What is the role of steroids, such as prednisolone, in the treatment of a patient with post-herpes simplex virus (HSV) inflammatory encephalitis?

Steroids for Post-HSV Inflammatory Encephalitis

Corticosteroids should not be used routinely in post-HSV inflammatory encephalitis, but may be considered under specialist neurological supervision in specific circumstances, particularly when there is marked cerebral edema, brain shift, or raised intracranial pressure. 1, 2

Current Guideline Recommendations

The Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group explicitly state that while awaiting results of randomized controlled trials, corticosteroids should not be used routinely in patients with HSV encephalitis. 1, 2 However, they acknowledge that corticosteroids may have a role under specialist supervision, though definitive data are still needed. 1, 2

When to Consider Steroids in Post-HSV Encephalitis

Specific Clinical Scenarios Where Steroids May Be Beneficial:

• Marked cerebral edema with mass effect: When imaging demonstrates significant brain swelling causing midline shift or herniation risk 1, 2
• Raised intracranial pressure: Clinical signs include deteriorating consciousness, papilledema, or ICP monitoring showing elevated pressures 1, 2
• Brain shift on imaging: CT or MRI showing displacement of brain structures 1, 2

Dosing When Steroids Are Used:

If steroids are deemed necessary, a typical regimen is prednisolone 60-80 mg daily for 3-5 days (extrapolated from VZV encephalitis protocols where steroids have clearer evidence). 1

Evidence Supporting Cautious Use

Potential Benefits:

• A retrospective analysis of 45 patients identified that lack of corticosteroid administration was an independent predictor of poor outcome in HSV encephalitis, along with older age and lower Glasgow coma score. 1, 2
• A small pediatric case series showed better cognitive function, motor function, and seizure control in children who received early steroid therapy, though radiologic sequelae were similar in both groups. 3
• Animal model data demonstrate that dexamethasone does not increase viral replication or dissemination when combined with acyclovir, and may actually reduce viral load. 4

Theoretical Concerns:

• Corticosteroids have strong immunomodulatory effects that could theoretically facilitate viral replication. 1, 2
• The immunosuppressive properties might interfere with viral clearance mechanisms. 2

Current State of Evidence

A 2023 systematic review and meta-analysis of 50 studies (including 281 patients with various viral encephalitides) found that the pooled data could not demonstrate a survival benefit from steroid treatment (p = 0.245). 5 However, this analysis was limited by heterogeneous study designs and patient outcomes. 5

An ongoing randomized controlled trial (DexEnceph) is specifically evaluating dexamethasone in adults with HSV encephalitis, measuring verbal memory outcomes at 26 weeks, with safety monitoring including CSF HSV DNA detection at 2 weeks to assess for ongoing viral replication. 6

Critical Distinction: HSV vs. VZV Encephalitis

Do not extrapolate VZV encephalitis management to HSV encephalitis. 2, 7 For VZV encephalitis with vasculopathy (stroke-like presentation), both aciclovir and corticosteroids are routinely recommended. 1 This approach does not apply to HSV encephalitis, where the evidence base is different. 2

Clinical Decision Algorithm

1. Confirm HSV encephalitis diagnosis with positive CSF PCR and ensure patient is on appropriate acyclovir therapy (10 mg/kg IV three times daily). 1

2. Assess for life-threatening complications:

   • Obtain neuroimaging to evaluate for cerebral edema, mass effect, or brain shift 1, 2
   • Monitor level of consciousness using Glasgow Coma Scale 1, 2
   • Look for signs of raised intracranial pressure 1, 2

3. If marked cerebral edema, brain shift, or raised ICP present: Consider corticosteroids under specialist neurological supervision with close monitoring for signs of increased viral replication. 1, 2

4. If no life-threatening complications: Continue aciclovir alone without routine corticosteroid therapy. 1, 2

Common Pitfalls to Avoid

• Assuming improvement after steroids confirms their benefit: The natural disease course or aciclovir effect may be responsible for clinical improvement, not the steroids. 2
• Applying VZV encephalitis protocols to HSV: These are distinct conditions with different evidence bases for steroid use. 2, 7
• Using steroids routinely without specialist input: This should only occur under neurological specialist supervision with careful monitoring. 1, 2
• Failing to monitor for increased viral replication: If repeat lumbar puncture is performed, check CSF viral load to ensure steroids are not facilitating viral persistence. 2, 6