Comparison of Digital Biomarkers in Subjects With Radiologically Isolated Syndrome (RIS) and Multiple Sclerosis (MS) Patients With Clinically Normal Neurological Examination

Radiologically Isolated Syndrome (RIS) is the preclinical stage of Multiple Sclerosis (MS). It is the incidental discovery of white matter abnormalities on brain or spinal cord magnetic resonance imaging (MRI), whose shape, topography and number are compatible with the radiological diagnostic criteria for MS. Individuals with a diagnosis of RIS should have a strictly normal neurological examination and, by definition, no history of clinical signs or symptoms that might suggest demyelinating disease. As recommended, patients with RIS benefit from brain and spinal cord MRI and a neurological examination by year to assess temporal dissemination (new T2 lesions and/or Gd+ lesions) and clinical manifestations. Epidemiological studies of RIS in the international RIS Consortium cohort have identified prognostic factors for conversion to multiple sclerosis. Five distinct long-term conversion risk factors were identified: age (subjects under 37 years of age at RIS diagnosis), the presence of oligoclonal bands (OCBs) on cerebrospinal fluid (CSF), the presence of infratentorial lesions, spinal cord lesions or gadolinium-enhanced lesions on index MRI. The presence of new T2 lesions on follow-up or contrast-enhanced MRI is also prognostic of progression to the clinical stage of the disease. The identification of other biomarkers at the preclinical stage of demyelinating disease should shed light on sensitive points in the transition from preclinical to clinical, relapsing-remitting or progressive multiple sclerosis. Studies have been realized to identify biological prognostic markers, but the availability of the assay technique remains limited to a small number of laboratories, and there is as yet no consensus on the practicalities of using this marker on an individual scale. The silent progression of MS, leading to irreversible disability in the absence of immunointervention, has now been demonstrated. The SPAM 1 study, a retrospective study based on data from the French MS Obs