eMedicine Specialties > Emergency Medicine > Neurology

Herpes Simplex Encephalitis: Treatment & Medication

Author: Todd Pritz, MD, Intensivist, St Anthony's Medical Center and St John's Mercy Medical Center, St Louis, Missouri
Contributor Information and Disclosures

Updated: Aug 24, 2009

Treatment

Prehospital Care

Prehospital care consists of supportive management of the patient's airway, breathing, and circulation (ABCs).

Emergency Department Care

  • A high index of suspicion is required to make the diagnosis.
  • No pathognomonic clinical findings are associated with herpes simplex encephalitis (HSE).
  • The diagnosis of HSE should be considered in any patient with a progressively deteriorating level of consciousness, fever, abnormal CSF findings, and focal neurological abnormalities in the absence of any other causes.
  • Proceed with expeditious evaluation after the diagnosis is considered.
  • Empiric treatment of patients with suspected HSE is recommended pending confirmation of the diagnosis because acyclovir, the drug of choice, is relatively nontoxic and because the prognosis for untreated HSE is poor.
  • Rapid initiation of acyclovir therapy is crucial to reduce mortality and morbidity risks.

Consultations

  • Neurologist
  • Infectious disease specialist

Medication

Goals of therapy are to shorten the clinical course of the disease, to prevent complications, and to prevent recurrences.

Antiviral agents

The treatment of choice for herpes simplex encephalitis (HSE) is acyclovir.1,3,19 Through a series of in vivo reactions catalyzed by viral and host cellular enzymes, acyclovir is converted to acyclovir triphosphate, a potent inhibitor of HSV DNA polymerase, without which viral replication cannot occur. Human cells are not affected.

Acyclovir has relatively few serious adverse effects. The drug is excreted by the kidney, and the dose should be reduced in patients with renal dysfunction. Crystal-induced nephropathy may occur if the maximum solubility of free drug is exceeded. Risk factors for this are intravenous administration, rapid infusion, dehydration, concurrent use of nephrotoxic drugs, underlying renal disease, and high doses. The risk of renal toxicity is reduced by adequately hydrating the patient (eg, 1 mL fluid per day for each 1 mg/d of acyclovir).

Because of its high pH, intravenous acyclovir may cause phlebitis and local inflammation if extravasation occurs. Gastrointestinal disturbances, headache, and rash are among the more frequent adverse reactions. Acyclovir is considered appropriate for serious infections during pregnancy. The manufacturer cautions that it should be used in pregnancy only when the potential benefits outweigh the potential risks. However, a prospective registry of acyclovir use in pregnancy between 1984 and 1999, including 756 first trimester exposures, demonstrated a 3.2% rate of birth defects, similar to that expected in the general population.20

Since most relapses occur within 3 months of completing an initial course of intravenous acyclovir, a prolonged course of an oral antiviral agent (eg, valacyclovir) has been suggested following initial treatment. An ongoing clinical trial is currently evaluating a 90-day course of valacyclovir versus placebo post treatment with acyclovir in patients with HSE.21

The role of steroids in the treatment of HSE remains uncertain. To the extent that cellular damage in HSE is the result of immune-mediated inflammatory processes triggered by the viral infection, the anti-inflammatory effects of steroids may be beneficial. However, there is also concern that steroids might suppress immune responses of the host that are necessary to limit viral replication. Animal studies have demonstrated a beneficial effect of steroids on outcome, without evidence of increased viral replication or dissemination.22,23  Steroids have been used to reduce cerebral edema in patients with severe HSE.

One nonrandomized, retrospective human study compared the outcomes of patients with HSE who received steroids in addition to acyclovir versus those receiving acyclovir alone.24 The steroid group had improved outcomes at 3 months. While these results suggest a possible role for steroids in HSE, definitive recommendations must await the results of larger prospective studies.


Acyclovir (Zovirax)

DOC for HSE; selectively taken up by infected cells; has inhibitory activity against HSV-1 and HSV-2.

Adult

10 mg/kg (or 500 mg/m2) IV q8h for 14-21 d; dose infused over 1 h

Pediatric

Administer as in adults

Concomitant probenecid or zidovudine prolongs half-life and increases CNS toxicity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or when using nephrotoxic drugs

More on Herpes Simplex Encephalitis

Overview: Herpes Simplex Encephalitis
Differential Diagnoses & Workup: Herpes Simplex Encephalitis
Treatment & Medication: Herpes Simplex Encephalitis
Follow-up: Herpes Simplex Encephalitis
Multimedia: Herpes Simplex Encephalitis
References
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References

  1. Whitley RJ. Herpes simplex encephalitis: adolescents and adults. Antiviral Res. Sep 2006;71(2-3):141-8. [Medline].

  2. Whitley RJ, Kimberlin DW. Herpes simplex: encephalitis children and adolescents. Semin Pediatr Infect Dis. Jan 2005;16(1):17-23. [Medline].

  3. Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes. Jun 2004;11 Suppl 2:57A-64A. [Medline].

  4. Aurelian L. HSV-induced apoptosis in herpes encephalitis. Curr Top Microbiol Immunol. 2005;289:79-111. [Medline].

  5. DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL. Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J Infect Dis. Dec 1 2002;186(11):1547-57. [Medline].

