Herpes Encephalitis

Both Herpes simplex Type 1 and Type 2 can cause encephalitis. HSV-1 is the more common cause of adult encephalitis and HSV-2, is the more common cause of encephalitis in the newborn. Most cases are thought to be due to a reactivation of latent HSV-1 infection.

Herpes simplex encephalitis mainly affects the frontal and temporal cortexes and also the limbic system. Other herpes viruses may cause encephalitis but much less frequently than Herpes Simplex - however CMV encephalitis should be considered in those with immunodeficiency.

• Herpes simplex encephalitis is the most common non-epidemic encephalitis.
• The incidence is about 1 case per million population per year.¹
• About 30% of all infections occur in children, either acquired through maternal genital infection at birth or sporadic encephalitis in later childhood.²

Clinical diagnosis is suggested by encephalopathy, fever and focal neurological signs. However numerous other infections in the central nervous system can mimic HSE.³

• Prodrome of malaise, fever, headache, nausea and vomiting.
• This is followed by acute or subacute onset of altered consciousness, convulsions, features of raised intracranial pressure and focal neurological signs, including cranial nerve lesions. Psychiatric symptoms, confusion and delirium are also common.
• Other features include behavioural abnormalities, hallucinations of taste and smell, anosmia, amnesia, aphasia and visual field loss.
• Herpetic lesions are rarely seen on skin or mucosa, except for genital transmission of HSV-2.

• Meningitis
• Other infective causes of encephalitis, e.g. Togavirus, Rocky mountain spotted fever
• Postinfectious encephalomyelitis
• Intracranial abscess - bacterial, fungal, parasitic
• Intracranial haemorrhage
• Intracranial tumour - metastases or lymphoma
• Toxic and metabolic encephalopathies

• CT scan or MRI, may show temporal mass-like lesion: MRI is more sensitive than CT scan and is now the imaging study of choice.⁴
• EEG: shows abnormalities in about 80% of cases of Herpes simplex encephalitis. These include focal temporal changes, diffuse slowing, periodic complexes and periodic lateralising epileptiform discharges.
• Lumbar puncture:
  • Only after a mass-effect lesion has been excluded by imaging.
  • Mildly elevated protein, normal glucose, and a moderate pleocytosis (mostly mononuclear cells). Red blood cells and xanthochromia may be seen.
  • Herpes infection can usually be confirmed by identification of virus by polymerase chain reaction (PCR - diagnostic test of choice) to detect HSV DNA. PCR is highly specific and it remains positive for up to 5 days after initiation of treatment.⁴ PCR is therefore an excellent test but false negatives can occur early after disease onset.³
• Brain biopsy: rarely indicated because of effective methods of diagnosis and relatively non-toxic and effective antiviral medications.

• Start intravenous aciclovir as soon as herpes encephalitis is suspected and do not wait for confirmation.
• Intravenous acyclovir is usually given for at least 10 days and in some cases for up to 21 days.
• General nutritional and fluid support, with careful attention to fluid balance. Close monitoring of vital signs and signs of raised intracranial pressure.
• Increased intracranial pressure:
  • General measures e.g. elevating head of bed, diuretics.
  • More specific management includes mannitol, steroids, intubation with hyperventilation.
  • Surgical decompression is indicated for impending uncal herniation or intolerable increased intracranial pressure.⁵
• Control of seizures: first-line drugs include phenytoin and carbamazepine.

• Common sequelae among survivors include mental retardation, motor deficits, memory loss, ataxia, dysphasia seizures and cranial nerve lesions.
• Cognitive and memory deficits are common. Anterograde memory is often impaired even after successful treatment. Retrograde memory and language ability may also be impaired.⁶
• If treatment of HSE is delayed, permanent neurological deficits may occur in survivors. Even in treated cases of HSE, complications and sequelae are not uncommon.

• Untreated Herpes simplex encephalitis is progressive and often fatal within 7-14 days. There is a 70% mortality rate in untreated patients and most of the untreated survivors have severe neurological deficits.⁷
• Even with early administration of therapy, nearly two thirds of survivors will have significant residual neurological deficits.³
• Patients who have a shorter delay between presentation and treatment had better cognitive outcomes.⁵