TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: EPS2    
Epilepsy, Autoimmune Evaluation, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

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)

< or =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

< or =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 Provides information to assist in interpretation of the test results

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).

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Negative results do not exclude autoimmune epilepsy or cancer.

 

This test does not detect Ma2 antibody (alias MaTa). Ma2 antibody has been described in patients with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advisable in men who present with unexplained subacute encephalitis.

 

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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

Special Instructions Library of PDFs including pertinent information and forms related to the test