Neuromyelitis optica (NMO) is a rare inflammatory disorder of the central nervous system. The hallmark of NMO is the presence of specific autoantibodies directed against aquaporin 4 (AQP4-IgG). AQP4-IgG, included in diagnostic criteria, has enlarged the clinical spectrum of NMO and serves to predict relapses. Moreover AQP4-IgG has provided unprecedented insight in the immunopathology of NMO, representing a rationale for therapeutic intervention with relevant novel treatment strategies specific for NMO. However, some patients remain seronegative for AQP4-IgG despite a definite diagnosis of NMO and the use of the finest methods for antibody detection. Interestingly, seronegative NMO (NMO^neg ) patients exhibit different demographic and disease-related characteristics in comparison to seropositive patients. The recent association with autoantibodies specific for myelin oligodendrocyte glycoprotein (MOG) is the main indication that disease mechanisms might differ in NMO^pos and NMO^neg , challenging the position of NMO^neg patients in the spectrum of demyelinating diseases and therapeutic strategies to be adopted. Thus, a reappraisal of the NMO^neg population is needed to improve NMO care. Here the current knowledge regarding NMO^neg is reviewed and hypotheses on its pathogenesis are made including a comprehensive description of detection methods and the prevalence of AQP4-IgG and a review of the epidemiological, clinical and paraclinical characteristics of NMO^neg ; finally an integrated view of the general pathophysiological mechanisms underlying NMO^neg is provided.

© 2015 EAN.