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Serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG) are found in patients with acquired CNS demyelinating syndromes that are distinct from multiple sclerosis and aquaporin-4-seropositive neuromyelitis optica spectrum disorder. Based on an extensive literature review and a structured consensus process, we propose diagnostic criteria for MOG antibody-associated disease (MOGAD) in which the presence of MOG-IgG is a core criterion. According to our proposed criteria, MOGAD is typically associated with acute disseminated encephalomyelitis, optic neuritis, or transverse myelitis, and is less commonly associated with cerebral cortical encephalitis, brainstem presentations, or cerebellar presentations. MOGAD can present as either a monophasic or relapsing disease course, and MOG-IgG cell-based assays are important for diagnostic accuracy. Diagnoses such as multiple sclerosis need to be excluded, but not all patients with multiple sclerosis should undergo screening for MOG-IgG. These proposed diagnostic criteria require validation but have the potential to improve identification of individuals with MOGAD, which is essential to define long-term clinical outcomes, refine inclusion criteria for clinical trials, and identify predictors of a relapsing versus a monophasic disease course.

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0–7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0–8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0–8)] and 152 healthy controls (91 females) were studied. In young patients (

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population. Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.

Background Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. Objective To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. Methods This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. Results Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2–62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30–55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2–14.6). The included studies presented regular quality and substantial heterogeneity. Conclusion Even with antiviral therapy, half of patients will develop some type of disability.

Background and ObjectivesNeuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the CNS. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG)–seropositive NMOSD (eculizumab, inebilizumab, and satralizumab), prompting the need to consider best practice therapeutic decision-making for this indication. Our objective was to develop validated statements for the management of AQP4-IgG–seropositive NMOSD, through an evidence-based Delphi consensus process, with a focus on recommendations for eculizumab, inebilizumab, and satralizumab.MethodsWe recruited an international panel of clinical experts in NMOSD and asked them to complete a questionnaire on NMOSD management. Panel members received a summary of evidence identified through a targeted literature review and provided free-text responses to the questionnaire based on both the data provided and their clinical experience. Responses were used to generate draft statements on NMOSD-related themes. Statements were voted on over a maximum of 3 rounds; participation in at least 1 of the first 2 rounds was mandatory. Panel members anonymously provided their level of agreement (6-point Likert scale) on each statement. Statements that failed to reach a predefined consensus threshold (≥67%) were revised based on feedback and then voted on in the next round. Final statements were those that met the consensus threshold (≥67%).ResultsThe Delphi panel comprised 24 experts, who completed the Delphi process in November 2021 after 2 voting rounds. In round 1, 23/25 statements reached consensus and were accepted as final. The 2 statements that failed to reach consensus were revised. In round 2, both revised statements reached consensus. Twenty-five statements were agreed in total: 11 on initiation of or switching between eculizumab, inebilizumab, and satralizumab; 3 on monotherapy/combination therapy; 7 on safety and patient population considerations; 3 on biomarkers/patient-reported outcomes; and 1 on research gaps.DiscussionAn established consensus method was used to develop statements relevant to the management of AQP4-IgG–seropositive NMOSD. These international statements will be valuable for informing individualized therapeutic decision-making and could form the basis for standardized practice guidelines.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease of the central nervous system. Most of the cases are positive for autoantibodies targeting the water channel aquaporin-4 (AQP4-IgG). Activated B and T cells, innate immunity cells, pro-inflammatory cytokines, and activated complement contribute to the formation of the NMOSD lesions. Optic neuritis, longitudinally extensive myelitis, and area postrema syndrome are core clinical manifestations. NMOSD diagnosis is based on clinical manifestations, magnetic resonance imaging findings, and AQP4-IgG positivity. Cell-based assays are the preferred method for the detection of AQP4-IgG. Acute relapses are treated with IV methylprednisolone or plasma exchange. Recent advances on the NMOSD immunobiology led to approved treatments such as eculizumab, satralizumab, and inebilizumab.

