ArticleNature medicine2025
Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- Impact of Oral Cladribine on TSPO-PET-Measurable Immune Cell Activation in Multiple Sclerosis.Neurology and therapy · 2026Article
- What the 'negative space' tells us about the immunology of multiple sclerosis.Nature reviews. Immunology · 2026Article
- CAR-T Cell Therapy and Gut Microbiota Modulation in Multiple Sclerosis: Emerging Therapeutic Strategies and Current Limitations.Current issues in molecular biology · 2026Review
- Targeting progressive multiple sclerosis: Toward mechanism-informed precision medicine.Journal of internal medicine · 2026Review
- Genetic subtypes of multiple sclerosis severity are uncoupled from inflammatory lesion burden.Acta neuropathologica · 2026Article
- [XVIII Post-ECTRIMS Meeting: Review of the New Developments Presented at the 2025 ECTRIMS Congress (Part II)].Revista de neurologia · 2026Article
- [XVIII Post-ECTRIMS Meeting: Review of the New Developments Presented at the 2025 ECTRIMS Congress (Part I)].Revista de neurologia · 2026Article
- Deep Learning-Based Automated Detection and Burden Assessment of Paramagnetic Rim Lesions on Quantitative Susceptibility Mapping in Patients With Multiple Sclerosis.Korean journal of radiology · 2026Article
- Grey matter degeneration during multiple sclerosis is linked to activation of neuronal necroptosis by oxidized phosphatidylcholines.Research square · 2026Article
- Baseline Neuroinflammation Stratifies TSPO-PET Response to Disease-Modifying Therapy in Multiple Sclerosis.Annals of clinical and translational neurology · 2026Article
- Donor-specific pathological features associate with genetic background, lesion type distribution, and clinical heterogeneity in multiple sclerosis.Acta neuropathologica · 2026Article
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- Treatment Effects on Chronic Active Lesions in Multiple Sclerosis: Current Evidence and Future Perspectives.Neurology and therapy · 2026Review
- A CSF disease-associated macrophage signature defines progressive multiple sclerosis.Journal of neuroinflammation · 2026Article
- Investigations of remibrutinib in models pertinent to multiple sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways.Acta neuropathologica communications · 2026Article
- FKBP5 regulates interferon signaling leading to myeloid cell activation in multiple sclerosis.Journal of neuroinflammation · 2026Article
- Patient-reported gradual worsening reveals progression beyond MS subtypes.Journal of neurology · 2026Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- In vivo CRISPR screen reveals regulation of macrophage states in neuroinflammation.Nature neuroscience · 2026Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Current multiple sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail because of insufficient understanding of its underlying mechanisms. This study analyzed a clinically well-characterized MS autopsy cohort from the Netherland Brain Bank (186 individuals) from which we selected donors exhibiting opposite disease trajectories of slow versus rapid progression. We performed extensive unbiased histology and spatial transcriptomics, which unveiled a distinct MS lesion type marked by an extensive myeloid cell rim with cellular and transcriptional signatures of innate immune activation, inflammatory cytokine production, unfolded protein response and apoptosis. Presence of this particular lesion type was linked to rapid disease progression. An independent translocator protein 18-kDa positron emission tomography study (114 individuals) validates the association between lesions with a broad myeloid cell rim and disease progression in individuals with MS. Our findings offer crucial insights into the mechanisms behind MS progression, identifying broad rim lesions as a biomarker for rapid disease progression and potentially guiding patient selection for future therapeutic trials targeting central nervous system intrinsic inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.