Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta-Analysis

Most people with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS); however, not all individuals with CIS are subsequently diagnosed with MS.

A systematic literature review was conducted until December 2025. Observational studies of adults with CIS that were later diagnosed with MS were included. Odds ratios (ORs) were pooled using random-effects meta-analysis. Heterogeneity was assessed with I², sensitivity analyses with leave-one-out procedures, and publication bias with funnel plots and Egger's test. Meta-regression was performed to explore further sources of heterogeneity when appropriate.

Seventy-two studies with 9915 adults were included. In the meta-analysis, younger age (OR = 1.6, p < 0.01) and multifocal presentation (OR = 1.55, p = 0.02) were associated with a diagnosis of MS after a CIS. Magnetic resonance imaging findings, including a higher number of T2 lesions (OR = 7.46, p = 0.02), periventricular lesions (OR = 4.08, p < 0.01), corpus callosum lesions (OR = 14.89, p = 0.02), infratentorial lesions (OR = 2.16, p = 0.03), spinal cord lesions (OR = 1.4, p = 0.03), and gadolinium-enhancing lesions (OR = 1.91, p = 0.01), as well as cerebrospinal fluid inflammatory markers such as oligoclonal bands (OR = 3.57, p < 0.01) and pleocytosis (OR = 3.34, p = 0.02), were also associated with a subsequent diagnosis of MS.

This meta-analysis identified factors associated with an increased likelihood of MS after a CIS. These findings may help identify high-risk individuals and guide personalized treatment strategies.