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Purpose of Review: The clinical landscape associated to myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) has undergone a remarkable transformation over the past two decades, primarily driven by advancements in antibody detection techniques that have enhanced both the specificity and sensitivity of assays, enabling the identification of novel clinical phenotypes., Recent Findings: Recent pivotal research publications, comprehensive reviews from established research groups, and most notably the first proposed international criteria for MOG-Ab associated disease (MOGAD) have substantially enriched our understanding of the clinical features associated with MOG-Ab. This review presents a comprehensive overview of the clinical characteristics of patients with MOG-Ab, systematically examining each core clinical syndrome defined by the proposed international MOGAD criteria. We incorporated recent insights and discussed potential challenges in applying these criteria across diverse clinical scenarios., Summary: The proposed international MOGAD criteria provide a comprehensive, homogeneous, and specific framework for characterizing the clinical features of patients with MOG-Ab, encompassing both paediatric and adult populations. In the future, the widespread adoption of specific and reliable assays for MOG-Ab detection, complemented by the development of surrogate fluid and imaging markers, holds promise for better characterizing atypical presentations, only-cerebrospinal fluid positivity and the MOGAD "seronegative" situations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies., Methods: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers., Results: We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies., Discussion: GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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., Competing Interests: Declaration of interests RM reports personal fees from Viela Bio, Roche, and UCB; and non-financial support from Viela Bio, Merck, Biogen, and Roche, outside the submitted work. AC-C reports funding from the Instituto de Salud Carlos III (Spain) JR19/00007. A-KP reports grants from the Swiss National Science Foundation, the European Research Council, the National Multiple Sclerosis Society, the ProPatient Foundation, the Goldschmidt-Jacobson-Foundation, and intramural Funding from the University of Basel and personal fees (used for research) from Biogen. OA reports grants from German Research Foundation, German Ministry of Education and Research, Roche, Novartis, and Biogen; and personal fees from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, Teva, and Viela Bio, outside the submitted work. M-PA reports grants Merck, Biogen, Sanofi Genzyme, from Teva, Roche, and Novartis; and person fees from Merck, Biogen, Sanofi Genzyme, from Teva, Roche, and Novartis outside the submitted work. BB reports personal fees from Novartis, outside the submitted work. JB reports personal fees from Roche, Genentech, Viela Bio, Chugai Pharm, Alexion, Novartis, Genzyme, Teva Neuroscience, EMD Serono, Frequency Therapeutics, Equillium, Clene Nanoscience, Mitsubishi-Tanabe, and Reistone Bio; grants from Novartis, EMD Serono, National Institutes of Health, Guthy-Jackson Charitable Foundation, and National Multiple Sclerosis Foundation, outside the submitted work; and has a patent Aquaporumab, issued. FB reports grants from the Australian National Health Research Medical Council and the University of Sydney Research Excellence Initiative; personal fees from Biogen and Merck, outside the submitted work. TC reports consulting fees from Biogen Idec, Novartis, Sanofi, Bayer, Celgene, and Genentech; grants from Novartis, Octave Bioscience, EMD Serono, and Verily Life Sciences; all outside the submitted work. OC reports grants from Spinal Cord Research Foundation, Rosetrees Trust, Progressive Multiple Sclerosis Alliance, Bioclinica and GeNeuro, EU-H2020, UK Multiple Sclerosis Society, National Multiple Sclerosis Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, and National Institute for Health Research Research Professorship; and serves as a consultant for Merck, Novartis, and Roche; and receives an honorarium from the American Academy of Neurology as Associate Editor of Neurology. KD reports personal fees from Novartis, Biogen, Roche, and Merck; and non-financial support from Novartis, outside the submitted work. KF reports grants from Ministry of Education, Science and Technology of Japan, and Ministry of Health, Wellfare and Labor of Japan, during the conduct of the study; personal fees from Chugai/Roche, Alexion, Viela Bio, AsahiKasei Medical, Mitsubishi Tanabe, Biogen/Eisai, Novartis, Teijin, Bayer, Ono, Nihon Pharmaceutical, and Takeda, outside the submitted work; and personal fees from UCB during the conduct of the study. HJK reports grants from National Research