Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis

Luisa Klotz, Joost Smolders, Jussi Lehto, Markus Matilainen, Lukas Lütje, L. Buchholz, Stefanie Albrecht, Carolin Walter, Julian Varghese, Heinz Wiendl, Marjo Nylund, Christian Thomas, Maria Gardberg, Aletta M.R. van den Bosch, Laura Airas, Inge Huitinga, Tanja Kuhlmann

Nature Medicine · 2025

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Summary

This study identifies broad rim lesions—characterised by an extensive myeloid cell rim with distinct innate immune and inflammatory signatures—as a pathological and imaging biomarker associated with rapid disease progression in multiple sclerosis. Using unbiased histology and spatial transcriptomics on an autopsy cohort of 186 individuals with contrasting disease trajectories, alongside independent positron emission tomography validation in 114 individuals, the authors link this lesion phenotype to accelerated neurodegeneration. The findings offer mechanistic insights into MS progression and suggest broad rim lesions as a potential patient stratification tool for future therapeutic trials targeting central nervous system inflammation.

Regional applicability

This clinical neurology research was conducted primarily using Netherlands-based autopsy tissue and European clinical cohorts. The findings are directly applicable to MS patient management and clinical trial design in the United Kingdom and other high-income healthcare systems, though the study does not address UK-specific soil, farming, or food system contexts and falls outside the primary scope of Vitagri's agricultural and nutritional focus.

Key measures

Histological lesion characteristics, spatial transcriptomics signatures (innate immune activation, inflammatory cytokine production, unfolded protein response, apoptosis), translocator protein 18-kDa positron emission tomography imaging, disease progression trajectories

Outcomes reported

The study identified a distinct MS lesion type characterised by an extensive myeloid cell rim and linked its presence to rapid disease progression using histology and spatial transcriptomics in an autopsy cohort, validated by positron emission tomography imaging in an independent cohort.

Theme
Measurement & metrics
Subject
Other / interdisciplinary
Study type
Research
Study design
Observational cohort with validation study
Source type
Peer-reviewed study
Status
Published
Geography
Europe
System type
Human clinical
DOI
10.1038/s41591-025-03625-7
Catalogue ID
SNmp6e745k-fvu4ec

Topic tags

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