Prognostic indicators in pediatric clinically isolated syndrome

P Iaffaldano, M Simone, G Lucisano, A Ghezzi, G Coniglio, V Brescia Morra, G Salemi, F Patti, A Lugaresi, G Izquierdo, R Bergamaschi, JA Cabrera-Gomez, C Pozzilli, E Millefiorini, R Alroughani, C Boz, E Pucci, GB Zimatore, P Sola, G LusD Maimone, C Avolio, E Cocco, SA Sajedi, G Costantino, P Duquette, V Shaygannejad, T Petersen, R Fernández Bolaños, D Paolicelli, C Tortorella, T Spelman, L Margari, MP Amato, G Comi, H Butzkueven, M Trojano, on behalf of the Italian iMedWeb Registry, the MSBase Registry

Research output: Contribution to journalArticlepeer-review


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 (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06–1.55; 1.42, 1.10–1.84, respectively), whereas disease-modifying drug (DMD) 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 DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42–0.83; 0.75, 0.71–0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46–7.46). An exploratory RECPAM analysis highlighted a significantly 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 DMD 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 a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729–739. © 2017 American Neurological Association
Original languageEnglish
Pages (from-to)729-739
Number of pages11
JournalAnnals of Neurology
Issue number5
Publication statusPublished - 2017


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