Treatment for Herpes Simplex Encephalitis
Intravenous acyclovir is the treatment of choice for herpes simplex encephalitis and should be initiated immediately upon suspicion of the diagnosis at a dose of 10 mg/kg every 8 hours for 14-21 days in adults and children over 12 years. 1, 2
Initial Treatment Approach
Timing of Treatment
- Treatment should be started as soon as HSV encephalitis is suspected, ideally within 6 hours of admission 1
- Early initiation significantly improves outcomes:
Dosage Recommendations
- Adults and children >12 years: 10 mg/kg IV every 8 hours 1, 2, 3
- Children 3 months-12 years: 500 mg/m² IV every 8 hours 1, 2
- Neonates: 20 mg/kg IV every 8 hours 1, 2, 3
Duration of Treatment
- Standard duration: 14-21 days of intravenous therapy 1, 2
- For children aged 3 months-12 years, a minimum of 21 days is recommended due to higher relapse rates (up to 29%) in this age group 1, 2
- For adults, 21 days is now commonly recommended to reduce relapse risk 4, 5
Monitoring During Treatment
Renal Function
- Monitor renal function regularly, especially after 4 days of therapy when nephropathy risk increases 1, 2
- Dose adjustment is required in patients with renal impairment 1, 2, 3:
- For creatinine clearance 50-80 mL/min: adjust accordingly
- For creatinine clearance 15-50 mL/min: further dose reduction
- For anuric patients: significant dose reduction required
Treatment Response
- Consider repeat CSF examination at the end of therapy (14-21 days) 1, 2
- A negative CSF PCR at the end of therapy is associated with better outcomes 1
- If PCR remains positive, continue antiviral therapy 1, 2
When to Discontinue Empiric Treatment
Acyclovir can be stopped in an immunocompetent patient if:
- An alternative diagnosis has been made, or
- HSV PCR in CSF is negative on two occasions 24-48 hours apart, and MRI imaging (performed >72 hours after symptom onset) is not characteristic for HSV encephalitis, or
- HSV PCR in CSF is negative once >72 hours after neurological symptom onset, with normal level of consciousness, normal MRI, and CSF white cell count <5 × 10⁶/L 1
Prognostic Factors
Poor prognostic factors include:
- Age >30 years
- Low Glasgow Coma Score (<6)
- Treatment delay >4 days after symptom onset
- Simplified Acute Physiology Score >27 at hospital admission 1, 2
Important Considerations
Alternative Treatments
- Oral acyclovir does not achieve adequate CSF levels and should not be used for HSV encephalitis 1, 2
- For patients with severe acyclovir allergy, desensitization protocols may be necessary as there are limited alternative treatment options 6
- In cases of acyclovir-resistant HSV (rare in immunocompetent patients), foscarnet may be considered at 40 mg/kg three times daily or 60 mg/kg twice daily 7
Adjunctive Therapies
- There is insufficient evidence to recommend routine use of corticosteroids in HSV encephalitis 1
- Extended oral valacyclovir therapy after standard IV acyclovir treatment has not shown additional benefit in improving neuropsychological outcomes 8
Relapse Risk
- Relapse rates of approximately 5% in adults and up to 29% in children have been reported 1, 2
- Higher relapse risk is associated with shorter treatment courses (<14 days) 1, 2
Remember that despite optimal treatment, HSE still carries significant mortality (14-19%) and morbidity, with 45-60% of survivors experiencing neuropsychological sequelae at 1 year 8.