Prognostic indicators in pediatric clinically isolated syndrome

OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of Multiple Sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed-up for at least 10 years. Cox proportional hazard models and RECursive Partitioning and AMalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (HR, 95% CI: 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease modifying drugs (DMDs) exposure reduced this risk (HR, 95% CI: 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMDs exposure decreased the risk of a first EDSS worsening event (HR, 95% CI: 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse/s increased this risk (HR, 95% CI: 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significant higher incidence of a first EDSS worsening event in patients with multifocal or isolated spinal-cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMDs exposure as the most protective factor against EDSS worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents an important step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMDs treatment in preventing MS development and disability accumulation in this population.