# Slowly Expanding Lesions in Multiple Sclerosis: A Systematic Review and Meta-Analysis

**Authors:** Mohammad Yazdan Panah, Mehra Fekri, Zahra Zahedi, Hossein Bagheri, Saeed Vaheb, Farhad Mahmoudi, Vahid Shaygannejad, Omid Mirmosayyeb

PMC · DOI: 10.3390/neurosci7020034 · 2026-03-06

## TL;DR

This study reviews evidence showing that slowly expanding lesions are common in multiple sclerosis and linked to disease progression and disability.

## Contribution

The paper provides a systematic review and meta-analysis of the prevalence and clinical relevance of slowly expanding lesions in multiple sclerosis.

## Key findings

- The pooled prevalence of SELs in PwMS was 57.1%.
- SELs are associated with disability, brain atrophy, and axonal degeneration.
- Disease-modifying therapies reduced the number and volume of SELs.

## Abstract

Background: Slowly expanding lesions (SELs) have been introduced as a radiological marker of chronic active demyelination and smoldering inflammation. These lesions are recognized as indicators of disability worsening and brain atrophy in people with multiple sclerosis (PwMS). We aimed to provide an overview of the available evidence on the prevalence and clinical relevance of SELs in PwMS. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched up to 25 May 2025, to identify studies evaluating SELs in PwMS. Risk of bias was assessed using the Newcastle–Ottawa Scale. We conducted a thorough review to evaluate the clinical relevance of SELs in MS. Additionally, a meta-analysis was performed using R software to estimate the pooled prevalence of SELs in MS. Results: Twenty studies on 4970 PwMS met the inclusion criteria. Meta-analysis indicated that the pooled prevalence of SELs in PwMS was 57.1% (95% CI: 44.9% to 69.3%). Moreover, the systematic review showed that SELs were associated with chronic neuroinflammation, ongoing demyelination, disability, microstructural damage, and axonal degeneration. Intervention studies also indicated that the number and volume of SELs were decreased following the administration of disease-modifying therapies. Conclusions: SELs are revealed to affect around half of PwMS and are associated with disability and disease progression in MS. These results highlight the potential role of SELs as a critical radiomarker in MS. However, future studies are warranted to validate these preliminary findings.

## Linked entities

- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TSPO (translocator protein) [NCBI Gene 706] {aka BPBS, BZRP, DBI, IBP, MBR, PBR}, PVALB (parvalbumin) [NCBI Gene 5816] {aka D22S749}, NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, BTK (Bruton tyrosine kinase) [NCBI Gene 695] {aka AGMX1, AT, ATK, BPK, IGHD3, IMD1}, SELENOS (selenoprotein S) [NCBI Gene 55829] {aka AD-015, ADO15, SBBI8, SELS, SEPS1, VIMP}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}
- **Diseases:** brain atrophy (MESH:C566985), atrophy (MESH:D001284), disability (MESH:D009069), MS (MESH:D009103), tissue injury (MESH:D017695), primary (MESH:D010538), demyelinating lesions (MESH:D003711), CALs (MESH:D006521), axonal loss (MESH:D012183), axonal damage (MESH:D001480), autoimmune disease (MESH:D001327), injury to (MESH:D014947), WMLs (MESH:D056784), spinal cord atrophy (MESH:D013118), Relapsing remitting multiple sclerosis (MESH:D020529), grey matter damage (MESH:D055652), axonal degeneration (MESH:D009410), chronic inflammation (MESH:D007249), inflammatory cytokine (MESH:D000080424), T2 (MESH:C535434), immune system dysregulation (OMIM:614878), PwMS (MESH:C000719191), neurological deficits (MESH:D009461), neuroinflammation (MESH:D000090862), PMS (MESH:D020528)
- **Chemicals:** lactate (MESH:D019344), Evobrutinib (MESH:C000632111), Fingolimod (MESH:D000068876), Bruton's tyrosine kinase inhibitors (-), reactive oxygen species (MESH:D017382), Natalizumab (MESH:D000069442), gadolinium (MESH:D005682), iron (MESH:D007501), ocrelizumab (MESH:C533411), Ibudilast (MESH:C038366)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13010691/full.md

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Source: https://tomesphere.com/paper/PMC13010691