Differences in clinical phenotype, laboratory, and imaging manifestations between AQP4 IgG positive and AQP4 MOG IgG double negative NMOSD: How to correctly diagnose the two

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) is an uncommon autoimmune inflammatory demyelinating disorder of the central nervous system (CNS) and causes severe disability and even death. Aquaporin-4 immunoglobulin G (AQP4-IgG) antibody has been confirmed as the key pathogenic factor for development of NMOSD and leading to repeatting acute attacks. However, 20–40 % of NMOSD patients lack both AQP4-IgG and anti-myelin oligodendrocytes glycoproteins (MOG) IgG, in which the pathogenic factor is still unclear. There are differences in clinical, laboretory and imaiging minifestations between AQP4-IgG positive (AQP4-IgG⁺) and AQP4-IgG/MOG-IgG double negative (AQP4-IgG⁻) NMOSD. Although the treatments applied in NMOSD have made great progress, all treatments are failed in AQP4-IgG⁻ patients. Additionally, it is hard to identify NMOSD with AQP4-IgG⁻ from multiple sclerosis (MS). Therefore, it is suspected and challenged that AQP4-IgG could not be the only pathogenic factor in NMOSD or NMOSD with AQP4-IgG⁻ may be a separate disorder independent of NMOSD AQP4-IgG⁺? It is necessary to find more pathogenic factors and to explore the new pathogenesis and treatments of NMOSD with AQP4-IgG⁻ in the future, which has been a serious problem to be addressed by the neurology community.