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Herpes Simplex Encephalitis: Follow-up

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

Follow-up

Further Inpatient Care

  • All patients require admission to an intensive care unit.
  • Monitoring of intracranial pressure may be needed.

Transfer

  • Depending on availability of local expertise (eg, infectious disease, neurology, neurosurgery specialists), transfer to a tertiary care facility may be appropriate.

Deterrence/Prevention

  • No measures are known to be effective for preventing HSE.
  • Person-to-person transmission does not occur.
  • Prophylactic treatment of close contacts and special isolation precautions are unnecessary.

Complications

  • Seizures are common, and some authorities recommend prophylactic treatment with anticonvulsant drugs in patients with severe HSE.
  • Patients with HSE are subject to the same complications as those of all seriously ill and immobilized patients with depressed levels of consciousness (eg, aspiration, deep venous thromboses, decubiti).

Prognosis

  • The mortality rate in patients treated with acyclovir was 19% in the comparative trials that established its superiority to vidarabine. More recent trials have reported lower mortality (6-11%), perhaps because they included patients diagnosed by PCR rather than brain biopsy who thus may have been identified earlier with milder disease.1,3
  • Sequelae among survivors are significant and depend on the patient's age and neurological status at time of diagnosis.
    • Patients who are comatose at diagnosis have a poor prognosis regardless of their age.
    • In noncomatose patients, the prognosis is age related, with better outcomes occurring in patients younger than 30 years.
  • Neurological outcomes in survivors treated with acyclovir are as follows:
    • No deficits or mild deficits - 38%
    • Moderate deficits - 9%
    • Severe deficits - 53%
  • Relapses following HSE have been reported to occur in 5–26% of patients, with most relapses occurring within the first 3 months after completion of treatment. Relapses are more frequent in children than adults. It is unclear whether such relapses represent recurrence of viral infection or an immune-mediated inflammatory process. Some of the relapses reported in earlier studies may have been due to inadequate duration of treatment rather than true recurrences of HSE. A recent long-term follow-up study of patients with HSE suggests that different pathogenic mechanisms are present during relapses than during the initial infection.25 Serial measurements of inflammatory markers as well as HSV viral load in the CSF of relapsing patients demonstrated increased inflammatory markers without detectable HSV during relapses. This suggests that immune-mediated events, rather than direct viral-mediated neuronal toxicity, may predominate in relapses.

Patient Education

Miscellaneous

Medicolegal Pitfalls

  • Failure to consider the possibility of HSE can result in delayed diagnosis and treatment, with subsequent increased risks of mortality and morbidity. In a recent single-center study from a high volume academic emergency department, the authors reported that only 29% of patients with a presentation suggestive of viral encephalitis (fever, neuropsychiatric abnormalities, CSF pleocytosis, and a negative CSF Gram stain) received acyclovir in the ED.26
    • No pathognomonic clinical findings are associated with HSE.
    • The diagnosis can be confirmed only by means of PCR or brain biopsy.
    • In the absence of any other identifiable cause, consider HSE in any febrile patient with encephalopathy and CSF pleocytosis.
    • Start empiric acyclovir therapy promptly in such patients pending confirmation of the diagnosis.
  • Initial presentation may be mild or atypical in immunocompromised patients (eg, those with HIV infection or those receiving steroid therapy).
    • Focal neurological deficits, CSF pleocytosis, and CT abnormalities may be absent initially.
    • A high index of suspicion is required in all immunocompromised patients with febrile encephalopathy.

Special Concerns

  • Neonatal HSE27,28
    • The predominant pathogen is HSV-2 (75% of cases), which is usually acquired by maternal shedding (frequently asymptomatic) during delivery. The absence of a maternal history of prior genital herpes does not exclude risk; in 80% of cases of neonatal HSE, no maternal history of prior HSV infection is present. Prolonged rupture of the membranes (>6 h) and intrauterine monitoring (eg, attachment of scalp electrodes) are risk factors.
    • In about 10% of cases, HSV (often type 1) is acquired postpartum by contact with an individual who is shedding HSV from a fever blister, finger infection, or other cutaneous lesion.
    • HSE may occur as an isolated CNS infection or as part of disseminated multiorgan disease.
    • The mortality rate is substantial, even with appropriate treatment; 6% in patients with isolated HSE and 31% in those with disseminated infection.
    • Signs and symptoms of HSE develop about 6-12 days after delivery, at which time lethargy, poor feeding, irritability, tremors, or seizures may be noted.
      • Those with disseminated disease also have abnormal liver function test results and thrombocytopenia.
      • In contrast to older patients, neonates often have herpetic skin lesions.
    • Diagnostic modalities are similar to those in older children and adults. However, HSV can sometimes be confirmed by Tzanck preparations taken from vesicular lesions, and HSV can be cultured from the CSF in about one third of affected neonates.
    • Acyclovir in doses of 20 mg/kg IV q8h (60 mg/kg/d) is currently recommended. This dose is higher than that used in older children and adults (30 mg/kg/d), but, in neonates, it has been shown to improve mortality and morbidity when compared with the lower dose. The higher dose is associated with neutropenia, so the white blood cell count should be monitored closely.
    • Preventive measures include cesarean delivery in women with active herpetic genital infections at the time of delivery and protection of neonates from persons with active herpetic infections. Some authorities recommend a course of suppressive acyclovir therapy near the time of delivery in mothers with a history of genital herpes.
 


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

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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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