What is the recommended management for a patient with suspected encephalitis?

Management of Suspected Encephalitis

Immediate Empirical Treatment

Start intravenous acyclovir (10 mg/kg every 8 hours) immediately in all patients with suspected encephalitis, as soon as possible after presentation, without waiting for diagnostic confirmation. 1 This recommendation is based on randomized controlled trials demonstrating that acyclovir reduces mortality in HSV encephalitis from >70% to 20-30%, with outcomes dramatically better when treatment begins within 48 hours of hospital admission. 1

Dosing Specifications

• Adults and children with normal renal function: 10 mg/kg IV every 8 hours 1
• Neonates: 20 mg/kg IV every 8 hours 1
• Adjust dose in renal impairment 1, 2
• Duration: 14-21 days for confirmed HSV encephalitis 1
• Immunocompromised patients: Treat for at least 21 days, then reassess with CSF PCR 1

Critical Timing Considerations

The 6-hour window is crucial: if CSF results or imaging will not be available within 6 hours of admission, or if the patient is severely ill or deteriorating, start acyclovir immediately. 1 Mortality drops to 8% when acyclovir is initiated within 4 days of symptom onset, compared to 28% overall mortality at 18 months. 1

Additional Empirical Antimicrobials

• Add antibiotics for bacterial meningitis if clinically indicated (altered mental status with fever, meningismus, or CSF pleocytosis suggesting bacterial infection) 1
• Add doxycycline if rickettsial or ehrlichial infection suspected based on season, tick exposure, or rash 1

Urgent Diagnostic Workup (Parallel to Treatment)

Lumbar Puncture - Perform Immediately Unless Contraindicated

Obtain CSF as soon as possible after hospital admission 1, 3, but delay only if: 1

• Signs of raised intracranial pressure (papilledema, focal neurological deficits suggesting mass effect)
• Coagulopathy
• Significant brain shift on imaging

CSF studies required: 1

• Cell count with differential
• Protein and glucose
• HSV-1 and HSV-2 PCR (results should be available within 24-48 hours) 1, 3
• VZV PCR 1
• Enterovirus PCR 1
• Bacterial culture and Gram stain
• Consider: West Nile virus PCR, arbovirus serology based on epidemiology 1

Neuroimaging - Within 24 Hours

MRI brain is strongly preferred over CT (detects early changes in 90% of HSV encephalitis cases versus only 25% for CT) 4, 3. Perform under general anesthesia if needed for patient cooperation. 3

EEG - Within 24 Hours

Obtain EEG to assess for seizure activity and characteristic patterns (temporal lobe abnormalities in HSV encephalitis). 1, 3

Autoimmune Encephalitis Evaluation

Send autoimmune antibody panel from both serum and CSF simultaneously with infectious workup: 3

• NMDA receptor antibodies
• Voltage-gated potassium channel complex antibodies
• LGI1, CASPR2, IGLON5 antibodies
• Other neuronal surface and intracellular antibodies 3

Do not delay empirical acyclovir while awaiting autoimmune results, as HSV and autoimmune encephalitis can have overlapping presentations. 3

Critical Care Management

ICU Assessment Required for:

• Declining level of consciousness 1, 4, 3
• Glasgow Coma Score <6 1
• Respiratory compromise
• Hemodynamic instability

ICU Interventions: 1, 4, 3

• Airway protection and ventilatory support
• Management of raised intracranial pressure and optimization of cerebral perfusion pressure
• Correction of electrolyte imbalances (particularly hyponatremia, which is common) 5
• Seizure management: Use IV levetiracetam (30-60 mg/kg/day) or IV valproate (20-30 mg/kg loading dose); avoid phenytoin as first-line 4

Transfer to Neuroscience Center

Transfer within 24 hours if: 1, 3

• Diagnosis not rapidly established
• Patient fails to improve with initial therapy
• Need for neurosurgical consultation

Etiology-Specific Treatment Adjustments

If HSV PCR Returns Negative but Clinical Suspicion Remains High

Repeat CSF PCR 3-7 days later on a second specimen, as initial PCR can be falsely negative if performed very early. 1 Continue acyclovir until repeat testing completed. 1

If Autoimmune Encephalitis Confirmed or Strongly Suspected

Initiate first-line immunotherapy immediately after excluding active infection: 3

• High-dose IV methylprednisolone 1g daily for 3-5 days 4, 3
• Plus IVIG 0.4 g/kg/day for 5 days 4, 3
• Continue immunosuppression with gradual oral prednisone taper or monthly IVIG to prevent relapse 3

For Paraneoplastic Encephalitis

Search for occult malignancy with CT or PET scan of chest, abdomen, and pelvis. 4 Treat underlying tumor when identified. 4

For Returning Travelers

• Test for malaria with rapid antigen tests and three thick/thin blood films if returning from endemic areas 1
• Consider cerebral malaria treatment if high suspicion and delay in film results 1
• Evaluate for Japanese encephalitis, dengue, or other geographically relevant pathogens 1

Common Pitfalls to Avoid

1. Do not wait for LP or imaging results to start acyclovir if there will be any delay beyond 6 hours or if patient is deteriorating 1, 3

2. Do not rely on negative CSF PCR to exclude HSV encephalitis if performed very early; repeat testing may be needed 1

3. Do not use CT brain alone - MRI is far superior for detecting early encephalitic changes 4, 3

4. Do not delay immunotherapy while awaiting antibody results if autoimmune encephalitis is suspected and infection has been reasonably excluded 3

5. Predictors of poor outcome include: age >30 years, Glasgow Coma Score <6, and delay >4 days before starting acyclovir 1 - emphasizing the critical importance of early treatment

Brain Biopsy - Reserved for Specific Situations

Consider stereotactic brain biopsy only if: 1

• Patient is HSV PCR-negative and deteriorates despite acyclovir
• Focal lesion on imaging suggests alternative diagnosis
• No diagnosis established after comprehensive workup

Modern stereotactic approaches have low complication rates, and biopsy identifies alternative treatable diagnoses in 20% of suspected HSV cases. 1

Discharge Planning and Rehabilitation

Never discharge patients without: 1, 3

• Definitive or suspected diagnosis established
• Outpatient follow-up appointment scheduled (at least one) 1, 5, 3
• Comprehensive rehabilitation assessment arranged 1, 5, 4, 3

All patients require access to: 1, 5, 4, 3

• Neuropsychology evaluation (30-50% develop long-term cognitive deficits) 4
• Neuropsychiatry assessment (anxiety, depression, obsessive behaviors common) 1, 4
• Speech and language therapy
• Neurophysiotherapy
• Occupational therapy

Sequelae may not be immediately apparent at discharge - structured follow-up is essential to identify delayed neurological and psychiatric complications. 1, 5, 4