Slowly eroding lesions in multiple sclerosis
Open accessAbstract
Background: At autopsy, 20%–40% of chronic multiple sclerosis (MS) lesions are labeled “slowly expanding” and feature myelin phagocytosis at the lesion edge. As pathological lesion classification relies on a single, terminal time point, the rate of lesion expansion cannot be directly measured. Objective: To study long-term volume changes in individual MS lesions. Methods: Volumes of individual lesions on proton density magnetic resonance imaging (MRI) acquired between 1992 and 2015 were measured in 22 individuals (one lesion per person). After correction for acquisition protocol, a mixed model evaluated lesion volume changes. Results: The mean (standard deviation) lesion volume at baseline was 142 (82) mL, falling to 74 (51) mL after 16 (3) years. All lesions shrank over time. Change in lesion volume did not correlate with change in supratentorial brain volume ( p = 0.33). In simulations, the results could be explained by a process of slow radial expansion superimposed on substantially more rapid resorption of damaged tissue. Conclusion: We noted sustained radiological contraction of MS lesions, a surprising result given that fresh myelin breakdown products within chronic active lesions are observed relatively frequently at autopsy. Therefore, the primary pathological process in chronic lesions, even those described as “slowly expanding,” is likely to be tissue loss.
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Neuropathological active lesions with homogeneously high TSPO expression may define those most likely to decrease in volume over time.
“The neuropathological active lesions with homogeneously high TSPO expression may define those most likely to decrease in volume over time (Sethi et al., 2017; Elliott et al., 2018).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Sethi et al., 2017
The Results and Discussion report that the chronic MS lesions studied by MRI shrank over time. The paper does not assess TSPO expression or show that neuropathologically active lesions with homogeneously high TSPO expression are most likely to shrink. (LLM, conf=0.84)
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“Historically, these lesions have been referred to as being “slowly expanding”[5], “slowly eroding”[22], “chronic active”[14, 29], or “smoldering”[19].”
ResultQuantitative MRI texture analysis in chronic active multiple sclerosis lesions
Weber, C. E., Wittayer, M., Kraemer, M., Dabringhaus, A., Platten, M., Gass, A., & Eisele, P. (2021) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2021.03.016 · Cited by 12 · see citing works
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“4 years, found no associa‐ tion of WML shrinking with changes in supratentorial brain vol‐ ume (Sethi et al., 2016).”
BackgroundInfluentialVenous Diameter Changes in Chronic Active Multiple Sclerosis Lesions
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“We allow the lesion volume to increase or decrease [12, 14, 26] within certain percentages, α high and α low , and only apply the penalty if any change is beyond this.”
BackgroundSlowly Expanding Lesions in Multiple Sclerosis: A Systematic Review and Meta-Analysis
Panah, M. Y., Fekri, M., Zahedi, Z., Bagheri, H., Vaheb, S., Mahmoudi, F., Shaygannejad, V., & Mirmosayyeb, O. (2026) · The Neuroscientist · doi:10.3390/neurosci7020034 · Cited by 3
“…chronic T2 lesions that expand radially over time [26,30,32], while some applied quantitative criteria (e.g., lesions enlarging by a certain volume or ≥ 12.5% per year on serial scans) [29,39], or required evidence of chronic active inflammation at the lesion edge (such as a paramagnetic rim) [37].”
InfluentialChronic lesion expansion as an imaging biomarker in multiple sclerosis
Hayes, M., Beadnall, H. N., Merlo, D., Monif, M., Klistorner, S., Zhu, C., van der Walt, A., & Butzkueven, H. (2026) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2026.107093 · Cited by 3 · see citing works
An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis
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“26 – 30 In contrast, while lesion expansion also occurred parallel to veins, it also did so orthogonal to them.”
Basaran, B. D., Matthews, P. M., & Bai, W. (2024) · arXiv.org · doi:10.48550/arxiv.2412.10946 · Cited by 2
“It permits variations in lesion volume to either rise or fall [30,33,34] within specified thresholds, denoted as α high and α low .”
- Authors
- Sethi, V., Nair, G., Absinta, M., Sati, P., Venkataraman, A., Ohayon, J., Wu, T., Yang, K., Shea, C., Dewey, B. E., Cortese, I. C., & Reich, D. S.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2016-07-11
- Volume
- 23
- Issue
- 3
- Pages
- 464-472
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- PMC
- PMC5182188
- OpenAlex
- W2463861876
- Cited by
- 34
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 3 · 2016: 1
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Funders
- National Institutes of Health (Z99 NS999999)
- National Institute of Neurological Disorders and Stroke (ZIANS003119)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- multiple sclerosis, chronic active lesions, lesion shrinkage, myelin phagocytosis, tissue resorption, lesion classification, proton density MRI, longitudinal MRI follow-up
- MeSH terms
- Adolescent, Adult, Age Factors, Brain, Disability Evaluation, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Time Factors, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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