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Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.

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The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. METHODS: From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. RESULTS: Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. CONCLUSIONS: NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.

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Inflammatory demyelinating disease of the CNS (IDD) is a heterogeneous group of autoimmune diseases, and multiple sclerosis is the most common type. Dendritic cells (DCs), major antigen-presenting cells, have been proposed to play a central role in the pathogenesis of IDD. The AXL+SIGLEC6+ DC (ASDC) has been only recently identified in humans and has a high capability of T cell activation. Nevertheless, its contribution to CNS autoimmunity remains still obscure. Here, we aimed to identify the ASDC in diverse sample types from IDD patients and experimental autoimmune encephalomyelitis (EAE). A detailed analysis of DC subpopulations using single-cell transcriptomics for the paired cerebrospinal fluid (CSF) and blood samples of IDD patients (total n = 9) revealed that three subtypes of DCs (ASDCs, ACY3+ DCs, and LAMP3+ DCs) were overrepresented in CSF compared with their paired blood. Among these DCs, ASDCs were also more abundant in CSF of IDD patients than in controls, manifesting poly-adhesional and stimulatory characteristics. In the brain biopsied tissues of IDD patients, obtained at the acute attack of disease, ASDC were also frequently found in close contact with T cells. Lastly, the frequency of ASDC was found to be temporally more abundant in acute attack of disease both in CSF samples of IDD patients and in tissues of EAE, an animal model for CNS autoimmunity. Our analysis suggests that the ASDC might be involved in the pathogenesis of CNS autoimmunity.

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Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

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Anti-myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) associated disorder (MOGAD) is an immune-mediated central nervous system (CNS) inflammatory demyelinating disorder that has been widely recognized in recent years. It is distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), which are separate disease spectrums. Here we report the case of a 5-year-old boy who was admitted for 3 days with fever, headache, and vomiting. Magnetic resonance imaging revealed abnormal hyperintensity in the left thalamus and positive serum IgM for M. pneumoniae. After treatment with azithromycin, the headache gradually disappeared, but paralysis and urinary retention occurred on the 6th day after admission. MRI re-examination showed that the original abnormal signal in the left thalamus was significantly weakened, but new abnormal signals appeared in the brain and cerebrospinal cord, and the serum MOG-IgG was positive. After treatment, the child has fully recovered and is still receiving follow-up care. We believe that this is a case of MOGAD in a child with a biphasic ADEM phenotype secondary to M. pneumoniae infection, which has potential value in elucidating the pathophysiology of MOGAD.

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Neuromyelitis optica spectrum disease (NMOSD) is a debilitating autoimmune inflammatory demyelinating disease of the central nervous system. The relationship between harboring an infection and NMOSD is currently unclear and needs further investigation. This article reports meningoencephalitis-like manifestations, including fever, headache, neck resistance, seizures, and pleocytosis, accompanied by nausea and vomiting, in a patient with serum AQP4 antibody-positive area postrema syndrome (APS). In the presence of aseptic meningitis combined with clinical symptoms such as optic neuritis and myelitis, the possibility of NMOSD diagnosis can be considered. However, for patients with unknown causes, especially combined with aseptic meningitis, a probable differential diagnosis of NMOSD is considered.

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Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare inflammatory disease of the central nervous system. There are a variety of clinical and imaging manifestations of MOG antibody disease (MOG-AD). At present, there is no report on related cases of MOG antibody positivity complicated with teratoma in China, and one case admitted to our hospital is reported. By reviewing relevant literature to increase the study of MOG-AD.

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BACKGROUND: Combined central and peripheral demyelination (CCPD) is a disease of inflammatory demyelination that affects central and peripheral nerves simultaneously or temporally separated. OBJECTIVES: This study evaluated the clinical characteristics and the existence of antinodal/paranodal antibodies in patients with CCPD. METHODS: We reviewed the clinical manifestations, laboratory tests, electrophysiological examinations, neuroimaging findings, treatment, and prognosis of 31 patients with CCPD. Using a live cell-based assay, we tested antinodal/paranodal antibodies. RESULTS: The most common symptoms were motor weakness (83.3%), hyporeflexia (63.3%), and sphincter disturbance (58.1%). In total, 16.6% of patients had impaired vision symptoms, whereas 33.3% of patients had abnormal visual-evoked potentials (VEPs). A total of 21.1% (4/19) of patients were positive for anti-AQP4 (aquaporin 4) antibodies, 20.0% (2/10) of patients were positive for anti-NF155 (neurofascin-155) antibodies, and 10.0% (1/10) of patients were positive for anti-MAG (myelin-associated glycoprotein) antibodies. The effective rates of intravenous corticosteroids, intravenous immunoglobulins, and rituximab were 72.2%, 37.5%, and 100%, respectively. At the illness peak, 75% of patients with CCPD had an mRS (modified Rankin Scale) score of 4 or greater. In remission, 37.5% had an mRS score of 4 or greater. CONCLUSION: The clinical manifestations of patients with CCPD are highly heterogeneous. We recommend testing antinodal/paranodal antibodies for patients with CCPD.

