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Radiologically isolated syndrome (RIS) is the incidental finding of MRI evidence of demyelination suggesting multiple sclerosis in someone with no corresponding clinical signs or symptoms. RIS can be challenging for neurologists to manage. In this article, we discuss its diagnosis and misdiagnosis and how to approach and manage a suspected case, as well as potential therapies. We also discuss how the updated 2024 McDonald criteria have changed the diagnosis and management of some patients with RIS.