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Test ID: EPC2 Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid


Ordering Guidance


Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, see Autoimmune Neurology Test Ordering Guide.

 

When more than one evaluation is ordered on the same order number the duplicate will be canceled.

 

For a list of antibodies performed with each evaluation, see Autoimmune Neurology Antibody Matrix.



Necessary Information


Provide the following information:

-Relevant clinical information

-Ordering provider name, phone number, mailing address, and e-mail address



Specimen Required


Container/Tube: Sterile vial

Preferred: Collection vial number 1

Acceptable: Any collection vial

Specimen Volume: 4 mL


Useful For

Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of fewer than 2 years using spinal fluid specimens

 

Investigating new onset cryptogenic epilepsy plus 1 or more of the following accompaniments:

-Psychiatric accompaniments (psychosis, hallucinations)

-Movement disorder (myoclonus, tremor, dyskinesias)

-Headache

-Cognitive impairment/encephalopathy

-Autoimmune stigmata (personal history or family history or signs of diabetes mellitus, thyroid disorder, vitiligo, premature graying of hair, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus, idiopathic adrenocortical insufficiency) or "multiple sclerosis"

-History of cancer

-Smoking history (20 or more pack-years) or other cancer risk factors

-Investigating seizures occurring within the context of a subacute multifocal neurological disorder without an obvious cause, especially in a patient with a past or family history of cancer

Profile Information

Test ID Reporting Name Available Separately Always Performed
AEPCI Epilepsy, Interpretation, CSF No Yes
AMPCC AMPA-R Ab CBA, CSF No Yes
AMPHC Amphiphysin Ab, CSF No Yes
AGN1C Anti-Glial Nuclear Ab, Type 1 No Yes
ANN1C Anti-Neuronal Nuclear Ab, Type 1 No Yes
ANN2C Anti-Neuronal Nuclear Ab, Type 2 No Yes
ANN3C Anti-Neuronal Nuclear Ab, Type 3 No Yes
CS2CC CASPR2-IgG CBA, CSF No Yes
CRMC CRMP-5-IgG, CSF No Yes
DPPCC DPPX Ab CBA, CSF No Yes
GABCC GABA-B-R Ab CBA, CSF No Yes
GD65C GAD65 Ab Assay, CSF Yes Yes
GFAIC GFAP IFA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
GL1IC mGluR1 Ab IFA, CSF No Yes
NCDIC Neurochondrin IFA, CSF No Yes
NMDCC NMDA-R Ab CBA, CSF No Yes
PCTRC Purkinje Cell Cytoplasmc Ab Type Tr No Yes
PCA2C Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PDEIC PDE10A Ab IFA, CSF No Yes
T46IC TRIM46 Ab IFA, CSF No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AGNBC AGNA-1 Immunoblot, CSF No No
AMPIC AMPA-R Ab IF Titer Assay, CSF No No
AMIBC Amphiphysin Immunoblot, CSF No No
AN1BC ANNA-1 Immunoblot, CSF No No
AN2BC ANNA-2 Immunoblot, CSF No No
CRMWC CRMP-5-IgG Western Blot, CSF Yes No
DPPTC DPPX Ab IFA Titer, CSF No No
GABIC GABA-B-R Ab IF Titer Assay, CSF No No
GFACC GFAP CBA, CSF No No
GFATC GFAP IFA Titer, CSF No No
GL1CC mGluR1 Ab CBA, CSF No No
GL1TC mGluR1 Ab IFA Titer, CSF No No
NMDIC NMDA-R Ab IF Titer Assay, CSF No No
PCTBC PCA-Tr Immunoblot, CSF No No
AGNTC AGNA-1 Titer, CSF No No
AN1TC ANNA-1 Titer, CSF No No
AN2TC ANNA-2 Titer, CSF No No
AN3TC ANNA-3 Titer, CSF No No
APHTC Amphiphysin Ab Titer, CSF No No
CRMTC CRMP-5-IgG Titer, CSF No No
NCDCC Neurochondrin CBA, CSF No No
NCDTC Neurochondrin IFA Titer, CSF No No
PC2TC PCA-2 Titer, CSF No No
PCTTC PCA-Tr Titer, CSF No No
PDETC PDE10A Ab IFA Titer, CSF No No
T46CC TRIM46 Ab CBA, CSF No No
T46TC TRIM46 Ab IFA Titer, CSF No No

Testing Algorithm

To determine the necessity of laboratory testing for patients with suspected autoimmune encephalitis, epilepsy or dementia, see the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scorecard.

 

If the client requests or if the indirect immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.

 

If the IFA patterns suggest amphiphysin antibody, then the amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests antiglial nuclear antibody (AGNA)-1, then the AGNA-1 immunoblot and AGNA-1 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.