Foundation of Korea, Aprilbio; personal fees from Alexion, Aprilbio, Celltrion, Eisai, HanAll BioPharma, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and Viela Bio. M-IL is funded by the UK National Health Service National Specialised Commissioning Group for Neuromyelitis optica and the UK NIHR Oxford Biomedical Research Centre; has been awarded research grants from The Myaware and University of Oxford; received speaker honoraria or travel grants from Biogen Idec, Novartis, and the Guthy-Jackson Charitable Foundation; and serves on scientific or educational advisory boards for UCB, Argenx, and Viela Bio. MC reports personal fees from Biogen, Merck, Sanofi, Novartis, and Roche; and non-financial support from Merck, Sanofi, and Roche, outside the submitted work. IK reports personal fees from Biogen, Novartis, Merck, Sanofi Genzyme, Roche, Mylan, Alexion, Celgene, Chugai, and IQVIA; and grants from Chugai, outside the submitted work. HL reports personal fees from Biogen, Merck, Roche, Novartis, Sanofi Aventis, and MedDay, outside the submitted work. EM reports personal fees from Roche, Novartis, Sanofi, Bioeq, Merck, and Biogen; and grants from Sanofi, Merck, and Novartis, outside the submitted work. JP reports grants from Merck Serono, Chugai, Medlmmum, Alexion, and ABIDE; personal fees from Merck Serono, Teva, Chugai, MedImmun, Alexion, Novartis, Roche, ABIDE, MedDay, ARGENX, Mitsubushi, UCB, and Viela Bio, outside the submitted work; and has a patent Isis: Diagnosing Multiple Sclerosis, issued, and a patent Know-how from the Numares Collaboration, pending. FP receives honoraria for lecturing, and travel expenses for attending meetings from Guthy-Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Alexion, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; and research funding from the German Ministry for Education and Research, Deutsche Forschungsgemeinschaft, Einstein Foundation, Guthy-Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Alexion, Roche, Parexel and Almirall. AP reports personal fees from Novartis, Heidelberg Engineering, and Zeiss; and grants from Novartis, outside the submitted work; and is part of the steering committee of the OCTiMS study which is sponsored by Novartis and the ANGI network which is sponsored by ZEISS (he has not received honoraria for these activities). AP is supported by the National Institute for Health Research, Biomedical Research Centre based at Moorfields Eye Hospital National Health Service Foundation Trust, and University College London Institute of Ophthalmology. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health. SP reports grants from Grifols, NIH, Guthy-Jackson Charitable Foundation, Autoimmune Encephalitis Alliance, MedImmune, UCB, and Alexion Pharmaceuticals, outside the submitted work; and has a patent (Patent# 8,889,102, Application#12–678350) Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia, issued, a patent (Patent# 9 891 219B2, Application#12–573942) Methods for Treating Neuromyelitis Optica by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive, issued, a patent GFAP-IgG, pending, a patent Septin-5-IgG, pending, a patent MAP1B-IgG, pending, a patent Kelch-like protein 11, pending, and a patent PDE10A, pending. MR reports grants from Euroimmun and Roche, during the conduct of the study; and The University Hospital and Medical University of Innsbruck (Austria; employer of MR) receives payments for antibody assays (MOG, AQP4, and other autoantibodies). DKS reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, TEVA, and Merck; and personal fees from TEVA, Merck, Biogen, Roche, and Viela Bio, outside the submitted work. KS reports personal fees from Biogen, Novartis, Merck, Roche, Celgene, and TG Therapeutics; and grants from Merck and Roche, outside the submitted work. AS reports personal fees from F Hoffmann-La Roche, Sanofi-Genzyme, Novartis, Merck-Serono, Teva, and Biogen Idec/Gen Pharma of Turkey; and non-financial support from F Hoffmann-La Roche and Sanofi-Genzyme, outside the submitted work. BS has received research grants from Sanofi-Genzyme, Roche, and Merck-Serono, and personal fees for lectures from Sanofi-Genzyme, Merck-Serono, Teva, Biogen and Novartis. MT reports personal fees from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio, and Teva Pharmaceuticals; and grants from Biogen-Idec and Genzyme, outside the submitted work. AT reports grants from Roche and personal fees from Roche, Sanofi Genzyme, Novartis, EMD Serono, Teva, and Biogen, outside the submitted work. PW reports personal fees from Alexion, F Hoffmann La-Roche, and BC Neuroimmunology, outside the submitted work; and has a patent Antibodies in Autoimmune Neurology, with royalties paid. EW reports personal fees from DBV, Jazz Pharma, and Emerald, outside the submitted work. BW reports personal fees from RSR, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr Volkmann und Kollegen; personal