What is the treatment for herpes encephalitis?

Treatment of Herpes Simplex Encephalitis

Initiate intravenous acyclovir immediately at 10 mg/kg every 8 hours for all patients with suspected herpes encephalitis, even before diagnostic confirmation, as early treatment reduces mortality from 70% to 8-25%. 1, 2, 3

Immediate Empiric Treatment

• Start acyclovir within 6 hours of admission for any patient presenting with altered mental status, fever, focal neurological signs, or seizures suggestive of encephalitis 2
• Do not wait for CSF PCR results or neuroimaging before initiating treatment, as delays beyond 48 hours significantly worsen outcomes 1, 2
• The standard adult dose is 10 mg/kg IV every 8 hours in patients with normal renal function 1, 3

Age-Specific Dosing

Neonates (Birth to 3 months)

• Use higher-dose acyclovir at 20 mg/kg IV every 8 hours for 21 days, which has reduced mortality to 5% with approximately 40% of survivors developing normally 1, 2
• Standard 10 mg/kg dosing in neonates resulted in 8% relapse rates, while the higher dose eliminated documented relapses 1

Children (3 months to 12 years) and Adults

• 10 mg/kg IV every 8 hours is the established dose 1, 2, 3

Geriatric Patients

• Reduce dose in elderly patients with underlying renal impairment due to higher plasma concentrations from age-related changes in renal function 3

Treatment Duration

• Continue IV acyclovir for 14-21 days in confirmed HSV encephalitis 1, 2
• The 21-day duration is preferred over 14 days to minimize relapse risk, which occurs in up to 5% of adult patients 1
• Consider repeating lumbar puncture at the end of treatment; if CSF PCR remains positive for HSV, continue antiviral therapy 1, 2

Renal Function Monitoring

• Monitor renal function throughout treatment, as acyclovir-induced nephropathy affects up to 20% of patients, typically after 4 days of IV therapy 2, 3
• Ensure adequate hydration during treatment, as inadequate fluid administration increases nephropathy risk 2, 4
• Adjust dosing based on creatinine clearance: patients with severe renal impairment may require dose reduction to prevent crystalluria and obstructive nephropathy 2, 3

Prognostic Factors and Treatment Timing

Early treatment is the single most critical determinant of outcome:

• Mortality drops to 8% when acyclovir is started within 4 days of symptom onset, compared to 28% overall mortality at 18 months 1
• Patients under 30 years of age with Glasgow Coma Score ≥6 who receive early treatment have the best outcomes, with up to 65% returning to normal function 1, 5
• Delays beyond 2 days from hospital admission to acyclovir initiation are independent predictors of poor outcome 1

Diagnostic Considerations During Treatment

• A single negative CSF PCR does not rule out HSV encephalitis, especially if obtained within 72 hours of symptom onset or after acyclovir has been started 1
• If clinical suspicion remains high despite negative initial CSF PCR, continue acyclovir and repeat lumbar puncture at 24-48 hours 1
• HSV encephalitis is very unlikely if two CSF PCRs separated by 24-48 hours are both negative in a patient with low clinical probability (normal imaging, CSF WBC <5 cells/mm³, normal consciousness) 1

Adjunctive Corticosteroids

• Corticosteroids should not be used routinely in HSV encephalitis, as their role remains unestablished and they may theoretically facilitate viral replication through immunomodulation 1
• One retrospective study suggested benefit, but this requires confirmation in randomized controlled trials currently underway 1
• Consider corticosteroids only in cases with marked cerebral edema, brain shift, or critically elevated intracranial pressure under specialist supervision 1

Common Pitfalls to Avoid

• Never delay acyclovir while awaiting brain biopsy or definitive diagnostic confirmation - the mortality benefit of early empiric treatment far outweighs the risk of unnecessary antiviral therapy 1, 2, 6
• Do not stop acyclovir based solely on a single negative CSF PCR if obtained early (<72 hours) or if clinical suspicion remains high 1
• Avoid inadequate treatment duration - the 10-day courses used in early studies resulted in relapses; 14-21 days is now standard 1, 7
• Do not use oral acyclovir or valacyclovir as initial therapy - only IV acyclovir achieves adequate CNS penetration for acute treatment 1, 3

Clinical Trial Evidence

The pivotal trial comparing acyclovir to vidarabine in 62 patients with brain biopsy-proven HSE demonstrated mortality of 25% with acyclovir versus 59% with vidarabine at 12 months, with 32% of acyclovir-treated patients functioning normally or with only mild sequelae compared to 12% with vidarabine 3