• Darin T Okuda, Aksel Siva, Orhun Kantarci, Matilde Inglese, Ilana Katz, Melih Tutuncu, B Mark Keegan, Stacy Donlon, Le H Hua, Angela Vidal-Jordana, Xavier Montalban, Alex Rovira, Mar Tintoré, Maria Pia Amato, Bruno Brochet, Jérôme de Seze, David Brassat, Patrick Vermersch, Nicola De Stefano, Maria Pia Sormani, Daniel Pelletier, Christine Lebrun, Radiologically Isolated Syndrome Consortium (RISC), and Club Francophone de la Sclérose en Plaques (CFSEP).
• University of Texas Southwestern Medical Center, Department of Neurology & Neurotherapeutics, Clinical Center for Multiple Sclerosis, Dallas, Texas, United States of America.
• Plos One. 2014 Jan 1; 9 (3): e90509.

ObjectiveTo report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria.MethodsRetrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model.ResultsData were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11-74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y). Clinical events were identified in 34% (standard error=3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96-0.99); p=0.03], sex (male) [HR: 1.93 (1.24-2.99); p=0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62); p=<0.001] were identified as significant predictors for the development of a first clinical event.InterpretationThese data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.

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