What is the recommended acute management for a pediatric patient with suspected herpes simplex virus encephalitis?

Acute Management of Pediatric Herpes Simplex Virus Encephalitis

Immediate Empiric Treatment

Start intravenous acyclovir within 6 hours of admission when HSV encephalitis is suspected, even before confirmatory testing or lumbar puncture, because delays beyond 48 hours increase mortality from 8% to 28%. 1

• Do not wait for CSF results, imaging, or brain biopsy to initiate therapy—clinical suspicion alone warrants immediate treatment. 1
• In deteriorating patients, administer acyclovir concurrently with empirical antibiotics for bacterial meningitis. 2
• Continue acyclovir despite normal initial CSF microscopy or neuroimaging if clinical suspicion remains high. 1

Age-Specific Dosing Regimens

Neonates (Birth to 3 Months)

• 20 mg/kg IV every 8 hours for 21 days due to higher mortality and worse outcomes in this age group. 2, 1, 3

Children 3 Months to 12 Years

• 500 mg/m² IV every 8 hours (approximately 20 mg/kg) for a minimum of 21 days. 2, 1, 4
• This age group has the highest relapse rates (26–29%) with shorter courses, making the full 21-day duration mandatory. 2, 4
• Do not perform repeat lumbar puncture before completing 21 days of therapy. 4

Adolescents ≥12 Years

• 10 mg/kg IV every 8 hours for 14–21 days. 2, 1, 4

Diagnostic Work-Up

• Perform lumbar puncture immediately unless contraindicated by focal neurological signs, papilledema, or immunocompromise requiring CT first. 1
• HSV PCR in CSF remains positive for 7–10 days after starting acyclovir, so delayed lumbar puncture can still confirm diagnosis. 2, 1
• MRI is the investigation of choice, revealing characteristic T2/FLAIR hyperintensity in medial temporal lobes, insular cortex, and inferior frontal lobes. 1
• CT scans are frequently normal in encephalitis and should not be used to rule out disease. 1

Critical Pitfalls to Avoid

• Never use oral acyclovir for acute HSV encephalitis—it does not achieve therapeutic CSF concentrations; IV administration is mandatory. 2, 1, 4
• Do not delay lumbar puncture for unnecessary CT scans in patients without focal signs or raised intracranial pressure. 5
• Do not stop acyclovir based on a single negative HSV PCR if obtained <72 hours after symptom onset. 4
• Avoid premature discontinuation before 14–21 days (or 21 days minimum in children 3 months–12 years), as shorter courses lead to 26–29% relapse rates. 2, 4

Treatment Monitoring and Duration

• Obtain repeat lumbar puncture with HSV PCR at 14–21 days to confirm viral clearance. 2, 1, 4
• If CSF PCR remains positive, extend IV acyclovir and repeat PCR weekly until conversion to negative. 2, 1
• For children 3 months–12 years, do not perform repeat LP before completing the minimum 21-day course. 2, 4

Renal Function Management

• Acyclovir is 62–91% renally excreted; dose adjustments are mandatory in renal impairment. 2, 1, 3
• Nephrotoxicity occurs in up to 20% of patients after approximately 4 days of IV therapy, presenting as crystalluria, rising creatinine, or obstructive nephropathy. 2, 1
• Maintain aggressive hydration throughout treatment to prevent crystal nephropathy. 2, 1
• Monitor serum creatinine and urine output regularly during therapy. 2, 1

Intensive Care Considerations

• Any decline in level of consciousness warrants urgent ICU assessment for airway protection, ventilatory support, and intracranial pressure management. 1
• Seizures occur in approximately 38% of HSV encephalitis cases; treat with IV levetiracetam and use EEG monitoring to detect non-convulsive seizures. 1
• Consider corticosteroids in patients with marked cerebral edema, brain shift, or raised intracranial pressure, though their use remains controversial. 1

Acyclovir Resistance and Alternative Therapy

• Suspect 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. 1
• Foscarnet 40 mg/kg IV every 8 hours for 2–3 weeks is the recommended second-line agent for acyclovir-resistant HSV. 2, 1
• Immunocompromised patients may require treatment beyond 21 days if PCR remains positive. 1

Prognosis and Outcomes

• With acyclovir, mortality is 20–30%, compared with approximately 70% in untreated patients. 2, 1, 6
• Initiating therapy within 4 days of symptom onset reduces mortality to 8%. 2, 1
• Patients <30 years of age and those with less severe neurologic involvement at presentation have the best outcomes. 3
• Worse outcomes are linked to advanced age, low Glasgow Coma Scale on admission, and treatment delays >48 hours. 1

Adverse Effects Monitoring

• Reversible nephropathy develops after approximately 4 days in up to 20% of patients; routine creatinine monitoring and aggressive hydration are essential. 2, 1
• Rare but serious adverse events include hepatitis, bone marrow suppression, and acyclovir-induced encephalopathy; vigilance and appropriate dosing mitigate these risks. 2, 1