What is the treatment for Herpes Simplex Virus (HSV) encephalitis?

Treatment of Herpes Simplex Virus Encephalitis

Intravenous acyclovir at a dose of 10 mg/kg every 8 hours for 14-21 days is the standard treatment for HSV encephalitis and should be initiated immediately upon suspicion of the disease, without waiting for diagnostic confirmation. 1

Initial Management

• Immediate treatment: Start IV acyclovir as soon as HSV encephalitis is suspected, as early initiation significantly reduces mortality from over 70% to less than 20-30% 1
• Dosing by age group:
  • Adults and children >12 years: 10 mg/kg IV every 8 hours
  • Children 3 months-12 years: 500 mg/m² IV every 8 hours
  • Neonates: 20 mg/kg IV every 8 hours 1

Treatment Duration and Monitoring

• Standard duration: 14-21 days of IV acyclovir 2, 1
  • Minimum 21 days recommended for children 3 months-12 years due to higher relapse rates 1
• Monitoring during treatment:
  • Regular assessment of renal function (serum creatinine, BUN)
  • Maintain adequate hydration to prevent crystalluria and nephropathy
  • Watch for nephrotoxicity, especially after 4 days of therapy 1
• End-of-treatment assessment:
  • Perform repeat lumbar puncture with HSV PCR testing at the end of treatment to confirm viral clearance 2, 1
  • If CSF remains positive for HSV by PCR, continue acyclovir with weekly PCR until negative 2

When to Stop Empiric Treatment

Acyclovir can be stopped in immunocompetent patients if:

1. An alternative diagnosis has been made, or
2. HSV PCR in CSF is negative on two occasions 24-48 hours apart, and MRI is not characteristic for HSV encephalitis, or
3. HSV PCR in CSF is negative once >72 hours after symptom onset, with:
   • Unaltered consciousness
   • Normal MRI (performed >72 hours after symptom onset)
   • CSF white cell count <5 × 10^6/L 2

Role of Corticosteroids

• Current recommendation: Corticosteroids should not be used routinely in HSV encephalitis 2, 1
• Special considerations: May be considered in patients with marked cerebral edema or raised intracranial pressure under specialist supervision 2, 1
• Evidence: A retrospective analysis showed that lack of corticosteroid administration was a predictor of poor outcome, but randomized controlled trial results are still awaited 2

Management of Complications

• Altered consciousness: Patients with falling level of consciousness require urgent ICU assessment for:
  • Airway protection and ventilatory support
  • Management of raised intracranial pressure
  • Optimization of cerebral perfusion pressure
  • Correction of electrolyte imbalances 2

Special Situations

• Renal impairment: Dose adjustment required based on creatinine clearance 1, 3
• Allergic reactions: In rare cases of severe acyclovir allergy, intravenous desensitization protocols have been successfully used 4
• Relapse: Cases of relapse have been reported after 10-day treatment courses, which is why longer treatment durations (14-21 days) are now recommended 5, 6

Poor Prognostic Factors

• Age >30 years
• Low Glasgow Coma Score (<6)
• Duration of symptoms >4 days before starting acyclovir
• Persistence of confusion, aphasia, or impaired consciousness >5 days 1

Common Pitfalls to Avoid

• Delaying treatment while waiting for diagnostic confirmation
• Administering incorrect acyclovir dosage
• Stopping treatment based on a single negative CSF PCR
• Using oral acyclovir instead of IV formulation (oral acyclovir does not achieve adequate CSF levels) 1

Early diagnosis and prompt initiation of appropriate antiviral therapy are critical for improving outcomes in HSV encephalitis, with mortality increasing significantly when treatment is delayed beyond 48 hours after hospital admission.