What is the treatment for herpes encephalitis?

Treatment of Herpes Simplex Encephalitis

Initiate intravenous acyclovir immediately at 10 mg/kg every 8 hours for adults and children with normal renal function, or 20 mg/kg every 8 hours for neonates, and continue for 14-21 days. 1

Immediate Empiric Treatment

Start acyclovir as soon as herpes encephalitis is suspected—do not wait for diagnostic confirmation. 1, 2 Early treatment is critical because:

• Mortality drops from 70% to 8% when acyclovir is started within 4 days of symptom onset 1
• Delaying treatment beyond 48 hours after hospital admission significantly worsens outcomes 2
• Even with treatment, 18-month mortality remains 28%, but this is far better than untreated disease 1

The IDSA guidelines explicitly state that acyclovir should be initiated in all patients with suspected encephalitis as soon as possible, pending diagnostic results. 1

Dosing Regimens

Adults and Children (>3 months)

• 10 mg/kg intravenously every 8 hours for patients with normal renal function 1, 2, 3
• Adjust dose downward in patients with pre-existing renal impairment to prevent crystalluria and obstructive nephropathy 2

Neonates

• 20 mg/kg intravenously every 8 hours 1, 2
• This higher dose has reduced neonatal mortality to 5%, with approximately 40% of survivors developing normally 1
• Lower doses (10 mg/kg every 8 hours) resulted in 8% relapse rates in neonates 1

Weight-Based Considerations

• For patients weighing <79 kg, ensure a minimum total daily dose of 2550 mg/day (850 mg every 8 hours) when clinically feasible, as lower doses are associated with worse outcomes 4

Treatment Duration

Continue intravenous acyclovir for 14-21 days. 1, 2, 5 The longer duration (21 days) is preferred because:

• Relapse rates as high as 5% have been reported in adults and children after shorter courses 1
• In neonates, no relapses occurred when 20 mg/kg every 8 hours was given for 21 days 1
• A documented case showed relapse 4 days after completing a 10-day course, requiring retreatment 6

Monitoring and End-of-Treatment Assessment

Repeat lumbar puncture at the end of therapy to confirm CSF HSV PCR is negative. 1, 2 This is important because:

• A negative CSF PCR at end of therapy is associated with better outcomes 1
• If PCR remains positive and clinical response is inadequate, continue antiviral therapy 1
• Some patients require individualized treatment duration based on persistent CSF abnormalities 7

Monitor renal function throughout treatment, as acyclovir-induced nephropathy affects up to 20% of patients, typically after 4 days of IV therapy. 2 Ensure adequate hydration to reduce nephropathy risk. 2

Stopping Empiric Acyclovir

If HSV encephalitis is ruled out, acyclovir can be stopped when:

• CSF HSV PCR is negative AND sampled >72 hours into illness 1
• Patient has low probability features: normal neuroimaging, CSF white blood cells <5×10⁶/mm³, and normal level of consciousness 1
• If uncertainty remains with one negative PCR, repeat CSF examination at 24-48 hours; two negative HSV PCRs make HSV encephalitis very unlikely 1

Predictors of Poor Outcome

Be aware that the following factors predict worse outcomes despite treatment:

• Age >30 years 1
• Glasgow Coma Score <6 at admission 1
• Duration of symptoms >4 days before starting acyclovir 1
• Simplified Acute Physiology Score ≥7 at admission 1
• Delay >2 days between hospital admission and acyclovir administration 1
• Persistent confusion, aphasia, or impaired consciousness lasting >5 days 4

Adjunctive Corticosteroids

Do not routinely use corticosteroids in HSV encephalitis. 1 While one retrospective study of 45 patients suggested better outcomes with corticosteroids, 1 this evidence is insufficient to recommend routine use. 1 A randomized controlled trial is ongoing to definitively answer this question. 1

Corticosteroids may have a role in selected patients under specialist supervision, particularly those with marked cerebral edema, brain shift, or raised intracranial pressure, but data are lacking. 1

Common Pitfalls to Avoid

• Never delay acyclovir while awaiting diagnostic confirmation—the mortality benefit of early treatment far outweighs the minimal risk of unnecessary treatment 1, 2, 5
• Do not stop acyclovir based solely on a single negative CSF PCR if sampled early (<72 hours) or if clinical suspicion remains high 1
• Ensure adequate hydration during treatment to prevent acyclovir-induced crystalluria and nephropathy 2
• Do not use standard 10-day courses—14-21 days is required to prevent relapse 1, 6
• Do not underdose low-weight patients—ensure adequate total daily dosing based on actual weight 4