Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta-Analysis
In brief
Corpus callosum lesions raise post-CIS multiple sclerosis risk about fourteen-fold
A meta-analysis of 72 studies (9,915 adults) found that MRI evidence of corpus callosum lesions increased the odds of developing MS after a clinically isolated syndrome by roughly 15 times, while younger age, multifocal symptoms, and other lesion patterns also predicted conversion. These factors can help clinicians identify high-risk patients, though prospective validation is needed.
- Journal
- European journal of neurology (Q1)
- Published
- 1 August 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- María Paula Zafra-Sierra, Carolina Ferreira-Atuesta, Daniela Sofía Rodríguez, Jairo Gaitán, Susana Otero, Mar Tintoré, et al.
- PMID
- 42538767
- DOI
- 10.1111/ene.70711
Why clinicians should know about it
- Picked for Immunology and Allergy (paper of the day, 2 August 2026).
Abstract
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 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. 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.