 

If the IFA pattern suggests ANNA-2 antibody, then the ANNA-2 IFA titer, ANNA-2 immunoblot, and ANNA-1 immunoblot will be performed at an additional charge.

 

If the client requests or the IFA pattern suggests ANNA-3 antibody, then the ANNA-3 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests Purkinje cytoplasmic antibody type 2 (PCA-2), then the PCA-2 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests PCA-Tr antibody, then the PCA-Tr immunoblot and PCA-Tr IFA titer will be performed at an additional charge.

 

If the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-receptor antibody cell-binding assay (CBA) result is positive, then the AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

 

If the gamma-aminobutyric acid B (GABA-B)-receptor antibody CBA result is positive, then the GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.

 

If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP IFA titer and GFAP CBA will be performed at an additional charge.

 

If the N-methyl-D-aspartate (NMDA) receptor antibody CBA result is positive, then the NMDA-receptor antibody IFA titer assay will be performed at an additional charge.

 

If the dipeptidyl-peptidase-like protein-6 (DPPX) antibody CBA result is positive, then the DPPX IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then the mGluR1 antibody CBA and mGluR1 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests neurochondrin antibody, then the neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests tripartite motif-containing protein 46 (TRIM46) antibody, then the TRIM46 antibody CBA and TRIM46 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests phosphodiesterase 10A (PDE10A) antibody, then the PDE10A antibody IFA titer will be performed at an additional charge.

 

For more information see Autoimmune/Paraneoplastic Epilepsy Evaluation Algorithm-Spinal Fluid.

Method Name

AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, NCDIC, NCDTC, NMDIC, PCA2C, PC2TC, PCTRC, PCTTC, PDEIC, PDETC, T46IC, T46TC: Indirect Immunofluorescence Assay (IFA)

 

AMPCC, CS2CS, DPPCC, GABCC, GFACC, LG1CC, GL1CC, NCDCC, NMDCC, T46CC: Cell Binding Assay (CBA)

 

CRMWC: Western Blot (WB)

 

AGNBC, AMIBC, AN1BC, AN2BC, PCTBC: Immunoblot (IB)

 

GD65C: Radioimmunoassay (RIA)

Reporting Name

Epilepsy, Autoimm/Paraneo, CSF

Specimen Type

CSF

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
CSF Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Clinical Information

Antiepileptic drugs (AED) are the mainstay of treatment for epilepsy, but seizures continue in one-third of patients despite appropriate AED therapeutic trials. The etiology of epilepsy often remains unclear. Seizures are a common symptom in autoimmune neurological disorders, including limbic encephalitis and multifocal paraneoplastic disorders. Seizures may be the exclusive manifestation of an autoimmune encephalopathy without evidence of limbic encephalitis.

 

Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid (CSF) and responsiveness to immunotherapy. The advent of more sensitive and specific serological detection methods is increasingly revealing previously underappreciated autoimmune epilepsies. Neural autoantibodies specific for intracellular and plasma membrane antigens aid the diagnosis of autoimmune epilepsy, but no single antibody is specific for this diagnosis.

 

Autoantibody specificities most informative for autoimmune epilepsies include leucine-rich glioma inactivated protein-1 (LGI1), glutamic acid decarboxylase-65 (GAD65), N-methyl-D-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPA-R), and gamma-aminobutyric acid type B receptor (GABA-B-R)  antibodies.

 

Autoantibodies recognizing onconeural proteins shared by neurons, glia, or muscle (eg, antineuronal nuclear antibody, type 1 [ANNA 1]; collapsin response-mediator protein-5 neuronal [CRMP-5-IgG]; N-type calcium channel antibody), also serve as markers of paraneoplastic or idiopathic autoimmune epilepsies. A specific neoplasm is often predictable by the individual patient's autoantibody profile.

 

Suspicion for autoimmune epilepsy on clinical grounds justifies comprehensive evaluation of CSF and serum for neural autoantibodies. Selective testing for individual autoantibodies is not advised because each is individually rare, and a timely diagnosis is critical. Collectively, the antibodies tested for in the autoimmune epilepsy evaluations represent a broad spectrum of treatable disorders, some of which are associated with occult cancer. Testing of CSF for autoantibodies is particularly helpful when serum testing is negative, although, in some circumstances, testing both serum and CSF simultaneously is pertinent. Testing of CSF is recommended for some antibodies (eg, NMDA-R antibody and glial fibrillary acidic protein [GFAP]-IgG) because CSF testing is more sensitive and specific. In contrast, serum testing for LGI1 antibody is more sensitive than CSF testing. Failure to detect a neural antibody does not exclude the diagnosis of autoimmune epilepsy when other clinical clues exist. A trial of immunotherapy is justifiable in those cases.

