Herpes simplex encephalitis (HSE) is an acute or subacute illness that causes both general and focal signs of cerebral dysfunction. Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve. The exact pathogenesis is unclear, and factors that precipitate HSE are unknown. See the image below.

Axial diffusion-weighted image reveals restricted diffusion in left medial temporal lobe consistent with herpes encephalitis. This patient also had positive result on polymerase chain reaction assay for herpes simplex virus, which is both sensitive and specific. In addition, patient had periodic lateralized epileptiform discharges on electroencephalography, which supports diagnosis of herpes encephalitis. View Media Gallery

See Herpes Simplex Viruses: Test Your Knowledge, a Critical Images slideshow, for more information on clinical, histologic, and radiographic imaging findings in HSV-1 and HSV-2.

Signs and symptoms

Patients with HSE may have a prodrome of malaise, fever, headache, and nausea, followed by acute or subacute onset of an encephalopathy whose symptoms include lethargy, confusion, and delirium. However, no pathognomonic clinical findings reliably distinguish HSE from other neurologic disorders with similar presentations. [4]

The following are typically the most common symptoms of HSE [5] :

Fever (90%)

Headache (81%)

Psychiatric symptoms (71%)

Seizures (67%)

Vomiting (46%)

Focal weakness (33%)

Memory loss (24%)

The initial presentation may be mild or atypical in immunocompromised patients (eg, those with HIV infection or those receiving steroid therapy). [6]

See Clinical Presentation for more detail.

Diagnosis

There are no pathognomonic clinical findings associated with HSE. Focal neurologic deficits, CSF pleocytosis, and abnormalities on CT scanning may be absent initially. Therefore, a high index of suspicion is required to make the diagnosis, particularly in immunocompromised patients with febrile encephalopathy. Expeditious evaluation is indicated after the diagnosis of HSE is considered.

HSE occurs as 2 distinct entities:

In children older than 3 months and in adults, HSE is usually localized to the temporal and frontal lobes and is caused by HSV-1

In neonates, however, brain involvement is generalized, and the usual cause is HSV-2, which is acquired at the time of delivery

Typical findings on presentation include the following [5] :

Alteration of consciousness (97%)

Fever (92%)

Dysphasia (76%)

Ataxia (40%)

Seizures (38%): Focal (28%); generalized (10%)

Hemiparesis (38%)

Cranial nerve defects (32%)

Visual field loss (14%)

Papilledema (14%)

Meningeal signs may be present, but meningismus is uncommon. Unusual presentations also 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 brainstem encephalitis, and HSV-2 may produce a myelitis.

Lab tests

Routine laboratory tests are generally not helpful in the diagnosis of HSE but may show evidence of infection or detect renal disease. The diagnosis can be confirmed only by means of PCR or brain biopsy.

Studies that may be helpful in patients with suspected HSE include the following:

Serologic analysis of blood or CSF: Retrospective diagnosis only; not for acute diagnosis and management

Tzanck preparations of vesicular lesions: For confirmation of HSV in neonates with HSE

Quantification of intrathecal antibodies: For evidence of CNS antibody response

Imaging tests

The following are imaging studies used in the evaluation of suspected HSE:

MRI of the brain: The preferred imaging study

CT scanning of the brain: Less sensitive than MRI

EEG: Low specificity (32%) but 84% sensitivity to abnormal patterns in HSE

Procedures

Lumbar puncture for CSF analysis

PCR assay of CSF for HSV-1 and HSV-2: Essentially replaced brain biopsy as the criterion standard for diagnosis [7, 8]

Brain biopsy: Diminishing role; rarely used in current practice for either confirming diagnosis of HSE or establishing alternative diagnoses

Viral CSF cultures are rarely positive and should not be relied on to confirm the diagnosis. However, HSV can be cultured from the CSF in about one third of affected neonates.

See Workup for more detail.

Management

HSE is primarily managed with antiviral therapy in the form of acyclovir. Start empiric acyclovir therapy promptly in patients with suspected HSE pending confirmation of the diagnosis, because acyclovir is relatively nontoxic and because the prognosis for untreated HSE is poor.

Pharmacotherapy

Medications used in the management of HSE include the following:

Antivirals (eg, acyclovir, famciclovir): Drug of choice for HSE; to shorten the clinical course, prevent complications, prevent development of latency and subsequent recurrences, decrease transmission, and eliminate established latency

Anticonvulsants (eg, carbamazepine, phenytoin): To terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence

Diuretics (eg, furosemide, mannitol): To manage increased intracranial pressure in complications resulting from HSE

Nonpharmacotherapy

Supportive care in patients with HSE includes the following:

Airway, breathing, circulatory support

Nutritional and fluid support

Universal precautions

Monitoring for increase intracranial pressure and seizures

Admission to ICU as needed

See Treatment and Medication for more detail.