Only the discovery of pathogenic antibodies to aquaporin-4 in a subset of patients with NMO but not MS and the demonstration of corresponding pathological differences [4,82-87] has led to the recognition of ‘NMO-IgG-positive NMO’ as an immunopathologically defined disease entity in its own right distinct from classical MS. The gene discussed is AQP4; the disease is neuromyelitis optica.