eMedicine Specialties > Radiology > Brain/Spine

Herpes Encephalitis: Follow-up

Author: Mahesh R Patel, MD, Chief, MRI, Department of Diagnostic Imaging, Santa Clara Valley Medial Center
Contributor Information and Disclosures

Updated: Feb 24, 2009

Intervention

Radiologic intervention

No radiologic interventions for herpes encephalitis have been described to date.

Medical intervention with acyclovir

Drug description

Acyclovir exerts an antiviral effect on HSV by interfering with DNA synthesis and inhibiting viral replication. Acyclovir is a synthetic purine nucleoside analogue and highly selective in its affinity for thymidine kinase encoded by HSV. In vitro studies indicate that acyclovir triphosphate is the active form and competes with deoxyguanosine triphosphate for viral DNA polymerase and then incorporated predominantly into viral DNA. Viral DNA polymerase has a 10- to 30-fold or greater affinity in vitro for acyclovir phosphatase than does cellular DNA polymerase.

The mechanism of action includes competitive inhibition of viral DNA polymerase, incorporation into and subsequent termination of the growing viral DNA chain, and inactivation of DNA polymerase. Its highest antiviral activity in vitro is against HSV-1, then HSV-2 and varicella-zoster virus. Acyclovir-resistant mutants have been described and occur in immunocompromised patients who have thymidine kinase-deficient HSV. Consider the possibility of viral resistance in patients with a poor response.

Adult dosage

In patients with normal renal function, administer 10 mg/kg infused at a constant rate for a minimum of 1 hour, every 8 hours, for a total of 15 mg/kg/d, for 14-21 days. Rapid infusion of acyclovir can cause crystalluria and subsequent renal failure.38 A therapeutic duration of 10 days may result in a relapse rate of up to 10%. Consequently, longer therapy of 3 weeks has been suggested.

Taira et al analyzed specific variables as predictors of a need for a prolonged course of acyclovir therapy in 23 patients with HSV encephalitis. A lower Glasgow Coma Scale score and a greater number of lesions detected on CT were predictors of prolonged therapy. The investigators therefore concluded that standard initial ACV treatment may not be sufficient for patients with such predictors and that initial treatment modifications may be necessary in such patients.16


Pediatric dosage

In children younger than 12 years, administer 250 mg/m2 at a constant intravenous rate over 1 hour, every 8 hours, for a total of 750 mg/m2/d for 7 days.

Mejias et al found that detection of HSV DNA in the CSF of 4 neonates with HSV encephalitis following 15-21 days of high-dose acyclovir therapy may be a risk factor for worse neurodevelopmental outcome.15


Drug interactions

  • Acyclovir and phenytoin: Acyclovir may decrease the serum concentration of phenytoin. The mechanism is uncertain.
  • Acyclovir and xanthine (theophylline): The serum concentration of theophylline may increase, resulting in toxicity. Acyclovir is believed to inhibit the oxidative metabolism of theophylline.
  • Acyclovir and valproic acid: The serum concentration of valproic acid may decrease, and acyclovir may interfere with the pharmacologic activity of the anticonvulsant.
  • Acyclovir and probenecid: Probenecid may decrease the renal excretion of acyclovir. Toxicity may manifest as dizziness, fatigue, headache, and depression.
  • Acyclovir and zidovudine: Patients may experience excessive lethargy and fatigue. If severe symptoms result, the acyclovir dosage may need to be decreased or eliminated.

Pregnancy

Acyclovir is a category C drug; its safety for use during pregnancy has not been established. Animal reproduction studies at standard doses did not result in teratogenic effects, but doses at 5-10 times human levels resulted in rat fetal head and tail anomalies and maternal toxicity. Although acyclovir is not teratogenic in standard animal studies, a potential for chromosome damage at high concentrations may exist.

A prospective epidemiologic registry of acyclovir use in pregnancy has been ongoing since 1984. As of June 1996, in 494 woman exposed to systemic acyclovir in the first trimester, the occurrence rate of birth defects was approximately that of the general population; however, this is a small sample. To monitor maternal-fetal outcomes in the setting of systemic acyclovir, GlaxoSmithKline established an Acyclovir in Pregnancy Registry in 1984, which was completed in 1999. Physicians and healthcare providers may obtain a final study report by calling the GlaxoSmithKline Customer Response Center at 1-888-825-5249.

