Common and Rare Manifestations of Neuromyelitis Optica Spectrum Disorder

The discovery of a highly specific biomarker of neuromyelitis optica (NMO)-the anti-aquaporin-4 (AQP4) antibody-has opened new paths to understanding disease pathogenesis and afforded a way to confirm the diagnosis in clinical practice. An important consequence of the discovery is the broadening of the spectrum of syndromes seen in the context of AQP4 autoimmunity. These syndromes have been subsumed under the rubric of NMO spectrum disorder (NMOSD). The current classification recognizes not only optic neuritis and myelitis as core syndromes of NMOSD but also cerebral, diencephalic, brainstem, and area postrema syndromes. These neurologic syndromes are the focus of our review. AQP4 is also expressed in many organs outside of the central nervous system, and this may explain some of the unusual, non-neurologic features that have been occasionally reported in NMOSD. Our review catalogues non-neurologic manifestations seen in NMOSD and concludes with a discussion of frequently associated autoimmune and neoplastic comorbidities of NMOSD.