Most radiologically isolated syndromes does not convert to MS within 5 years

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?

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  • What does 'sub-clinical mean'? How can a relapse be sub-clinical? What does a sub-clinical relapse feel like and what is its duration?

    • Sub-clinical means that a lesion/lesions are detected by MRI but there are no obvious symptoms as the lesion is in an area that does not produce any obvious symptoms of a relapse. The MSer presumably will feel no different.

    • To follow, why would a MRI be done on an individual with no obvious symptoms? Also, this population would seem to be valuable to study for early demyelinating mechanisms.

    • A quick look at the paper reports "identification of disc pallor on funduscopic examination, mild alterations in visual acuity, mild deficits in vibratory sensation, mild urinary complaints or constipation, depression, fatigue, or pyramidal function system scores >0.0 due to weakness secondary to peripheral neurological disorders."
      So mild neurological symptoms not obviously MS but lesions identified by MRI.
      It's a PLOS paper so free for all to look at.

    • "why would a MRI be done on an individual with no obvious symptoms?"
      Maybe to investigate headaches & rule out tumours, after a head injury, for some infections, as a healthy subject in a research study, …

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