What is the diagnostic workup and treatment for autoimmune encephalopathy?

Diagnostic Workup for Autoimmune Encephalopathy

The diagnostic workup for autoimmune encephalopathy requires comprehensive CSF analysis, neuroimaging, antibody testing in both serum and CSF, and screening for associated neoplasms. 1, 2

Initial Evaluation

Brain Imaging

• MRI Brain (first step) 1
  • Look for focal or multifocal abnormalities
  • Common findings: T2/FLAIR hyperintensities in medial temporal lobes, basal ganglia, or cortical/subcortical regions
  • Note: MRI may be normal in up to 20% of autoimmune encephalitis cases

Cerebrospinal Fluid Analysis

• Lumbar Puncture (critical second step) 1, 2
  • Collect 8-15 mL total CSF in 3-4 sequential tubes
  • Standard CSF tests:
    • Cell count with differential (expect mild to moderate lymphocytic pleocytosis, commonly 20-200 cells)
    • Protein (often elevated)
    • Glucose and CSF/serum glucose ratio
    • Albumin quotient
    • IgG index and synthesis rate
    • Oligoclonal bands (often positive and unmatched in serum)
  • Exclude infections:
    • Viral studies including HSV1/2 PCR, VZV PCR, and IgG/IgM
    • Bacterial/fungal cultures when appropriate
  • Special studies:
    • Cytology and flow cytometry
    • Neural autoantibody (NAA) panel
    • Prion disorder panel (RTQuIC when available) if indicated

Antibody Testing

Serum and CSF Testing

• Test neural autoantibodies in both serum and CSF 1, 2
  • Some antibodies more sensitive in CSF (NMDAR, GFAP)
  • Others more sensitive in serum (onconeuronal, LGI1, AQP4)
  • Comprehensive autoimmune encephalopathy/encephalitis panel
  • Note: Blood samples should be collected prior to immunotherapy to avoid false results

Additional Blood Tests

• Serum studies to exclude other etiologies 1
  • Antithyroid antibodies
  • Toxicology screen
  • Ammonia, vitamin B1/B12 levels
  • HIV testing
  • Inflammatory markers
  • Autoimmune workup: ANA, ENA, antiphospholipid antibodies, lupus anticoagulant
  • Immunoglobulin levels
  • Metabolic and hormonal panels when appropriate
  • Sodium level monitoring (especially important in LGI1 antibody encephalitis)

Additional Diagnostic Tests

Electroencephalography (EEG)

• EEG findings 2
  • Sensitivity: 70-80%, Specificity: 90-95%
  • Look for:
    • Diffuse or focal slowing
    • Epileptiform discharges
    • Extreme delta brush pattern (in NMDAR encephalitis)
    • Status epilepticus

FDG-PET Scan

• Consider when MRI is normal or non-specific 1
  • Can show characteristic metabolic patterns:
    • Medial temporal hypermetabolism (limbic encephalitis)
    • Occipito-parietal hypometabolism (NMDAR-antibody encephalitis)
  • Note: Results can be affected by immunosuppressants, anesthetics, antiseizure medications, and seizures

Neoplasm Screening

Cancer Evaluation

• Thorough cancer screening 2
  • Detection rate of 70-80% if comprehensive screening performed
  • Guided by antibody type (e.g., NMDAR with ovarian teratoma, ANNA-1/anti-Hu with small cell lung cancer)
  • May include:
    • CT chest/abdomen/pelvis
    • Mammography
    • Pelvic/testicular ultrasound
    • Whole-body PET scan in selected cases

Important Considerations

Diagnostic Challenges

• CSF may be normal in some autoimmune encephalitis patients 1
• Negative antibody testing does not exclude autoimmune encephalitis when clinical suspicion is high 2
• Consider brain biopsy in challenging cases showing perivascular lymphocytic infiltrates 3

Treatment Timing

• Do not delay empiric immunotherapy while waiting for antibody results if clinical suspicion is high 2
• First-line immunotherapy (IV corticosteroids, IVIG, or plasma exchange) should be initiated promptly in an inpatient setting 2

Diagnostic Algorithm

1. Brain MRI (first step)
2. CSF analysis (critical second step)
3. Serum and CSF antibody testing
4. EEG
5. Additional blood tests to exclude other etiologies
6. Cancer screening based on clinical and antibody findings
7. Consider FDG-PET if other tests inconclusive

This structured approach to diagnosis ensures comprehensive evaluation while prioritizing the most critical tests to guide timely treatment decisions for optimal outcomes in terms of morbidity, mortality, and quality of life.