Central vein sign and paramagnetic rim lesions in pediatric-onset multiple sclerosis: a systematic review and meta-analysis

Abstract

Susceptibility-based MRI biomarkers, including paramagnetic rim lesions (PRLs) and central vein sign (CVS), were incorporated into the 2024 McDonald criteria because they improve diagnostic specificity in adult-onset MS; however, their role in pediatric-onset MS (POMS) remains incompletely defined. To synthesize current evidence on the prevalence and diagnostic value of PRLs and CVS in POMS. We conducted a PRISMA-compliant systematic review and random-effects meta-analysis of studies reporting PRLs and/or CVS in POMS. Outcomes included the proportion of patients with ≥1 PRL, the mean proportion of CVS-positive lesions, and fulfillment of CVS-based thresholds. Eleven studies were included. Across seven studies, the pooled proportion of POMS patients with ≥1 PRL was 71.6% (95% CI 61.1–80.2; n=149), with low between-study heterogeneity. Across six studies, the pooled mean proportion of CVS-positive lesions was 57.9% (95% CI 39.7–76.2; n=99), and 66.2% (95% CI 10.5–97.0; n=219) of patients fulfilled the 40%-CVS rule, with substantial variability across studies. In comparative analyses, PRLs showed high specificity for POMS, while CVS was more prevalent than in mimics; however, limited data precluded quantitative evaluation. PRLs are frequent in POMS. Limited comparative data suggest that PRLs may have high diagnostic specificity, whereas CVS appears more variable; however, pediatric diagnostic accuracy evidence remains scarce. Further pediatric-specific studies are needed to define the optimal diagnostic use of these biomarkers in POMS.