Myelin oligodendrocyte glycoprotein (MOG) is a unique CNS-specific mammalian protein that is expressed on the surface of compact myelin and oligodendrocyte cell bodies. MOG is an accessible target for autoantibodies, associated with immune-mediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G antibodies (MOG-IgG) helps to distinguish a subgroup of patients from multiple sclerosis and other CNS disorders, reducing the risk of clinical misdiagnosis. The development of the cell-based assays (CBA) improved the detection of clinically meaningful MOG-IgG binding to conformational MOG expressed in the cell membrane surface. In this review, we describe factors that impact on the results of CBA, such as MOG conformation, protein glycosylation, addition of fluorescent tags, serum dilution, secondary antibodies, and data interpretation.

Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic mechanisms of B lymphocytes in CNS inflammatory diseases. It has been demonstrated that B lymphocytes participate in the pathogenesis of these conditions as antigen-presenting cells, producing proinflammatory cytokines that induce Th1 and Th17 responses and producing antibodies. However, they are also able to produce anti-inflammatory cytokines, such as interleukin-10, functioning as regulators of autoimmunity. Understanding these diverse effects is essential for the development of focused treatments. In this review, we discuss the possible mechanisms that underlie B-lymphocyte involvement in MS, NMOSD, and AE and the outcomes obtained by treatments targeting B lymphocytes.

Around 5% of all Neuromyelitis Optica Spectrum Disorders (NMOSD) cases start before 18 years of age. Clinical and radiological manifestations of AQP4-IgG positive NMOSD were revised in 2015, and the importance of neuroimaging in the diagnosis is well recognized. Neuroimaging findings in pediatric-onset NMOSD were scarcely described, and longitudinal evaluation of NMOSD lesions was only accessed in a few adult-onset cohorts.This study evaluated brain, spinal cord, and optic nerve MRI of sixteen pediatric-onset AQP4-IgG positive NMOSD through a qualitative evaluation of lesion evolution. Lesions were classified as symptomatic or asymptomatic in acute or chronic phase (30 days from last attack) MRI.Seventy MRI scans and 54 subsequent exams were evaluated. Most NMOSD lesions (74.5%) reduced, remained stable, or developed atrophy/cavitation. New brain lesions or enlargement of existing brain lesions were found in two patients (12.5%) without any clinical symptom and in five patients (31.2%) in the course of an attack from other topography (optic neuritis or acute myelitis). One patient (6.3%) presented an asymptomatic spinal cord lesion irrespective of clinical manifestation. No asymptomatic lesion was described in optic nerve MRI. In acute phase exams, longitudinally extensive transverse myelitis (13/19 vs 8/24; p = 0.033), cervical myelitis (15/19 vs 10/24, p = 0.028), lumbar myelitis (5/19 vs 0/24; p = 0.012), and a higher number of segments [median 8 (range 4-17) vs 3.5 (range 1-14); p = 0.003] were affected.Asymptomatic brain and spinal cord lesions can occur in pediatric-onset NMOSD, especially in the course of acute optic neuritis or myelitis. More longitudinal studies are necessary to guide recommendations on neuroimaging frequency in pediatric patients with AQP4-IgG NMOSD.

Background Neuromyelitis optica spectrum disorders (NMOSD) is a severe condition associated with high disability and low quality of life (QoL) in adults. Since this evaluation had been rarely perfomed in children, this study aimed to describe QoL in pediatric-onset NMOSD with positive aquaporin4 antibody (AQP4-IgG) patients. Methods This was a cross-section evaluation of patients and parents’ proxy QoL from individuals enrolled in a longitudinal cohort of AQP4-IgG positive NMOSD with onset ≤ 18 years of age. Results Eighteen patients were included, sixteen girls. The mean (SD) age at disease onset was 11.5 (3.6) years. Eleven of patients experienced disability during a mean (SD) of 8.3 (5.3) years of follow-up. NMOSD had impact in QoL in 10 patients, being associated with higher EDSS and poor academic performance at last follow-up. Results from the PEDsQL inventory for 13 patients and 10 parents disclosed low QoL specially in emotional functioning. Conclusion This study indicates impaired quality of life, high disability and high impact of the disease in daily life of adolescents and young adults with pediatric onset NMOSD.

