Guideline Summary for Management of Herpes Simplex Virus Encephalitis

Empiric Antiviral Therapy

Initiate intravenous acyclovir at 10 mg/kg every 8 hours within 6 hours of admission when clinical suspicion for HSV encephalitis is high, even before confirmatory testing; delays > 48 hours raise mortality from 8 % to 28 %【1】.
Continue acyclovir despite normal initial CSF microscopy and neuro‑imaging if suspicion remains high【1】.
Do not postpone lumbar puncture in deteriorating patients; HSV PCR stays positive for 7–10 days after the first acyclovir dose, allowing delayed CSF confirmation【4】.

Adults and children > 12 years: 10 mg/kg IV every 8 hours【1】.
Children 3 months–12 years: 500 mg/m² IV every 8 hours【1】.
Neonates with CNS HSV disease: 20 mg/kg IV every 8 hours for 21 days (higher dose due to poorer outcomes)【3】.
Adjust dose according to creatinine clearance because acyclovir is 62–91 % renally excreted; monitor renal function throughout therapy【3】.
Nephrotoxicity typically appears after ~4 days in up to 20 % of patients; maintain adequate hydration to prevent crystalluria and obstructive nephropathy【4】.

Perform lumbar puncture immediately unless contraindicated; do not wait for CT unless focal neurological signs, papilledema, or immunocompromise are present【1】.
CT scans are frequently normal in encephalitis and should not be used to rule out the disease【1】.
MRI is the investigation of choice, revealing characteristic T2/FLAIR hyperintensity in the medial temporal lobes, insular cortex, and inferior frontal lobes【1】.

For confirmed HSV encephalitis, continue IV acyclovir for 14–21 days; in children 3 months–12 years a minimum of 21 days is advised because shorter courses are associated with a 26–29 % relapse rate【4】.
Obtain a repeat lumbar puncture with HSV PCR at 14–21 days; if PCR remains positive, extend acyclovir and repeat weekly until clearance【4】.
Oral acyclovir is not appropriate for acute HSV encephalitis because CSF concentrations are insufficient; IV administration is mandatory【3】.

Any decline in level of consciousness warrants urgent ICU assessment for airway protection, ventilatory support, and intracranial pressure management【5】.
Seizures occur in approximately 38 % of HSV encephalitis cases; treat with intravenous levetiracetam and use EEG monitoring to detect non‑convulsive seizures【6】.

Suspect acyclovir resistance when clinical deterioration persists after 7–10 days of appropriate therapy or when HSV PCR stays positive after 21 days, especially in immunocompromised patients【3】【4】.
Foscarnet (40 mg/kg IV every 8 hours, or every 12 hours) for 2–3 weeks or until clinical improvement is the recommended second‑line agent【3】.
Immunocompromised patients may require treatment beyond 21 days if PCR remains positive; higher acyclovir doses (e.g., 15 mg/kg every 8 hours) can be considered when renal function permits【5】.

The use of corticosteroids is controversial; they may reduce cerebral edema but could theoretically enhance viral replication. Consider steroids in patients with marked edema, brain shift, or raised intracranial pressure【5】.

With acyclovir, mortality is 20–30 %, compared with ≈ 70 % in untreated patients【1】.
Worse outcomes are linked to advanced age, low Glasgow Coma Scale on admission, and treatment delays > 48 hours【4】.
Initiating therapy within 4 days of symptom onset reduces mortality to 8 %【3】.

Reversible nephropathy develops after ~4 days in up to 20 % of patients; routine creatinine monitoring and aggressive hydration are essential【4】.
Rare but serious adverse events include hepatitis, bone‑marrow suppression, and acyclovir‑induced encephalopathy; vigilance and appropriate dosing mitigate these risks【4】.