Okuda DT, Siva A, Kantarci O, Inglese M, Katz I, Tutuncu M, Keegan BM, Donlon S, Hua le H, Vidal-Jordana A, Montalban X, Rovira A, Tintoré M, Amato MP, Brochet B, de Seze J, Brassat D, Vermersch P, De Stefano N, Sormani MP, Pelletier D, Lebrun C; Radiologically Isolated Syndrome Consortium (RISC) and Club Francophone de la Sclérose en Plaques (CFSEP). Radiologically isolated syndrome: 5-year risk for an initial clinical event. PLoS One. 2014 Mar;9(3):e90509. doi: 10.1371/journal.pone.0090509. eCollection 2014.
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 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.
Radiologically isolated syndrome may be a precursor for the development of MS that is detected by MRI in the absence of clinical evidence. In this case 34% developed clinical indicators of MS within 5 years, and about 10% developed primary progressive MS and perhaps suggests that PPMS may have a relapsing phase abut it was just sub-clinical. However it also shows that about 70% of people did not yet develop MS within 5 years, thus would it be too early to start exposing people to treatments?