Radiologically Isolated Syndrome: 5-Year Risk for an Initial Clinical Event

Abstract

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.

Incidence of Radiologically Isolated Syndrome: A Population-Based Study

“…23 These results suggest that RIS may reflect a more benign entity, but longitudinal data on the natural history of RIS are needed to better understand its prognosis. 4,5,11,18 Whether individuals with RIS should receive MS treatment is debated, 32,33 but a clinical treatment trial is already planned. 34 Due to the low incidence of RIS, conducting studies on patients with RIS may necessitate large nation-based cohorts or multicenter studies.…”

“…It is therefore of further interest to determine the frequency of RIS in clinical practice. 3,5,[11][12][13][14][15][16][17][18] However, despite the interest in RIS, its epidemiology remains largely unclear. Postmortem studies have shown a prevalence of incidental MS findings ranging from 0.06% to 0.7%.…”

Thoracic spinal cord lesions are influenced by the degree of cervical spine involvement in multiple sclerosis

“…Involvement of the spinal cord parenchyma is correlated with disability outcomes in MS, [1][2][3] as well as higher conversion rates to clinically definite MS and risk for a first clinical event related to central nervous system demyelination in clinically and radiologically isolated syndromes, respectively. [4][5][6][7] To improve visualization of the spinal cord, cervical and thoracic segments are acquired separately. Unfortunately, previous scientific efforts either focused on the cervical spine exclusively or lacked differentiation between clinical correlations of the cervical versus thoracic spine.…”

Evoked potentials and other guiding factors of conversion from radiologically isolated syndrome to definite multiple sclerosis

“…Approximately in two-thirds of the patients develop radiographic progression within the first 5 years. When the number of lesions in the MRI is high (> 9), gadolinium (Gd) enhancement of the asymptomatic lesions is present and in particular if cervical cord lesions are seen, clinical conversion rate is higher (2,5,6,7,17,18,19). In our study, 8 of 49 patients had subsequent neurological episodes during the follow-up period, and thus began to be followed by a diagnosis of Clinically Isolated Syndrome (CIS) -MS accordingly.…”