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Herpes Simplex Encephalitis: an Update

  • Central Nervous System Infections (K Bloch, Section Editor)
  • Published:
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Abstract

Purpose of Review

The goal of this review is to provide an update on current thinking regarding herpes simplex encephalitis (HSE), emphasizing new information about pathogenesis, diagnosis, and immune responses. Specific questions to be addressed are the following: (1) Is there a genetic predisposition to HSE? (2) What clinical approaches have the greatest impact on improving the long-term outcomes in patients with HSE? And (3) are there immune-mediated mechanisms that may account for relapsing HSE?

Recent Findings

Toll-like receptor 3 (TLR 3) plays an important role in innate immune responses, including generation of interferons. Multiple single-gene errors in TLR 3 interferon pathways have recently been described in children that result in increased susceptibility to HSE. Conversely, studies in both animal models and humans indicate that both cytolytic viral replication and immune-mediated responses (including cytotoxic T lymphocytes and immune mechanisms mediated by TLR 2) contribute to the pathology of HSV, suggesting possible new therapeutic approaches. In terms of treatment, data clearly indicate that a longer duration between onset of symptoms and initiation of effective antiviral therapy correlates directly with less favorable clinical outcome. Recurrent or relapsing HSE may occasionally occur, but recent observations indicate that many instances of “relapsing HSE”, especially in children, are more often anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis triggered by the antecedent HSV infection.

Summary

Innate immune responses are critical for defense against HSV; genetic defects in this system may predispose patients to HSE. During acute HSE, exuberant immune responses may contribute to the CNS pathology, suggesting that selective immunosuppressive therapy, coupled with potent antiviral drugs, may eventually play a role in the therapeutic management of HSV. While overall clinical outcomes of HSE remain suboptimal, the initiation of high-dose acyclovir therapy as early as possible in the course of the illness provides the best chance for a patient to survive with minimal neurologic damage. Distinguishing relapsing HSE from autoimmune anti-NMDAR antibody encephalitis is critically important because therapeutic approaches will be very different.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, 135 Rutledge Avenue, MSC 752, Charleston, SC, 29425, USA

    John W. Gnann Jr.

  2. University of Alabama at Birmingham, 303 CHB, 1600 7th Ave. S, Birmingham, AL, 35233-1711, USA

    Richard J. Whitley

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Correspondence to John W. Gnann Jr..

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Dr. Gnann declares serving as a DSMB member with GlaxoSmithKline & BioCryst and clinical adjudication member with Merck.

Dr. Whitley declares grants from NIH and serving as a board member of Gilead Sciences..

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This article is part of the Topical Collection on Central Nervous System Infections

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Gnann, J.W., Whitley, R.J. Herpes Simplex Encephalitis: an Update. Curr Infect Dis Rep 19, 13 (2017). https://doi.org/10.1007/s11908-017-0568-7

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