Background: Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). Objective: The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of São Paulo (São Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. Results: Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients’ median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1-2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. Conclusion: Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required. RESUMO Introdução: A azatioprina é um tratamento comum de primeira linha para os transtornos do espectro neuromielite óptica (NMOSD). Objetivo: Este estudo visou determinar a segurança do tratamento a longo prazo (>10 anos) da NMOSD com a azatioprina. Métodos: Foi realizada revisão retrospectiva de todos os prontuários de pacientes que preenchiam critérios de NMOSD de acordo com o “International Consensus Diagnostic Criteria for NMOSD” de 2015 em uso de azatioprina por ao menos 10 anos matriculados no ambulatório de Doenças Desmielinizantes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Resultados: De 375 pacientes avaliados, 19 preencheram critérios de inclusão para análise. A mediana de idade foi de 44 anos (variância=28-61); os pacientes eram predominantemente do sexo feminino (17/19) e AQP4-IgG soropositivos (18/19). A mediana do tempo de duração de doença foi 11,9 anos (variância=10,0-23,8), a mediana da taxa anualizada de surtos pré e pós-tratamento foi de 1 (variância=0,1-2) e 0,1 (variância=0-0,35), p=0,09. Três pacientes (15,7%) apresentaram registro de eventos adversos durante o seguimento: deficiência crônica de vitamina B12, tuberculose pulmonar e câncer de mama. Conclusão: A azatioprina provavelmente pode ser considerada segura para o tratamento a longo prazo (>10 anos) da NMOSD, porém vigilância contínua de neoplasias e infecções é necessária.

BACKGROUND Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p

Human antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) from immunoglobulin-G subclasses (MOG-IgG) have been recently associated with a new subgroup of neurological autoimmune diseases with distinct clinical characteristics from multiple sclerosis and neuromyelitis optica spectrum disorders. The use of MOG-IgG as a biomarker is an essential tool to assist in the diagnosis and clinical prognosis. The cell-based assay (CBA) is a methodology that expresses high levels of natively folded human MOG protein in the cell membrane being the methodology most used for clinical MOG-IgG diagnosis. However, there is still no consensus about the best approach to perform CBA to improve the results. The CBA using flow cytometry (CBA-FC) is an automated technique with objective quantification, reducing the subject of human bias that occurred at CBA using immunofluorescence (CBA-IF). In this study, we compared the performance of CBA-IF and CBA-FC as an acquisition tool analysis. The sera of 104 patients diagnosed with inflammatory Central Nervous System diseases were tested in both CBA-IF and CBA-FC. We used the dilution of 1:128 for CBA-IF and three different dilutions (1:20, 1:100, and 1:640) for CBA-FC. The CBA-FC and CBA-IF results had 88.5% agreement between assays and the CBA-IF titers by endpoint-dilution correlated with the CBA-FC titers. The highest serum dilution resulted in an increased CBA-FC specificity, but there was a reduction in the CBA-FC sensitivity. Our study showed that CBA-FC can be used in clinical practice as a diagnostic technique for MOG-IgG. In addition, in some specific cases, the combination of both techniques could be used as a tool to discriminate unspecific binding and overcome single assay limitations.

