Identification and characterization of predictive markers of inflammation and neurodegeneration in subjetc with radiologically isolated syndrome

Radiologically Isolated Syndrome (RIS) is the pre-clinical phase of multiple sclerosis (MS). It corresponds to the incidental discovery of white matter abnormalities suggestive of MS based on their location, size, and shape on Magnetic Resonance Imaging (MRI) performed for a reason other than for suspicion of demyelinating disease in subjects with no history of neurological symptoms and presenting a strictly normal neurological clinical examination. The diagnostic criteria for RIS were first described in 2009 and revised in 2023, increasing the sensitivity of the criteria and the risks of diagnostic errors. This observation was at the origin of the first work of this thesis relating to a French survey of identification of white matter lesions in MRI showing that many practitioners use the diagnostic criteria for MS even if white matter abnormalities do not correspond to demyelinating lesions, which may cause errors in the application of the MS diagnostic criteria. These results highlight the importance of having diagnostic markers in current practice.The second study of this thesis focuses on the evaluation of a diagnostic marker called "central vein sign" (CVS) in the diagnosis of RIS. Indeed, recent studies using high-resolution MRI and a specific magnetic susceptibility sequence, SWI (Susceptibility-Weighted Imaging), make it possible to visualize this CVS. As MRI is mandatory for the diagnosis and monitoring of RIS, the identification of diagnostic markers such as CVS makes it possible to increase the specificity and sensitivity of the diagnosis and to reduce diagnostic errors. Once the diagnosis of RIS is certain and established, identifying predictive markers of clinical conversion to MS constitutes a crucial issue for RIS patients.The third objective of this thesis involves the study of the volume of the choroid plexuses in a large cohort of RIS patients compared with healthy control subjects to explore its relationship with other brain volumes, clinical and radiological activity of the disease, and biological markers.The next step in this work will be to introduce an analysis of digital biomarkers. Indeed, we have demonstrated that RIS subjects perform poorer than control subjects facing digital tests using mobile applications. We hypothesize that digital measurements, collected easily using a smartphone or a tablet, would make it possible to detect subclinical anomalies, which would indicate a silent evolution of the disease and predict a clinical evolution.This thesis project mainly focuses on analyzing biomarkers in imaging to improve the diagnosis of RIS and identify predictive factors of the clinical evolution of RIS subjects in MS.