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Background: Currently, there are no available recommendations or guidelines on how to perform MRI monitoring in the management of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The issue is to determine a valuable MRI monitoring protocol to be applied in the management of NMOSD and MOGAD, as previously proposed for the monitoring of multiple sclerosis., Objectives: The objectives of this work are to establish proposals for a standardized and feasible MRI acquisition protocol, and to propose control time points for systematic MRI monitoring in the management of NMOSD and MOGAD., Methods: A steering committee composed of 7 neurologists and 5 neuroradiologists, experts in NMOSD and MOGAD from the French group NOMADMUS, defined 8 proposals based on their expertise and a review from the literature. These proposals were then submitted to a Rating Group composed of French NMOSD / MOGAD experts., Results: In the management of NMOSD and MOGAD, a consensus has been reached to perform systematic MRI of the brain, optic nerve and spinal cord, including cauda equina nerve roots, at the time of diagnosis, both without and after gadolinium administration. Moreover, it has been agreed to perform a systematic MRI scan 6 months after diagnosis, focusing on the area of interest, both without and after gadolinium administration. For long-term follow-up of NMOSD and MOGAD, and in the absence of clinical activity, it has been agreed to perform gadolinium-free MRI of the brain (+/- optic nerves) and spinal cord, every 36 months. Ideally, these MRI scans should be performed on the same MRI system, preferably a 3T MRI system for brain and optic nerve MRI, and at least a 1.5T MRI system for spinal cord MRI., Conclusions: This expert consensus approach provides physicians with proposals for the MRI management of NMOSD and MOGAD., Competing Interests: Declaration of competing interest Françoise DURAND-DUBIEF has nothing to disclose. Natalia SHOR has nothing to disclose. Bertrand AUDOIN has nothing to disclose. Bertrand BOURRE serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, Sandoz and Roche. Mikael Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Sanofi, Roche, Celgene-BMS, Janssen, Alexion, Horizon Therapeutics and Ad Scientiam. Stéphane KREMER has nothing to disclose. Elisabeth MAILLART reports research support from Biogen and personal fees for lectures and advisory boards from Alexion, Biogen, Horizon, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. Caroline PAPEIX has received personal compensation for consulting, serving on a scientific advisory board, speaking from Alexion, Horizon, Roche. Aurélie RUET has received funding for travel or speaker or consultant honoraria from Biogen, Alexion, Novartis, Sanofi, Merck, Horizon Therapeutic; and received research support from Biogen, BMS, Sanofi, Roche, Merck. Julien SAVATOVSKY has nothing to disclose. Thomas TOURDIAS has nothing to disclose. Xavier AYRIGNAC has received consulting fees and lecturing fess, travel grants and undoncitional research support from Alexion, Biogen, Genzyme, Janssen, Merck Serono, Novartis, Roche, Sanofi Aventis and Teva Pharma. Jonathan CIRON has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi, Roche, Alexion, Horizon Therapeutics, none related to this study. Nicolas COLLONGUES has received honoraria for consulting or presentation from Alexion, Biogen Idec, Bristol-Myers Squibb, Horizon Therapeutics, Merck Serono, Novartis, Roche and Sanofi-Genzyme and is a member of the Editorial Board of the Journal de la Ligue Française contre la Sclérose en plaques and the Neurology and Therapy Journal. David LAPLAUD served on scientific advisory boards for Alexion, BMS, Roche, Sanofi, Novartis, Merck, Janssen and Biogen, received conference travel support and/or speaker honoraria from Alexion, Novartis, Biogen, Roche, Sanofi, BMS and Merck and received research support from Fondation ARSEP, Fondation EDMUS and Agence Nationale de la Recherche. Laure MICHEL has nothing to disclose. Romain DESCHAMPS has received personal compensation for serving on a scientific advisory board or travel grants from Biogen, Roche, Alexion, and Novartis. Eric THOUVENOT received consulting and lecturing fees, travel grants or unconditional research support from Actelion, Biogen, BMS, Merck, Novartis, Roche, Teva pharma. Hélène ZEPHIR received consulting fees and invitation for congresses from Alexion, Horizon Therapeutics, Roche, Sanofi, Janssen, Biogen Idex, Merck, BMS. HZ received research supports from Novartis, Roche. Romain MARIGNIER serves on scientific advisory boards for Horizon Therapeutics/Amgen; and has received funding for travel and fees from Alexion, Amgen Biogen, Roche, Sanofi. François COTTON reports grants, consulting fees, and non-financial support from Biogen, Bracco imaging, Merck-Serono, Novartis, Philips and Roche., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Background and Objectives: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD)., Methods: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab., Results: Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD ( p = 0.04; for the brain) and in AQP4-IgG+ NMOSD ( p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy., Discussion: This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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.)

Objectives: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis., Material and Methods: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0., Results: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p  = 0.007 and p  = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p  = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p  < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)), p  = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95, p  = 0.046)., Conclusion: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease., Methods: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment., Results: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab., Conclusion: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD.

Objective: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions., Methods: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI., Results: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype., Conclusion: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.

Objective: To describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis., Methods: Clinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included., Results: Median age at onset was 36.46 (range 18.0-76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26-0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22-0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07-0.72). Finally, MOG-Ab titers were higher at relapse than in remission ( p = 0.009)., Conclusion: In adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients., (© 2018 American Academy of Neurology.)