MS-Related Disability Worsening and Thalamic Volume Loss

Rationale: Whole-brain volume loss is an established marker of tissue damage in MS, but evidence suggests thalamic and deep-gray-matter atrophy may be a distinct, possibly independent, driver of disability worsening. Once confirmed in an adequately powered longitudinal setting, pathological TVL could serve as a complementary marker of disease activity and a treatment target.

Design and data collection: Disability (EDSS) is assessed at baseline, at approximately 6-month intervals, and at 24 months; SDMT and serum neurofilament light chain (sNfL) are optional. Each participant undergoes standardized brain MRI (2021 MAGNIMS-CMSC-NAIMS protocol, including high-resolution T1w) at baseline and follow-up. Data are collected annually as part of routine care via a network of centers operating since 2015; no visit or procedure is mandated by the study. A preceding retrospective secondary-data phase validates the statistical design. Annual change in EDSS is estimated by linear regression across all visits; annualized TVL and brain volume change are estimated from consecutive T1w MRI using validated methods (Opfer et al. 2020) and the Biometrica MS / BrainLossNet pipeline.

Inclusion criteria

General: Patients aged 15 to 55 with MS diagnosed by the revised 2017 McDonald criteria; ACTIVE MS group: a) Meet one disease-activity criterion: more than 10 T2 lesions at the first visit, OR at least one documented relapse in the 12 months before the first visit, OR ≥1 Gd-enhancing lesion on brain MRI in the prior 12 months, OR ≥1 new or enlarging T2 lesion in the prior 12 months. b) Receiving or about to receive first-line immune therapy (as first or second DMT), e.g., teriflunomide, ozanimod, dimethylfumarate, ponesimod, diroximelfumarate; or receiving or about to receive second-line therapy after prior first-line DMT (e.g., monoclonal antibodies); PROGRESSIVE MS group: a) no relapses in the last two years and progressive disease defined clinically (disability worsening) or by imaging (abnormal whole-brain volume loss); b) participants initially in the active group may switch to the progressive group if they later meet its criteria. Exclusion Criterion: Not eligible to receive MRI.