Presymptomatic multiple sclerosis: Insights from the Radiologically Isolated Syndrome

Radiologically isolated syndrome (RIS) represents the initial phase of multiple sclerosis (MS) and is identified incidentally in asymptomatic individuals who display typical brain or spinal cord lesions indicative of autoimmune inflammatory demyelination. The 2023 RIS criteria enhance diagnostic precision against imaging mimics by requiring one T2-weighted hyperintense lesion in two of four specified locations (periventricular, juxtacortical/cortical, infratentorial, spinal cord) alongside at least two of the following: a spinal cord lesion, CSF-restricted oligoclonal bands (OCB), or a new T2/gadolinium-enhancing lesion on MRI at any point, defining dissemination in time (DIT). After confirming the diagnosis, established risk factors for transition to clinical MS need to be assessed. Key factors include a younger age, male sex, the presence of infratentorial, spinal cord, or gadolinium-enhancing lesions, and CSF-restricted OCBs or increased kappa-free light chains. Two randomized trials showed the efficacy of two oral disease-modifying therapies in delaying the first clinical event in RIS. However, as some individuals remain asymptomatic, it's crucial to identify suitable candidates to balance treatment benefits with potential risks. Reviewing each RIS case with an MS expert team is advisable for better care and monitoring. The updated 2024 McDonald criteria classify RIS patients with additional features, such as positive CSF and susceptibility MRI biomarkers, as having preclinical MS.