Paramagnetic Rim Lesions and Immune Profiling in Multiple Sclerosis Progression: Simon Thebault, MD, PhD

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"We know that these paramagnetic rim lesions and their presence are associated with worse outcomes, but we don't really understand the biology underlying that at the level of the immune cells—and this has potential, for instance, as a biomarker."

Recent studies have established a significant association between paramagnetic rim lesions (PRLs) and markers of compartmentalized inflammation in multiple sclerosis (MS). PRLs, identifiable through susceptibility-sensitive MRI, are indicative of chronic active lesions characterized by ongoing inflammation within the central nervous system. Research has shown that patients exhibiting PRLs often presented with pathogenic cerebrospinal fluid (CSF) profiles, including elevated levels of intrathecal inflammation and blood-brain barrier disruption, which correlated with more severe clinical manifestations of MS. These findings highlight the importance of PRLs as potential biomarkers for disease progression.¹

Building on this, further investigations have demonstrated that the presence of PRLs may be linked to distinct immune cell alterations in both CSF and peripheral blood, reinforcing the concept of compartmentalized inflammation in MS. The ability to identify these immune signatures in conjunction with PRLs could provide a promising avenue for improving diagnostic specificity and prognostic accuracy. By leveraging PRLs as noninvasive biomarkers, clinicians may be able to facilitate early intervention and develop personalized therapeutic strategies aimed at mitigating disease progression.

Simon Thebault, MD, PhD, an assistant professor of neurology and neurosurgery at McGill University, expanded on these findings in a presentation at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida.³ In an interview with NeurologyLive^®, Thebault discussed how the association between PRL burden and immune cell markers enhances our understanding of compartmentalized inflammation and its clinical implications. He also explored how these insights could improve monitoring of disease progression and treatment response, ultimately guiding more personalized therapeutic strategies for MS.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Hemond CC, Baek J, Ionete C, Reich DS. Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical status in multiple sclerosis: A retrospective cross-sectional study. Mult Scler. 2022;28(13):2046-2056. doi:10.1177/13524585221102921
2. Martire MS, Moiola L, Rocca MA, Filippi M, Absinta M. What is the potential of paramagnetic rim lesions as diagnostic indicators in multiple sclerosis?. Expert Rev Neurother. 2022;22(10):829-837. doi:10.1080/14737175.2022.2143265
3. Thebault S PRL Burden is Associated with CSF and Blood Immune Cell Measures Indicative of Compartmentalized Inflammation in MS. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. S1.1