Bourre, Bertrand

ABSTRACT Objectives We aimed to determine the frequency of subclinical optic nerve (ON) lesions using MRI, optical coherence tomography (OCT), and visual evoked potentials (VEP) in radiologically isolated syndrome (RIS), and to assess their diagnostic and prognostic significance. Methods We conducted a retrospective, multicenter study of 179 RIS individuals followed in clinical practice who met the 2023 RISC criteria. The diagnostic performance of the 2024 McDonald criteria, with and without optic nerve assessment, was evaluated and compared with that of the 2017 criteria. Associations with clinical conversion, comorbidities, and MRI disease activity were analyzed using multivariate models. Results Silent ON lesions appeared in 107/179 (59.8%) individuals, mainly detected by VEP (100/164; 61.0%) and OCT (69/118; 58.5%), with routine MRI identifying 31/166 (18.7%). During follow‐up, 71 (39.7%) had a first clinical event. The presence, laterality, or number of silent ON lesions did not correlate with clinical conversion, event type, or MRI activity. Younger age and the absence of comorbidities associated with other MRI lesions, rather than with ON lesions, were associated with clinical conversion. Including ON in the 2024 McDonald criteria increased sensitivity but decreased specificity, with 17/179 (9.5%) meeting dissemination‐in‐space criteria solely due to ON lesions. Interpretation Subclinical ON lesions are common in RIS and are mainly found by OCT and VEP, not routine MRI. Including ON increases sensitivity but does not predict clinical conversion and may lower specificity. These findings suggest cautious interpretation of ON and support a multimodal assessment approach in RIS.

This international multicenter study seeks to determine the frequency and characteristics of meningitis in myelin oligodendrocyte glycoprotein antibody (MOGAD)–associated disease and highlight its pathology.

Importance Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. Objective To determine the time to onset of symptoms consistent with MS. Design, Setting, and Participants From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Interventions Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Main outcomes Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Results Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Conclusion and Relevance Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. Trial Registration ClinicalTrials.gov Identifier: NCT03122652

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.