Pelletier, Daniel

AbstractObjectiveThe radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS.MethodsPatients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age‐matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility‐based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions.Results180 participants (45 RIS, 45 MS, 90 non‐MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non‐MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non‐MS than MS from non‐MS (p = 0.837). When a 6‐lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis.InterpretationThis study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non‐MS, with similar performances to those in MS.

Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5‐year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10‐year, multinational, retrospectively identified RIS dataset. Methods RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models. Results Additional follow‐up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11–74 years), with a median clinical follow‐up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium‐enhanced lesions during follow‐up was also associated with the risk of a seminal event. The reason for MRI and gadolinium‐enhancing lesions at baseline did not influence the risk of a subsequent clinical event. Interpretation Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407–417.

ObjectiveThe aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).MethodsA multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing‐remitting MS) and were also compared to two other population‐ and clinic‐based PPMS cohorts.ResultsOf the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow‐up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6–5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow‐up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow‐up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS.InterpretationSubjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age‐dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum. Ann Neurol 2016;79:288–294