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Background: The combination of anatomical MRI and deep learning‐based methods such as convolutional neural networks (CNNs) is a promising strategy to build predictive models of multiple sclerosis (MS) prognosis. However, studies assessing the effect of different input strategies on model's performance are lacking. Purpose: To compare whole‐brain input sampling strategies and regional/specific‐tissue strategies, which focus on a priori known relevant areas for disability accrual, to stratify MS patients based on their disability level. Study Type: Retrospective. Subjects: Three hundred nineteen MS patients (382 brain MRI scans) with clinical assessment of disability level performed within the following 6 months (~70% training/~15% validation/~15% inference in‐house dataset) and 440 MS patients from multiple centers (independent external validation cohort). Field Strength/Sequence: Single vendor 1.5 T or 3.0 T. Magnetization‐Prepared Rapid Gradient‐Echo and Fluid‐Attenuated Inversion Recovery sequences. Assessment: A 7‐fold patient cross validation strategy was used to train a 3D‐CNN to classify patients into two groups, Expanded Disability Status Scale score (EDSS) ≥ 3.0 or EDSS < 3.0. Two strategies were investigated: 1) a global approach, taking the whole brain volume as input and 2) regional approaches using five different regions‐of‐interest: white matter, gray matter, subcortical gray matter, ventricles, and brainstem structures. The performance of the models was assessed in the in‐house and the independent external cohorts. Statistical Tests: Balanced accuracy, sensitivity, specificity, area under receiver operating characteristic (ROC) curve (AUC). Results: With the in‐house dataset, the gray matter regional model showed the highest stratification accuracy (81%), followed by the global approach (79%). In the external dataset, without any further retraining, an accuracy of 72% was achieved for the white matter model and 71% for the global approach. Data Conclusion: The global approach offered the best trade‐off between internal performance and external validation to stratify MS patients based on accumulated disability. Evidence Level: 4 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. Methods: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. Results: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. Conclusion: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS. [ABSTRACT FROM AUTHOR]

Objective: Myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) distinguish multiple sclerosis (MS) from MOG‐associated disease in most cases. However, studies analyzing MOG‐Ab at the time of a first demyelinating event suggestive of MS in adults are lacking. We aimed to (1) evaluate the prevalence of MOG‐Ab in a first demyelinating event suggestive of MS and (2) compare clinical and paraclinical features between seropositive (MOG‐Ab+) and seronegative (MOG‐Ab−) patients. Methods: Six hundred thirty adult patients with available serum samples obtained within 6 months from the first event were included. MOG‐Ab were analyzed using a live cell‐based assay. Statistical analyses included parametric and nonparametric tests, logistic regression, and survival models. Results: MOG‐Ab were positive in 17 of 630 (2.7%). Fourteen out of 17 (82.4%) MOG‐Ab+ patients presented with optic neuritis (ON) compared to 227of 613 (37.0%) MOG‐Ab− patients (p = 0.009). Cerebrospinal fluid‐restricted oligoclonal bands (CSF‐OBs) were found in 2 of 16 (12.5%) MOG‐Ab+ versus 371 of 601 (61.7%) MOG‐Ab− subjects (p < 0.001). Baseline brain magnetic resonance imaging (MRI) was normal in 9 of 17 (52.9%) MOG‐Ab+ versus 153 of 585 (26.2%) MOG‐Ab− patients (p = 0.029). Absence of CSF‐OBs and ON at onset were independently associated with MOG‐Ab positivity (odds ratio [OR] = 9.03, 95% confidence interval [CI] = 2.04–53.6, p = 0.009; and OR = 4.17, 95% CI = 1.15–19.8, p = 0.042, respectively). Of MOG‐Ab+ patients, 22.9% (95% CI = 0.0–42.7) compared to 67.6% (95% CI = 63.3–71.3) of MOG‐Ab− patients fulfilled McDonald 2017 criteria at 5 years (log‐rank p = 0.003). Interpretation: MOG‐Ab are infrequent in adults with a first demyelinating event suggestive of MS. However, based on