Paramagnetic iron rim lesions as a prognostic factor for disability progression in multiple sclerosis: A systematic review of the literature

Background: Chronic inflammation is a key driver of disability progression in multiple sclerosis (MS). Paramagnetic rim lesions (PRLs), which correspond to imaging markers of chronic active lesions (CALs), have emerged as candidate biomarkers of disease severity. Although associated with progression, the current evidence is limited by small sample sizes, short follow-up periods, and incomplete adjustment for confounding factors. Objectives: To evaluate whether PRLs detected by susceptibility-weighted imaging (SWI), filtered phase, or quantitative susceptibility mapping (QSM) using 3T or 7T MRI predict progression independent of relapse activity (PIRA) or disability progression confirmed at 6 months (CDP), as measured by the Expanded Disability Status Scale (EDSS), in adults with MS. Methods: We systematically searched PubMed and Embase to identify studies evaluating associations between PRLs and disability progression in MS. Risk of bias was assessed with the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Results: Five studies including 744 patients were analyzed. The presence of PRLs was associated with a higher risk of PIRA (odds ratio [OR] 2.24; 95 % confidence interval [CI]: 1.17–4.29; p = 0.01) and CDP (OR 2.87; 95 % CI: 1.01–8.1; p = 0.05). In studies with ≤4 years of follow-up, the association with PIRA was stronger (OR 2.84; 95 % CI: 1.72–4.68; p < 0.0001). Certainty of evidence was rated as moderate for PIRA and low for CDP. Conclusions: PRLs are associated with an increased risk of MS progression through PIRA. Clinical trials investigating novel disease-modifying therapies (DMTs) that target chronic inflammation and prevent disability progression should consider the presence of PRLs at baseline.