NEFL and multiple sclerosis: <h4>Background</h4>We report the first case of findings suggestive of progressive multifocal leukoencephalopathy and immune restitution syndrome (PML-IRIS) in a patient with multiple sclerosis receiving ozanimod preceded by an unexpected increase in the serum neurofilament light-chain (sNfL) levels.<h4>Case report</h4>A 57-year-old-woman treated with ozanimod for the last 8 years presented, during surveillance MRI, with findings compatible with PML-IRIS.