Purpose of review: The discovery of neuromyelitis optica (NMO)-immunoglobulin (Ig)G and its target antigen aquaporin 4 (AQP4) redefined NMO, historically considered a multiple sclerosis (MS) variant, as a specific disease entity. NMO and MS have divergent responses to immunotherapy and it is important to distinguish the conditions at disease onset. In this article, we review new pathological, imaging and clinical trial data pertaining to NMO, and discuss emerging concepts of molecular immunopathogenesis in NMO that can inform the development of targeted therapies.

Recent findings: Recent studies illustrate the range of brain lesions associated with NMO, and the importance of diagnostic biomarkers in patients with atypical or limited presentations. Neuropathological studies showing perivascular astrocyte destruction and preserved myelin in early NMO lesions indicate a pathogenesis distinct from MS. Characterisation of NMO-IgG binding to AQP4 isoforms and the development of novel disease models have elucidated complement-mediated and cell-mediated mechanisms of astrocyte injury.

Summary: NMO-IgG positive NMO is not an MS variant. Further work is required to delineate the pathogenesis of NMO syndromes without antibodies to AQP4. Methodological flaws inherent to small, open label trials of current NMO therapies limit extrapolation to clinical practice. In the coming years, NMO will be treated with targeted therapies that are emerging from an enhanced understanding of the molecular immunopathogenesis of the disease.