What is the treatment for acute necrotizing encephalitis?

Treatment of Acute Necrotizing Encephalitis

Initiate intravenous acyclovir 10 mg/kg every 8 hours immediately upon suspicion of acute necrotizing encephalitis, even while awaiting diagnostic confirmation, as early treatment within 48 hours dramatically reduces mortality from 70% to 8-30%. 1, 2

Immediate Antimicrobial Therapy

Start empiric acyclovir within 6 hours of hospital admission for all patients with suspected acute necrotizing encephalitis, as treatment delay beyond 48 hours significantly worsens outcomes and increases mortality. 1, 2

Dosing Regimens by Age:

• Adults and children ≥12 years with normal renal function: Acyclovir 10 mg/kg IV every 8 hours 3, 1, 2
• Children 3 months to 12 years: Acyclovir 10 mg/kg IV every 8 hours 3
• Neonates: Higher-dose acyclovir 20 mg/kg IV every 8 hours, which has reduced mortality to 5% 2
• Patients with renal impairment: Reduce dose and monitor renal function closely to prevent crystalluria and obstructive nephropathy 3, 2

Treatment Duration:

• Continue IV acyclovir for 14-21 days in confirmed cases 1, 2
• Consider repeat lumbar puncture at end of treatment to confirm CSF negativity by PCR 1, 2

Pathogen-Specific Considerations

While HSV is the primary target of empiric therapy, acute necrotizing encephalitis can be caused by multiple viral pathogens requiring different approaches:

Human Herpesvirus-6 (HHV-6):

• High-dose ganciclovir 18 mg/kg/day should be considered for HHV-6-associated acute necrotizing encephalitis, particularly in severe cases with multiple necrotic lesions 4
• This is especially important as HHV-6 can cause acute necrotizing encephalopathy with severe neurologic sequelae including epilepsy and ataxia 4

Cytomegalovirus (CMV):

• Combination therapy with ganciclovir (5 mg/kg IV every 12 hours) plus foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) for 3 weeks 1, 2
• This combination shows improvement or stabilization in 74% of CMV encephalitis patients 2

Varicella Zoster Virus (VZV):

• Acyclovir 10-15 mg/kg IV every 8 hours for 7-14 days 3, 1
• Because VZV is less sensitive to acyclovir than HSV, the higher dose (15 mg/kg) should be used if renal function is normal 3

Adjunctive Corticosteroid Therapy

Consider corticosteroids (prednisolone 60-80 mg daily for 3-5 days) in specific scenarios:

• VZV-associated vasculopathy presenting with stroke-like episodes 3
• Inflammatory lesions with significant edema 3
• However, corticosteroids are not routinely recommended for acute viral encephalitis as evidence remains controversial and they may facilitate viral replication 5, 6

Critical Care Management

Patients with declining consciousness require immediate ICU assessment for: 3, 1

• Airway protection and ventilatory support
• Management of raised intracranial pressure
• Optimization of cerebral perfusion pressure
• Correction of electrolyte imbalances

Essential Monitoring

Monitor renal function throughout acyclovir treatment, as acyclovir-induced nephropathy affects up to 20% of patients, typically after 4 days of IV therapy. 1, 2

Ensure adequate hydration during acyclovir administration to prevent crystalluria and nephropathy. 2

Diagnostic Workup (Concurrent with Treatment)

• Urgent MRI brain to identify characteristic bilateral thalamic lesions and other necrotic areas 1
• CSF analysis with PCR for HSV, VZV, enterovirus, and other viral pathogens; results should be available within 24-48 hours 3, 1
• EEG monitoring for seizure activity 1

Critical Pitfalls to Avoid

• Never delay acyclovir beyond 48 hours waiting for diagnostic confirmation—this is the single most important factor affecting mortality 1, 2
• Do not withhold treatment based on normal CSF findings, as acute necrotizing encephalitis can present with normal CSF early in disease course 7
• Inadequate hydration during acyclovir therapy dramatically increases nephropathy risk 1, 2
• Missing bacterial meningitis: Add appropriate antibacterial coverage (ceftriaxone plus vancomycin) if bacterial infection cannot be excluded 1

Transfer Criteria

Transfer to specialized neuroscience unit within 24 hours if: 3, 1

• Diagnosis not rapidly established
• Patient fails to improve with therapy
• Need for advanced neuroimaging or neurosurgical intervention