What is the management approach for encephalitis?

Management of Encephalitis

Start intravenous acyclovir immediately—within 6 hours of admission—at 10 mg/kg every 8 hours for all patients with suspected encephalitis, even before diagnostic confirmation, as this reduces mortality from 70% to 8-30%. 1, 2

Initial Emergency Management

Immediate Actions

• Initiate acyclovir empirically as soon as encephalitis is suspected, without waiting for lumbar puncture or diagnostic test results 1, 2, 3
• Ensure urgent neurological specialist assessment within 24 hours of presentation 1
• Assess for airway protection needs—patients with declining consciousness require immediate ICU evaluation for intubation, ventilatory support, and management of raised intracranial pressure 1

Critical Diagnostic Workup (Performed Concurrently with Treatment)

• Lumbar puncture for CSF opening pressure, glucose (with paired serum glucose), protein, cell count, microbiology culture, and viral PCR (especially HSV, VZV, CMV, EBV) 1
• CSF PCR results must be available within 24-48 hours 1
• MRI brain is preferred over CT; arrange under general anesthesia if needed 1
• EEG to assess for seizure activity and characteristic patterns 1
• Consider metabolic, toxic, and autoimmune causes early in the differential 1

Pathogen-Specific Treatment Regimens

Herpes Simplex Virus (HSV) Encephalitis

• Adults and adolescents ≥12 years: Acyclovir 10 mg/kg IV every 8 hours for 14-21 days 2, 3
• Children 3 months to 12 years: Acyclovir 20 mg/kg IV every 8 hours for 10 days 3
• Neonates (birth to 3 months): Acyclovir 20 mg/kg IV every 8 hours for 10 days (higher dose than older children) 2, 3
• Low-weight adults (<79 kg): Consider minimum dosage of 2550 mg/day (850 mg every 8 hours) when renal function permits, as lower doses correlate with worse outcomes 4
• Infuse each dose over 1 hour at concentrations ≤7 mg/mL to prevent phlebitis 3
• Consider repeat lumbar puncture at end of treatment to confirm CSF HSV PCR negativity 1, 2

Varicella Zoster Virus (VZV) Encephalitis

• Adults and adolescents ≥12 years: Acyclovir 10-15 mg/kg IV every 8 hours for 7 days 5, 1
• Children <12 years: Acyclovir 20 mg/kg IV every 8 hours for 7 days 3
• Consider short course of corticosteroids as adjunct therapy 1

Cytomegalovirus (CMV) Encephalitis

• Combination therapy: Ganciclovir 5 mg/kg IV every 12 hours PLUS foscarnet 60 mg/kg IV every 8 hours (or 90 mg/kg every 12 hours) for 3 weeks 1, 2
• This combination shows improvement or stabilization in 74% of patients 2
• Acyclovir is NOT effective for CMV 2

Epstein-Barr Virus (EBV) Encephalitis

• Acyclovir has limited benefit and is NOT recommended for EBV encephalitis 2, 6
• Corticosteroids (e.g., prednisolone 60-80 mg daily for 3-5 days) may be beneficial for the inflammatory component 6
• Immunocompromised patients: Consider rituximab 375 mg/m² weekly until EBV DNA negativity (typically 1-4 doses) with reduction of immunosuppression 6

Toxoplasma gondii

• Pyrimethamine plus sulfadiazine OR clindamycin 5
• Alternative: Trimethoprim-sulfamethoxazole alone 5

Parasitic Encephalitis

• Baylisascaris procyonis: Albendazole plus diethylcarbamazine; add corticosteroids 5
• Gnathostoma species: Albendazole OR ivermectin 5
• Taenia solium (neurocysticercosis): Albendazole plus corticosteroids; praziquantel is alternative 5

Acute Disseminated Encephalomyelitis (ADEM)

• High-dose corticosteroids are first-line 5
• Alternatives: Plasma exchange OR intravenous immunoglobulin 5

Dose Adjustments for Special Populations

Renal Impairment

• CrCl >50 mL/min: 100% dose every 8 hours 3
• CrCl 25-50 mL/min: 100% dose every 12 hours 3
• CrCl 10-25 mL/min: 100% dose every 24 hours 3
• CrCl 0-10 mL/min: 50% dose every 24 hours 3
• Hemodialysis: Administer additional dose after each dialysis session 3

Obese Patients

• Dose acyclovir using ideal body weight, not actual body weight 3

Immunocompromised Patients

• May require longer treatment courses and closer monitoring 1, 2
• Broader differential diagnosis—test for CMV, HHV-6/7, toxoplasmosis, cryptococcus 6

Critical Monitoring During Treatment

Renal Function

• Monitor creatinine and BUN throughout treatment—acyclovir-induced nephropathy occurs in up to 20% of patients, typically after 4 days of IV therapy 1, 2
• Ensure adequate hydration (60-150 mL fluid per dose in average 70 kg adult) to prevent crystalluria 3
• Reduce dose immediately if renal function deteriorates 2, 3

Neurological Status

• Daily assessment of consciousness level, focal deficits, and seizure activity 1
• Persistence of confusion, aphasia, or impaired consciousness beyond 5 days predicts poor outcome 4

Seizure Management

• Treat seizures appropriately with antiepileptic medications 6
• Monitor for status epilepticus, which correlates with worse outcomes 4

Common Pitfalls to Avoid

• Delaying acyclovir beyond 48 hours after admission significantly worsens outcomes—treatment delay >4 days after symptom onset is a major predictor of poor prognosis 1, 2, 4
• Inadequate hydration during acyclovir treatment increases nephropathy risk—ensure proper fluid administration 2, 3
• Using acyclovir for EBV encephalitis—it is ineffective and delays appropriate immunomodulatory therapy 2, 6
• Rapid or bolus IV injection of acyclovir—must infuse over 1 hour to prevent toxicity 3
• Intramuscular or subcutaneous injection—acyclovir must only be given intravenously 3
• Concentrations >10 mg/mL—may cause phlebitis or inflammation at injection site 3
• Missing bacterial meningitis—encephalitis and meningitis share clinical features; consider both diagnoses and add appropriate antibacterial coverage if bacterial infection cannot be excluded 5

Prognostic Factors

Poor outcomes are associated with: 4

• Age >30 years
• Glasgow Coma Score <6
• Treatment delay >4 days after symptom onset
• Prolonged confusion/aphasia/impaired consciousness (>5 days)
• Status epilepticus
• Superinfection
• Prolonged ICU stay