Characterizing iron rim lesions in multiple sclerosis: a biomarker for disease activity and progression: a systematic review and meta-analysis.

BACKGROUND

Iron rim lesions (IRLs) have emerged as important biomarkers in multiple sclerosis (MS), indicating chronic active inflammation and neurodegeneration. The purpose of this systematic review and meta-analysis is to assess the prognostic value of IRLs in MS, their impact on clinical outcomes, and their relationship with therapeutic responses.

METHODS

A thorough search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, covering studies published until June 10, 2024. The inclusion criteria included studies on MS patients who had IRLs detected using advanced MRI techniques, particularly susceptibility-weighted imaging (SWI). The meta-analysis included 13 studies and a total of 924 MS patients. The data on clinical outcomes (EDSS scores, relapse rates), brain volume, and white matter lesion (WML) burden were combined. For continuous variables, effect sizes were calculated using standardized mean differences (SMDs), and for binary outcomes, relative risks (RRs).

RESULTS

This meta-analysis indicated significant correlations between IRLs and poorer clinical outcomes. IRL-positive individuals had higher EDSS scores (SMD 0.77, 95% CI: 0.34-1.21, p = 0.000), indicating a more severe impairment. They also had a larger WML load (SMD 0.52, 95% CI: 0.01-1.03, p = 0.000) and a smaller brain volume (SMD -0.50, 95% CI -0.82 to -0.19, p = 0.015). The relapse rate ratio was 1.10 (95% CI 0.73-1.65, p = 0.499), indicating a trend toward more frequent relapses in IRL-positive patients, though not statistically significant. Treatment response to disease-modifying treatments (DMTs) was similar in IRL-positive and negative individuals (RR 0.97, 95% CI: 0.89-1.06, p = 0.424). However, IRL-positive patients who received high-dose DMTs (HDMT) had a trend toward better outcomes (RR 1.2, 95% CI 0.94-1.52, p = 0.424).

CONCLUSIONS

IRLs are strongly linked to higher disease severity, lesion burden, and neurodegeneration in MS patients. These lesions should be considered in routine medical evaluations since they are reliable prognostic indicators. Early intervention with high-dose treatment might offer potential benefits for IRL-positive patients, but further research is needed to determine the long-term clinical implications.