Broad Rim Lesions Identified as a Biomarker in Multiple Sclerosis
Broad rim lesions have emerged as a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis (MS), according to research integrating autopsy data and neuroimaging. The findings provide important clues into the mechanisms driving MS progression beyond relapse activity and may refine future therapeutic targeting.
Distinct Lesion Type Tied to Aggressive Disease
Researchers analyzed brain tissue from 186 individuals with MS, distinguishing between donors with slow versus rapid disease trajectories. Through detailed histology and spatial transcriptomics, they identified a specific lesion type characterized by a broad rim of activated myeloid cells. These cells displayed transcriptional signatures consistent with innate immune activation, inflammatory cytokine release, unfolded protein response, and apoptosis.
This pattern of cellular activity, distinct from typical MS lesions, was consistently associated with faster neurological decline. The results highlight that chronic inflammation within the central nervous system, rather than acute relapses, may be a key driver of disease worsening in certain patients.
Imaging Validation and Clinical Implications
To confirm these findings, an independent study using translocator protein (TSPO) positron emission tomography in 114 patients validated the presence of lesions with broad myeloid rims as a strong indicator of disease progression. This dual confirmation strengthens the evidence that such lesions are not only pathological but also detectable through imaging, creating potential for clinical use as a non-invasive biomarker.
Identifying broad rim lesions in multiple sclerosis could help clinicians stratify patients by disease trajectory, tailor treatment intensity, and improve trial design for therapies targeting central nervous system–intrinsic inflammation.
Reference: Klotz L et al. Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis. Nat Med. 2025;31:2016–2026.
