What is the treatment approach for zoster (varicella-zoster virus) encephalitis?

Treatment of Varicella-Zoster Virus (VZV) Encephalitis

For VZV encephalitis, intravenous aciclovir at a dose of 10-15 mg/kg three times daily for 14-21 days is the recommended treatment, with consideration of adjunctive corticosteroids if there is evidence of vasculopathy. 1

Pathophysiology of VZV Encephalitis

VZV encephalitis can occur through three primary mechanisms:

1. Primary VZV infection - Direct viral invasion of the CNS during primary varicella (chickenpox)
2. VZV reactivation - Reactivation of latent virus in cranial nerve or dorsal root ganglia (as in herpes zoster/shingles)
3. VZV vasculopathy - Virus-induced inflammation of cerebral blood vessels leading to stroke-like presentations

The virus typically reaches the CNS either through direct neural spread or hematogenous dissemination, causing inflammation of brain parenchyma.

Diagnostic Approach

• CSF analysis - Typically shows pleocytosis (elevated white blood cells) 2
• PCR testing - Detection of VZV DNA in CSF is the gold standard diagnostic test 2, 3
• Neuroimaging - MRI may show:
  • Encephalitic changes (especially in brainstem and deep brain structures)
  • Evidence of vasculitis, infarction, or hemorrhage in 16% of cases 2

Treatment Algorithm

First-line Treatment:

• Intravenous aciclovir:
  • Adults and children >12 years: 10-15 mg/kg IV every 8 hours 1
  • Children 3 months-12 years: 10-15 mg/kg IV every 8 hours 1
  • Treatment duration: 14-21 days 1

Dosage Considerations:

• Higher dose (15 mg/kg) is often preferred for VZV encephalitis because VZV is less sensitive to aciclovir than HSV 1, 4
• Dose adjustment required for patients with renal impairment 1
• Maintain adequate hydration and monitor renal function 4

Adjunctive Therapy:

• Corticosteroids:
  • Recommended when vasculopathy/stroke is present 1
  • Typical regimen: Prednisolone 60-80 mg daily for 3-5 days 1
  • Not routinely recommended without evidence of vasculitis 1

Special Populations:

• Immunocompromised patients:
  • May require prolonged courses of IV aciclovir 1
  • More likely to present with cutaneous lesions (100% in one study) 3

Treatment Failure:

• If clinical deterioration occurs despite aciclovir treatment, consider:
  • Aciclovir resistance (rare but documented) 5
  • Alternative antiviral therapy such as vidarabine may be effective in aciclovir-resistant cases 5
  • Transfer to a specialist neurological unit 1

Monitoring and Follow-up

• Regular monitoring of renal function throughout treatment 1
• Follow-up CSF examination may be useful to document viral clearance
• Monitor for neurological improvement or deterioration

Prognosis

• Risk factors for unfavorable outcomes include:
  • Advanced age
  • Presence of cerebral vasculitis
  • Decreased level of consciousness (Glasgow Coma Scale <15) 2
• Mortality rates:
  • In-hospital: 4%
  • 1-month: 9%
  • 3-month: 11% 2
• Unfavorable outcome (Glasgow Outcome Score 1-4) in 69% of patients at discharge 2

Important Clinical Considerations

• Treatment should be initiated promptly upon suspicion of VZV encephalitis, as early treatment improves outcomes
• VZV encephalitis primarily affects elderly and immunocompromised patients 2, 3
• Diagnosis is often delayed, with median time to treatment of 13.4 hours after admission 2
• Absence of cutaneous lesions does not rule out VZV encephalitis, especially in immunocompetent patients 3

VZV encephalitis is likely underdiagnosed and has a higher incidence than previously estimated (5.3/1,000 per year) 2. Prompt recognition and treatment are essential to improve outcomes in this serious neurological condition.