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The spectrum of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE), and aquaporin-4-IgG (AQP4-IgG)-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF) and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial two-fold dilutions to determine endpoint titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relations between MOG-IgGSERUM, MOG-IgGCSF, and the phenotypes with multivariable regression. A total of 671 patients were tested (405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD, and 119 with other neurological diseases [OND]) before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15, and Others 11), 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5, and Others 4), and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0, and Others 7) cases. None of AQP4-IgG-positive NMOSD, multiple sclerosis, or OND cases tested positive for MOG-IgGSERUM but two with multiple sclerosis were MOG-IgGCSF-positive; the specificity of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% (95%CI 99%–100%) and 99% (97%–100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM were associated with ON and ADEM, whereas MOG-IgGCSF were associated with ADEM and CE. The number needed to test (NNT) of MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY, and 6.1 for Others). In the status of MOG-IgGSERUM/CSF, most cases were double-positive, while including either serum-restricted (13%) or CSF-restricted (17%). These statuses were independently associated with clinical phenotypes, especially with ON in serum and CE in CSF, suggesting these pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted for the clinical and pathological significance of compartmentalized MOG-IgG.

Objective The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD). Methods In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments. Results Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined. Conclusions The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.

A 26-year-old woman developed a sudden headache, ptosis, and diplopia. Magnetic resonance imaging and angiography demonstrated a symmetrical lesion from the midbrain to the brainstem, involving the solitary nucleus and multifocal cerebral artery narrowing. Reversible cerebral vasospasm syndrome (RCVS) was suspected, and the patient improved after vasodilatation. Leigh syndrome was suspected due to the elevated serum lactate levels, so mitochondrial DNA was analyzed, and an m.9176 TC mutation was detected. The final diagnosis was adult-onset Leigh syndrome manifesting as RCVS. An uncontrolled baroreflex due to a solitary nuclear lesion or endothelial dysfunction may have contributed to her unique presentation.

Objective To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey. Methods Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS. Results Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG. Conclusions MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS.

Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46–71 years) and a median disease duration of 62.5 months (range, 0.6–252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.

Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P

Myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) are associated with various central nervous system demyelinating disorders. Recently, they were detected in cerebral cortical encephalitis (CCE), which often causes seizures. We performed a literature review to elucidate the electroclinical features of CCE. In addition to the published cases, we describe a new, illustrative case of MOG-Ab-associated CCE (MOG-CCE) with multifocal seizures documented by video electroencephalograph (EEG).We searched PubMed with the keywords "[MOG] AND [encephalitis]" and reviewed relevant articles. The articles included reports of patients with CCE (as demonstrated by magnetic resonance imaging) and serum MOG Ab positivity. Cases were excluded if no epileptic seizures were reported or if details of the seizures were unavailable.Our literature review identified 34 patients with MOG-CCE. An analysis of these 34 cases and the new case showed that 20 patients were male (57.1%), and the median age at presentation was 23 years (range, 6 to 46 years). Focal to bilateral tonic-clonic seizure was the most common seizure type, followed by focal motor seizure in the face or an arm or leg. EEG findings were available for 26 patients. Interictal epileptiform discharges (IEDs) and ictal EEG patterns were seen in 10 (38.5%) and 5 (19.2%) patients, respectively. Focal EEG abnormalities, including slow waves and IEDs, were observed in the central, parietal, occipital, or posterior temporal region.MOG-CCE has distinctive electroclinical features that differ from those of other autoimmune encephalitides. Careful electroclinical analysis of seizures can be helpful for diagnosing MOG-CCE.

Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p p p = 0.0027), and neutrophil (p

The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD).In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments.Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined.The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.

A 66-year-old woman presented with upper abdominal pain and weakness in the limbs. She had bilateral uveitis and gastric ulcers. A neurological examination revealed tetraparesis and sensory disturbance in the right arm. A cerebrospinal fluid (CSF) examination showed polymorphonuclear pleocytosis with elevated pro-inflammatory cytokine levels. Magnetic resonance imaging showed brain lesions and a long spinal cord lesion. She was initially diagnosed with neuro-Behcet's disease and was treated with corticosteroids, resulting in no improvement. A gastric mucosa biopsy indicated T-cell lymphoma colocalizing with neutrophils. The cytokine-mediated neutrophilic inflammation probably caused characteristic CSF and histopathological features. It is noteworthy that T-cell lymphoma may present with CSF neutrophilic inflammation.

Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear.Patients with these diseases were repeatedly evaluated using optical coherence tomography (OCT) for the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) in the ON-involved eyes during relapse-free period after the first ON episode before relapse. Optic MRI with short tau inversion recovery (STIR) sequences was further evaluated retrospectively.Twelve patients with MOGAD (20 eyes with ON-involvement) and 14 with AQP4-Ab-positive NMOSD (16 eyes with ON-involvement) were enrolled. The progression of retinal atrophy ≥12 months after onset was observed in AQP4-Ab-positive NMOSD, but was not apparent in MOGAD. A decrease in retinal thickness by the same amount results in more severe visual impairment in AQP4-Ab-positive NMOSD. On optic MRI, the residual STIR hyperintensity in the optic nerves remained in the chronic phase in almost all eyes with ON in both diseases. Optic nerve atrophy occurred in all evaluated ON-involved eyes in AQP4-Ab-positive NMOSD, while it was observed in half of ON-involved eyes in MOGAD.Progression of retinal atrophy in the chronic phase has been observed in patients with AQP4-Ab-positive NMOSD, while it remains uncertain in patients with MOGAD. The visual impairments upon similar levels of retinal atrophy would be worse in AQP4-Ab-positive NMOSD, possibly attributable in part to a higher incidence of optic nerve atrophy in this disease.

ObjectiveTo elucidate the differences in the source and in the level of intrathecal synthesis between anti–aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).MethodsThirty-eight patients with MOG-IgG–associated disease and 36 with AQP4-IgG–positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients.ResultsEleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG–positive cases and 43.8% of AQP4-IgG–positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability.ConclusionsIntrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG–associated disease and AQP4-IgG–positive NMOSD.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may develop concurrently with or separate from episodes of demyelinating disorders. Previously, we reported a patient with relapsing anti-NMDAR encephalitis who had presented with bilateral medial frontal cerebral cortical lesions at onset. Recently, we assessed CSF anti-myelin oligodendrocyte glycoprotein (MOG) antibody for the first time in this case and found that the patient had been double positive for anti-NMDAR and anti-MOG antibodies from onset. The two antibody titres, CSF cells, IL-6 and CXCL13 were all elevated at onset. Anti-NMDAR encephalitis may develop concurrently with anti-MOG antibody-associated cortical encephalitis and relapse with elevated levels of CSF cytokines.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Objective: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Methods: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Results: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this ‘relapsing group’, relapse rate declined by 37% (95%CI=19–52%, p Conclusion: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

Myelin oligodendrocyte glycoprotein (MOG)-IgG detected by the cell-based assay is associated with demyelinating diseases of the central nervous system, such as optic neuritis, myelitis, and acute disseminated encephalomyelitis, but rarely with peripheral neuropathy. Here, we describe the case of a 32-year-old MOG-IgG+ woman who developed central and peripheral demyelinating lesions. In contrast to previous similar cases, she uniquely presented with repeated subsequent relapses in the peripheral nerve, mimicking chronic inflammatory demyelinating polyneuropathy. Possible pathogenic implications of MOG-IgG in combined central and peripheral nervous system diseases are considered.

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been detected in inflammatory demyelinating central nervous system diseases. A 30-year-old woman had blurred vision, marked optic nerve disc swelling, serous retinal detachment at the macular on optic coherence tomography, and MOG-IgG seropositivity. The patient was thought to have optic papillitis associated with MOG-IgG. Her symptoms rapidly improved after high-dose methylprednisolone therapy. We hypothesize that serous retinal detachment was secondary, arising from optic papillitis. This is the first report of the concurrence of optic papillitis with MOG-IgG and serous retinal detachment. MOG-IgG should be tested in patients with marked optic disc swelling.

Background Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in developmental regression after normal development during infancy. Transient presentation of many autistic features is also commonly seen in RTT. Anti-myelin oligodendrocyte glycoprotein (MOG)-antibody encephalitis is an acquired relapsing demyelinating syndrome characterized by a variety of neuroinflammatory symptoms. Here, we report a case of anti-MOG antibody encephalitis in a patient with genetically confirmed RTT, which mimicked many of the features of RTT. Case report A three-year-old girl presented with subacute verbal and motor dysfunction, along with involuntary movements and marked irritability. Magnetic resonance imaging (MRI) revealed extensive white matter lesions, with anti-MOG antibodies detected in the serum and cerebrospinal fluid, resulting in an initial diagnosis of anti-MOG antibody encephalitis. However, additional testing of the MECP2 gene was performed in response to persistent involuntary hand movements in combination with progressive verbal and motor deterioration. Sequencing analysis revealed a known pathogenic mutation in MEPC2, indicating a concurrent diagnosis of RTT. Conclusion Both RTT and anti-MOG antibody encephalitis are rare conditions. Similarities in disease presentation suggest that anti-MOG antibody encephalitis may mimic many of the symptoms of RTT.

