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Neuromyelitis optica (NMO) is presumably mediated by an autoantibody against aquaporin-4 densely expressed at the blood-brain barrier. In 18 patients with NMO, brain magnetic resonance imaging (MRI) findings were systematically reviewed. Brain MRI abnormalities were found for 89% of the patients, and the most prominent feature was "cloud-like enhancement," multiple patchy enhancing lesions with blurred margin, found in 90% of the patients with positive contrast enhancement. In NMO, brain MRI abnormalities are frequent, and cloud-like enhancement appears to be an MRI finding specific to NMO, possibly caused by primary involvement of the blood-brain barrier by the autoantibodies.