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Poly (ADP-ribose) polymerase 1 (PARP1) plays a fundamental role in DNA repair and gene expression. Excessive PARP1 hyperactivation, however, has been associated with cell death. PARP1 and/or its activity are dysregulated in the immune and central nervous system of multiple sclerosis (MS) patients and animal models. Pharmacological PARP1 inhibition is shown to be protective against immune activation and disease severity in MS animal models while genetic PARP1 deficiency studies reported discrepant results. The inconsistency suggests that the function of PARP1 and PARP1-mediated PARylation may be complex and context-dependent. The article reviews PARP1 functions, discusses experimental findings and possible interpretations of PARP1 in inflammation, neuronal/axonal degeneration, and oligodendrogliopathy, three major pathological components cooperatively determining MS disease course and neurological progression, and points out future research directions. Cell type specific PARP1 manipulations are necessary for revisiting the role of PARP1 in the three pathological components prior to moving PARP1 inhibition into clinical trials for MS therapy.

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OBJECTIVE: . To review the Mayo clinic experience of cyclophosphamide in the treatment of tumefactive Multiple Sclerosis (TMS). METHODS: . Retrospective chart review was performed to identify patients with TMS who did not respond to corticosteroid and plasma exchange and were treated with cyclophosphamide. Demographic, clinical, treatment, and outcome parameters were collected. RESULTS: . We identified 12 patients with TMS who were treated with cyclophosphamide. Median follow-up was 17 (range 1-72) months after cyclophosphamide administration. The tumefactive attack was the first clinical symptom in 5/12 patients. The median age at index attack onset was 36 (range 22-57). The median age at the first demyelinating attack was 29.3 (range 20-55). The most common clinical presentation at the index attack was the visual disturbance, followed by motor symptoms. The index attack was accompanied by headache in 5/12 patients. Median attack related Expanded Disability Status Scale (EDSS) score was 6 (range 3-9.5), which improved to 5.25 (range 1-10) after treatment with cyclophosphamide. All patients were treated with corticosteroids and plasma exchange prior to treatment with cyclophosphamide. EDSS score improved in 8/12 patients and targeted neurological deficits improved to a moderate or marked degree in 9/12 patients after cyclophosphamide administration. The number of gadolinium enhancing lesions decreased in 10/12 and 8/12 patients had lack of disease activity (no new T2 or GAD lesions) in a median (range) time of 11 months (1-16) after the last dose of cyclophosphamide. CONCLUSION: . Cyclophosphamide could be an effective option for the treatment of TMS, refractory to corticosteroids and plasmapheresis, and is associated with improvement of clinical and radiological disease activity.

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OBJECTIVES: To identify and analyze the characteristics of the most influential articles about central nervous system (CNS) inflammatory demyelinating disease. MATERIALS AND METHODS: The Institute for Scientific Information (ISI) Web of Science database and the 2014 Journal Citation Reports Science Edition were used to retrieve the top 100 cited articles on CNS inflammatory demyelinating disease. The citation numbers, journals, years of publication, authorships, article types, subjects and main issues were analyzed. For neuromyelitis optica (NMO), articles that were cited more than 100 times were regarded as a citation classic and described separately. RESULTS: The top 100 cited articles were published between 1972 and 2011 in 13 journals. The highest number of articles (n = 24) was published in Brain, followed by The New England Journal of Medicine (n = 21). The average number of citations was 664 (range 330-3,897), and 64% of the articles were from the United States and the United Kingdom. The majority of the top 100 cited articles were related to multiple sclerosis (n = 87), and only a few articles reported on other topics such as NMO (n = 9), acute disseminated encephalomyelitis (n = 2) and optic neuritis (n = 2). Among the top 100 cited articles, 77% were original articles. Forty-one citation classics were found for NMO. CONCLUSIONS: Our study provides a historical perspective on the research progress on CNS inflammatory demyelinating disease and may serve as a guide for important advances and trends in the field for associated researchers.

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We report a 35-year-old healthy male who developed central nervous system inflammatory demyelinating disease consistent with tumefactive multiple sclerosis. About 2 weeks after onset of symptoms and prior to initiation of therapy, the patient had lymphopenia and low CD4 and CD8 levels. His lymphocyte count was 400 cells/µl (850-3,900 cells/µl), CD4 was 193 cells/µl (490-1,740 cells/µl) and CD8 was 103 cells/µl (180-1,170 cells/µl). He was treated with intravenous methylprednisolone followed by therapeutic plasma exchange, the levels of CD4 and CD8 normalized, and ultimately, he recovered completely.