  6. Esiri MM. Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci. May 1982;54(2):209-26. [Medline].

  7. Cinque P, Vago L, Marenzi R, Giudici B, Weber T, Corradini R. Herpes simplex virus infections of the central nervous system in human immunodeficiency virus-infected patients: clinical management by polymerase chain reaction assay of cerebrospinal fluid. Clin Infect Dis. Aug 1998;27(2):303-9. [Medline].

  8. Fodor PA, Levin MJ, Weinberg A, Sandberg E, Sylman J, Tyler KL. Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology. Aug 1998;51(2):554-9. [Medline].

  9. Osih RB, Brazie M, Kanno M. Multifocal herpes simplex virus type 2 encephalitis in a patient with AIDS. AIDS Read. Feb 2007;17(2):67-70. [Medline].

  10. Baringer JR, Pisani P. Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction. Ann Neurol. Dec 1994;36(6):823-9. [Medline].

  11. Whitley RJ, Cobbs CG, Alford CA Jr, Soong SJ, Hirsch MS, Connor JD, et al. Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group. JAMA. Jul 14 1989;262(2):234-9. [Medline].

  12. Whitley RJ, Soong SJ, Linneman C Jr, Liu C, Pazin G, Alford CA. Herpes simplex encephalitis. Clinical Assessment. JAMA. Jan 15 1982;247(3):317-20. [Medline].

  13. Mook-Kanamori B, van de Beek D, Wijdicks EF. Herpes simplex encephalitis with normal initial cerebrospinal fluid examination. J Am Geriatr Soc. Aug 2009;57(8):1514-5. [Medline].

  14. Lakeman FD, Whitley RJ. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Gr. J Infect Dis. Apr 1995;171(4):857-63. [Medline].

  15. Cinque P, Cleator GM, Weber T, Monteyne P, Sindic CJ, van Loon AM. The role of laboratory investigation in the diagnosis and management of patients with suspected herpessimplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis. J Neurol Neurosurg Psychiatry. Oct 1996;61(4):339-45. [Medline].

  16. Domingues RB, Lakeman FD, Mayo MS, Whitley RJ. Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis. J Clin Microbiol. Aug 1998;36(8):2229-34. [Medline].

  17. Wildemann B, Ehrhart K, Storch-Hagenlocher B, Meyding-Lamadé U, Steinvorth S, Hacke W, et al. Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis. Neurology. May 1997;48(5):1341-6. [Medline].

  18. Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. Apr 15 2002;34(8):1154-7. [Medline].

  19. Rathmann K, Scott SA. Acyclovir. In: Drug Evaluation Monographs. Micromedex:2005.

  20. Stone KM, Reiff-Eldridge R, White AD, Cordero JF, Brown Z, Alexander ER. Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999. Birth Defects Res A Clin Mol Teratol. Apr 2004;70(4):201-7. [Medline].

  21. National Institute of Allergy and Infectious Diseases. A Phase III Double-Blind, Placebo-Controlled Trial of Long Term Therapy of Herpes Simplex Encephalitis (HSE): An Evaluation of Valacyclovir (CASG-204). ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct/show/NCT00031486?order=1. Accessed August 8, 2007.

  22. Sergerie Y, Boivin G, Gosselin D, Rivest S. Delayed but not early glucocorticoid treatment protects the host during experimental herpes simplex virus encephalitis in mice. J Infect Dis. Mar 15 2007;195(6):817-25. [Medline].

  23. Thompson KA, Blessing WW, Wesselingh SL. Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis. J Neurovirol. Feb 2000;6(1):25-32. [Medline].

  24. Kamei S, Sekizawa T, Shiota H, Mizutani T, Itoyama Y, Takasu T, et al. Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. Nov 2005;76(11):1544-9. [Medline].

  25. Sköldenberg B, Aurelius E, Hjalmarsson A, Sabri F, Forsgren M, Andersson B, et al. Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults. J Neurol. Feb 2006;253(2):163-70. [Medline].

  26. Benson PC, Swadron SP. Empiric acyclovir is infrequently initiated in the emergency department to patients ultimately diagnosed with encephalitis. Ann Emerg Med. Jan 2006;47(1):100-5. [Medline].

  27. Kohl S. Herpes Simplex Virus. In: Behrman RE, Kliegman RM, Jenson HB. Behrman: Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders; 2004.

  28. Kimberlin D. Herpes simplex virus, meningitis and encephalitis in neonates. Herpes. Jun 2004;11 Suppl 2:65A-76A. [Medline].

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Further Reading

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Keywords

herpes simplex encephalitis, HSE, herpes encephalitis, herpes simplex virus, HSV, herpes simplex virus type 1, HSV-1, herpes simplex virus type 2, HSV-2, sporadic fatal encephalitis, sporadic lethal encephalitis, viral encephalitis

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Contributor Information and Disclosures

Author

Todd Pritz, MD, Intensivist, St Anthony's Medical Center and St John's Mercy Medical Center, St Louis, Missouri
Todd Pritz, MD is a member of the following medical societies: Massachusetts Medical Society and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robin R Hemphill, MD, MPH, Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University
Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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