Background The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known. Patient We are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti-myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by recurrent ON. She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment with AZA when CD19 cells reappeared 6 months after the first rituximab infusion. However, she has not relapsed since her CD19 count was reduced and kept low with rituximab infusion. Conclusions It is conceivable that anti-MOG antibodies are involved in the pathology of “ADEM followed by recurrent ON,” and that the early introduction of rituximab, which is involved in the suppression of antibody production and has effects on CD20 T lymphocytes, may be a feasible treatment for ON. Due to the small number of patients, additional reports on prospectively followed patients are needed.

Myelin oligodendrocyte glycoprotein (MOG) is localized at the outermost layer of the myelin sheath and is accessible for autoantibodies. Although experimental autoimmune encephalitis induced with MOG immunization has been studied for 30 years, the results of previous reports on MOG immunoglobulin G (IgG) detection with enzyme-linked immunosorbent assay and Western blot are confusing. However, after the development of human MOG-transfected cell-based assay to detect conformational-sensitive MOG-IgG, unique groups of patients have been found seropositive, and MOG-IgG-associated disease has become a hot topic in clinical neuroimmunology. Currently, the clinical spectrum of MOG-IgG-associated disease includes idiopathic optic neuritis, acute disseminated encephalomyelitis, encephalitides (brainstem and cerebral cortical), idiopathic myelitis, atypical multiple sclerosis, aquaporin-4 IgG-negative neuromyelitis optica spectrum disorders and others. MOG-IgG-associated disease occurs in both children and adults, and the female:male ratio is almost 1:1. Pleocytosis in the cerebrospinal fluids during acute exacerbation is often seen, but oligoclonal IgG bands are usually negative. T helper cell 17, B cells and neutrophil-related cytokines appear to be upregulated intrathecally. The pathology of acute lesions is characterized by active inflammation demyelination with deposition of immunoglobulins and complements. Just like aquaporin 4 IgG-positive neuromyelitis optica spectrum disorders, some disease-modifying drugs for multiple sclerosis seem to be inefficacious in MOG-IgG-associated disease, and chronic immunosuppression is required to prevent relapse, especially in patients persistently positive for MOG-IgG. Our understanding of this newly recognized disease remains insufficient, and the progress of research is much expected.

We report an 18 year-old-male, who had been aware of decreased visual acuity for 6 months, newly presented with paresis and sensory disturbance in his right leg. On admission, his critical flicker frequency was reduced bilaterally, and his spinal cord MRI revealed T2-hyperintense lesions in cervical and thoracic cord with occasional contrast enhancements, but none of them were longitudinally extensive. There was no evidence of T2-hyperintense in his brain MRI. Anti-aquapolin-4 (AQP4) antibody was negative but the patient was positive for oligoclonal bands in his cerebrospinal fluid. The patient was tentatively diagnosed as opticospinal multiple sclerosis (OSMS). However, he later tuned out to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The 2017 revised McDonald criteria don't take anti-MOG antibody into account in detail as to how clinicians should deal with patients fulfilling the MS criteria when they were also positive for anti-MOG antibody, because of its difficult problem of independence. So, we need to accumulate knowledge about these cases.

We compared the retinal thickness in the unaffected eyes among the following subtypes of unilateral optic neuritis (ON): multiple sclerosis (MS-ON), neuromyelitis optica spectrum disorder with anti-AQP4 autoantibody (AQP4-ON), patients with serum anti-MOG antibody (MOG-ON), and idiopathic ON. In the chronic phase, macular GCC and circum-papillary RNFL in the unaffected eyes were both atrophied in MS-ON and AQP4-ON, but were not atrophied in the others. Titers of anti-AQP4-Ab was suggested to be associated with such latent neurodegenerative process in AQP4-ON. Long-term follow up of OCT is recommended even in the unaffected side in MS-ON and AQP4-ON.

