Herpes simplex virus encephalitis is a trigger of brain autoimmunity

Ann Neurol. 2014 Feb;75(2):317-23. doi: 10.1002/ana.24083. Epub 2014 Feb 25.


In 5 prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), N-methyl-D-aspartate receptor (NMDAR) antibodies were identified. Antibody synthesis started 1 to 4 weeks after HSE, preceding the neurological relapse. Three of 5 patients improved postimmunotherapy, 1 spontaneously, and 1 has started to improve. Two additional patients with NMDAR antibodies, 9 with unknown neuronal surface antibodies, and 1 with NMDAR and unknown antibodies, were identified during retrospective assessment of 34 HSE patients; the frequency of autoantibodies increased over time (serum, p=0.004; cerebrospinal fluid, p=0.04). The 3 retrospectively identified NMDAR antibody-positive patients also had evidence of relapsing post-HSE. Overall, these findings indicate that HSE triggers NMDAR antibodies and potentially other brain autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity / physiology*
  • Brain / physiopathology*
  • Child, Preschool
  • Encephalitis, Herpes Simplex / blood
  • Encephalitis, Herpes Simplex / cerebrospinal fluid
  • Encephalitis, Herpes Simplex / pathology*
  • Female
  • HEK293 Cells
  • Humans
  • Infant
  • Male
  • Prospective Studies
  • Rats
  • Receptors, N-Methyl-D-Aspartate / blood
  • Retrospective Studies
  • Transfection
  • Young Adult


  • Receptors, N-Methyl-D-Aspartate