fees from Viela Bio, Alexion, Roche Group (includes Genentech and Chugai), Mitsubishi Tanabe, and Roivant, outside the submitted work; and has a patent NMO-IgG (AQP4-IgG) for diagnosis of NMOSD, with royalties paid. TD reports grants from Novartis, Biogen, and Roche; and financial compensation to his institution for activities on advisory boards, steering committees, or data safety monitoring boards from Alexion, Actelion, Novartis, Merck, Biogen, Genzyme, GeNeuro, Mitsubishi Pharma, Roche, Celgene, and MedDay. TD's wife is an employee of Novartis and holds stock options of Novartis. SV reports grants from Biogen, MedDay, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; personal fees from Biogen, Celgene, MedDay, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; and non-financial support from Biogen, MedDay, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme, outside the submitted work. BH reports personal fees from Desitin, Novartis, Allergy Care, and TG Therapeutics, outside the submitted work. The other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acquired demyelinating syndromes (ADS) are frequently associated with myelin oligodendrocytes glycoprotein (MOG) antibodies in children. Clinical phenotypes are heterogeneous and may delay the diagnosis, especially when they relapse and are atypical, mimicking diseases such as multiple sclerosis or neuromyelitis optica spectrum disorders . Here, we describe two children: one with a progressive cognitive and behavioral deterioration with seizures after only one relapse and the other with similar clinical impairments associated with multiple relapses. Brain magnetic resonance imaging revealed a subsequent progressive leukodystrophy-like lesion with diffuse bilateral white matter injuries in both patients. Cerebrospinal fluid analysis showed pleiocytosis, increased level of proteins with no oligoclonal bands. Metabolic and inflammatory blood markers were all negative. Brain biopsy was performed in the second child and nonspecific inflammatory lesions with no argument for histiocytosis or tumor were observed. Clinical and radiological stabilization were obtained after active immunotherapy. Retrospective analysis of anti-MOG antibodies in these two children was positive at the earlier stage of the disease and turned negative after treatment and during follow-up. Leukodystrophy-like ADS with anti-MOG-antibodies may display distinct progressive phenotype and have a severe neurological prognosis. Early diagnosis and appropriate treatment may improve outcome in these children., Competing Interests: EY, HM, CL, PH, SN, ML, CA, BH, CS have nothing to disclose; KD received speaking honoraria at meetings and for participation in advisory boards from Novartis, Sanofi, Servier., (Thieme. All rights reserved.)

Background: Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative., Aims: To identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD., Methods: Three groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4 + T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (T regs , Foxp3 + ), CD45RA - Foxp3 + T regs and subpopulation naive T regs (CD45RA + Foxp3 int ), effector T regs (CD45RA - Foxp3 high ) and non-suppressive T regs (CD45RA - Foxp3 int ) proportions were determined., Results: The mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4 + T regs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA - Foxp3 + T regs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector T regs /non suppressive-T regs, which was significantly higher than in MOGNR., Conclusions: Our findings suggest that CD4 + Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of T regs to rh-MOG in MOGNR, where CD4 + T regs increased, and in MOGR, where CD45RA - Foxp3 + T regs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Horellou, de Chalus, Giorgi, Leroy, Chrétien, Hacein-Bey-Abina, Bourgeois, Mariette, Serguera, Le Grand and Deiva.)

Objective: The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG-Ab-associated disease (MOGAD)., Methods: This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time-to-event data and Kaplan-Meier curves for time to antibody negativity were performed for the objectives., Results: Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow-up reached only by 10 of 97 [10.3%] vs 66/247 [26.7%], p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval [CI] = 1.12-1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9-86.5) of nonrelapsing children became MOG-Ab negative compared to 14.1% (95% CI = 4.7-38.3) of relapsing children (log-rank p < 0.001), with no differences observed in adults (log-rank p = 0.280)., Interpretation: MOGAD patients differ in the clinical presentation at onset, showing an age-related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG-Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30-41., (© 2020 American Neurological Association.)

