What is the treatment approach for a patient presenting with fever and hallucinations, suspected of having herpes simplex encephalitis?

Treatment of Fever with Hallucinations Suspected as Herpes Simplex Encephalitis

Start intravenous acyclovir 10 mg/kg every 8 hours immediately—within 6 hours of admission—without waiting for CSF or imaging results if the patient presents with fever and hallucinations concerning for viral encephalitis. 1, 2

Immediate Management Algorithm

Empiric Antiviral Therapy

• Initiate IV acyclovir 10 mg/kg every 8 hours (30 mg/kg/day total) as soon as HSV encephalitis is suspected 1, 2
• Do not delay treatment waiting for diagnostic confirmation—acyclovir reduces mortality from >70% to 20-30% in HSV encephalitis, and delays beyond 48 hours significantly worsen outcomes 1, 3
• Treatment must begin within 6 hours of admission if CSF/imaging results are unavailable or if the patient is severely ill or deteriorating 1, 2
• CSF remains PCR-positive for several days after starting acyclovir, so delayed lumbar puncture can still confirm diagnosis 1, 2

Concurrent Bacterial Coverage

• Add empiric antibiotics for bacterial meningitis if there is any diagnostic uncertainty, as recommended by British Infection Association guidelines 1
• The differential diagnosis for fever with hallucinations is broad, and bacterial meningitis must not be missed 1

Dose Adjustments

• Reduce acyclovir dose in patients with pre-existing renal impairment to prevent crystalluria and obstructive nephropathy, which affects up to 20% of patients after 4 days of IV therapy 1, 2
• Monitor renal function closely throughout treatment 2

Diagnostic Workup (Performed Concurrently, Not Delaying Treatment)

Lumbar Puncture

• Perform LP as soon as possible unless contraindicated by signs of increased intracranial pressure 2
• CSF PCR for HSV should be available within 24-48 hours 2
• Initial CSF PCR can be negative if performed <72 hours after symptom onset—do not stop acyclovir based on a single negative PCR if clinical suspicion remains high 1, 4

Neuroimaging

• MRI is preferred over CT for detecting temporal lobe abnormalities characteristic of HSV encephalitis 2
• Brain biopsy has no role in initial assessment but may be considered after the first week if no diagnosis is established, especially with focal imaging abnormalities 1

Duration of Treatment

For Confirmed HSV Encephalitis

• Continue IV acyclovir for 14-21 days 1, 2, 4
• Perform repeat LP at completion of treatment to confirm CSF is HSV PCR-negative 1, 2
• If CSF remains positive, continue acyclovir with weekly PCR monitoring until negative 1, 2

When to Stop Empiric Acyclovir

Acyclovir can be safely discontinued if: 1

• An alternative diagnosis has been established, OR
• HSV PCR is negative on two occasions 24-48 hours apart AND MRI (performed >72 hours after symptom onset) is not characteristic for HSV encephalitis, OR
• HSV PCR is negative once >72 hours after neurological symptom onset WITH normal consciousness, normal MRI (>72 hours after onset), AND CSF white cell count <5×10⁶/L 1

Corticosteroid Considerations

HSV Encephalitis

• Do not use corticosteroids routinely in HSV encephalitis while awaiting results of ongoing randomized controlled trials 1, 5
• Exception: Consider steroids only under specialist supervision for marked cerebral edema, brain shift, or raised intracranial pressure 1, 5
• Theoretical concern exists that immunosuppression could facilitate viral replication 1, 5

VZV Encephalitis (If Diagnosed)

• Add corticosteroids (prednisolone 60-80 mg daily for 3-5 days) for VZV encephalitis, particularly if vasculitic component or stroke-like presentation is present 1, 2, 5
• Use acyclovir 10-15 mg/kg three times daily for VZV encephalitis 1, 2

Critical Care Requirements

Immediate Hospitalization Needs

• Patients require access to intensive care units for potential airway protection, ventilatory support, and management of increased intracranial pressure 2
• Falling level of consciousness demands urgent ICU evaluation 2
• EEG monitoring is essential to identify non-convulsive seizures in confused or comatose patients 2

Multidisciplinary Involvement

• Engage neurology, infectious disease, virology, neurophysiology, neuroradiology, and intensive care teams 2
• Transfer to specialized neurology service within 24 hours if diagnosis is not rapidly established or patient fails to improve 2

Common Pitfalls to Avoid

• Never delay acyclovir waiting for PCR confirmation—early treatment (within 48 hours) is critical for reducing mortality and morbidity 1, 2, 3
• Do not stop acyclovir based on a single negative CSF PCR if obtained <72 hours after symptom onset or if clinical suspicion remains high 1, 4
• Do not assume improvement after steroid use confirms their benefit in HSV encephalitis—the natural course or acyclovir effect may be responsible 5
• Do not discharge without a definitive or suspected diagnosis 2
• Empirical use of antimicrobials without diagnostic workup can prematurely halt the diagnostic pathway and delay identification of alternative treatable etiologies 1