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) is a unique CNS-specific mammalian protein that is expressed on the surface of compact myelin and oligodendrocyte cell bodies. MOG is an accessible target for autoantibodies, associated with immune-mediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G antibodies (MOG-IgG) helps to distinguish a subgroup of patients from multiple sclerosis and other CNS disorders, reducing the risk of clinical misdiagnosis. The development of the cell-based assays (CBA) improved the detection of clinically meaningful MOG-IgG binding to conformational MOG expressed in the cell membrane surface. In this review, we describe factors that impact on the results of CBA, such as MOG conformation, protein glycosylation, addition of fluorescent tags, serum dilution, secondary antibodies, and data interpretation.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The remyelination process requires the activation, migration and differentiation of oligodendrocyte progenitor cells (OPC) in demyelinated areas. The metabolic dysfunction in chronic demyelinating lesions impairs the activation of OPCs, the myelin debris clearance by microglia decreases with age, along with diminished secretion of factors promoting OPC differentiation. Conventional magnetic resonance imaging (MRI) sequences have limited ability to differentiate unmyelinated and remyelinated lesions. Advanced MRI sequences based on magnetization transfer ratio (MTR), myelin water fraction (MWF) and diffusion tensor imaging (DTI) have been used to evaluate remyelination in clinical trials. More recently, the q-space myelin map (qMM) has been used on experimental and exploratory clinical studies. The improvement of myelin-specific MRI sequences with high reliability and standardization among centers will allow a more accurate evaluation of new therapies to improve remyelination. These new remyelination promoting treatments alone or in combination with current options may reduce the risk of long-term disability in MS.

Background: MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Limited data are available regarding the predictors of relapse in this condition. Objective: We aimed to evaluate the longitudinal serostatus of patients with MOG-IgG and to correlate serostatus with long-term clinical outcomes. Methods: Of 574 consecutive patients who presented with demyelinating inflammatory CNS disorders, we included 31 patients who were MOG-IgG-positive. Patients with MOG-IgG were followed up from 2011 to 2017 at the School of Medicine, University of São Paulo, Brazil. Results: Relapsing disease occurred in 23 out of 31 patients (74%), while 8 (26%) exhibited a monophasic course. All monophasic patients, as well as the majority of relapsing patients, became seronegative during clinical remission. Patients exhibiting disease activity in the last 2 years were more likely to remain positive, with higher medium titres than those found in patients in clinical remission. Conclusion: MOG-IgG patients usually present with a relapsing course, and the risk of relapse was associated with longitudinally persistent MOG-IgG seropositivity. In contrast, patients who experienced a single attack became spontaneously seronegative for MOG-IgG during long-term follow-up.

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.

Case report : a 42-year-old man presented with bilateral longitudinally extensive optic neuritis, associated with longitudinally extensive hyperintensity ranging from cervical to thoracic spinal cord. Anti-MOG and Anti-AQP4 antibodies were negative, as well as IgG and IgM antibodies against SARS-CoV-2. The patient showed dramatic recovery after 5 days of high dose intravenous methylprednisolone. Discussion : Vaccination is imperative, but clinicians should be aware of its potential adverse events, particularly when immediate treatment can avoid debilitating consequences. Considering the speed up approval processes of vaccines against SARS-CoV-2, permanent pharmacovigilance of severe adverse events in the real world is a paramount.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis initially promotes memory deficits, behavioral changes, and epileptic seizures. We developed a new animal model of anti-NMDAR encephalitis using a single cerebroventricular injection of CSF from patients in adult zebrafish. We observed a reduction of the seizure threshold and recent memory deficits in those animals injected with CSF from patients with anti-NMDAR encephalitis. The locomotor activity was similar in the CSF and control groups. This zebrafish model consistently recapitulates symptoms seen in patients with anti-NMDAR encephalitis. It may provide a reliable, fast and cost-effective platform to investigate new therapeutic strategies to anti-NMDAR encephalitis.

Introduction: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective: To survey the current global clinical practice of clinicians treating MOGAD. Method: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February–April 2019). Results: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

ObjectiveTo describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD).MethodsRetrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged ResultsA total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2–10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0–4), 0 on mycophenolate mofetil (n = 18, range 0–3), and 0 on rituximab (n = 29, range 0–2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764–42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644–0.959, p = 0.018).ConclusionsAQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide.Classification of evidenceThis study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.

ObjectiveTo explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis.MethodsCerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37).ResultsGFAP and GS concentrations differed significantly across groups (both ps=0.70, pConclusionsOur data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.