What is the initial workup for a patient with suspected encephalopathy?

Initial Workup for Suspected Encephalopathy

The initial workup for suspected encephalopathy should include urgent neuroimaging (preferably MRI brain with and without contrast), lumbar puncture (if no contraindications), comprehensive laboratory testing, and EEG to identify the underlying cause. 1

Neuroimaging

• MRI brain with and without contrast is preferred when available as it provides better visualization of brain parenchyma 1
• CT scan should be performed before lumbar puncture if any of these contraindications exist 2:
  • Moderate to severe impairment of consciousness (GCS < 13) or fall in GCS > 2
  • Focal neurological signs (including unequal, dilated or poorly responsive pupils)
  • Abnormal posture or posturing
  • Papilledema
  • Recent seizures (until stabilized)
  • Relative bradycardia with hypertension
  • Abnormal 'doll's eye' movements
  • Immunocompromise
  • Systemic shock
  • Coagulation abnormalities (abnormal coagulation results, platelet count <100×10⁹/L, anticoagulant therapy)
  • Local infection at the lumbar puncture site
  • Respiratory insufficiency
  • Suspected meningococcal septicaemia (extensive or spreading purpura)

Lumbar Puncture

• Should be performed as soon as possible unless contraindicated 2
• CSF analysis should include 2, 1:
  • Opening pressure
  • Cell count and differential
  • Protein and glucose levels (with paired serum glucose)
  • Gram stain, culture, and viral PCR (particularly HSV)
  • Consider cytology if malignancy suspected
  • Consider oligoclonal bands
  • Consider autoimmune encephalitis panel

Laboratory Testing

• Complete blood count
• Comprehensive metabolic panel
• Blood cultures
• Ammonia level
• Thyroid function tests
• Vitamin B12 level
• HIV testing
• Toxicology screen
• Consider autoimmune panels (ANA, ANCA, anti-TPO antibodies)
• Consider paraneoplastic antibody panels if appropriate 2

Electroencephalogram (EEG)

• Particularly useful to 1:
  • Distinguish organic from psychiatric causes
  • Identify non-convulsive or subtle seizures
  • Evaluate encephalopathic changes

Specific Considerations Based on Clinical Presentation

For Suspected Viral Encephalitis

• Start IV aciclovir (10 mg/kg three times daily) immediately if suspected 2, 1
• Continue for 14 days if HSV encephalitis is confirmed 1

For Suspected Autoimmune Encephalitis

• Additional testing should include 2:
  • Serum studies: ESR, CRP, thyroid panel including TPO and thyroglobulin, AM cortisol and ACTH
  • CSF analysis for autoimmune encephalopathy and paraneoplastic panels
  • Consider GQ1b antibodies (Bickerstaff encephalitis and rhomboencephalitis)

For Suspected Immune Checkpoint Inhibitor-Related Encephalitis

• Neurologic consultation
• Consider holding immunotherapy
• Consider empiric steroids (methylprednisolone 1-2 mg/kg/day) 2

Important Pitfalls to Avoid

1. Delaying treatment: If viral encephalitis is suspected, start empiric aciclovir before CSF results are available 2
2. Missing metabolic causes: Always rule out metabolic, toxic, and systemic causes of encephalopathy before pursuing neurologic diagnoses 2
3. Performing LP without checking for contraindications: Always assess for signs of increased intracranial pressure before LP 2
4. Inadequate CSF studies: Ensure appropriate viral PCRs and antibody panels are ordered based on clinical suspicion 2, 1
5. Overlooking non-convulsive status epilepticus: EEG is essential to identify this treatable cause of encephalopathy 1

By following this systematic approach to the initial workup of encephalopathy, clinicians can rapidly identify the underlying cause and initiate appropriate treatment to improve patient outcomes.