Radiologically isolated syndrome: 5-year risk for an initial clinical event.
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ABSTRACT: 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.
SUBMITTER: Okuda DT
PROVIDER: S-EPMC3943959 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed "radiologically isolated syndrome" or RIS).MethodsClinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.ResultsWe identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%-60%) in a median of 2.0 years (interquartile range [IQR] 1.0-4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%-76%) in a median of 1.1 years (IQR 0.5-1.9 years). The presence of ?2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4-86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4-43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex.ConclusionsWe describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.
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Project description:Background and purpose: Whether some gray matter (GM) regions are differentially vulnerable at the early stages of MS is still unknown. The objective of this study is to investigate whether deep and cortical GM are differentially vulnerable after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: Fifty-six patients with CIS (PwCIS) and 38 healthy controls (HC) had conventional and diffusion tensor imaging (DTI) at baseline and 46 PwCIS and 20 HC were rescanned after 1 year. Deep GM (DGM) volumes, cortical thickness (CTh), and DTI metrics (FA: fractional anisotropy; MD: mean diffusivity) within these structures were calculated for each participant at each time-point and compared between PwCIS and HC. Linear regression models were used to investigate whether baseline DTI parameters could predict GM volume loss over time. Results: At baseline, GM volumes did not differ between PwCIS and HC, but hippocampal MD was higher in PwCIS than HC (p < 0.01). Over 1 year, GM alterations became more widespread with putamen and hippocampus volumes decreasing in PwCIS (p < 0.01), and cortical thinning in different parts of the cortex along with a significant increase of MD. Hippocampus MD at baseline could predict its volume loss (R 2 = 0.159; p < 0.05) and cortical thinning was associated to microstructural damage (Spearman's rho ranging from -0.424 to -0.603 with p < 0.003). Conclusion: Along with MS being a diffuse inflammatory disease, GM showed a differential vulnerability at the early stage spreading from hippocampus to the cortex. Hippocampus volume loss could be predicted by its MD at baseline.
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