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BACKGROUND: Tumefactive demyelinating lesions (TDLs) are associated with a variety of demyelinating diseases in the central nervous system (CNS). However, there are no current guidelines describing how to classify and treat patients with this rare phenotype. Thus, the present study aimed to determine the long-term evolution and disease course of patients initially presenting with TDLs and to describe their clinical and radiographic characteristics. METHODS: From the National Cancer Center registry of inflammatory diseases of the CNS, 31 patients initially presenting with TDLs with follow-up for at least 12 months were enrolled and their demographic, clinical, and radiographic characteristics were evaluated. RESULTS: The median follow-up duration was 37.6 months, during which time 11 patients were diagnosed with neuromyelitis optica spectrum disorder (NMOSD), seven with multiple sclerosis (MS), and 11 remained idiopathic; six did not experience any further clinical events (isolated demyelinating syndrome), and five patients experienced recurrent demyelinating events that were not consistent with either MS or NMOSD. Of the remaining two patients, one was diagnosed with hyperthyroidism-associated demyelination and one with tacrolimus-induced demyelination. CONCLUSIONS: The majority of TDLs evolve into MS or NMOSD. However, despite extensive diagnostic work-ups and long-term follow-ups, the etiology of TDLs was unknown for some patients.

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Acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome (GBS) are distinct demyelinating disorders that share an autoimmune pathogenesis and prior history of viral infection or vaccination. Our patient is a 10 years with acute flaccid paralysis, quadriparesis (lower limbs affected more than upper limbs), generalized areflexia and urinary retention. He had difficulty in speech and drooling of saliva. He also presented with raised intracranial pressure with papilledema; then bilateral optic neuritis developed during the later course of illness. Based on the temporal association and exclusion of alternative etiologies, diagnosis of the association between ADEM and GBS was made. Electro-diagnosis (electromyography-nerve conduction velocity) and magnetic resonance imaging study supported our diagnosis. He improved remarkably after treatment with intravenous immunoglobulin and intravenous methylprednisolone.

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Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating autoimmune inflammatory diseases that affect the central nervous system (CNS). Previous genome-wide or candidate gene studies have suggested that genetic variants might be associated with the risk of MS or NMO. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the CNS, and its expression is decreased in NMO lesions due to astrocyte cytotoxicity. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with MS and/or NMO. However, there have been few replication studies in various ethnic populations. This study, as the first of its kind performed in an Asian population, investigated associations of AQP4 SNPs with the risk of inflammatory demyelinating disease (IDD), including MS and NMO, in a Korean population. A total of seven common AQP4 SNPs were selected based on status of linkage disequilibrium (LD), and then genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of IDD, including MS and NMO (P>0.05). Further replications in larger cohorts and other ethnic groups are needed.

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AIMS: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory autoimmune diseases that affect the central nervous system. Several genome-wide and candidate gene studies have identified genetic polymorphisms associated with the risk of MS or NMO. In particular, two recently published studies of meta-analysis in European-origin populations have suggested associations of single-nucleotide polymorphisms (SNPs) in CD6, TNFRSF1A and IRF8 with MS. The aim of our study was to assess the associations between SNPs in these three genes and the risk of inflammatory demyelinating disease (IDD) including MS and NMO. To the best of our knowledge, this is the first time such a study has been performed in an Asian population. METHODS: A total of 21 SNPs of CD6, TNFRSF1A and IRF8 were genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls in a Korean population. RESULTS: Logistic analyses revealed that one SNP in CD6 (rs12288280, P = 0.04) and three SNPs in TNFRSF1A (rs767455, rs4149577 and rs1800693, P = 0.01-0.03) were associated with NMO. However, there was no association of IRF8 polymorphisms with IDD, including MS and NMO. Using further information from the SNP Function Prediction website, two exonic splicing enhancers (ESEs), including the polymorphic site of rs767455, were predicted to be binding sites for splicing factors (SRp55, SF2/ASF2 and SF2/ASF1). CONCLUSION: Although additional studies are needed, our findings could provide information regarding the genetic aetiology of IDD in the Korean population.

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Objective To investigate the clinical and imaging characteristics of tumor like inflammatory demyelinating disease of CNS, We have analyzed the reason of misdiagnosis, and summed up the main point of differential diagnosis.Methods We have analyzed 14 cases which were confirmed as demyelinating disease in pathology after the operation, and all the clinical and image data were included.Results CNS inflammatory demyelinating disease could present edema and mass effect by CT or MRI, there was ring potentialization after enhancement, it was difficulty to distinguish from CNS demyelinating disease. All the 14 patients were misdiagnosis as CNS tumor before the operation.Conclusion CNS inflammatory demyelinating disease could have some atypical representation on CT or MRI image, they were made easily the misdiagnosis. We should get the differential diagnosis by many ways including clinical manifestation, course, laboratory examination and imaging characteristics.