RIS International Cohort

Study Overview
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Brief Summary
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The Radiologically Isolated Syndrome (RIS) corresponds to the discovery of white matter (WM) abnormalities suggestive of multiple sclerosis (MS) by their location, size, and appearance, on the brain or spinal cord Magnetic Resonance Imaging (MRI). This imaging is performed for a reason other than for suspicion of demyelinating disease in subjects without a history of neurological symptoms and a strict routine clinical neurological examination. It was defined and named in 2009 (Okuda et al.) after publishing 3 case series (French, USA, Turkey). The Radiologically Isolated Syndrome Consortium (RISC) published a cohort of subjects with an extended follow-up after the first brain MRI of MS, with 34% presenting an event (clinical conversion) at five years, 51.2 % of these subjects showed an event at ten years. The patients who offer a higher risk of developing a first clinical demyelinating event were identified such as male sex, young age, the presence of oligoclonal bands (BOCs) in the Cerebrospinal Fluid (CSF), the presence of infratentorial lesions and spinal cord lesions on the first MRI suggestive of RIS. The location and morphology of the lesions appear to be decisive for studying the risk of conversion. Our first objective is to prospectively collect data to identify the subjects who present a higher risk of developing a first clinical demyelinating event and the progression of the disease in these subjects. Among the objectives of this worldwide cohort is the analysis of (1) environmental factors (Vit D, EBV, tobacco…), (2) MRI biomarkers, including atrophy, central veins signs, paramagnetic rings, and DTI. (3) digital biomarkers (4) oculography (5) biological markers To summarize, this cohort will allow for analyzing features in imaging, biology and the exploration of digital and oculographic characteristics to identify predictive factors of clinical evolution of a large cohort of subjects presenting WM abnormalities suggestive of multiple sclerosis.

Official Title
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The Radiologically Isolated Syndrome International Cohort

Conditions
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Multiple Sclerosis, Radiologically Isolated Syndrome

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: white matter T2 lesions suggestive of demyelination asymptomatic normal neurological exam Exclusion Criteria: abnormal neurological exam, suspicion of another disease explaining MRI lesions.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RIS/1-2 criteria<br> | Other: No intervention<br>* No intervention<br>|
| RIS/3-4 criteria<br> | Other: No intervention<br>* No intervention<br>|
| NON RIS/0 criteria<br> | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of lesions T2-weighted sequence at the index scan | number of T2-weighted sequence | at inclusion | 
| Identification of lesions T2-weighted sequence at the index scan | localisation of interest of T2 lesion (juxtacortical, periventricular, infratentorial, spinal cord) | at inclusion | 
| Identification of lesions T1 sequence with and without Gd at the index scan. | Lesions number | at inclusion | 
| Identification of lesions T1 sequence with and without Gd at the index scan. | localisation of interest | at inclusion | 
| Radiological progression : new T2 lesions | localisation of interest | year 1 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | year 1 | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | year 1 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | year 1 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | year 2 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | year 3 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | year 4 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | year 5 | 
| Brain atrophy | measurement of global and regional grey matter volume measurement of global and regional white matter volume | MS onset assessed up to 2 years | 
| Radiological progression : new T2 lesions | number of T2-weighted sequence | year 2 | 
| Radiological progression : new T2 lesions | localisation of interest of T2 lesion | year 2 | 
| Radiological progression : new T2 lesions | number of T2-weighted sequence | year 3 | 
| Radiological progression : new T2 lesions | localisation of interest of T2 lesion | year 4 | 
| Radiological progression : new T2 lesions | number of T2-weighted sequence | year 5 | 
| Radiological progression : new T2 lesions | localisation of interest of T2 lesion | MS onset assessed up to 2 years | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | year 2 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | year 2 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | year 3 | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | year 3 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | year 4 | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | year 4 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | year 5 | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | year 5 | 
| Radiological progression : new contrast enhancing lesions | Lesions number | MS onset assessed up to 2 years | 
| Radiological progression : new contrast enhancing lesions | localisation of interest | MS onset assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collect biological data | number of plasma samples | At inclusion | 
| Collect biological data | number of plasma samples | MS onset assessed up to 2 years | 
| Collect digital markers | The number of abnormalities identified by the eVOG application correlated with cerebral atrophy | at inclusion | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | year 1 | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | year 2 | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | year 3 | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | year 4 | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | year 5 | 
| Collect digital markers | Progression of the number of abnormalities identified by the eVOG application correlated with cerebral atrophy | MS onset assessed up to 2 years |