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

Herpes simplex virus encephalitis is a trigger of brain autoimmunity.

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August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Neurology Service, Hospital Clinic, University of Barcelona, Barcelona, Spain; Department of Pediatric Neurology, Materno-Infantil Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.


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.

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