Prognostic indicators in pediatric clinically isolated syndrome.
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Iaffaldano Pietro, Simone Marta, Lucisano Giuseppe, Ghezzi Angelo, Coniglio Gabriella, Brescia Morra Vincenzo, Salemi Giuseppe, Patti Francesco, Lugaresi Alessandra, Izquierdo Guillermo, Bergamaschi Roberto, Cabrera-Gomez Jose Antonio, Pozzilli Carlo, Millefiorini Enrico, Alroughani Raed, Boz Cavit, Pucci Eugenio, Zimatore Giovanni Bosco, Sola Patrizia, Lus Giacomo, Maimone Davide, Avolio Carlo, Cocco Eleonora, Sajedi Seyed Aidin, Costantino Gianfranco, Duquette Pierre, Shaygannejad Vahid, Petersen Thor, Fernández Bolaños Ricardo, Paolicelli Damiano, Tortorella Carla, Spelman Tim, Margari Lucia, Amato Maria Pia, Comi Giancarlo, Butzkueven Helmut, Trojano Maria, Italian iMedWeb Registry and the MSBase Registry
Аннотация
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.