Autoimmune encephalitis after herpes simplex encephalitis: A still undefined condition

Autoimmun Rev. 2022 Dec;21(12):103187. doi: 10.1016/j.autrev.2022.103187. Epub 2022 Sep 8.


Herpes simplex encephalitis (HSE) is one of the most common sporadic viral encephalitis. Generally, HSE is characterized by a monophasic short course, although in some patients neurological relapses or worsening of deficits can develop some weeks later, when viral therapy has been discontinued and signs and symptoms of the central nervous system (CNS) damage seem to have stabilized. The second HSE stage is generally identified as autoimmune encephalitis after HSE (AEaHSE). Aim of this paper is to discuss which are the present knowledge in this regard. Literature analysis showed that AEaHSE exists, it is more common in younger children and it has different clinical manifestations according to age. All the patients with AEaHSE are positive for one or more neuronal cell-surface and synaptic antibodies, mainly anti-NMDAR antibodies, and the earlier the appearance of the antibodies the greater the risk of AEaHSE development. This means that a careful monitoring of antibody production starting from anti-NMDAR antibodies in all HSE cases could lead to the early identification of AEaHSE and the prompt administration of a potentially effective therapy. Further studies are needed to clarify which are the main pathogenetic mechanisms, whether there are differences in risk of development and clinical course of AEaHSE according to the type of antibody production, why response to immunosuppressive therapy significantly varies and whether administration of steroids to patients with HSE during the first phase of disease can play a role for reducing the risk of AEaHSE development.

Keywords: Anti-NDMAR antbodies; Autoimmune encephalitis; Central nervous system; Herpes simplex encephalitis; Immunosuppressive therapy.

Publication types

  • Review

MeSH terms

  • Antibodies
  • Autoimmune Diseases of the Nervous System*
  • Child
  • Encephalitis, Herpes Simplex* / complications
  • Encephalitis, Herpes Simplex* / diagnosis
  • Encephalitis, Herpes Simplex* / drug therapy
  • Hashimoto Disease* / complications
  • Humans
  • Receptors, N-Methyl-D-Aspartate


  • Antibodies
  • Receptors, N-Methyl-D-Aspartate

Supplementary concepts

  • Hashimoto's encephalitis