Herpes simplex virus encephalitis is a trigger of brain autoimmunity

Thaís Armangue, Frank Leypoldt, Ignacio Málaga, Miquel Raspall-Chaure, Itxaso Marti, Charles Nichter, John Pugh, Monica Vicente-Rasoamalala, Miguel Lafuente-Hidalgo, Alfons MacAya, Michael Ke, Maarten J. Titulaer, Romana Höftberger, Heather Sheriff, Carol Glaser, Josep Dalmau*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

373 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalAnnals of Neurology
Volume75
Issue number2
DOIs
Publication statusPublished - Feb 2014

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