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Test ID: EPS2 Epilepsy, Autoimmune Evaluation, Serum


Necessary Information


Provide the following information:

-Relevant clinical information

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



Specimen Required


Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin (IVIg) treatment.

2. This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.

3. Patient should have no general anesthetic or muscle-relaxant drugs in the previous 24 hours.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL


Useful For

Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of less than 2 years using serum 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+ pack years) or other cancer risk factors

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

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

Profile Information

Test ID Reporting Name Available Separately Always Performed
AEPSI Epilepsy, Interpretation, S No Yes
AMPCS AMPA-R Ab CBA, S No Yes
AMPHS Amphiphysin Ab, S No Yes
AGN1S Anti-Glial Nuclear Ab, Type 1 No Yes
ANN1S Anti-Neuronal Nuclear Ab, Type 1 No Yes
ANN2S Anti-Neuronal Nuclear Ab, Type 2 No Yes
ANN3S Anti-Neuronal Nuclear Ab, Type 3 No Yes
CS2CS CASPR2-IgG CBA, S No Yes
CRMS CRMP-5-IgG, S No Yes
DPPIS DPPX Ab IFA, S No Yes
GABCS GABA-B-R Ab CBA, S No Yes
GD65S GAD65 Ab Assay, S Yes Yes
GFAIS GFAP IFA, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
GL1IS mGluR1 Ab IFA, S No Yes
NMDCS NMDA-R Ab CBA, S No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
ARBI ACh Receptor (Muscle) Binding Ab Yes No
AGNBS AGNA-1 Immunoblot, S No No
AMPIS AMPA-R Ab IF Titer Assay, S No No
AMIBS Amphiphysin Immunoblot, S No No
AN1BS ANNA-1 Immunoblot, S No No
AN2BS ANNA-2 Immunoblot, S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No
DPPCS DPPX Ab CBA, S No No
DPPTS DPPX Ab IFA Titer, S No No
GABIS GABA-B-R Ab IF Titer Assay, S No No
GFACS GFAP CBA, S No No
GFATS GFAP IFA Titer, S No No
GL1CS mGluR1 Ab CBA, S No No
GL1TS mGluR1 Ab IFA Titer, S No No
NMDIS NMDA-R Ab IF Titer Assay, S No No
PC1BS PCA-1 Immunoblot, S No No
PCTBS PCA-Tr Immunoblot, S No No
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No

Testing Algorithm

If client requests or if indirect immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then CRMP-5-IgG Western blot and acetylcholine receptor (AChR) muscle binding are performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

If IFA pattern suggests antiglial nuclear antibody (AGNA)-1 antibody, then AGNA-1 immunoblot is performed at an additional charge.

 

If IFA pattern suggests antineuronal nuclear antibodies (ANNA)-1 antibody, then ANNA-1 immunoblot is performed at an additional charge.

 

If IFA pattern suggests ANNA-2 antibody, then ANNA-2 immunoblot is performed at an additional charge.

 

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 immunoblot is performed at an additional charge.

 

If IFA pattern suggests PCA-Tr antibody, then PCA-Tr immunoblot is performed at an additional charge.

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-R) antibody, and AMPA-R antibody cell-binding assay (CBA) is positive, then AMPA-R antibody IF titer assay is performed at an additional charge.

 

If AMPA-R antibody CBA is positive, then CRMP-5-IgG Western blot and AChR (muscle) binding antibody are performed at an additional charge.

 

If contactin-associated protein-like-2 (CASPR2)-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, and AChR (muscle) binding antibody are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B receptor (GABA-B-R)antibody, and GABA-B-R antibody is positive, then GABA-B-R antibody IF titer assay is performed at an additional charge.

 

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

 

If IFA pattern suggests N-methyl-D-aspartate receptor (NMDA-R) antibody, and NMDA-R antibody CBA is positive, then NMDA-R antibody IF titer assay is performed at an additional charge.

 

See Epilepsy Autoimmune Evaluation Algorithm, Serum in Special Instructions.

Method Name

AGN1S, AMPHS, AMPIS, ANN1S, ANN2S, ANN3S, CRMS, DPPIS, DPPTS, GABIS, GFAIS, GFATS, GL1IS, GL1TS, NMDIS, PCAB2, PCABP, PCATR: Indirect Immunofluorescence Assay (IFA)

AMPCS, CS2CS, DPPCS, GABCS, GFACS, GL1CS, LG1CS, NMDCS: Cell Binding Assay (CBA)

CRMWS: Western Blot (WB)

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)

ARBI, GD65S: Radioimmunoassay (RIA)

Reporting Name

Epilepsy-Autoimmune Evaluation, S

Specimen Type

Serum

Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum 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 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 currently 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-isoxazolepropionic 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 cerebrospinal fluid (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, though in some circumstances testing both serum and CSF simultaneously is pertinent. Testing of CSF is recommended for some antibodies in particular (such as NMDA-R antibody and GFAP-IgG) because CSF testing is both 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

