NMDAR Encephalitis Following Herpes Simplex Virus Encephalitis

Purpose of Review Herpes simplex virus encephalitis (HSVE) is often associated with significant morbidity and mortality, and despite appropriate treatment with antivirals, worsening of neurological symptoms or relapse occurs in a subset of patients. Recent data suggests that many relapses are likely caused by a secondary immune response, with the Nmethyl- D-aspartate receptor (NMDAR) antibody being the most commonly associated autoantibody. We provide a review of the relevant literature, examining the relationship between HSVE and development of autoimmunity. Recent Findings Autoantibodies, including pathogenic NMDAR antibody, have been demonstrated in the cerebrospinal fluid (CSF) of patients following HSVE. This occurs usually several weeks following initial HSV infection. Summary There is growing evidence of a relationship between HSVE and the subsequent development of NMDAR encephalitis. Possible mechanisms include molecular mimicry or an immune response to direct neuronal damage. Future studies should address if the use of immunotherapy can prevent the development of autoimmunity following HSVE.