What is the role of steroids in the treatment of Herpes Simplex Virus (HSV) viral encephalitis?

Steroids in HSV Viral Encephalitis

Corticosteroids should not be used routinely in HSV encephalitis, but may be considered under specialist supervision in patients with marked cerebral edema, brain shift, or raised intracranial pressure who are already receiving appropriate acyclovir therapy. 1, 2

Current Guideline Recommendations

The Infectious Diseases Society of America (IDSA) and Association of British Neurologists explicitly state that adjunctive corticosteroids cannot be recommended as standard practice for HSV encephalitis, as the evidence base remains insufficient. 1 The British guidelines specifically note that while steroids may have a role in specific circumstances, current evidence does not support their routine use. 1, 2

The Evidence Dilemma

Potential Benefits

• One retrospective study of 45 patients found that lack of corticosteroid administration was an independent predictor of poor outcome in HSV encephalitis, alongside older age and lower Glasgow coma score. 1, 2
• Corticosteroids theoretically reduce cerebral edema and inflammatory damage that contributes to morbidity. 2, 3
• Animal model data suggests corticosteroids do not increase viral replication when combined with acyclovir, and may actually decrease infection extent. 3

Potential Risks

• The major theoretical concern is that immunosuppression from steroids could facilitate viral replication and interfere with viral clearance. 1, 2
• Case reports document fatal HSV-1 encephalitis occurring in patients on steroids for other indications (brain radiation, chemotherapy), suggesting steroids may enable viral reactivation in immunosuppressed states. 4

Why Guidelines Remain Cautious

The single retrospective study showing benefit was non-randomized and observational, meaning patients who received steroids may have differed systematically from those who did not. 1 The IDSA guidelines explicitly state these results "need to be confirmed before this adjunctive treatment can be recommended." 1 A prospective randomized controlled trial was initiated across European countries to definitively answer this question, but results are still awaited. 1

Clinical Decision Algorithm

When to Consider Steroids (All criteria should be met):

• Patient is already receiving appropriate dose acyclovir (10 mg/kg IV q8h for adults, 20 mg/kg IV q8h for neonates). 1
• Marked cerebral edema, brain shift, or raised intracranial pressure documented on imaging or clinical assessment. 1, 2
• Specialist neurological supervision is available. 1, 2
• Clinical deterioration despite appropriate antiviral therapy with decreasing CSF viral load. 5, 6

When NOT to Use Steroids:

• As routine therapy in all HSV encephalitis patients. 1, 2
• Before initiating acyclovir or in absence of antiviral coverage. 3, 6
• Early in disease course when viral replication is the primary mechanism of damage. 6

Timing Considerations

A systematic review suggests that timing is critical: early steroid administration might be harmful because initial damage is mediated by viral replication, whereas later administration may benefit by inhibiting the subsequent inflammatory response. 6 CSF inflammatory markers might guide appropriate timing in future clinical practice. 6

Important Distinction: VZV vs HSV

Do not confuse HSV encephalitis management with VZV encephalitis, where corticosteroids are more commonly recommended alongside acyclovir, particularly when there is a vasculitic component. 1, 2 For VZV encephalitis, a short course of steroids (60-80 mg prednisolone daily for 3-5 days) is often given due to the inflammatory nature of the lesion. 1, 2 This difference reflects virus-specific pathogenic mechanisms. 2

Critical Pitfalls to Avoid

• Do not delay acyclovir initiation while debating steroid use—acyclovir remains the only proven life-saving therapy, and early initiation (within 4 days of symptom onset) reduces mortality from 28% to 8%. 1
• Do not assume improvement after steroid use confirms their benefit, as the natural course or acyclovir effect may be responsible. 2
• Do not use steroids in isolation without concurrent acyclovir therapy, as this could theoretically worsen outcomes by enhancing viral replication. 3, 6
• Monitor for signs of increased viral replication if steroids are used, ideally with repeat CSF PCR if clinical response is inadequate. 1, 2