eMedicine Specialties > Neurology > Neurological Infections

Herpes Simplex Encephalitis

Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Contributor Information and Disclosures

Updated: Mar 13, 2007

Introduction

Background

The human herpesvirus (HHV) family includes 2 clinically important strains, also known as herpes simplex virus (HSV). Human herpesvirus 1 (HHV-1), also called herpes simplex virus type 1 (HSV-1), causes oral lesions (so-called fever blisters); these are common and may respond to antiviral medications, although they spontaneously remit in most cases. Human herpesvirus 2 (HHV-2), also known as herpes simplex virus type 2 (HSV-2), causes genital lesions. It was previously thought to appear within 1-2 weeks of primary infection, then to recur with lessening severity. That lesions may appear clinically at any interval after primary infection is now known. HSV-2 may be treated with antiviral medications.

Patients with HSV may require long-term antiviral treatment if they have recurrent lesions or involvement of other organ systems (eg, herpes simplex keratitis). HSV remains dormant in the nervous system; rarely, it presents as encephalitis, possibly by direct transmission through peripheral nerves to the CNS. This encephalitis is a neurologic emergency and the most important neurologic sequela of HSV.

Pathophysiology

Besides causing local outbreaks, HSV-1 and HSV-2 are associated with encephalitis. HSV-1 is the more common cause of adult encephalitis. HSV-2 is the more common cause of newborn encephalitis, which is associated with maternal genital infections. Pathophysiology of this encephalitis is poorly understood in humans. Animal models suggest that the virus enters the CNS via peripheral nerves. Virus-induced apoptosis may play a role in the molecular pathogenesis of herpes simplex encephalitis (HSE). HSV is an enveloped, double-stranded DNA virus. It is part of the herpes family, which also includes varicella-zoster virus (VZV, or HHV-3) and cytomegalovirus (CMV, or HHV-5).

The encephalitis affects the temporal lobes of the brain in most cases. Wasay et al report temporal lobe involvement in 60% of patients. Fifty-five percent of patients demonstrated temporal and extratemporal pathology, and 15% of patients demonstrated extratemporal pathology exclusively.

Frequency

United States

HSE is the most common nonepidemic encephalitis. Incidence is 2 cases per million population per year. HSE may occur year-round. HSV-1 is ubiquitous and HSV-2 is also common.

International

International incidence is similar to that in the United States.

Mortality/Morbidity

HSV-1 and HSV-2 infections often recur. HSE rarely occurs. Untreated HSE is progressive and often fatal in 7-14 days. However, significant morbidity exists among those treated. A landmark study by Whitley et al in 1977 revealed a 70% mortality rate in untreated patients and severe neurologic deficits in most of the survivors (Whitley, 1977). The following demonstrate the variety of complications.

• Elbers and colleagues followed properly treated children for 12 years after the HSE. They found seizures in 44% of the children and developmental delay in 25% of the children. They concluded that HSE continues to be associated with poor long-term neurologic outcomes despite appropriate therapy (Elbers, 2007).
• Shelley and colleagues reported a case of intracerebral hematoma occurring in a patient successfully treated with a full course of acyclovir after apparent eradication of the virus. The hematoma occurred in the region of the encephalitis (Shelley, 2007).
• Marschitz and colleagues reported a case of chorea after HSE (Marschitz, 2007).

Sex

• Herpes affects both sexes equally.
• Genital herpes may be more apparent in the male because of anatomy.

Age

One third of HSE cases occur in children.

Clinical

History

• In HSE, patients may have a prodrome of malaise, fever, headache, and nausea.
• This is followed by acute or subacute onset of an encephalopathy whose symptoms include lethargy, confusion, and delirium.
• Headaches, seizures, aphasia, and other focal deficits also may occur.

Physical

• On neurological examination, global and focal neurologic findings include encephalopathy, delirium, aphasia, cranial nerve deficits, and hemiparesis.
• Meningeal signs may be present.
• Unusual presentations occur. Both HSV-1 and HSV-2 may produce a more subacute encephalitis, apparent psychiatric syndromes, and benign recurrent meningitis. Less commonly, HSV-1 may produce a brain stem encephalitis and HSV-2, a myelitis.
  • Ku et al discussed the unique presentation of HSE in a bilingual patient. He developed global aphasia for 1 language (his most recently learned language) but retained most of his birth language ability.
  • McGrath et al reported on 4 patients with confirmed HSE, each with an anterior opercular syndrome. The syndrome (ie, paralysis of the masticatory, facial, pharyngeal, and lingual muscles) occurred as the primary manifestation of HSE in 2 patients and as part of the encephalitis picture in the other 2 patients. The authors suggested that unique presentations, such as the anterior opercular syndrome, should alert the clinician to the possibility of HSE.

Causes

• In adults, the host immune response, combined with viral factors, determines invasiveness and virulence.
  • Mitchell et al showed that invasiveness of HSV-1 glycoprotein variants is controlled by host response.
  • Geiger et al used interferon-gamma–knockout mice to show how interferon-gamma protected against HSV-1–mediated neuronal death.
  • These data suggested that the presentation and severity of encephalitis vary.
• Evidence from a European study suggested that socioeconomic status and geography might affect levels of virus seropositivity. However, clinical correlation is difficult because HSE can occur at any time, regardless of the patient's socioeconomic status, age, race, or sex.
• In children, encephalitis often results from primary infection with HSV. Approximately 80% of children with HSE do not have a history of labial herpes.
• In newborns, a preexisting but recurrent maternal genital herpes infection results in 8% risk of symptomatic infection, usually transmitted at the second stage of labor via direct contact. Should the mother acquire genital herpes during pregnancy, the risk increases to 40%.
• Cathomas et al report a case of HSE as a complication of chemotherapy for breast cancer.

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