What is the role of steroids, such as dexamethasone, in the management of Herpes Simplex Virus 1 (HSV1) encephalitis?

Role of Steroids in HSV-1 Encephalitis

Corticosteroids should not be used routinely in patients with HSV-1 encephalitis, as current evidence does not support their standard use and results from definitive randomized controlled trials are still awaited. 1

Current Recommendations on Steroid Use in HSV-1 Encephalitis

• Corticosteroids are not recommended for routine use in HSV-1 encephalitis according to the Association of British Neurologists and British Infection Association guidelines 1
• Aciclovir remains the established first-line antiviral treatment for HSV-1 encephalitis, with proven efficacy in reducing mortality and morbidity 2, 3
• Steroids may have a role in specific circumstances under specialist supervision, particularly in cases with marked cerebral edema, brain shift, or raised intracranial pressure 1

Evidence for Steroid Use in HSV-1 Encephalitis

Potential Benefits

• A retrospective analysis of 45 patients with HSV encephalitis identified that lack of corticosteroid administration was an independent predictor of poor outcome, along with older age and lower Glasgow coma score on admission 1
• Corticosteroids may help reduce brain swelling and inflammatory damage in HSV-1 encephalitis 1

Potential Risks

• Theoretical concern exists that immunosuppression from corticosteroids could facilitate increased viral replication 1
• Experimental studies in animal models have shown that dexamethasone can induce reactivation of latent HSV-1 infections 4, 5
• Immunomodulatory effects of steroids could potentially interfere with viral clearance 1

Ongoing Research

• A randomized controlled trial (DexEnceph) is currently evaluating dexamethasone therapy in adults with HSV encephalitis to determine whether patients who receive dexamethasone alongside standard aciclovir treatment have improved clinical outcomes 6
• The primary outcome being measured is verbal memory, as assessed by the Weschler Memory Scale fourth edition Auditory Memory Index at 26 weeks after randomization 6

Contrast with VZV Encephalitis Management

• For Varicella Zoster Virus (VZV) encephalitis, corticosteroids are more commonly recommended alongside aciclovir, particularly if there is a vasculitic component 1
• A short course of steroids (e.g., 60-80 mg of prednisolone daily for 3-5 days) is often given for VZV encephalitis due to the inflammatory nature of the lesion 1
• This difference in approach highlights the virus-specific considerations in encephalitis management 1

Clinical Decision-Making Algorithm for HSV-1 Encephalitis

1. Initiate intravenous aciclovir (10 mg/kg three times daily) immediately upon suspicion of HSV encephalitis 1, 3
2. Consider corticosteroids only in the following scenarios:
   • Patients with significant cerebral edema, brain shift, or raised intracranial pressure 1
   • Under specialist neurological supervision 1
3. If steroids are deemed necessary, use them cautiously while monitoring for:
   • Signs of increased viral replication 6, 5
   • CSF viral load (if repeat lumbar puncture is performed) 1
4. Continue aciclovir for a full 14-21 day course regardless of steroid use decision 3, 7

Common Pitfalls and Caveats

• Delaying aciclovir treatment while deciding on steroid use can worsen outcomes; aciclovir should always be started promptly 3
• Misinterpreting improvement after steroid use as confirmation of their benefit, when the natural course of the disease or aciclovir effect may be responsible 1, 7
• Assuming that the approach for HSV-1 encephalitis should mirror that of other viral encephalitides (particularly VZV) where steroids have a clearer role 1