Radiologically isolated syndrome: 5-year risk for an initial clinical event

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 SormaniDaniel Pelletier, Christine Lebrun

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


Objective: To 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. Methods: Retrospectively 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. Results: Data 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. Interpretation: These data provide supportive evidence that ameaningful 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.

Original languageEnglish (US)
Article numbere90509
JournalPloS one
Issue number3
StatePublished - Mar 5 2014

ASJC Scopus subject areas

  • General


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