for GAD65 and NMDAR antibodies. CONCLUSIONS: In the present study, we found no simultaneous presence of serum GAD65, NMDAR and AQP4 antibodies in patients with NMO/NMOSD.

[Correlation of AQP4 gene polymorphism with NMO clinical phenotypes and its underlying mechanism].

OBJECTIVE: To explore the correlation between aquaporin-4 (AQP4) gene single nucleotide polymorphism (SNP) and clinical phenotypes of neuromyelitis optica (NMO) and its underlying mechanism. METHODS: Eight SNPs in AQP4 gene regulatory region were selected and genotyped for 208 anti-AQP4 autoantibodies (NMO-IgG) seropositive cases during January 2010 to January 2014 and 204 healthy subjects. Then the correlation was further analysed between genotypes and NMO phenotypes. And the effect of microRNA (miRNA) on the expression of AQP4 gene was examined by dual-luciferase reporter technique. RESULTS: The A/T genotype of rs1058424 (50.61% vs 70.45%, OR = 0.430, 95% CI 0.210-0.880) and C/T (50.00% vs 68.18%, OR = 0.467, 95%CI 0.231-0.994) genotype of rs3763043 in 3'-UTR were correlated with longitudinal extensive transverse myelitis; the A/T genotype of rs1058424 (46.72% vs 66.28%, OR = 0.525, 95% CI 0.276-0.999) and A/C genotype of rs335929 (45.08% vs 58.14%, OR = 0.527, 95% CI 0.281-0.987) in 3'-UTR as well as C/T genotype of rs151244 (50.82% vs 69.77%, OR = 0.450, 95% CI 0.230-0.881) in promoter 0 region were correlated with optic neuritis. The polymorphism of rs6508459 in 3'-UTR and rs3763040 in intron region were correlated with concurrent systemic autoimmune diseases (P = 0.012 and 0.023 respectively).miRNA 323-3p could regulate AQP4 gene expression.However, variation in SNP rs1058424 failed to affect this regulation. CONCLUSION: SNP in 3'-UTR of AQP4 gene may be associated with NMO phenotypes.miRNA 323-3p may participate in the pathogenesis of NMO by binding to certain SNP sites in 3'-UTR of AQP4 gene and regulating its expression.