Anti-aquaporin-4 antibody (NMO-IgG) is used as a diagnostic marker for neuromyelitis optica (NMO). Although the mechanism of spinal cord lesions in NMO has been investigated, that of extensive hemispheric lesions with brain edema remains unclear. Here we report a 36-year-old woman with NMO positive for NMO-IgG, who developed an acute disseminating encephalomyelitis (ADEM)-like episode after Mycoplasma pneumoniae infection. Brain MRI T2-weighted images demonstrated asymmetric tumefactive hyperintense lesions in the subcortical white matter. Importantly, no lesions on T1-weighted images were enhanced after intravenous gadolinium administration on serial brain MRIs, suggesting preserved integrity of the blood-brain barrier (BBB). Likewise, the corresponding apparent diffusion coefficient maps demonstrated persistent hyperintensity changes, which represented vasogenic edema associated with glial damage and consequent neuronal loss. The findings suggest possible involvement of deficient water elimination associated with seropositivity to NMO-IgG in the induction of vasogenic edema even in the presence of intact and functional BBB.