Reference Values

Test ID

Reporting Name

Methodology*

Reference Value

AEPCI

Epilepsy, Interpretation, CSF

Medical interpretation

Interpretive report

 

AMPCC

AMPA-R Ab CBA, CSF

CBA

Negative

 

AMPHC

Amphiphysin Ab, CSF

IFA

Negative

 

AGN1C

Anti-Glial Nuclear Ab, Type 1

IFA

Negative

 

ANN1C

Anti-Neuronal Nuclear Ab, Type 1

IFA

Negative

 

ANN2C

Anti-Neuronal Nuclear Ab, Type 2

IFA

Negative

 

ANN3C

Anti-Neuronal Nuclear Ab, Type 3

IFA

Negative

 

CS2CC

CASPR2-IgG CBA, CSF

CBA

Negative

 

CRMC

CRMP-5-IgG, CSF

IFA

Negative

 

DPPCC

DPPX Ab CBA, CSF

CBA

Negative

 

GABCC

GABA-B-R Ab CBA, CSF

CBA

Negative

 

GD65C

GAD65 Ab Assay, CSF

RIA

≤0.02 nmol/L

Reference values apply to all ages.

 

GFAIC

GFAP IFA, CSF

IFA

Negative

 

LG1CC

LGI1-IgG CBA, CSF

CBA

Negative

 

GL1IC

mGluR1 Ab IFA, CSF

IFA

Negative

 

NCDIC

Neurochondrin IFA, CSF

IFA

Negative

 

NMDCC

NMDA-R Ab CBA, CSF

CBA

Negative

 

PCTRC

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

Negative

 

PCA2C

Purkinje Cell Cytoplasmic Ab Type 2

IFA

Negative

 

PDEIC

PDE10A Ab IFA, CSF

IFA

Negative

T46IC

TRIM46 Ab IFA, CSF

IFA

Negative

 

Reflex Information:

Test ID

Reporting Name

Methodology*

Reference Value

AGNBC

AGNA-1 Immunoblot, CSF

IB

Negative

AGNTC

AGNA-1 Titer, CSF

IFA

<1:2

AMPIC

AMPA-R Ab IF Titer Assay, CSF

IFA

<1:2

AMIBC

Amphiphysin Immunoblot, CSF

IB

Negative

AN1BC

ANNA-1 Immunoblot, CSF

IB

Negative

AN1TC

ANNA-1 Titer, CSF

IFA

<1:2

AN2BC

ANNA-2 Immunoblot, CSF

IB

Negative

AN2TC

ANNA-2 Titer, CSF

IFA

<1:2

AN3TC

ANNA-3 Titer, CSF

IFA

<1:2

APHTC

Amphiphysin Ab Titer, CSF

IFA

<1:2

CRMTC

CRMP-5-IgG Titer, CSF

IFA

<1:2

CRMWC

CRMP-5-IgG Western Blot, CSF

WB

Negative

DPPTC

DPPX Ab IFA Titer, CSF

IFA

<1:2

GABIC

GABA-B-R Ab IF Titer Assay, CSF

IFA

<1:2

GFACC

GFAP CBA, CSF

CBA

Negative

GFATC

GFAP IFA Titer, CSF

IFA

<1:2

GL1CC

mGluR1 Ab CBA, CSF

CBA

Negative

GL1TC

mGluR1 Ab IFA Titer, CSF

IFA

<1:2

NCDCC

Neurochondrin CBA, CSF

CBA

Negative

NCDTC

Neurochondrin IFA Titer, CSF

IFA

<1:2

NMDIC

NMDA-R Ab IF Titer Assay, CSF

IFA

<1:2

PC2TC

PCA-2 Titer, CSF

IFA

<1:2

PCTBC

PCA-Tr Immunoblot, CSF

IB

Negative

PCTTC

PCA-Tr Titer, CSF

IFA

<1:2

PDETC

PDE10A Ab IFA Titer, CSF

IFA

<1:2

T46CC

TRIM46 Ab CBA, CSF

CBA

Negative

T46TC

TRIM46 Ab IFA Titer, CSF

IFA

<1:2

 

*Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Western blot (WB)

Radioimmunoassay (RIA)

Immunoblot (IB)

 

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, ANNA-3, PCA-2, or PCA-Tr may be reported as "unclassified antineuronal IgG." Complex patterns that include non-neuronal elements may be reported as "uninterpretable."

 

Note: CRMP-5 titers lower than 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (held for 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 to request CRMP-5 Western blot.

