Neuromyelitis optica (NMO) is an inflammatory disorder predominantly affecting the optic nerves and spinal cord. Limited forms of disease including isolated optic neuritis, brainstem encephalitis and longitudinal extensive transverse myelitis (LETM) or acute disseminated encephalomyelitis (ADEM) have been referred to as NMO spectrum disorder (NMOSD). The majority of individuals with NMO and many with NMOSD have antibodies against aquaporin 4 (AQP4). MOG antibodies have been reported without AQP4 antibodies in individuals with NMO and other non-multiple sclerosis demyelinating diseases. The presence of MOG antibodies in AQP4 antibody negative individuals can help differentiate between multiple sclerosis (MS) and non-MS demyelinating diseases and aid in clinical management decisions.