Introduction: Clinically isolated syndrome (CIS) represents the first demyelinating event suggestive of multiple sclerosis (MS). However, the risk of conversion to MS varies widely among individuals. Identifying clinical and paraclinical predictors of conversion is essential for early risk stratification and timely therapeutic decision-making. This study aimed to evaluate the clinical, neuroimaging, laboratory, and neurophysiological factors associated with MS conversion in a real-world CIS cohort.

Methods: A retrospective analysis was conducted with 273 patients diagnosed with CIS. The primary outcome was conversion to MS, defined by the treating neurologist using standard diagnostic criteria. Bivariate analyses (t-tests, χ², and Fisher’s exact test) were used to compare clinical and paraclinical variables between converters and non-converters. Predictors with p < 0.20 and clinically relevant variables were included in a multivariate logistic regression model to identify independent predictors of conversion.

Results: Of the 273 patients included, 148 (54.2%) converted to MS. Age did not differ significantly between converters and non-converters (33.4 vs. 34.8 years, p=0.29). Neuroimaging markers were strongly associated with conversion: periventricular lesions (74.3% vs. 20.0%; OR_adj ≈ 8.1, 95%CI 4.0–16.1), infratentorial lesions (88.5% vs. 49.6%; OR_adj ≈ 4.8, 95%CI 2.2–10.3), and spinal cord lesions (73.6% vs. 62.4%; OR_adj ≈ 2.16, 95%CI 1.02–4.59). Oligoclonal bands in CSF were significantly different across groups (χ²=48.3; p≈3.3×10⁻¹¹) and remained an independent predictor (p≈0.014). Gender exhibited a trend toward significance after adjustment (p≈0.051). Initial EDSS could not be reliably compared due to missing data.

Conclusions: In this CIS cohort, the strongest independent predictors of conversion to MS were periventricular, infratentorial, and spinal cord lesions, along with the presence of oligoclonal bands. These findings support the central prognostic role of MRI and CSF biomarkers in early MS risk stratification and highlight the need for prompt monitoring and therapeutic considerations in high-risk CIS patients.