A 51-year-old woman had developed fever and consciousness disturbance at 47 years of age. Brain magnetic resonance imaging (MRI) revealed acute disseminating encephalomyelitis (ADEM)-like lesions without gadolinium enhancement (GDE). One year later, she had an episode of bilateral optic neuritis and cerebellar ataxia. Speech deficit and right hand weakness occurred at the age of 51 years. Neurological examination showed motor aphasia, finger agnosia, right-left disorientation, and right hand paresis. Neuromyelitis optica (NMO)-IgG was seropositive. Cerebrospinal fluid examination showed negative results for myelin basic protein and oligoclonal IgG band. The IgG index was normal. Brain MRI revealed a tumefactive lesion in the left temporo-parietal region and conglomerate ovoid lesions in the pericallosal regions. No GDE was found in the brain lesions. Visual evoked potential test showed bilateral prolongation of P100 latencies. She was treated twice with methylprednisolone pulse therapy followed by oral prednisolone, but the motor aphasia did not respond to steroid treatment. She had no prior history of myelitis and was diagnosed as NMO spectrum disorder (NMOSD). Similar to previous studies of NMO-IgG seropositive extensive brain lesions, this patient with NMOSD indicated no GDE in tumefactive lesions at two episodes of encephalopathy. Compared to multiple sclerosis (MS), a high frequency of non-enhancing tumefactive lesions is reported in patients with NMO or NMOSD. The absence of GDE in tumefactive lesions could help to differentiate between NMO and MS.