A 65-year-old man initially developed numbness and hypesthesia in the right shoulder and brachial regions that disappeared within several months. MRI revealed a small lesion extending to a vertebral segment in the right dorsal region of the cervical spinal cord at the vertebral height of C2/3. About 15 months later, the intermittent lancinating pain identical to the right trigeminal and occipital neuralgia with pain and hypesthesia distributed in the right C2-C4 dermatome regions appeared. MRI revealed a new oval lesion with gadolinium enhancement in the right dorsal region of the cervical spinal cord at the vertebral height of C1, which was thought to involve the posterior column and lower part of the spinal tract nucleus of the trigeminal nerve. There was no optic nerve, brain, or other spinal cord lesions that suggested demyelination on MRI. A titer of serum anti-aquaporin-4 antibody was negative, but anti-myelin oligodendrocyte glycoprotein (MOG) antibody was found to be positive. The symptoms were relieved by corticosteroid treatment. Our report presents a rare case of anti-MOG antibody-positive recurrent myelitis that developed only as localized short upper cervical spinal cord lesions, not meeting the diagnostic criteria for neuromyelitis optica spectrum disorders.

Background There are few reports of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive, unilaterally dominant cerebral cortical encephalitis onset with epilepsy. We present such a case in a young female patient with myelitis. Case presentation A 19-year-old female developed generalized tonic seizures lasting several minutes. She had a low-grade fever and headache without other clinical neurological abnormalities while at our hospital. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Other laboratory tests indicated no apparent abnormalities. Unilateral meningeal hyperintensity was seen on T2 fluid-attenuated inversion recovery MRI with associated cortical swelling and gadolinium enhancement of the cortical layer. One thousand mg/day of levetiracetam and a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered. Dysuria appeared on the twentieth day of illness, and spinal MRI revealed a longitudinally extensive cord lesion from C5 to L1 consistent with myelitis. Two cycles of a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered, and all symptoms disappeared. We found the patient to be anti-MOG antibody-positive using serum and CSF (titer: serum 1:256; CSF 1:128). Conclusion Our report illustrates a unique case of anti-MOG presenting as new onset epilepsy secondary to unilaterally dominant meningoencephalitis preceding the onset of longitudinally extensive transverse myelitis.

We compared the clinical features of optic neuritis (ON) that are frequently observed in various central nervous system demyelinating diseases, including multiple sclerosis (MS), anti-aquaporin 4 (AQP4) antibody- and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody-related diseases. Almost all the AQP4-ON patients were female, whereas half of the MOG-ON patients were male. The ON-onset age was younger in MS-ON and was older in AQP4-ON. The ON-lesion detected using optic MRI in the acute phase was longer in MOG-ON and showed severe swelling and twisting. The worst visual acuity was similar between the diseases; however, the final visual acuity was significantly worse in AQP4-ON.

Encephalitis seldom causes paraparesis as the initial symptom. Here, we report a case of steroid-responsive bilateral frontal cortical encephalitis involving leg motor areas in a patient who presented with paraparesis on admission. Interestingly, the initial paraparesis evolved into an acute disseminated encephalomyelitis (ADEM)-like illness and optic neuritis, and the patient was found to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. A 46-year-old man experienced transient dizziness in early September 2008. Brain MRI retrospectively showed a slight fluid attenuation inversion recovery (FLAIR) high-intensity lesion involving the left frontal cortex (figure 1). One week later, the patient experienced a focal motor seizure in the right leg that subsequently generalised. Thereafter, he gradually developed headache and paraparesis over the course of a week. On admission, he presented with paraparesis without other neurological deficits, but the spinal MRI was normal. An electroencephalogram revealed that there were no epileptic discharges. A cerebrospinal fluid (CSF) examination revealed elevated leucocytes (56 /µL; 93% mononuclear cells, 3% polymorphonuclear leucocytes) and normal protein (36 mg/dL) and glucose (59 mg/dL) levels. The myelin basic protein (MBP) and glial fibrillary acidic protein levels in the CSF were not elevated. Cell-based assays for anti-N-methyl-D-aspartate receptor (NMDAR) antibodies, anti-voltage-gated potassium channel (VGKC) antibodies, anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibodies and anti-γ-aminobutyric acid-B receptor (GABA(B)R) antibodies in the CSF were negative. Blood and CSF examinations for infectious central nervous system (CNS) CNS diseases, collagen diseases, vasculitis, Behcet disease, sarcoidosis, lymphoma, paraneoplastic syndrome, vitamin B deficiency and Hashimoto encephalopathy were unremarkable. Figure 1 Upper panel: axial fluid attenuation inversion recovery (FLAIR) images (1.5 T; TR 6000 ms, TE 105 ms). (A) Brain MRI at …

This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring-summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn-winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG.