AEPSI

Epilepsy, Interpretation, S

Interpretation

NA

AMPCS

AMPA-R Ab CBA, S

Cell-binding assay (CBA)

Negative

AMPHS

Amphiphysin Ab, S

Indirect immunofluorescence assay (IFA)

<1:240

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

<1:240

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

<1:240

ANN2S

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:240

ANN3S

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:240

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMS

CRMP-5-IgG, S

IFA

<1:240

DPPIS

DPPX Ab IFA, S

IFA

Negative

GABCS

GABA-B-R Ab CBA, S

CBA

Negative

GD65S

GAD65 Ab Assay, S

Radioimmunoassay (RIA)

≤0.02 nmol/L

Reference values apply to all ages

GFAIS

GFAP IFA, S

IFA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:240

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

Reflex Information:

Test ID

Reporting Name

Methodology

Reference Value

ARBI

ACh Receptor (Muscle) Binding Ab

RIA

≤0.02 nmol/L

AGNBS

AGNA-1 Immunoblot, S

Immunoblot (IB)

Negative

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

AMIBS

Amphiphysin Immunoblot, S

IB

Negative

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

CRMWS

CRMP-5-IgG Western Blot, S

Western blot

Negative

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPTS

DPPX Ab IFA Titer, S

IFA

<1:240

GABIS

GABA-B-R Ab IF Titer Assay, S

IFA

<1:120

GFACS

GFAP CBA, S

CBA

Negative

GFATS

GFAP IFA Titer, S

IFA

<1:240

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1TS

mGluR1 Ab IFA Titer, S

IFA

<1:240

NMDIS

NMDA-R Ab IF Titer Assay, S

IFA

<1:120

PC1BS

PCA-1 Immunoblot, S

IB

Negative

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:240

 

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

 

Note: CRMP-5 titers lower than 1:240 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored serum (held 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 of 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 dementia.

-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-amino butyric acid: GABA-B receptor). These autoantibodies are all potential effectors of dysfunction.

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

Clinical Reference

1. Quek AM, Britton JW, McKeon A, et al: Autoimmune epilepsy: clinical characteristics and response to immunotherapy. Arch Neurol. 2012 May;69(5):582-593

2. Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 Feb;49(2):146-154

3. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc. 2006 Sep;81:1207-1214

4. Klein CJ, Lennon VA, Aston PA, et al: Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol. 2013 Feb;70(2):229-234

5. Lancaster E, Martinez-Hernandez E, Dalmau J: Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011 Jul;77(2):179-189

Day(s) Performed

ARBI, AGN1S, AMPHS, AMPIS, ANN1S, ANN2S, ANN3S, CRMS, DPPIS, DPPTS, GABIS, GD65S, GFAIS, GFATS, GL1IS, GL1TS, NMDIS, PCAB2, PCABP, PCATR: Monday through Sunday

 

AMPCS, CS2CS, DPPCS, GABCS, LG1CS, NMDCS: Monday through Thursday, Sunday

 

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Monday through Friday

 

CRMWS: Monday through Thursday

 

GL1CS: Monday, Thursday

 

GFACS: Monday, Wednesday, Friday

Report Available

10 to 13 days

Test Classification

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

CPT Code Information

86255 x 16

86341

83519-ARBI (if appropriate)

84182-AGNBS (if appropriate)

86256-AMPIS (if appropriate)

84182-AMIBS (if appropriate)

84182-AN1BS (if appropriate)

84182-AN2BS (if appropriate)

84182-CRMWS (if appropriate)

86255-DPPCS (if appropriate)

86256-DPPTS (if appropriate)

86256-GABIS (if appropriate)

86255-GFACS (if appropriate)

86256-GFATS (if appropriate)

86255-GL1CS (if appropriate)

86256-GL1TS (if appropriate)

86256-NMDIS (if appropriate)

84182-PC1BS (if appropriate)

84182-PCTBS (if appropriate)

86255-PCABP (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
EPS2 Epilepsy-Autoimmune Evaluation, S 94698-8

 

Result ID Test Result Name Result LOINC Value
61516 NMDA-R Ab CBA, S 93503-1
61518 AMPA-R Ab CBA, S 93489-3
61519 GABA-B-R Ab CBA, S 93428-1
34259 Epilepsy, Interpretation, S 69048-7
64279 LGI1-IgG CBA, S 94287-0
64281 CASPR2-IgG CBA, S 94285-4
64930 DPPX Ab IFA, S 82976-2
64928 mGluR1 Ab IFA, S 94347-2
605155 GFAP IFA, S 94346-4
89080 AGNA-1, S 94341-5
81722 Amphiphysin Ab, S 94340-7
80150 ANNA-1, S 94342-3
80776 ANNA-2, S 94343-1
83137 ANNA-3, S 94344-9
83077 CRMP-5-IgG, S 94815-8
81596 GAD65 Ab Assay, S 94345-6
83138 PCA-2, S 94351-4
83076 PCA-Tr, S 94352-2
36349 Reflex Added 77202-0
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-neuroimmunology