A first episode of acquired demyelinating disorder (ADS) in children is a diagnostic challenge as different diseases can express similar clinical features. Recently, antibodies against myelin oligodendrocyte glycoprotein (MOG) have emerged as a new ADS biomarker, which clearly allow the identification of monophasic and relapsing ADS forms different from MS predominantly in children. Due to the novelty of this antibody there are still challenges and controversies about its pathogenicity and best technique to detect it. In this manuscript we will discuss the recommendations and caveats on MOG antibody assays, role in the pathogenesis, and additionally discuss the usefulness of other potential new biomarkers in MOG-antibody associated disorders (MOGAD)., Competing Interests: Declaration of competing interest TA received consultation and speaker honoraria from Novartis and Biogen and travel expenses from Roche to attend scientific meetings unrelated to the submitted work. MC received consultation and speaker honoraria from Almirall, Biogen, Merck, Novartis, Roche, Sanofi, TEVA. ADC has nothing to disclose. GL has nothing to disclose. KD received consultation and speaker Honoria from Novartis, Sanofi, Teva., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species., Methods: The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared., Results: Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG-. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG- children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration., Conclusions: Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.

Background: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation., Methods: We implemented a preclinical scheme to foster immune tolerance to myelin oligodendrocyte glycoprotein (MOG), in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), in which administration of recombinant human MOG (rhMOG) elicits brain inflammation mediated by MOG-autoreactive CD4 + lymphocytes and anti-MOG IgG. For immunotherapy, we used a recombinant antibody (Ab) directed against the dendritic cell-asialoglycoprotein receptor (DC-ASGPR) fused either to MOG or a control antigen PSA (prostate-specific antigen)., Findings: rhMOG and the anti-DC-ASGPR-MOG were respectively detected in CD1a + DCs or CD163 + cells in the skin of macaques. Intradermal administration of anti-DC-ASGPR-MOG, but not control anti-DC-ASGPR-PSA, was protective against EAE. The treatment prevented the CD4 + T cell activation and proinflammatory cytokine production observed in controls. Moreover, the administration of anti-DC-ASGPR-MOG induced MOG-specific CD4 + CD25 + FOXP3 + CD39 + regulatory lymphocytes and favoured an upsurge in systemic TGFβ and IL-8 upon rhMOG re-administration in vivo., Interpretation: We show that the delivery of an anti-DC-ASGPR-MOG allows antigen-specific adaptive immune modulation to prevent the breach of immune tolerance to MOG. Our findings pave the way for therapeutic vaccines for long-lasting remission to grave encephalomyelitis with identified autoantigens, such as ADD associated with anti-MOG autoantibodies. FUND: Work supported by the French ANR (ANR-11-INBS-0008 and ANR-10-EQPX-02-01), NIH (NIH 1 R01 AI 105066), the Baylor Scott and White Healthcare System funding and Roche Research Collaborative grants., (Copyright © 2019. Published by Elsevier B.V.)

Importance: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated., Objective: To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease., Design, Setting, and Participants: This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016. Patients were treated according to local protocols., Main Outcomes and Measures: Annualized relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) scores before and during treatment with disease-modifying drugs (DMDs)., Results: A total of 102 children were identified (median [range] age, 7.0 [1.5-7.9] years; male to female ratio, 1.0:1.8; white to other race/ethnicity ratio, 3.6:1.0). Original diagnoses were neuromyelitis optica spectrum disorder (44 patients [43.1%]), acute disseminated encephalomyelitis followed by optic neuritis (20 [19.6%]), multiphasic disseminated encephalomyelitis (20 [19.6%]), and relapsing optic neuritis (18 [17.6%]). In all, 464 demyelinating events were reported. Treated patients had more relapses (median, 3.0; range, 1.0-17.0) than untreated patients (median, 1.0; range 1.0-7.0) (P = .009) and higher EDSS scores (median, 1.5; interquartile range, 0-2.5) than untreated patients (median, 1.0; interquartile range, 0-1.5) (P < .001). Fifty-two children (51.0%) received DMDs: 28 (53.8%) were treated with 1 DMD, 17 (32.7%) with 2, and 7 (13.5%) with 3 or more sequential DMDs. Patients relapsed during all treatments, with a total of 127 relapses on treatment reported. No changes in median ARR and EDSS score were observed between the preinitiation and postinitiation phases of interferon beta and glatiramer acetate treatment (n = 11). The median ARR was reduced from 1.84 to 1.0 with azathioprine (n = 20, P < .001), 1.79 to 0.52 with mycophenolate mofetil (n = 15, P = .003), and 2.12 to 0.67 with rituximab (n = 9, P < .001), although the median EDSS score remained unchanged. An improvement in ARR (from 2.16 to 0.51, P < .001) and EDSS score (from 2.2 to 1.2, P = .01) was observed in the 12 patients treated with regular intravenous immunoglobulins., Conclusions and Relevance: Although commonly used to treat patients with multiple sclerosis, DMDs were not associated with clinical improvement in children with MOG-Ab-associated disease, whereas azathioprine, mycophenolate mofetil, rituximab, and particularly intravenous immunoglobulins were associated with a reduction in relapse frequency. A correct diagnosis of relapsing MOG-Ab-associated disorders is therefore important to optimize immune treatment.

