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Background and purpose: There are few clinico‐radiological data on optic neuritis (ON) with myelin oligodendrocyte glycoprotein antibody (MOG‐IgG). The objective was to characterize the clinico‐radiological phenotype and outcome of patients with MOG‐IgG‐related ON. Methods: The records of all adult patients admitted in three medical centres with MOG‐IgG‐associated ON who underwent orbital and brain magnetic resonance imaging (MRI) at the acute phase were reviewed. Spinal cord MRI within 1 month from the ON and all of the follow‐up MRI were reviewed. Results: Of 62 patients, 41.9% had bilateral ON and 66.2% optic disc swelling. On initial MRI, lesions were anterior (92%), extensive (63%) and associated with optic perineuritis (46.6%). Silent brain lesions were found in 51.8% of patients but were mainly non‐specific (81%). Of 39 individuals with spinal MRI at onset, nine had abnormal findings (four were asymptomatic). Two symptomatic patients had longitudinally extensive myelitis with concurrent H‐sign. At last follow‐up, 5% of patients had visual acuity ≤0.1. Brain MRI remained unchanged in 41 patients (87%). Conclusions: Our study supports a mostly benign ophthalmological course of MOG‐IgG‐associated ON, despite initially longitudinally extensive lesions and development of optic nerve atrophy on orbital MRI. Spinal MRI could be of interest in detecting silent suggestive lesions. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk., Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS)., Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal., Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations., Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. 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. Françoise Durand-Dubief has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, BMS-Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Christine Lebrun Frenay has nothing to disclose. Géraldine Androdias has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Bertrand Audoin has nothing to disclose. Xavier Ayrignac has received consulting fees and lecturing fess, travel grants, and unconditional research support from Alexion, Biogen, Genzyme, Janssen, Merck Serono, Novartis, Roche, Sanofi Aventis, and Teva Pharma. Caroline Bensa has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, and Novartis. Kevin Bigaut has received lecturing fees and travel grants from Biogen, Celgene-BMS, Novartis, Roche, and Sanofi-Genzyme. Julie Boucher has nothing to disclose. Bertrand Bourre serves on the scientific advisory board and has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, and Roche. Clemence Boutiere has nothing to disclose. Pierre Branger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, and Sanofi-Genzyme. C. Carra-Dalliere has received travel grants and/or consulting fees from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Jonathan Ciron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Novartis, Merck, Sanofi, Roche, Celgene-BMS, Alexion, and Horizon Therapeutics. Angelique Da Silva has received personal fees from Daichi and Leopharma. Gilles Defer has received personal fees from Biogen, Bristol-Myers Squibb, Merck Serono, Novartis, Sanofi-Genzyme, and Teva Pharmaceuticals. Sarah Demortière has nothing to disclose. Maxime Guillaume has received honoraria from Novartis, Merck, and Sanofi. Benjamin Hebant has nothing to disclose. Edouard Januel has nothing to disclose. Anne Kerbrat has nothing to disclose. Arnaud Kwiatkowski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva. Emmanuelle Leray has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Elisabeth Maillart has received research support from Biogen and personal fees for lectures and serving on advisory boards from Biogen, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. Guillaume Mathey has nothing to disclose. Xavier Moisset has received financial support from Allergan-Abbvie, Biogen, BMS, Grünenthal, Lilly, Lundbeck, Teva, Merck Serono, Novartis, Pfizer, Roche, and Sanofi-Genzyme and non-financial support from SOS Oxygène not related to the submitted work. Alexis Montcuquet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Alexison, Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva. Nathalie Morel has nothing to disclose. Romain Marignier has received personal fees from Horizon Therapeutics, Alexion, Roche, and UCB; and nonfinancial support from Horizon Therapeutics, Merck, Biogen, and Roche. Chloe Pierret has nothing to disclose. Julie Pique has received travel grants and personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Teva, Biogen, Novartis, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, and Alexion. Julien Poupart has nothing to disclose. Chloe Prunis has nothing to disclose. Eric Thouvenot has received personal fees from Actelion and Teva and grants from Biogen, Merck Serono, Novartis, and Roche. Thomas Roux has received personal compensation for consulting, speaking, or serving on a scientific advisory board from Alexion, Biogen, BMS-Celgene, Merck, Novartis, and Sanofi-Genzyme. Perrine Schmitt has nothing to disclose. Helene Zephir has nothing to disclose. Mikael Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Ad Scientiam, Biogen, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, Alexion, and Horizon Therapeutics.

