Autoimmune Epilepsy Panel, Serum and CSF

Content Review: May 2023 Last Update:
Method

Semi-Quantitative Cell-Based Indirect Fluorescent Antibody/Semi-Quantitative Indirect Fluorescent Antibody (IFA)/Qualitative Immunoblot/Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)

Method

Semi-Quantitative Cell-Based Indirect Fluorescent Antibody/Semi-Quantitative Indirect Fluorescent Antibody (IFA)/Qualitative Immunoblot/Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)

Autoimmune epilepsy is characterized by acute to subacute onset of epilepsy that is often refractory to standard treatment with antiseizure drugs but responds to immunotherapy.  Recognition of autoimmune causes of neurologic symptoms and detection of antineural antibodies may help to establish a diagnosis, support treatment decisions, serve as a prerequisite for enrollment in clinical trials, and guide the search for an associated malignancy.

Disease Overview

Autoimmune epilepsy accounts for 15-20% of epilepsies previously considered to be cryptogenic.  In patients with new-onset seizure activity, the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score can be used to predict the likelihood of the presence of an antineural antibody  and should therefore be considered before ordering antineural antibody testing. Factors associated with autoimmune epilepsy include autonomic dysfunction, brain magnetic resonance imaging (MRI) findings suggestive of encephalitis, elevated cerebrospinal fluid (CSF) protein or pleocytosis, faciobrachial dystonic seizures, history of autoimmunity, history of malignancy, neuropsychiatric changes, orofacial dyskinesias, seizures refractory to antiseizure drugs, and viral prodrome.  It is important to note that autoimmune epilepsy may exist in the absence of detectable, known antineural antibodies, and empiric immunotherapy trials may be considered in the appropriate clinical context. 

For more information about laboratory testing for autoimmune neurologic diseases, refer to the ARUP Consult Autoimmune Neurologic Disease - Antineural Antibody Testing topic.

Test Description

These serum and CSF antineural antibody panel tests can be used for the evaluation of patients with a neurologic phenotype consisting predominantly of new, acute to subacute onset of epilepsy that is refractory to more than two antiseizure medications. Testing for the presence of antineural antibodies in both serum and CSF is recommended to improve diagnostic yield. 

These phenotype-targeted panels test for the presence of antibodies associated with epilepsy. Clinical phenotypes for specific antineural antibody-associated syndromes often overlap, and phenotype-specific panels allow for rapid identification of associated antibodies, which may have implications for treatment, prognosis, and cancer screening.  Other panels may be more appropriate, depending on the patient’s clinical phenotype:

ARUP Phenotype-Specific Panels to Consider for Autoimmune Neurologic Disease
ARUP Panel
Test Code
Serum CSF

Autoimmune Movement Disorder Panel

3006206

3006207

Autoimmune Encephalopathy/Dementia Panel

3006201

3006202

Autoimmune Pediatric CNS Disorders Panel

3006210

3006211

Regardless of the panel chosen, order only one panel for serum and/or one panel for CSF; many antineural antibodies are redundant between these panels, and choosing based on the predominant phenotype will provide the most meaningful results. To compare these panels and the antibodies included, refer to ARUP Autoimmune Neurology Panel Components.

Testing for individual antibodies is also available separately.

Antibodies Tested and Methodology

Autoimmune Epilepsy Panel, Serum (3006204) and Autoimmune Epilepsy Panel, CSF (3006205): Antibodies Tested and Methodology
Autoantibody Markers Methodology
Individual Autoantibody or Focused Panel Test Code
Serum CSF

AMPAR Ab, IgG

CBA-IFA, reflex titer

3001260

3001257

Amphiphysin Ab, IgG

IB

2008893

3004510

ANNA-1 (Hu)

IFA, reflex IB, reflex titer

2007961

2010841

ANNA-2 (Ri)

IFA, reflex IB, reflex titer

2007961

2010841

CASPR2 Ab, IgG

CBA-IFA, reflex titer

2009452

3001986

CV2 (CRMP-5) Ab, IgG

CBA-IFA, reflex titer

3016999

3017001

DPPX Ab, IgG

CBA-IFA, reflex titer

3004359

3004512

GABA-AR Ab, IgG

CBA-IFA, reflex titer

3006008

3006003

GABA-BR Ab, IgG

CBA-IFA, reflex titer

3001270

3001267

GAD65 Ab

ELISA

2001771

3002788

LGI1 Ab, IgG

CBA-IFA, reflex titer

2009456

3001992

mGluR1 Ab, IgG

CBA-IFA, reflex titer

3006044

3006039

NMDAR Ab, IgG

CBA-IFA, reflex titer

2004221

2005164

PCCA-1 (Yo)

IFA, reflex IB, reflex titer

2007961

2010841

PCCA-Tr/DNER

IFA, reflex IB, reflex titer

2007961

2010841

SOX1 (AGNA) Ab, IgG

IB

3002885

3002886

Ab, antibody; AGNA, antiglial nuclear antibody; AMPAR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANNA-1, antineuronal nuclear antibody type 1; ANNA-2, antineuronal nuclear antibody type 2; CASPR2, contactin-associated protein 2; CBA, cell-binding assay/cell-based assay; CRMP-5, collapsin response-mediator protein 5; DNER, Delta/notch-like epidermal growth factor-related receptor; DPPX, dipeptidyl-aminopeptidase-like protein 6; ELISA, enzyme-linked immunosorbent assay; GABA-AR, gamma-aminobutyric acid receptor, type A; GABA-BR, gamma-aminobutyric acid receptor, type B; GAD65, glutamic acid decarboxylase 65-kd isoform; IB, immunoblot; IFA, indirect immunofluorescence assay; LGl1, leucine-rich, glioma-inactivated protein 1; mGluR1, metabotropic glutamate receptor 1; NMDAR, N-methyl-D-aspartate receptor; PCCA, Purkinje cell cytoplasmic antibody; SOX1, SRY-box transcription factor 1

Reflex Patterns

Autoimmune Epilepsy Panel, Serum (3006204) and Autoimmune Epilepsy Panel, CSF (3006205): Reflex Patterns

Reflex patterns for Autoimmune Epilepsy Panels

Limitations

This panel does not include every antibody that has been associated with autoimmune epilepsy:

  • ANNA-3 and PCCA-2 are not included in this panel because they are extremely rare (present in approximately 0.0001% of specimens submitted for evaluation using a paraneoplastic antibody panel), and commercial assays to confirm the specificity of these antibodies are not currently available. 
  • Glial fibrillary acidic protein (GFAP) and neurochondrin are not included because they have been only recently identified and their prevalence is currently not well established.
    • GFAP has been reported in 0.17% of samples screened, often co-occurring with other antineural antibodies. 
    • Neurochondrin has been reported in 0.002% of samples tested. 
  • As testing for newly described antibodies becomes available and their clinical relevance is established, these panels will evolve to reflect these discoveries.

Test Interpretation

Results

Results must be interpreted in the clinical context of the individual patient; test results (positive or negative) should not supersede clinical judgment.

Autoimmune Epilepsy Panel, Serum (3006204) and Autoimmune Epilepsy Panel, CSF (3006205): Results Interpretation
Result Interpretation

Positive for ≥1 autoantibodies

Autoantibody(ies) detected

Supports a clinical diagnosis of autoimmune epilepsy

Consider a focused search for malignancy based on antibody-tumor associations

Negative

No autoantibodies detected

A diagnosis of autoimmune epilepsy is not excluded

Immunotherapy trials may be considered in the appropriate clinical context

References