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Test ID: EPC2 Epilepsy, Autoimmune Evaluation, Spinal Fluid


Necessary Information


Provide the following information:

-Relevant clinical information

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



Specimen Required


Collection Container/Tube: Sterile vial

Specimen Volume: 4 mL


Useful For

Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of less 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+ 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

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
DPPIC DPPX Ab IFA, 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
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

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
DPPCC DPPX Ab CBA, CSF No 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
PC1BC PCA-1 Immunoblot, CSF No No
PCTBC PCA-Tr Immunoblot, CSF No No
PCA1C 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 is performed at an additional charge.

 

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

 

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

 

If IFA pattern suggests 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 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 AMPA-receptor antibody, and AMPA-receptor antibody cell-binding assay (CBA) is positive, then AMPA-receptor antibody IF titer assay is performed at an additional charge.

 

If IFA pattern suggests GABA-B-receptor antibody, and GABA-B-receptor antibody is positive, then GABA-B-receptor antibody IF titer assay is performed at an additional charge.

 

If IFA pattern suggests GFAP antibody, then GFAP IFA titer and GFAP CBA are performed at an additional charge.

 

If IFA pattern suggests NMDA-receptor antibody, and NMDA-receptor antibody CBA is positive, then NMDA-receptor antibody IF titer assay is performed at an additional charge.

 

If IFA patterns suggest PCA-1, then PCA1C assay is performed at an additional charge.

 

If IFA pattern suggests DPPX antibody, then DPPX antibody CBA and DPPX titer are performed at an additional charge.

 

If IFA pattern suggests mGluR1 antibody, then mGluR1 antibody CBA and mGluR1 titer are performed at an additional charge.

 

See Epilepsy Autoimmune Evaluation Algorithm, Spinal Fluid in Special Instructions.

Method Name

AGN1C, AMPHC, AMPIC, ANN1C, ANN2C, ANN3C, CRMC, DPPIC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, NMDIC, PCA1C, PCA2C, PCTRC: Indirect Immunofluorescence Assay (IFA)

AMPCC, CS2CC, DPPCC, GABCC, GFACC, GL1CC, LG1CC, NMDCC: Cell-Binding Assay (CBA)

CRMWC: Western Blot (WB)

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Immunoblot (IB)

GD65C:  Radioimmunoassay (RIA)

Reporting Name

Epilepsy-Autoimmune Evaluation, 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 (AEDs) 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 (NMDAR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), and gamma aminobutyric acid type B receptor (GABABR) 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

AMPCC

AMPA-R Ab CBA, CSF

Cell-binding assay (CBA)

Negative

AMPHC

Amphiphysin Ab, CSF

Indirect immunofluorescence assay (IFA)

<1:2

AGN1C

Anti-Glial Nuclear Ab, Type 1

IFA

<1:2

ANN1C

Anti-Neuronal Nuclear Ab, Type 1

IFA

Negative at <1:2

ANN2C

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:2

ANN3C

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:2

CS2CC

CASPR2-IgG CBA, CSF

CBA

Negative

CRMC

CRMP-5-IgG, CSF

IFA

<1:2

DPPIC

DPPX Ab IFA, CSF

IFA

Negative

GABCC

GABA-B-R Ab CBA, CSF

CBA

Negative

GD65C

GAD65 Ab Assay, CSF

Radioimmunoassay (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

NMDCC

NMDA-R Ab CBA, CSF

CBA

Negative

PCTRC

Purkinje Cell Cytoplasmc Ab Type Tr

IFA

<1:2

PCA2C

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:2

Reflex Information:

Test ID

Reporting Name

Methodology

Reference Value

AGNBC

AGNA-1 Immunoblot, CSF

Immnuoblot (IB)

Negative

AMPIC

AMPA-R Ab IF Titer Assay, CSF

IFA

<1:2

AMIBC

Amphiphysin Immunoblot, CSF

IB

Negative

AN1BC

ANNA-1 Immunoblot, CSF

IB

Negative

AN2BC

ANNA-2 Immunoblot, CSF

IB

Negative

 

 

 

 

CRMWC

CRMP-5-IgG Western Blot, CSF

Western blot

Negative

DPPCC

DPPX Ab CBA, CSF

CBA

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

NMDIC

NMDA-R Ab IF Titer Assay, CSF

IFA

Negative at <1:2

PC1BC

PCA-1 Immunoblot, CSF

IB

Negative

PCTBC

PCA-Tr Immunoblot, CSF

IB

Negative

 

 

 

 

PCA1C

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:2

 

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, ANN3C, CA-1, PCA-2, or PCA-Tr may be reported as "unclassified antineuronal IgG." Complex patterns that include nonneuronal 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 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 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-amino butyric acid: GABA-B receptor). These autoantibodies are all potential effectors of dysfunction.

-Neuronal nuclear autoantibody, 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).

 

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

Clinical Reference

1. Quek AL, 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, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 Feb;49(2):146-154; Editorial: 49:141-142

3. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc 2006;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;70(2):229-234

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

Day(s) Performed

AMPHC, AGN1C, ANN1C, ANN2C, ANN3C, CRMC, DPPIC, GD65C, GFAIC, GL1IC, PCTRC, PCA2C, AMPIC, DPPTC, GABIC, GFATC, GL1TC, NMDIC, PCA1C: Monday through Sunday

 

AMPCC, CS2CC, GABCC, LG1CC, NMDCC, DPPCC: Monday through Thursday, Sunday

 

GL1CC: Monday, Thursday

 

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Monday through Friday

 

CRMWC: Monday through Thursday

 

GFACC: Monday, Wednesday, Friday

Report Available

5 to 10 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

86255x16

86341 x1

84182-AGNBC (if appropriate)

86256-AMPIC (if appropriate)

84182-AMIBC (if appropriate)

84182-AN1BC (if appropriate)

84182-AN2BC (if appropriate)

84182-CRMWC (if appropriate)

86255-DPPCC (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)

86256-NMDIC (if appropriate)

84182-PC1BC (if appropriate)

84182-PCTBC (if appropriate)

86255-PCA1C (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
EPC2 Epilepsy-Autoimmune Evaluation, 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
64280 LGI1-IgG CBA, CSF 94288-8
64282 CASPR2-IgG CBA, CSF 94286-2
64929 DPPX Ab IFA, CSF 82989-5
64927 mGluR1 Ab IFA, CSF 94361-3
605156 GFAP IFA, CSF 94360-5
89079 AGNA-1, CSF 94355-5
5906 Amphiphysin Ab, CSF 94354-8
3852 ANNA-1, CSF 94356-3
7472 ANNA-2, CSF 94357-1
21633 ANNA-3, CSF 94358-9
21650 CRMP-5-IgG, CSF 94706-9
21632 PCA-2, CSF 94364-7
21631 PCA-Tr, CSF 94362-1
21702 GAD65 Ab Assay, CSF 94359-7
36429 Reflex Added 77202-0
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-neuroimmunology