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

Area of Science:

• Neurology
• Neuroimmunology
• Clinical Medicine

Background:

• Multiple sclerosis (MS) often begins with a clinically isolated syndrome (CIS).
• Not all individuals experiencing CIS are ultimately diagnosed with MS.
• Identifying predictors of MS conversion from CIS is crucial for early intervention.

Purpose of the Study:

• To systematically review and meta-analyze factors associated with the conversion of CIS to MS.
• To identify specific clinical, imaging, and cerebrospinal fluid (CSF) markers that predict MS diagnosis.

Main Methods:

• Systematic literature review conducted up to December 2025.
• Inclusion of observational studies on adults with CIS who later developed MS.
• Random-effects meta-analysis of pooled odds ratios (ORs), with heterogeneity assessed using I² statistics.

Main Results:

• Younger age (OR=1.6) and multifocal presentation (OR=1.55) were linked to higher MS risk.
• Specific MRI findings, including T2 lesions (OR=7.46), periventricular lesions (OR=4.08), and corpus callosum lesions (OR=14.89), significantly predicted MS.
• Cerebrospinal fluid markers like oligoclonal bands (OR=3.57) and pleocytosis (OR=3.34) were also associated with increased MS likelihood.

Conclusions:

• This meta-analysis highlights key factors predicting MS development post-CIS.
• Findings support the identification of high-risk individuals for tailored treatment approaches.
• Early identification can potentially optimize management and outcomes for patients with CIS.