Precautions

Adjust the dosage when acyclovir is administered to patients with renal impairment. Take precautions when administering the medication concurrently with nephrotoxic drugs, which may increase risk of renal dysfunction and/or the risk of CNS symptoms (confusion, dizziness, hallucinations, paresthesia, seizure, somnolence).

Demonstrable levels of acyclovir have been reported in women after the oral administration of acyclovir and have ranged from 0.6-4.1 times the plasma level. This potentially exposes a nursing infant to a dose of 0.3 mg/kg/d. Consequently, nursing is not advised while patients are taking acyclovir.

Contraindications

Acyclovir is contraindicated in patients who develop hypersensitivity or intolerance to the formulation.

Medicolegal Pitfalls

  • HSV polymerase chain reaction of the CSF is highly sensitive and specific. However, in rare cases, false-positive and false-negative results can occur. False-negative results occur in neonates and young infants because of the presence of heme or other inhibitors. False-negative results occur when CSF samples are obtained too early in the disease course of encephalitis. Repeat sampling may be necessary.
  • Early in the clinical course of the disease, CT and even MRI results may be negative. A negative MRI does not rule out HSV encephalitis. Therapy should be empirically continued until laboratory tests definitely exclude the diagnosis.
  • Adverse neurologic problems can also occur due to the neurotoxicity of acyclovir, as well as nephrotoxicity. These problems respond to termination of the drug.
  • A case report of West Nile Virus causing focal temporal lobe findings has been described in the literature.39

Special Concerns

  • HSV encephalitis rarely has been reported during pregnancy and is often misdiagnosed.
  • HSV encephalitis manifests with a multifocal clinical appearance, including seizures and neurologic or psychiatric disorders.
  • Over 1100 pregnant patients have received acyclovir, and birth defects have not increased relative to the general population.
  • The guidelines from the Centers for Disease Control and Prevention (CDC) state that acyclovir therapy is indicated in life-threatening maternal HSV infection.40
 


More on Herpes Encephalitis

Overview: Herpes Encephalitis
Imaging: Herpes Encephalitis
Follow-up: Herpes Encephalitis
Multimedia: Herpes Encephalitis
References
Further Reading
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References

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Further Reading

Related eMedicine topics

 Herpes Simplex Encephalitis (Emergency Medicine)

Herpes Simplex Encephalitis (Neurology)

HIV-1 Associated Opportunistic Infections: Cytomegalovirus Encephalitis
Viral Encephalitis

Clinical guidelines

Neurologic complications in HIV-infected children and adolescents.
New York State Department of Health - State/Local Government Agency [U.S.]. 2003 Mar. 19 pages. NGC:003047

Treating opportunistic infections among HIV-infected adults and adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2004 Dec 17. 112 pages. NGC:003994

2007 national guideline for the management of genital herpes.
British Association for Sexual Health and HIV - Medical Specialty Society. 1999 Aug (revised 2007). 26 pages.  NGC:006299
 
Screening for genital herpes: recommendation statement.
United States Preventive Services Task Force - Independent Expert Panel. 2005 Mar 18. 11 pages. NGC:004067

Viral encephalitis: a review of diagnostic methods and guidelines for management.
European Federation of Neurological Societies - Medical Specialty Society. 2005 May. 13 pages. NGC:005163

Clinical trials
Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valtrex

Structure of the Herpes Simplex Virus Receptor

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Keywords

herpes encephalitis, viral encephalitis, herpesvirus infection, HSV encephalitis, HSV-1, HSV-2, herpes-induced encephalitis, herpes infection, brain herpes, herpes simplex virus type 1, herpes simplex virus type 2, herpes simplex virus encephalitis

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Contributor Information and Disclosures

Author

Mahesh R Patel, MD, Chief, MRI, Department of Diagnostic Imaging, Santa Clara Valley Medial Center
Mahesh R Patel, MD is a member of the following medical societies: American Roentgen Ray Society, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey L Creasy, MD, Associate Professor, Associate Section Head, Division of Neuroradiology, Director, Neuroradiology Fellowship, Department of Radiology, Vanderbilt University
Jeffrey L Creasy, MD is a member of the following medical societies: American College of Radiology, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Val Runge, MD, Robert and Alma Moreton Centennial Chair in Radiology, Professor, Editor-in-Chief of Investigative Radiology, Department of Radiology, Scott and White Clinic and Hospital
Val Runge, MD is a member of the following medical societies: Society for Health and Human Values
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences
James G Smirniotopoulos, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, American Society of Head and Neck Radiology, American Society of Neuroradiology, American Society of Pediatric Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

 
 
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