In five prospectively diagnosed patients with relapsing post-herpes simplex encephalitis (HSE), NMDAR-antibodies were identified. Antibody synthesis started 1–4 weeks post-HSE, preceding the neurological relapse. Three of five patients improved post-immunotherapy, one spontaneously, and one has started to improve. Two additional patients with NMDAR-antibodies, 9 with unknown neuronal surface-antibodies, and one 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, CSF p=0.04). The three 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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