our results, we suggest to determine these antibodies in those patients with ON and absence of CSF‐OBs, as long as the brain MRI is not suggestive of MS. ANN NEUROL 2024;95:116–128 [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS)., Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials., Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis., Results: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7-36.9]) and treatment failure (OR 10.6 [3.4-32.5]) but did not predict radiological activity (OR 1.9 [0.7-5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder., Conclusion: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully., 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: A.P. has received funding travel from Roche and speaking honoraria from Novartis; he developed this project during a 2021 ECTRIMS Clinical Training Fellowship program and is currently performing an MSIF-ARSEP Fellowship program. R.C. has received consulting services and speaking honoraria from Roche, Novartis, BIIB-Colombia, Merck, Sanofi, and was funded by an ECTRIMS Clinical Training Fellowship program. C.T. is currently being funded by a Junior Leader La Caixa Fellowship; she has also received the 2021 Merck’s Award for the Investigation in Multiple Sclerosis (Spain) and a grant (PI/01860) from Instituto de Salud Carlos III, Spain; and she has also received speaker honoraria from Roche and Novartis. A.C.C. has received a grant from Instituto de Salud Carlos III, Spain; JR19/00007. P.C.M.’s yearly salary is supported by a grant from Biogen to Fundació Privada Cemcat for statistical analysis. N.B. has received travel expenses for scientific meetings and speaking honoraria from Roche, Novartis, Biogen, and Merck, and is currently being funded by ECTRIMS Fellowship. A.V.J. receives support for contracts Juan Rodes (JR16/00024) from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain; and has received speaking honoraria and travel expenses from Novartis, Roche, Teva, Biogen, and Sanofi-Genzyme. G.A. has received speaking honoraria, compensation for consulting services or participation in advisory boards from Sanofi, Merck, Roche, and Horizon Therapeutics; travel support for scientific meetings from Novartis, Roche, and ECTRIMS; is editor for Europe of the Multiple Sclerosis Journal—Experimental, Translational and Clinical; is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee; and is a member of the European Biomarkers in MS (BioMS-eu) consortium steering committee. N.M.O. has a predoctoral grant Rio Hortega, from the Instituto de Salud Carlos III (Spain). C.N. has received funding for travel from Biogen Idec and F. Hoffmann-La Roche, and speaker honoraria from Novartis. B.R.A. has received honoraria for consulting services from Wellspect. A.Z. has received travel expenses for scientific meetings from Biogen Idec, Merck Serono, and Novartis; speaking honoraria from Eisai; and a study grant from Novartis. M.C. has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen Idec, Teva Pharmaceuticals, Sanofi-Aventis, and Novartis. J.S.G. has received compensation for participating on Advisory Boards, speaking honoraria, and travel expenses for scientific meetings, consulting services, or research support from Celgene, Novartis, Biogen, Teva, Merck, Almirall, and Genzyme. M.T. has received compensation for consulting services, speaking honoraria from Almirall, Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Sanofi Aventis, and Teva Pharmaceuticals, and is co-editor of Multiple Sclerosis Journal—ETC. A.R. serves on scientific advisory boards for Novartis, Sanofi Genzyme, Icometrix, SyntheticMR, Bayer, Biogen, and OLEA Medical, and has received speaker honoraria from Bayer, Sanofi Genzyme, Bracco, Merck Serono, Teva Pharmaceutical Industries Ltd., Novartis, Roche, and Biogen. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, MedDay, Merck, Mylan, NervGen, Novartis, Sandoz, Sanofi Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS. J.R. has received speaking honoraria and personal compensation for participating on Advisory Boards from Almirall, Bayer Schering Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi Aventis. C.A., A.S.A., J.C.J., L.B., L.M., A.S., I.G., and M.R.B. report no disclosures.