What is the treatment for necrotizing encephalitis?

Treatment of Necrotizing Encephalitis

Immediate empiric treatment with intravenous acyclovir 10 mg/kg every 8 hours should be initiated for suspected necrotizing encephalitis, as herpes simplex virus (HSV) is the most common treatable cause and delays in treatment significantly worsen mortality and morbidity. 1

Immediate Management and Critical Care

Airway protection and intensive care assessment are paramount:

• Patients with falling level of consciousness require urgent ICU assessment for airway protection, ventilatory support, management of raised intracranial pressure, optimization of cerebral perfusion pressure, and correction of electrolyte imbalances 1
• Transfer to a neurological unit with immediate specialist opinion should occur within 24 hours if diagnosis is unclear or patient fails to improve 1
• Access to neuroimaging (MRI preferred, CT if unavailable) and EEG should be available, under general anesthesia if needed 1

Antiviral Therapy

HSV and VZV encephalitis:

• Acyclovir 10 mg/kg IV every 8 hours for 14-21 days is the standard treatment 1, 2
• Some experts recommend 15 mg/kg three times daily for VZV given its lower sensitivity to acyclovir, though most clinicians use 10 mg/kg due to renal toxicity concerns 1
• Dose adjustment is mandatory in renal impairment: monitor creatinine clearance frequently 1, 2
• In immunocompromised patients, prolonged courses may be necessary 1

Influenza-associated ANE:

• High-dose oseltamivir (150 mg twice daily) combined with methylprednisolone has shown success in case reports, particularly when continued for extended duration (2+ weeks) 3
• Standard oseltamivir dosing may be insufficient; relapse has been documented after premature discontinuation 3

Immunomodulatory Therapy

Corticosteroids:

• A short course of corticosteroids (60-80 mg prednisolone daily for 3-5 days, or equivalent methylprednisolone) is recommended for VZV encephalitis due to its inflammatory nature 1
• For acute necrotizing encephalopathy (ANE), high-dose methylprednisolone is standard, though optimal dosing remains unclear 4, 3
• Retrospective data suggest corticosteroid use in HSV encephalitis may improve outcomes, though a definitive RCT is ongoing 1

Novel immunotherapy for severe ANE:

• Tocilizumab (IL-6 receptor blockade) administered within the first 24 hours as add-on therapy shows promising long-term outcomes in high-risk ANE patients 4
• Early administration (within 22 hours) resulted in modified Rankin Scale of 3 at 2 years versus delayed administration (53 hours) resulting in mRS of 5 4
• Consider in patients with high ANE severity scores, particularly with brainstem involvement 4

Intravenous immunoglobulin:

• May be beneficial in severe enterovirus 71 infection and chronic enterovirus meningitis, though no randomized trials exist 1
• Can be considered as adjunctive therapy in severe cases 1

Etiology-Specific Considerations

Enterovirus encephalitis:

• No specific treatment is recommended; pleconaril (if available) or IVIG may be considered in severe disease 1
• Pleconaril has broad enterovirus activity but is not widely available and lacks trial data for encephalitis 1

Toxoplasma gondii (in immunocompromised):

• Pyrimethamine plus sulfadiazine or clindamycin is first-line 1
• Trimethoprim-sulfamethoxazole is an alternative 1

Diagnostic Workup Priorities

Essential investigations:

• CSF PCR results should be available within 24-48 hours of lumbar puncture 1
• Blood cultures and respiratory specimens before antimicrobial therapy 1
• MRI brain with contrast is superior to CT for identifying necrotizing changes 1
• Gram stain and culture of CSF to guide therapy 1

Common Pitfalls and Caveats

Critical errors to avoid:

• Delaying acyclovir while awaiting diagnostic confirmation—empiric treatment must begin immediately upon clinical suspicion 1
• Inadequate renal function monitoring with acyclovir, leading to nephrotoxicity and neurotoxicity 1, 2
• Premature discontinuation of antiviral therapy before completing 14-21 day course 1
• Missing the narrow window for tocilizumab in severe ANE—administration beyond 24 hours may be less effective 4
• Failing to recognize that normal CSF and chest X-ray do not exclude viral encephalitis, particularly COVID-19-associated ANE 5

Special populations:

• Geriatric patients require dose reduction due to age-related renal decline 2
• Neonates and infants have different pharmacokinetics; dosing should follow pediatric guidelines 2
• Immunocompromised patients may require prolonged therapy and consideration of resistant organisms 1

Prognostic factors:

• Younger age (<30 years) and less severe neurologic involvement at presentation predict better outcomes with acyclovir in HSV encephalitis 2
• Brainstem involvement in ANE portends worse prognosis even with optimal therapy 4, 6
• Early steroid treatment provides best outcomes in ANE patients without brainstem lesions 6