What is the initial management approach for a patient presenting with suspected encephalitis, considering demographics, medical history, and potential causes?

Initial Management of Suspected Encephalitis

Intravenous acyclovir (10 mg/kg every 8 hours) must be started within 6 hours of admission in all patients with suspected encephalitis, regardless of whether CSF or imaging results are available. 1, 2

Immediate Actions Upon Presentation

Hospitalization and Care Environment

• Admit immediately to a setting with access to intensive care capabilities—patients are at high risk for seizures, increased intracranial pressure, aspiration, and death 2
• Transfer to a neurology service or tertiary center within 24 hours if diagnosis is unclear or patient fails to improve 2, 3
• Patients with decreased consciousness require urgent ICU evaluation for airway protection, ventilatory support, and management of increased intracranial pressure 2, 3

Empiric Acyclovir Therapy: The 6-Hour Rule

Start acyclovir within 6 hours even if initial CSF microscopy or imaging is normal, as long as clinical suspicion for HSV or VZV encephalitis persists. 1, 2 This recommendation is based on randomized trials showing acyclovir reduces mortality in HSV encephalitis from 70% to 20-30%, with outcomes worsening significantly when treatment is delayed beyond 48 hours. 1

Dosing by Age:

• Adults and children ≥12 years: 10 mg/kg IV every 8 hours 1, 4
• Children 3 months to 12 years: 20 mg/kg IV every 8 hours (or 500 mg/m² every 8 hours) 1, 4
• Neonates (birth to 3 months): 10 mg/kg IV every 8 hours 4
• Reduce dose in pre-existing renal impairment to prevent crystalluria and obstructive nephropathy 1, 3, 4

The evidence strongly supports this aggressive approach: unlike meningococcal septicemia where minutes matter, encephalitis allows time for lumbar puncture before treatment in mildly confused patients, but severely ill or deteriorating patients cannot wait. 1

Diagnostic Workup (Performed Concurrently with Treatment Initiation)

Lumbar Puncture

• Perform as soon as possible after admission unless contraindicated by signs of increased intracranial pressure 2, 3
• If contraindication exists, obtain brain imaging first, then LP as soon as safe 2
• CSF PCR results must be available within 24-48 hours 2
• Initial CSF PCR can be negative if obtained <72 hours after symptom onset or late in illness—do not stop acyclovir based on a single negative PCR 1

Neuroimaging

• MRI is preferred over CT for detecting temporal lobe abnormalities characteristic of HSV encephalitis 1
• CT may be normal in severe encephalitis and should not be relied upon to exclude the diagnosis 1
• Perform CT first if MRI unavailable or patient too unstable, then obtain MRI when feasible 1

EEG

• Obtain if subtle motor or non-convulsive seizures suspected 1, 3
• Useful to distinguish organic encephalitis from primary psychiatric disease 1
• PLEDs (periodic lateralized epileptiform discharges) occur in HSV encephalitis but are not diagnostic 1

When to Stop Acyclovir

Acyclovir can be discontinued in immunocompetent patients only if: 1

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

Common pitfall: Stopping acyclovir after a single negative PCR obtained early (<72 hours) is dangerous—the sensitivity of PCR increases with time and repeat testing is essential. 1

Duration of Treatment for Confirmed Cases

• HSV encephalitis: Continue IV acyclovir for 14-21 days (not the 10 days used in original trials, as relapses were subsequently reported) 1, 3, 4
• Repeat LP at completion to confirm CSF is HSV PCR-negative; if positive, continue acyclovir with weekly monitoring until negative 1, 3
• VZV encephalitis: 10-15 mg/kg three times daily for up to 14 days 3
• VZV with vasculopathy/stroke presentation: Add corticosteroids (prednisolone 60-80 mg daily for 3-5 days) due to inflammatory pathogenesis 3

Special Considerations

Bacterial Meningitis Coverage

• If meningitis is also suspected, treat according to bacterial meningitis guidelines concurrently 1
• Notify appropriate public health authorities 1

Malaria-Endemic Areas

• Obtain rapid antigen tests and three thick/thin blood smears for malaria parasites 2
• If cerebral malaria likely and results delayed, start antimalarial treatment while awaiting confirmation 2

Corticosteroids

• Do not use routinely in HSV encephalitis while awaiting results of ongoing randomized controlled trials 1, 3
• Exception: VZV vasculopathy with stroke presentation warrants corticosteroids in addition to acyclovir 3

Brain Biopsy

• No role in initial assessment 1, 2
• Consider stereotactic biopsy after the first week if no diagnosis established, especially with focal imaging abnormalities 1, 2, 3
• Alternative diagnoses found in 20% of biopsied cases, half of which are treatable 1

Multidisciplinary Involvement

Management requires coordination among neurology, infectious disease, virology, microbiology, neurophysiology, neuroradiology, neurosurgery, and intensive care teams. 2, 3 Do not discharge patients without a definitive or suspected diagnosis, and ensure rehabilitation assessment for all patients regardless of age. 2, 3