The Prognostic Value of Paramagnetic Rim Lesions in People With Multiple Sclerosis

Paramagnetic rim lesions (PRLs) have been established as a radiologic surrogate for chronic active inflammation in multiple sclerosis (MS). Although associations between PRLs and disability have been observed, data on their prognostic value for long-term risk of clinical worsening, especially in the form of progression independent of relapse activity (PIRA), remain limited. In this study, we assessed the association of PRLs with future disability accumulation over a median follow-up of 5 years and their relation to other (para) clinical parameters.

From a large, ongoing single-center cohort study, people with MS were included according to the availability of susceptibility-sensitive MRI. PRLs were segmented on reconstructed quantitative susceptibility mapping scans using a deep learning-based segmentation model, visually inspected for plausibility, and corrected if necessary. Multivariable Cox proportional hazards models were used to investigate the prognostic value of PRLs for disability outcomes, including confirmed disability accumulation (CDA) and PIRA. Sensitivity analyses based on PRL count, MS diagnosis, prior disability accumulation, and treatment during follow-up were performed to evaluate the robustness of our findings. In addition, associations between PRL status and CSF parameters as well as future brain atrophy, measured by annual percentage brain volume change, were assessed in an exploratory manner.

Among 862 participants (mean age 40.3 years, 64.7% female), 395 (45.8%) had at least 1 PRL. Over a median follow-up of 5.1 years, 142 of 801 individuals with clinical follow-up for longitudinal analysis experienced CDA (17.7%), and 104 of these CDA events (73.2%) occurred as PIRA. The presence of PRLs was associated with a higher risk of PIRA (adjusted hazard ratio 1.8, 95% CI 1.1-2.8; p = 0.02). Exploratory subgroup analyses showed increased markers of chronic intrathecal inflammation in individuals with PRLs as well as a correlation between the number of PRLs and future brain atrophy (PBVC: β = -0.012%, 95% CI -0.018% to -0.005%; p < 0.001).

PRLs are associated with an increased risk of future PIRA and accelerated rates of brain atrophy. These findings emphasize their potential as a prognostic biomarker for risk stratification in MS.