Recent clinical and laboratory findings have substantially advanced our understanding of neuromyelitis optica (NMO) as a humorally mediated, autoimmune disorder. We report on a patient who suffered a first episode of transverse myelitis at the age of 6 months following diphtheria-pertussis-tetanus (DPT) vaccination which had therefore been considered suggestive of acute disseminated encephalomyelitis (ADEM). Fifteen years later, the further disease course revealed typical NMO meeting all diagnostic criteria. This development points to a broad clinical and temporal heterogeneity of NMO, with ADEM probably occurring in the context of a shared autoimmune diathesis. Despite therapy response following B-cell depletion by rituximab, positive NMO-IgG autoantibody status remained unchanged, whereas direct testing for anti-aquaporin-4 (AQP-4)-antibodies was negative throughout. Our findings challenge the pathogenic relevance of NMO-IgG and indicate a varying diagnostic value of testing for NMO-IgG and AQP-4-autoantibodies.