Diagnostic Panel for Autoimmune Encephalitis
Yes, comprehensive neuronal autoantibody panels should be tested in both serum and CSF when autoimmune encephalitis is suspected, as recommended by current diagnostic guidelines. 1
Core Antibody Panel Components
The standard autoimmune encephalitis panel includes testing for antibodies against both surface antigens and intracellular antigens 1:
High Clinical Relevance Antibodies (Surface Antigens)
- NMDAR (N-methyl-D-aspartate receptor)
- LGI1 (Leucine-rich glioma inactivated protein 1)
- CASPR2 (Contactin-associated protein-like 2)
- AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor)
- GABA-A and GABA-B receptors
- DPPX (Dipeptidyl-peptidase-like protein 6)
- Glycine receptor
- AQP4 (Aquaporin-4)
- MOG (Myelin oligodendrocyte glycoprotein)
- GFAP (Glial fibrillary acidic protein) 1, 2
Classical Paraneoplastic Antibodies (Intracellular Antigens)
- GAD65 (in high titers indicates autoimmune encephalitis phenotype) 1
- Other onconeuronal antibodies as clinically indicated 1
Critical Testing Principles
Both serum AND CSF samples must be tested because sensitivity varies by antibody type—some antibodies are better detected in serum while others are more reliably found in CSF 2, 3. Testing only one compartment risks false negatives 2.
Timing is crucial: Collect blood samples before administering intravenous immunoglobulins or plasmapheresis to avoid false positive or false negative results 1, 2.
When Antibody Testing is Negative
Antibody-negative autoimmune encephalitis exists and should only be diagnosed after comprehensive testing with both cell-based and tissue-based assays. 4 In one study, only 1.5% of tested patients had true antibody-negative AE after comprehensive retesting 4.
Supporting Diagnostic Evidence When Antibodies Are Negative
Even without detectable antibodies, autoimmune encephalitis can be diagnosed based on:
- CSF inflammatory markers: Elevated IgG index, oligoclonal bands, IgG synthesis rate, and pleocytosis indicate intrathecal antibody synthesis 1, 3, 5
- MRI patterns: Bilateral limbic encephalitis on MRI is sufficient for definite AE diagnosis in the correct clinical setting (e.g., negative viral studies) even without antibodies 1, 3
- FDG-PET findings: Bilateral temporal hypermetabolism or bilateral occipito-parietal hypometabolism suggest specific AE patterns 3
- EEG abnormalities: Focal slowing, lateralized periodic discharges, or extreme delta brush support the diagnosis 2, 3
Common Pitfalls to Avoid
Do not delay antibody testing if routine CSF studies are normal—autoimmune encephalitis can present with normal CSF cell counts 2, 3. The guideline explicitly states to test neuronal autoantibody panels even when CSF appears normal 1.
Do not rely solely on commercial assays—false negatives occur frequently, especially in CSF samples 2. Comprehensive testing using multiple methodologies (cell-based and tissue-based assays) is essential 4.
Do not skip cancer screening—perform CT chest/abdomen/pelvis with contrast in relevant cases, as paraneoplastic presentations are clinically indistinguishable from non-paraneoplastic forms 1, 2, 5.
Additional Exclusionary Testing
Beyond the antibody panel, order these tests to exclude competing diagnoses 1, 2:
- Antinuclear antibodies (ANA), extractable nuclear antigens (ENA)
- Antiphospholipid antibodies and lupus anticoagulant
- Vitamin B1/B12 levels, ammonia, comprehensive metabolic panel
- Toxicology screen
- Treponemal antibodies (syphilis)
- Sodium level (hyponatremia common with LGI1-antibody encephalitis)
- Viral PCR (HSV1/2, VZV) to exclude infectious causes 2
The diagnostic workup should proceed systematically: (1) confirm focal/multifocal brain pathology via MRI/EEG/FDG-PET, (2) establish inflammatory etiology through CSF analysis and antibody panels while excluding infections and metabolic causes, and (3) screen for associated malignancy 2.