Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis

The study of antibody (Ab)-mediated encephalitis has advanced dramatically since the discovery of antibodies directed against the N-methyl-D-aspartate receptor (NMDAR) in association with a unique neuro-psychiatric syndrome, over a decade-and-a-half ago. Anti-NMDAR Ab-mediated encephalitis now represents the most well characterised form of autoimmune encephalitis. The disease most commonly manifests in young women, but all ages and both sexes can be affected. Autoantibodies may arise in the context of two well-recognised disease triggers in a proportion of patients, and ultimately facilitate NMDAR displacement from synapses. Various CSF cytokines, chemokines, and other molecules have been explored as candidate biomarkers but are limited in sensitivity and specificity. The clinical spectrum is diverse, with evolution and a combination of neuro-psychiatric abnormalities at disease nadir common. Anti-NMDAR Ab-mediated encephalitis is immunotherapy responsive, and a near-majority ultimately acquire a broadly favourable clinical outcome. The diagnosis, and more particularly, the management of the disease can still hold considerable challenges. Moreover, well-defined biomarkers remain elusive. The present review will therefore delineate pathogenic and clinical advances to date in anti-NMDAR antibody-mediated encephalitis.