Background: Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder of the central nervous system. NMO and its abortive forms are referred to as NMO spectrum disorders (NMOSD). NMOSD are mostly associated with antibodies to aquaporin-4 (AQP4-IgG). However, recent studies have demonstrated antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) in a subset of patients. Data on NMOSD in North Africa are sparse., Objective: To describe the frequency of MOG-IgG and AQP4-IgG among patients with optic neuritis (ON) and/or myelitis in Algeria as well as the clinical and paraclinical features associated with these antibodies., Methods: Retrospective testing of 42 patients with optic neuritis and/or myelitis treated at the teaching hospital of TiziOuzou for MOG-IgG and AQP4-IgG, and retrospective evaluation of the patients' medical records., Results: Six of 42 (14.3%) patients were positive for AQP4-IgG and 3/42 (7.1%) were positive for MOG-IgG. No patient was positive for both AQP4-IgG and MOG-IgG. All antibody-positive patients were women. MOG-IgG was associated with severe episodes of ON in all MOG-IgG-positive patients. Steroid treatment was followed by complete remission in two patients. AQP4-IgG was associated with ON and/or longitudinally extensive transverse myelitis (LETM), often with severe onset. While all six of the AQP4-IgG-positive patients met the 2015 IPND criteria for NMOSD, only one of the three MOG-IgG-positive patients did so. Interestingly, clinically silent extensive spinal cord or brain lesions were present in two of the three MOG-IgG-positive patients, and altered visual evoked potentials without clinical evidence of ON were found in three of the six AQP4-IgG-positive patients., Conclusion: MOG-IgG and AQP4-IgG are found in a substantial subset of Algerian patients with ON and/or myelitis, are present predominantly in women, and may be associated with differences in clinical presentation and, possibly, outcome. Only a subset of MOG-IgG positive patients meets the current diagnostic criteria for NMOSD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (p = 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (p = 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.

Herpes simplex virus encephalitis (HSVE) is a devastating condition that relapses, often with a chorea in children, despite adequate antiviral treatment. At relapse, evidence of viral replication is frequently absent, suggesting that the relapse may be immune-mediated. Seven children who had a neurological relapse following their initial encephalitis, identified from 20 cases of pediatric HSVE, were studied. Serum and/or cerebrospinal fluid (CSF) were tested for N-methyl-D-aspartate receptor (NMDAR) and other antibodies previously reported in central nervous system autoimmunity. Five of the 7 relapsing children had choreoathetosis; 2 of these were NMDAR antibody-positive, 2 were negative (1 with HSV-positive CSF), and 1 was not available for testing. An additional patient, who relapsed with cognitive regression but with no movement disorder, was also NMDAR antibody-positive. In 2 of the NMDAR antibody-positive patients who were treated at relapse and in 1 who was treated only after 10 years of having a relapsing encephalopathy, a beneficial response was observed. Neurological relapses after HSVE may frequently be immune-mediated, particularly in children with chorea. NMDAR antibodies are common, and immunotherapy may be beneficial., (Copyright © 2013 Movement Disorder Society.)