Quantifying the Impact of Ocrelizumab on Paramagnetic Rim Lesions in Multiple Sclerosis

作者：Kimberly Markowitz, Neha V. Safi, Alexey Dimov, Ulrike W. Kaunzner, Ha Manh Luu, Mert Şişman, Yi Wang, Thanh D. Nguyen, Sandra Hurtado Rúa, Susan A. Gauthier · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.05.20.25328011 · 被引用次数：2 · 研究领域：Peripheral Neuropathies and Disorders

Abstract Paramagnetic rim lesions (PRLs) are a subset of chronic active multiple sclerosis (MS) lesions, characterized by a rim of iron-laden macrophages and microglia encircling a demyelinated core. These lesions signify persistent inflammatory activity in the central nervous system (CNS), yet their responsiveness to B cell depletion therapy has not been well established. Ocrelizumab, a humanized monoclonal antibody that targets CD20+ B cells, is effective in suppressing acute MS activity; however, its impact on chronic CNS inflammation, particularly within PRLs, remains unclear. To address this question, we conducted a retrospective longitudinal imaging study of MS patients undergoing Ocrelizumab treatment. All participants had pre-treatment imaging with at least one PRL identified via quantitative susceptibility mapping (QSM). Using an R2*QSM source separation (SS) framework, we disentangled the contribution from iron sources with positive susceptibility (QSMp) and myelin sources with negative susceptibility (QSMn) to quantify iron and myelin changes within lesions. Lesions were individually segmented, and PRLs were classified through expert consensus. Modeling of QSMp and QSMn was performed using mixed effects and joint-point regression analysis to assess temporal changes in lesion properties. Across 29 patients, we identified 97 PRLs. Prior to treatment, PRLs exhibited significantly elevated QSMp compared to non-PRLs (p=0.001), consistent with iron enrichment at the lesi...