Interpretation

Antibodies specific for neuronal, glial, or muscle proteins are valuable serological markers of autoimmune epilepsy and a patient's immune response to cancer. These autoantibodies are not found in healthy subjects and are usually accompanied by subacute neurological symptoms and signs. It is not uncommon for more than 1 of the following autoantibodies to be detected in patients with autoimmune epilepsy:

-Plasma membrane antibodies (N-methyl-D-aspartate [NMDA] receptor; 2-amino-3-[5-methyl-3-oxo-1,2-oxazol-4-yl] propanoic acid [AMPA] receptor; gamma-aminobutyric acid [GABA-B] receptor). These autoantibodies are all potential effectors of dysfunction

-Antineuronal nuclear antibody, type 1 (ANNA-1) or ANNA-3

-Neuronal or muscle cytoplasmic antibodies (amphiphysin, Purkinje cell antibody-type 2 [PCA-2], collapsin response-mediator protein-5 neuronal [CRMP-5-IgG], or glutamic acid decarboxylase [GAD65] antibody)

A rising autoantibody titer in a previously seropositive patient suggests cancer recurrence.

Clinical Reference

1. Smith KM, Britton JW, Thakolwiboon S, et al. Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies. Epilepsia. 2023;64(9):2385-2398. doi:10.1111/epi.17695

2. Garrido Sanabria ER, Zahid A, Britton J, et al. CASPR2-IgG-associated autoimmune seizures. Epilepsia. 2022;63(3):709-722. doi:10.1111/epi.17164

3. Smith KM, Zalewski NL, Budhram A, et al. Musicogenic epilepsy: Expanding the spectrum of glutamic acid decarboxylase 65 neurological autoimmunity. Epilepsia. 2021;62(5):e76-e81. doi:10.1111/epi.16888

4. Steriade C, Britton J, Dale RC, et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: Conceptual definitions. Epilepsia. 2020;61(7):1341-1351. doi:10.1111/epi.16571

5. Dubey D, Singh J, Britton JW, et al. Predictive models in the diagnosis and treatment of autoimmune epilepsy. Epilepsia. 2017;58(7):1181-1189. doi:10.1111/epi.13797

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

8 to 12 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

86255 x 19

86341 x 1

84182-AGNBC (if appropriate)

86256-AGNTC (if appropriate)

86256-AMPIC (if appropriate)

84182-AMIBC (if appropriate)

84182-AN1BC (if appropriate)

86256 AN1TC (if appropriate)

84182-AN2BC (if appropriate)

86256-AN2TC (if appropriate)

86256-AN3TC (if appropriate)

86256-APHTC (if appropriate)

86256-CRMTC (if appropriate)

84182-CRMWC (if appropriate)

86256-DPPTC (if appropriate)

86256-GABIC (if appropriate)

86255-GFACC (if appropriate)

86256-GFATC (if appropriate)

86255-GL1CC (if appropriate)

86256-GL1TC (if appropriate)

86255-NCDCC (if appropriate)

86256-NCDTC (if appropriate)

86256-NMDIC (if appropriate)

86256-PC2TC (if appropriate)

84182-PCTBC (if appropriate)

86256-PCTTC (if appropriate)

86256-PDETC (if appropriate)

86255-T46CC (if appropriate)

86256-T46TC (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
EPC2 Epilepsy, Autoimm/Paraneo, CSF In Process

 

Result ID Test Result Name Result LOINC Value
61513 NMDA-R Ab CBA, CSF 93502-3
61514 AMPA-R Ab CBA, CSF 93491-9
61515 GABA-B-R Ab CBA, CSF 93426-5
34258 Epilepsy, Interpretation, CSF 69048-7
89079 AGNA-1, CSF 90827-7
5906 Amphiphysin Ab, CSF 90815-2
3852 ANNA-1, CSF 44768-0
7472 ANNA-2, CSF 56959-0
21633 ANNA-3, CSF 90836-8
21650 CRMP-5-IgG, CSF 63216-6
21632 PCA-2, CSF 90843-4
21631 PCA-Tr, CSF 90845-9
21702 GAD65 Ab Assay, CSF 94359-7
64280 LGI1-IgG CBA, CSF 94288-8
64282 CASPR2-IgG CBA, CSF 94286-2
64927 mGluR1 Ab IFA, CSF 94361-3
64934 DPPX Ab CBA, CSF 94283-9
605156 GFAP IFA, CSF 94360-5
615866 Neurochondrin IFA, CSF 101451-3
620067 PDE10A Ab IFA, CSF 103842-1
616446 TRIM46 Ab IFA, CSF 103843-9
618897 IFA Notes 48767-8
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-neuroimmunology, mml-Epilepsy,