ArticleActa neuropathologica2017
Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 266 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Investigating Cortical Gray Matter Demyelination in Primary Progressive Multiple Sclerosis at 7 Tesla
Safety and Efficacy of Subcutaneous Cladribine for Nonrelapsing, Secondary Progressive Multiple Sclerosis (CLASP-MS): a Randomized, Placebo-controlled, Double-blind, Phase 2 Study.
Validation and Standardization of Paramagnetic Rim Lesion (PRL) Identification in Multiple Sclerosis Across MAGNIMS Centers - From Scientific Setting Towards Clinical Applicability
Who cites it
266 citing papers in PubMed, 7 syntheses or guidelines pooled it, 454 citations in OpenAlex.
- Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.Neurology · 2026Pooled it
- Expert Panel Consensus Guidelines of the German Society of Neuroradiology on the Use of Magnetic Resonance Imaging in the Diagnosis and Monitoring of Multiple Sclerosis.Clinical neuroradiology · 2026Guideline
- Iron accumulation in multiple sclerosis and implications for cognitive and clinical progression: a systematic review of advanced neuroimaging studies.Journal of neurology · 2026Pooled it
- Characterizing iron rim lesions in multiple sclerosis: a biomarker for disease activity and progression: a systematic review and meta-analysis.Neuroradiology · 2025Pooled it
- Choroid plexus volume in multiple sclerosis: a systematic review and meta-analysis of an emerging imaging biomarker.European journal of medical research · 2025Pooled it
- Associations between chronic active lesions and clinical outcomes in multiple sclerosis: A systematic literature review.Journal of managed care & specialty pharmacy · 2025Pooled it
- Reliability of paramagnetic rim lesion classification on quantitative susceptibility mapping (QSM) in people with multiple sclerosis: Single-site experience and systematic review.Multiple sclerosis and related disorders · 2023Pooled it
- Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.Neurology · 2024Trial
- Ibudilast reduces slowly enlarging lesions in progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Trial
- Brain oxygen extraction fraction mapping in patients with multiple sclerosis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Trial
- Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial.The Lancet. Neurology · 2021Trial
- Reduced Paramagnetic Rim Visibility Signals Lesion Aging and Tissue Degeneration in Progressive Multiple Sclerosis: Impact on Clinical Trials.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Use of MRI in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease - MAGNIMS consensus recommendations.Nature reviews. Neurology · 2026Review
- Multiancestry genome-wide association and multiomics analyses elucidate spatiocellular features of multiple sclerosis genetics.Nature genetics · 2026Article
- Targeting progressive multiple sclerosis: Toward mechanism-informed precision medicine.Journal of internal medicine · 2026Review
- ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates NMOSD pathology.Cell death and differentiation · 2026Article
- Beyond Relapses: A Multimodal Biomarker Framework for Progression Independent of Relapse Activity and Smouldering Multiple Sclerosis.Brain sciences · 2026Review
- Review
- Foamy microglia link oxylipins to disease progression in multiple sclerosis.Nature neuroscience · 2026Article
- TAnnals of clinical and translational neurology · 2026Article
206 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.
Indexed as
Identifiers
What OpenQuestion holds
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.