A 22-year-old woman acutely developed recurrent convulsive seizures followed by fever and headache. Cerebrospinal fluid study showed leukocytosis without hypoglycorrhachia. These clinical features suggested acute viral or aseptic encephalitis. The patient was treated only with an antiviral agent and improved immediately with good prognosis. Afterwards, the characteristic brain MRI findings required us to check the patient's serum, and the final diagnosis of myelin oligodendrocyte glycoprotein (MOG) antibody-positive cerebral cortical encephalitis (CCE) was confirmed. Most previously reported cases with MOG antibody-positive CCE clinically showed fever and/or headache, and some were initially misdiagnosed of having central nervous system infection. All previously reported cases were treated with immunotherapy. However, our case showed the very benign clinical course and improved rapidly without any immunotherapy. We should be reminded that MOG-antibody-positive CCE could be self-remitting and mimic acute viral or aseptic encephalitis. In addition, the characteristic neuroradiological findings could be an important clue to the correct diagnosis of CCE.

Myelin oligodendrocyte glycoprotein is a major target of the humoral immune response in children affected by inflammatory demyelinating diseases of the central nervous system. Although myelin oligodendrocyte glycoprotein causes autoimmune encephalitis in different animal models, the relevance of this mechanism in human autoimmune diseases of the central nervous system is unclear. We herein report a child with acute disseminated encephalomyelitis possibly triggered by central nervous system infection of primary herpes simplex virus in the presence of antimyelin oligodendrocyte glycoprotein antibody. A healthy 5-year-old Japanese boy suffered from acute disseminated encephalomyelitis. He was positive for antimyelin oligodendrocyte glycoprotein antibody in both the serum and the cerebrospinal fluid, and herpes simplex virus-1 DNA on polymerase chain reaction of the cerebrospinal fluid. We speculated that the central nervous system infection of primary herpes simplex virus disrupted the blood–brain barrier, and antimyelin oligodendrocyte glycoprotein antibody already present in serum was transferred to the cerebrospinal fluid, resulting in the onset of acute disseminated encephalomyelitis. This might be the mechanism underlying postinfectious acute disseminated encephalomyelitis associated with myelin oligodendrocyte glycoprotein antibody.

We report a 60-year-old male with anti-myelin oligodendrocyte glycoprotein (MOG) antibody who developed progressive cognitive deterioration and behavioral changes, with no other focal signs, over 9 months. MRI showed numerous T2-hyperintense lesions with partial contrast enhancement in white and grey matter of cerebrum, cerebellum and spinal cord. A brain biopsy revealed perivascular inflammatory cell infiltration, disturbed vascular continuity and no demyelination, indicative of a lymphocytic pattern of primary CNS vasculitis (PCNSV). Contrast enhancement disappeared after immunotherapy; however, cognitive impairment was not improved. Neurologists should note that MOG antibody disease can present as immunotherapy-resistant progressive cognitive impairment with PCNSV-like histopathology.

Introduction Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have recently been associated with epilepsy with FLAIR hyperintense cortical lesions on MRI. Association between anti-MOG antibodies and epilepsy without detectable structural brain lesion on MRI is unknown. Case report A 48-year-old right-handed man with a four-and-a-half year history of anti-MOG antibody associated demyelinating disease presented with persistent global aphasia. Brain MRI showed no new lesion or cortical lesion in the left hemisphere. Electroencephalogram, magnetoencephalography, and brain perfusion single-photon emission computed tomography suggested epileptic foci in the left temporal and parietal lobes, and the patient's aphasia transiently responded to intravenous diazepam, compatible with aphasic status epilepticus. Cerebrospinal fluid showed mildly elevated cell count and positive oligoclonal bands. The patient only partially responded to antiepileptic drugs but responded to steroid pulse therapy. Six months later, the patient again exhibited global aphasia. Brain MRI showed tumefactive white matter lesion in the left temporo-parietal lobes. Conclusion Autoimmune epilepsy without obvious causative lesion on MRI can be seen in the course of anti-MOG antibody associated demyelinating disease. The subsequent emergence of tumefactive lesion closely located to the epileptic foci may suggest some association between autoimmune epilepsy and demyelinating lesions.