The identification of aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) along with the description of their disease entities1,2,3,4,5 has paved the way for serological diagnoses in patients with central nervous system (CNS) demyelination,6 including neuromyelitis optica spectrum disorder (NMOSD)6,7 and MOG antibody–associated disease.4,8 Yet the differential diagnosis and management of patients with AQP4-/MOG-IgG double-seronegative disease remains a challenge. Here, MOG is linked to neuromyelitis optica.