Background: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021., Objectives: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022., Methods: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity., Results: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave ( p  < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25-1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51-2.67]), obesity (OR = 2.36, 95% CI = [1.52-3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46-3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43-3.06] for EDSS 3-5.5 and OR = 4.53, 95% CI = [3.04-6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85-3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60-0.69]) or off (RR = 0.32, 95% CI = [0.30-0.33]) anti-CD20., Discussion: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.J. reports no disclosure. E.J. reports no disclosure. P.L. reports no disclosure. E.M. has received research support from Fondation ARSEP and Biogen Idec, travel funding and/or consulting fees from Alexion, Biogen Idec, BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. J.D.S. reports no disclosure. H.Z. has no disclosure related to this manuscript. Unrelated to this manuscript H.Z. received consulting fees from Biogen Idec, Sanofi, Merck, Novartis, Roche, Horizon Therpaeutics, Alexion, BMS, and Grant Research Support from ROCHE. J.P. reports no disclosure. P.K. reports no disclosure. D.B. reports no disclosure. O.H. has received consulting and lecture fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. L.G. has received consulting and/or lecture fees and/or travel funding from Novartis, Merck, Sanofi, BMS, and Biogen. C.B. has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, Novartis, Roche, and Teva. M.T. reports receiving consulting and lecture fees from Merck, Novartis, and Biogen Idec, travel grants from Sanofi, Merck Serono, and Biogen Idec. S.V. has received lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. O.C. reports receiving personal fees from Biogen, Roche, Merck, Novartis, Janssen, and Sanofi and nonfinancial support from Roche, Merck, and Novartis outside the submitted work. A.M. reports no disclosure. D.L. reports receiving grants from Roche, Sanofi, the ARSEP Foundation, the EDMUS Foundation, and the National Agency of Research and receiving personal fees from Biogen, Novartis, Alexion, Merck, and MSD outside the submitted work. E.B. has received honoraria and consulting fees from Alexion, Novartis, Sanofi Aventis, Biogen Idec, Genzyme, Merck, Roche, and Teva. C.L-F. reports no disclosure. B.B. serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Sanofi, Roche, and Teva. P.B. reports receiving personal fees from Novartis, Biogen, Merck, BMS, Alexion, and Sanofi outside the submitted work. B.S. reports research support from Roche, Sanofi, and Merck and personal fees for lectures or advisory boards from Novartis, Sanofi, Biogen, Janssen, and Merck. P.C. reports receiving personal fees for board participation from Janssen and Novartis and for board participation and travel from Sanofi and Merck outside the submitted work. E.T. reports receiving personal fees from Biogen, BMS, Janssen, Horizon, Merck, Novartis, and Sanofi outside the submitted work. E.M. reports no disclosure. T.M. reports receiving travel grants and fees for advisory boards from Biogen, Roche, Novartis, Sanofi, and Teva outside the submitted work. F.S. reports receiving consulting and/or lecture fees and/or travel funding from Novartis-Pharma, Biogen, Roche, Sanofi, Linde, and LVL. M.Z. reports receiving expert testimony from Alexion and Novartis, and travel grants from Merck, Roche, and Sanofi Aventis France. C.P. reports receiving honoraria and consulting fees from Alexion, Biogen, Merck, Horizon, and Roche outside the submitted work and serving as president of the Francophone Multiple Sclerosis Society from 2021 to 2024. C.L. has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, and research grant from Biogen.

Background: The kappa free light chains index (κ-index) is increasing in importance as a fast, easy, cost-effective, and quantitative biomarker in multiple sclerosis (MS), which can replace cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) detection. In previous studies, controls often included mixed patients with several inflammatory central nervous system disorders. The aim of the present study was to assess the κ-index in patients with serum aquaporin-4 (AQP4)-IgG or myelin-oligodendrocyte-glycoprotein (MOG)-IgG., Methods: We analyzed CSF/serum samples of patients with AQP4-IgG or MOG-Ig and evaluated distinct κ-index cut-offs. We described clinical and magnetic resonance imaging (MRI) features of patients with the highest κ-index values., Results: In 11 patients with AQP4-IgG, median κ-index was 16.8 (range 0.2; 63) and 6/11 (54.5%) had κ-index >12. Among 42 patients with MOG-IgG, 2 had low positive MOG-IgG titers, were ultimately diagnosed with MS, and had a markedly increased κ-index (54.1 and 102.5 respectively). For the remaining 40 MOG-IgG-positive patients the median κ-index was 0.3 (range 0.1; 15.5). Some 6/40 (15%) and 1/40 (2.5%) patients had a κ-index >6 and >12, respectively. None fulfilled MRI dissemination in space and dissemination in time (DIS/DIT) criteria and the final diagnosis was MOG-IgG-associated disease (MOGAD) for these 40 patients. Four of the 40 (10%) MOG-IgG-positive patients had OCB., Conclusion: While a marked increase in κ-index could discriminate MS from MOGAD, a low κ-index threshold could lead to confusion between MS and MOGAD or AQP4 antibody-positive neuromyelitis optica spectrum disorder., (© 2023 European Academy of Neurology.)

Background: Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these reports often included the same number of patients in each group, not taking into account the disparity in frequencies of ON aetiologies in a real-life setting and thus, it remains unclear what are the truly useful features for distinguishing the different ON causes. To determine whether clinical evaluation, ophthalmological assessment including the optical coherence tomography (OCT), CSF analysis, and MRI imaging may help to discriminate the different causes of acute ON in a real-life cohort., Methods: In this prospective monocentric study, adult patients with recent acute ON (<1 month) underwent evaluation at baseline and 1 and 12 months, including, high- and low-contrast visual acuity, visual field assessment and OCT measurements, baseline CSF analysis and MRI., Results: Among 108 patients, 71 (65.7%) had multiple sclerosis (MS), 19 (17.6%) had idiopathic ON, 13 (12.0%) and 5 (4.6%) had myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, at last follow up respectively.At baseline, the distribution of bilateral ON, CSF-restricted oligoclonal bands, optic perineuritis, optic nerve length lesions and positive dissemination in space and dissemination in time criteria on MRI were significantly different between the four groups (p <0.001). No significant difference in visual acuity nor inner retinal layer thickness was found between the different ON aetiologies., Conclusions: In this large prospective study, bilateral visual involvement, CSF and MRI results are the most useful clues in distinguishing the different aetiologies of acute ON, whereas ophthalmological assessments including OCT measurements revealed no significant difference between the aetiologies., Competing Interests: Declaration of Competing Interest No disclosure relevant to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised., Objectives: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS)., Methods: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection., Results: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients., Conclusion: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)