Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta‐Analysis
María Paula Zafra‐Sierra, Carolina Ferreira‐Atuesta, Daniela Sofía Rodríguez, Jairo Gaitán, Susana Otero, Mar Tintoré, Fred Lublin, Gavin Giovannoni, Jaime Toro, Saúl ReyesABSTRACT
Background
Most people with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS); however, not all individuals with CIS are subsequently diagnosed with MS.
Methods
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 I 2 , 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.
Results
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.
Conclusions
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.