Anti-NMDA-Receptor Encephalitis: From Bench to Clinic

Abstract

NMDAR encephalitis is a common cause of autoimmune encephalitis, predominantly affecting young adults. Current data supports the idea that autoantibodies targeting NMDARs are responsible for disease pathogenesis. While these autoantibodies occur in the setting of underlying malignancy in approximately half of all patients, initiating factors for the autoimmune response in the remainder of patients are unclear. While there is increasing evidence supporting viral triggers such as herpes simplex encephalitis, this association and the mechanism of action have not yet been fully described. Although the majority of patients achieve good outcomes, those without an underlying tumor consistently show worse outcomes, prolonged recovery, and more frequent relapses. The cloning of patient-specific autoantibodies from affected individuals has raised important questions as to disease pathophysiology and clinical heterogeneity. Further advances in our understanding of this disease and underlying triggers are necessary to develop treatments which improve outcomes in patients presenting in the absence of tumors.

Non-paraneoplastic Anti-NMDAR Encephalitis: First Confirmed Adult Case Report in Latvia

“…Anti-NMDAR (Anti-N-Methyl-D-aspartic acid) encephalitis is the most common antibody mediated encephalitis accounting for about 4% of all encephalitides, though this is likely to be an underestimation [1,2]. The clinical characteristics of NMDAR encephalitis in association with ovarian teratoma were first described in 2005, anti-NMDAR antibody relation to the particular disease entity was first described in 2007 [3,4].…”

“…During this time, understanding of disease pathogenesis, clinical characteristics, tumor association and possible patient outcomes has considerably grown. While a noticeable female predominance is seen, as about 80 % of cases occur in women, this disease has been also identified in males [2]. Young adults are affected primarily in their third decade of life, however the disease also occurs in children and elderly.…”

“…It is now known that anti-NMDAR encephalitis is not necessarily a paraneoplastic disorder. In about half of female patients no underlying malignancy is found, the proportion of paraneoplastic anti-NMDAR encephalitis is even smaller in male and children patient groups [2,5]. Clinical criteria proposed by Graus et al [6] noteworthy feature of anti-NMDAR encephalitis is that it is unlikely to have associated neuroimaging abnormalities on initial presentation (89%) or follow-up MR imaging of the brain (79%) [7].…”

“…NMDARs are predominantly found in forebrain and the limbic system and are known to play an important role in learning, memory, cognition and behavior [2,9]. NMDA receptors are surface protein channels consisting of multiple subunits.…”

“…Anti-NMDAR antibodies are predominantly of the IgG1 subclass of IgG [11]. The antibody attachment to NMDA receptors, receptor crosslinking with subsequent internalization is the pathogenetic mechanism supported the most by current literature [2].…”