What is the recommended treatment for a patient with post-herpes simplex virus (HSV) inflammatory encephalitis?

Post-HSV Inflammatory Encephalitis Treatment

For post-HSV inflammatory encephalitis (relapse or immune-mediated disease after initial treatment), continue or restart intravenous acyclovir and consider adjunctive corticosteroids under specialist supervision, as this represents either ongoing viral replication or immune-mediated injury requiring both antiviral and immunomodulatory approaches. 1

Initial Assessment and Treatment Continuation

Confirm Viral Status

• Perform repeat lumbar puncture with HSV PCR at 14-21 days after initial treatment completion to determine if CSF remains positive for HSV 1
• If HSV PCR remains positive, this indicates ongoing viral replication requiring continued antiviral therapy rather than pure immune-mediated disease 1
• A negative CSF PCR with persistent symptoms suggests post-infectious immune-mediated encephalitis 1

Antiviral Management Based on PCR Results

If CSF HSV PCR is positive:

• Continue intravenous acyclovir 10 mg/kg every 8 hours (adults and children >12 years) 1, 2
• For children 3 months-12 years: 500 mg/m² every 8 hours 1
• Repeat CSF PCR weekly until negative 1, 2
• Treatment duration may extend beyond standard 14-21 days; some patients require 28 days or longer 3, 4

If CSF HSV PCR is negative but symptoms persist:

• This suggests post-infectious inflammatory encephalitis rather than active viral replication 1
• Consider transitioning to immunomodulatory therapy (see below) 5

Immunomodulatory Therapy Considerations

Corticosteroid Use

• Current guidelines recommend AGAINST routine corticosteroid use in HSV encephalitis due to unestablished efficacy and potential to facilitate viral replication 6
• However, corticosteroids may be considered under specialist supervision in select cases with marked cerebral edema or significantly raised intracranial pressure 6
• If corticosteroids are used, they MUST be combined with appropriate antiviral therapy (acyclovir 10 mg/kg IV every 8 hours) 6
• One retrospective study showed worse outcomes in patients NOT treated with corticosteroids, but this requires confirmation in randomized trials 1

Intravenous Immunoglobulin (IVIG)

• IVIG (0.5 g/kg daily for 3 days) has shown promise in case reports of severe HSV encephalitis with immune-mediated injury 5
• Consider IVIG in patients with persistent symptoms despite negative HSV PCR, particularly if autoimmune encephalitis antibodies (e.g., NMDA receptor) develop 5
• This is not guideline-recommended but represents emerging evidence for immune-driven pathology 5

Monitoring During Extended Treatment

Laboratory Monitoring

• Monitor renal function closely, as acyclovir-induced nephropathy occurs in up to 20% of patients 1
• Ensure adequate hydration to prevent crystalluria and obstructive nephropathy 1
• Reduce acyclovir dose in patients with pre-existing renal impairment 1, 7

Neurological Monitoring

• Monitor for signs of deterioration or lack of improvement despite treatment 4
• Consider repeat neuroimaging if clinical status worsens, as hemorrhagic conversion occurs in 2.7% of cases 4
• Seizures occur in 38% of HSV encephalitis cases and require appropriate management 4

Alternative Antiviral Therapy

Acyclovir Resistance

• If patient deteriorates despite acyclovir treatment, consider acyclovir resistance 8
• Switch to foscarnet in cases of suspected or confirmed acyclovir resistance 2, 8
• Foscarnet dosing: 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours 1

Oral Transition

• Oral valaciclovir may be considered after initial IV acyclovir course in select cases with documented viral clearance 1
• One case report demonstrated successful early transition to oral therapy, but this is not standard practice 3

Critical Pitfalls to Avoid

Timing Errors

• Delaying treatment beyond 48 hours after hospital admission significantly worsens prognosis 1, 2
• Mortality increases from 8% (treatment <4 days) to 28% (treatment ≥4 days after symptom onset) 1

Premature Treatment Discontinuation

• Do not stop acyclovir based on a single negative PCR if clinical suspicion remains high 2
• False-negative PCR results occur if CSF sampled <72 hours after symptom onset 2
• Relapse rates reach 5-8% with inadequate treatment duration 1

Inadequate Hydration

• Insufficient hydration during acyclovir therapy increases nephropathy risk 9
• Maintain adequate IV fluids throughout treatment course 1

Specialist Involvement

• All decisions regarding corticosteroid use or extended antiviral therapy should involve specialists experienced in managing HSV encephalitis 6
• Consider infectious disease and neurology consultation for complex cases 6