BACKGROUND AND AIMS: Chronic active lesions (CAL) are important component of multiple sclerosis (MS) disease pathology and indicate the presence of a smoldering neuroinflammatory processes. Yet, only recent advances in magnetic resonance imaging (MRI) and positron emission tomography have made it possible to identify CAL in vivo in people with MS (pwMS). Several studies have assessed the association between CAL and disability accumulation in pwMS.
METHODS: A systematic literature search was conducted following PRISMA guidelines 2020 using PubMed, Embase, and the Cochrane Library on April 21, 2023. The review included studies assessing associations between CAL and clinical/radiological outcome of disability accumulation in people with any MS phenotype.
RESULTS: A total of 149 unique studies were identified and 31 met the inclusion criteria. Of these, 21 evaluated paramagnetic rim lesions (PRL) using susceptibility-based MRI, 9 evaluated slow expanding lesions (SEL) on T1-weighted (T1-w)/T2-w MRI, and 1 studied both. The presence of PRL was associated with disability accumulation in 19 studies, with 9 of those studies reporting an association between the number or volume of PRL and disability accumulation. SEL were associated with disability accumulation in 10 studies, with 5 of those studies reporting association between the number or volume of SEL and disability accumulation.
CONCLUSION: This literature review found significant associations between CAL and disability accumulation that may lead to transitioning to progressive disease in pwMS. This illustrates the role of CAL and smoldering disease in MS in driving disability accumulation. CAL remains an important unmet therapeutic target and development of treatments promoting their resolution is crucial.
