Double-Seronegative Neuromyelitis Optica Spectrum Disorder

Double-seronegative neuromyelitis optica spectrum disorder (DN-NMOSD) is characterized by the absence of both aquaporin-4 immunoglobulin-G (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin-G. Growing recognition of this entity has raised questions regarding its epidemiology, underlying pathophysiology, and optimal management. In this review, we summarize the current evidence regarding the epidemiology of DN-NMOSD and discuss proposed immunopathogenic mechanisms. We also describe the reported clinical and radiological characteristics in comparison with AQP4-IgG-positive NMOSD and MOG antibody-associated disease, and review current therapeutic approaches.