A 17-year-old girl presented with intractable vomiting due to area postrema involvement in the first presentation of seronegative neuromyelitis optica (NMO). During the course of her illness, she developed mild hyponatremia, and magnetic resonance imaging revealed abnormalities consistent with the co-occurrence of osmotic demyelination syndrome (ODS). This combination of imaging features is novel, and this case expands the spectrum of brain abnormalities seen in NMO and NMO spectrum disorders. It was suspected that NMO may predispose to ODS by causing astrocyte dysfunction involving aquaporin 4 water channels, which are implicated in both conditions.