In the majority of patients with NMOSD, the disease is thought to be mediated by immunoglobulin G (IgG) autoantibodies specific for aquaporin-4 (AQP4), an abundant water-channel protein in the CNS that regulates the movements of astrocyte foot processes.^3–5 A cross-sectional study from the UK estimated the percentage of AQP4-IgG seropositive patients with NMOSD to be 73% (96/132).⁵ However, other sources estimate the percentage of NMOSD patients with AQP4 antibodies to vary between 70–90%.^3,5 In AQP4‑IgG seropositive patients, NMOSD is considered primarily an autoimmune astrocytopathic disease, with secondary damage to oligodendrocytes and neurons resulting from astrocyte dysfunction and/or inflammation.^6,7

In some (about 10–40%) of AQP4‑IgG seronegative patients with NMOSD, there are IgG autoantibodies against the myelin oligodendrocyte glycoprotein (MOG) in the outer myelin sheaths of the CNS neurons, resulting in primary demyelination.^6,7

Almost all AQP4‑IgG seropositive patients relapse if NMOSD is left untreated.⁸ Relapses may gradually result in blindness, paralysis and even death.^1,9 Relapses also occur in AQP4‑IgG seronegative patients, and while some reports claim lower relapse rates in seronegative patients, others have found no differences in frequency.¹⁰

AQP4, aquaporin-4; CNS, central nervous system; IgG, immunoglobulin G; MOG, myelin oligodendrocyte glycoprotein; NMOSD, neuromyelitis optica spectrum disorder.