Slowly Expanding Lesions in Multiple Sclerosis: A Systematic Review and Meta-Analysis

BACKGROUND: Slowly expanding lesions (SELs) have been introduced as a radiological marker of chronic active demyelination and smoldering inflammation. These lesions are recognized as indicators of disability worsening and brain atrophy in people with multiple sclerosis (PwMS). We aimed to provide an overview of the available evidence on the prevalence and clinical relevance of SELs in PwMS. METHODS: PubMed, Embase, Scopus, and Web of Science were systematically searched up to 25 May 2025, to identify studies evaluating SELs in PwMS. Risk of bias was assessed using the Newcastle-Ottawa Scale. We conducted a thorough review to evaluate the clinical relevance of SELs in MS. Additionally, a meta-analysis was performed using R software to estimate the pooled prevalence of SELs in MS. RESULTS: Twenty studies on 4970 PwMS met the inclusion criteria. Meta-analysis indicated that the pooled prevalence of SELs in PwMS was 57.1% (95% CI: 44.9% to 69.3%). Moreover, the systematic review showed that SELs were associated with chronic neuroinflammation, ongoing demyelination, disability, microstructural damage, and axonal degeneration. Intervention studies also indicated that the number and volume of SELs were decreased following the administration of disease-modifying therapies. CONCLUSIONS: SELs are revealed to affect around half of PwMS and are associated with disability and disease progression in MS. These results highlight the potential role of SELs as a critical radiomarker in MS. However, future studies are warranted to validate these preliminary findings.