What are the symptoms and treatment of Herpes Simplex Virus (HSV) encephalitis?

Symptoms and Treatment of Herpes Simplex Virus (HSV) Encephalitis

HSV encephalitis presents with fever, altered mental status, headache, and seizures as the most common symptoms, requiring immediate treatment with intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days to reduce mortality and improve outcomes. 1, 2

Clinical Presentation

Common Symptoms

• Fever: Present in 80-91% of cases, though can be low-grade in atypical presentations 1, 2
• Altered mental status/consciousness: Occurs in 40-76% of cases, ranging from confusion to coma 1, 2
• Headache: Often severe and hemicranial 2
• Seizures: Present in 33-61% of cases 1, 3
• Speech disturbances: Dysphasia and aphasia in approximately 59% of cases 1
• Focal neurological deficits: Present in 36-78% of cases 1
• Behavioral changes: Personality changes, disorientation, confusion 2, 4
• Memory impairment: Particularly short-term memory loss 2

Age-Specific Presentations

• Adults: More likely to present with classic symptoms of fever, headache, altered mental status, and speech disturbances 1
• Children: Often have non-specific symptoms including:
  • Feeding difficulties
  • Respiratory symptoms
  • Seizures (more common than in adults)
  • Low-grade fever rather than high fever 2

Atypical Presentations

• Subtle behavioral changes that may be mistaken for psychiatric illness 2, 1
• Low-grade fever instead of high fever 2
• Mild encephalitis with minimal symptoms 1
• Normal Glasgow Coma Score at presentation (doesn't exclude HSV encephalitis) 1

Diagnostic Approach

Laboratory Testing

• CSF PCR for HSV-1 and HSV-2: Gold standard with 95% sensitivity and 99% specificity 2
• CSF analysis: May show protein elevation and mild lymphocytic pleocytosis, though can be normal 2
• CSF antibodies: May be beneficial if obtained 1 week into therapy 2

Imaging

• MRI: Reveals temporal and/or inferior frontal lobe edema with high signal intensity on FLAIR and T2-weighted images 2
  • Bilateral temporal lobe involvement is nearly pathognomonic for HSV encephalitis
  • May be normal early in the disease course

Electroencephalogram (EEG)

• Usually diffusely abnormal, sometimes involving the temporal region 2

Treatment

Antiviral Therapy

• First-line treatment: Intravenous acyclovir 10 mg/kg every 8 hours for 14-21 days 5, 6
• Timing: Treatment should be initiated as soon as HSV encephalitis is suspected, without waiting for diagnostic confirmation 5
• Efficacy: Reduces mortality from 70% to 25% when started early 6, 7
• Monitoring: After completion of therapy, PCR of the CSF can confirm elimination of replicating virus 5

Special Populations

• Immunocompromised patients: May require longer treatment courses due to difficulty achieving viral clearance 2
• Elderly patients: May require dose adjustment due to age-related changes in renal function 6

Prognosis and Outcomes

• Mortality: Without treatment, mortality rates reach 70%; with acyclovir treatment, mortality decreases to 25% 5, 6
• Neurological sequelae: Memory defects and neuropsychological sequelae in 20-60% of survivors 2
• Epilepsy: Develops in approximately 35% of survivors, with acute symptomatic seizures associated with an 8-fold increased risk 3
• Better outcomes: Associated with:
  • Younger age (<30 years)
  • Less severe neurological involvement at presentation
  • Early initiation of treatment 6, 7

Important Clinical Pitfalls

• Diagnostic delay: Non-specific initial symptoms are the most common reason for failure to diagnose HSV encephalitis 1, 8
• Misdiagnosis: Behavioral changes may be mistaken for psychiatric illness, drug, or alcohol effects 2, 8
• Absence of fever: Does not rule out HSV encephalitis 1
• Normal initial imaging: CT scans are often normal; early MRI may also be normal 2, 8
• Reconsideration of diagnosis: High willingness to reconsider initial working diagnosis is essential to prevent diagnostic delay 8