Widespread CNS neurodegeneration is a feature of multiple sclerosis (MS) but not neuromyelitis optica (NMO), according to a new report. In a longitudinal advanced MRI study, Jacqueline Palace and colleagues found inflammatory brain lesions in both MS and NMO, but diffuse neurodegeneration was only detectable in patients with MS. These findings might explain why NMO almost invariably follows a relapsing–remitting course, whereas MS frequently enters a progressive phase.