What is the recommended treatment for viral encephalitis, particularly when caused by herpes simplex virus (HSV)?

Treatment of Viral Encephalitis

Intravenous acyclovir 10 mg/kg every 8 hours should be initiated immediately when viral encephalitis is suspected, ideally within 6 hours of admission, without waiting for diagnostic confirmation, as this reduces mortality from 70% to 20-30%. 1, 2

Immediate Initiation of Treatment

Start acyclovir empirically if:

• Initial CSF findings suggest viral encephalitis (lymphocytic pleocytosis, elevated protein) 1
• Brain imaging shows temporal lobe involvement 1
• The patient is severely ill or deteriorating, even if initial CSF/imaging is normal 1, 2
• Diagnostic results will not be available within 6 hours 1

Critical timing consideration: Delays beyond 48 hours after hospital admission significantly worsen outcomes, with mortality increasing substantially in patients treated late. 1, 2 Early treatment within 4 days of symptom onset reduces mortality from 28% to 8%. 3

Dosing Regimens

Adults and Children >12 Years

• Standard dose: 10 mg/kg IV every 8 hours 1, 4, 5
• Reduce dose in pre-existing renal impairment 1, 2

Children 3 Months to 12 Years

• Standard dose: 500 mg/m² IV every 8 hours 1
• Minimum treatment duration of 21 days before considering repeat lumbar puncture 1

Neonates

• Higher dose required: 20 mg/kg IV every 8 hours, which has reduced mortality to 5% 2, 3, 4

Treatment Duration and Monitoring

Continue IV acyclovir for 14-21 days in confirmed HSV encephalitis. 1, 2, 6

Perform repeat lumbar puncture at completion of treatment:

• Confirm CSF is negative for HSV by PCR 1, 2
• If CSF remains PCR-positive, continue IV acyclovir with weekly PCR testing until negative 1
• In children 3-12 years, give minimum 21 days before repeat LP 1

The rationale for extended duration: Original 10-day trials showed relapse rates of 26-29% in children, particularly with treatment <14 days, due to ongoing viral replication in some cases. 1

Safety Monitoring

Monitor renal function throughout treatment:

• Acyclovir-induced crystalluria and obstructive nephropathy can affect up to 20% of patients 1, 2
• Typically manifests after 4 days of IV therapy 1, 2
• Maintain adequate hydration to reduce nephropathy risk 1, 2
• Adjust dose in renal impairment as acyclovir is renally excreted 1, 2

Other rare adverse events include: hepatitis, bone marrow failure, and encephalopathy. 1

Prognostic Factors

Poor outcome predictors in HSV encephalitis:

• Age >30 years 2, 3
• Glasgow Coma Score <6 1, 2
• Treatment delay >4 days after symptom onset 2, 3
• Delay >48 hours between hospital admission and treatment initiation 1

When to Perform Lumbar Puncture Before Treatment

In patients with only mild confusion and encephalopathy, perform LP before starting acyclovir to establish diagnosis and avoid premature closure of the diagnostic pathway. 1 This differs from meningococcal septicemia where minutes matter; HSV encephalitis allows time for diagnostic workup in stable patients. 1

However, do not delay treatment for LP if:

• Strong clinical suspicion exists with potential LP delays 1
• Patient is rapidly deteriorating 1
• Patient is very unwell 1

Important note: CSF PCR typically remains positive for 7-10 days after starting acyclovir, so delayed LP can still confirm diagnosis. 1

Pathogen-Specific Considerations

Varicella-Zoster Virus (VZV)

• Same acyclovir dosing as HSV (10 mg/kg IV every 8 hours) 4
• May be combined with corticosteroids 7

Cytomegalovirus (CMV)

• Different treatment required: Combination ganciclovir (5 mg/kg IV every 12h) plus foscarnet (60 mg/kg IV every 8h or 90 mg/kg IV every 12h) for 3 weeks 2, 7
• This combination shows improvement/stabilization in 74% of patients 2

Epstein-Barr Virus (EBV)

• Acyclovir has limited benefit and is not routinely recommended 2, 7, 3
• Consider corticosteroids in selected patients with EBV neurologic complications 2

Critical Pitfalls to Avoid

Do not use empirical antivirals indiscriminately for all encephalopathy without diagnostic consideration - this leads to false reassurance and missed alternative diagnoses requiring different treatments. 1, 2

Do not use topical acyclovir - it is substantially less effective than IV therapy and is not recommended. 3

Do not stop treatment prematurely - relapse rates increase significantly with courses <14 days, and relapse can occur in up to 5% of cases even after appropriate treatment. 1, 3

Ensure adequate hydration during treatment - inadequate hydration significantly increases nephropathy risk. 2, 7

Special Populations

Immunocompromised patients require:

• Longer treatment courses 2, 3
• Closer monitoring 2, 3
• Higher vigilance for treatment failure 1

Notify appropriate public health authorities of suspected infectious encephalitis cases. 1