Is Amantadine (an antiviral and antiparkinsonian medication) recommended as a treatment for viral encephalitis caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV)?

Amantadine is NOT Recommended for Viral Encephalitis

Amantadine has no role in the treatment of herpes simplex virus (HSV) or varicella-zoster virus (VZV) encephalitis and should never be used for these conditions. Acyclovir is the definitive treatment for both HSV and VZV central nervous system infections 1, 2.

Why Amantadine is Inappropriate

• Amantadine is only active against influenza A virus, not herpesviruses 3, 4
• The drug has no demonstrated efficacy against HSV or VZV in any clinical context 3, 5
• Using amantadine for HSV or VZV encephalitis would delay appropriate acyclovir therapy, which is directly associated with worse outcomes 2

Correct Treatment for HSV Encephalitis

Intravenous acyclovir is the only appropriate antiviral treatment for HSV encephalitis 1, 6, 4:

• Dosing: 10 mg/kg IV every 8 hours for patients aged 3 months-12 years, or 10-15 mg/kg IV three times daily for those >12 years 1
• Duration: Typically 14-21 days 7
• Timing is critical: Acyclovir administered within 48 hours of presentation significantly reduces adverse clinical outcomes [OR 0.19, P=0.02] 2

Corticosteroid Considerations for HSV

• Corticosteroids should NOT be used routinely in HSV encephalitis 1, 8
• They may be considered under specialist supervision only for marked cerebral edema, brain shift, or raised intracranial pressure 1, 8
• The theoretical risk is that immunosuppression could facilitate viral replication 1, 8

Correct Treatment for VZV Encephalitis

Intravenous acyclovir at higher doses is recommended for VZV encephalitis 1, 7:

• Dosing: 10-15 mg/kg IV three times daily (VZV is less sensitive to acyclovir than HSV) 1, 7
• Duration: 14-21 days 7
• Renal adjustment: In end-stage renal disease, reduce to 5-7.5 mg/kg every 24 hours or after each dialysis session 7

Corticosteroid Use in VZV

• Corticosteroids ARE recommended if there is vasculopathy or stroke-like presentation 1, 8, 7
• Typical regimen: Prednisolone 60-80 mg daily for 3-5 days due to the inflammatory nature of the vascular lesion 1, 7
• This differs from HSV encephalitis management, where steroids are generally avoided 8

Critical Distinction: VZV Cerebellitis

• No antiviral treatment is needed for VZV cerebellitis 1, 9
• The condition is self-limiting (resolves in 1-3 weeks) and the pathogenesis is immune-mediated demyelination, not direct viral cytopathology 1, 9
• Initiating acyclovir for isolated cerebellitis wastes resources and exposes patients to unnecessary renal toxicity 9

Common Pitfalls to Avoid

• Never use amantadine for herpesvirus infections - it has zero activity against these pathogens 3, 4, 5
• Do not delay acyclovir while awaiting confirmatory testing - early treatment (within 48 hours) is associated with better outcomes 2
• Do not confuse VZV cerebellitis with VZV encephalitis - the former requires no antiviral treatment, while the latter requires high-dose IV acyclovir 1, 9
• Do not assume HSV and VZV encephalitis have identical steroid protocols - VZV with vasculopathy benefits from steroids, while HSV encephalitis generally does not 1, 8, 7