New MSBase Publication in Annals of Neurology

Prognostic indicators in pediatric clinically isolated syndrome.



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.


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.


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.


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.


"Prognostic indicators in pedicatric clinically isolated syndrome"

Iaffaldano, P., M. Simone, G. Lucisano, A. Ghezzi, G. Coniglio, V.B. Morra, F. Patti, A. Lugaresi, G. Izquierdo, R. Bergamaschi, J.A. Cabrera-Gomez, C. Pozzilli, S.A. Sajedi, G. Constantino, P. Duquette, V. Shaygannejad, T. Petersen, R.F. Bolanos, D. Paolicelli, C. Tortorella, T. Spelman, L. Margari, M.P. Amato, G. Comi, H. Butzkueven, M. Trojano, Italian iMedWeb Registry, MSBase Registry. Ann Neurol (Epub ahead of print, April 2017) doi: 10. 1002/ana.24938