Sign in →

Test Code EPC1 Epilepsy, Autoimmune Evaluation, Spinal Fluid

Secondary ID

48406

Useful For

Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of less than 2 years

 

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
NMDCC NMDA-R Ab CBA, CSF No Yes
VGKCC VGKC-complex Ab IPA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
CS2CC CASPR2-IgG CBA, CSF No Yes
GD65C GAD65 Ab Assay, CSF Yes Yes
GABCC GABA-B-R Ab CBA, CSF No Yes
AMPCC AMPA-R Ab CBA, CSF 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
AGN1C Anti-Glial Nuclear Ab, Type 1 No Yes
PCA2C Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCTRC Purkinje Cell Cytoplasmc Ab Type Tr No Yes
AMPHC Amphiphysin Ab, CSF No Yes
CRMC CRMP-5-IgG, CSF No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
WBNC Paraneoplas Autoantibody WBlot,CSF No No
CRMWC CRMP-5-IgG Western Blot, CSF Yes No
ABLTC Amphiphysin Western Blot, CSF No No
NMOFC NMO/AQP4 FACS, CSF Yes No
NMOTC NMO/AQP4 FACS Titer, CSF No No
AMPIC AMPA-R Ab IF Titer Assay, CSF No No
GABIC GABA-B-R Ab IF Titer Assay, CSF No No
NMDIC NMDA-R Ab IF Titer Assay, CSF No No
PCA1C Purkinje Cell Cytoplasmic Ab Type 1 No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) (ANN1C, ANN2C, ANN3C, PCA2C, PCTRC, AMPHC, CRMC, AGN1C) is indeterminate, then paraneoplastic autoantibody Western blot is performed at an additional charge.

 

If IFA patterns suggest CRMP-5-IgG, then CRMP-5-IgG Western blot is performed at an additional charge.

 

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

 

If IFA pattern suggest NMO/AQP4-IgG, then NMO/AQP4-IgG FACS is performed at an additional charge.

 

If NMO/AQP4-IgG FACS screen assay requires further investigation, then NMO/AQP4-IgG FACS titration assay is performed at an additional charge.

 

If IFA pattern suggest AMPA-Receptor antibody and AMPA-Receptor antibody CBA is positive, then AMPA-Receptor antibody IF titer assay is performed at an additional charge.

 

If IFA pattern suggest GABA-B-Receptor antibody and GABA-B-R Receptor Ab antibody is positive, then GABA-B-R Receptor Ab antibody IF titer assay is performed at an additional charge.

 

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

 

If IFA patterns suggest PCA-1, then Purkinje Cell Cytoplasmic antibody Type 1 assay is performed at an additional charge.

 

Western Blot:

1. Native neuronal antigens: performed to confirm neuronal nuclear and cytoplasmic Ab specificities when IF screening is uninterpretable.

2. Recombinant human collapsin response-mediator protein-5: performed to confirm CRMP-5-IgG when IF screening is uninterpretable. Also performed for more sensitive detection of CRMP-5-IgG.

 

See Epilepsy Autoimmune Evaluation Algorithm, Spinal Fluid in Special Instructions

Method Name

ANN1C, ANN2C, ANN3C, AGN1C, PCA1C, PCA2C, PCTRC, AMPHC, CRMC, AMPIC, GABIC, NMDIC: Indirect Immunofluorescence Assay (IFA)

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

GD65C: Immunoprecipitation Assay

VGKCC: Radioimmunoassay Assay (RIA)

WBNC, ABLTC: Western Blot

Reporting Name

Epilepsy-Autoimmune Evaluation, CSF

Specimen Type

CSF


Necessary Information


Include name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.



Specimen Required


Container/Tube: Sterile vial

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

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

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

NA

Other

NA

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 voltage-gated potassium channel-complex (VGKC-complex), 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, and acetylcholine receptor [muscle AChR] binding 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 cerebral spinal fluid and serum for neural autoantibodies. Selective autoantibody testing is not advised because no single neural antibody is definitively associated with seizures, and markers of occult cancer may be missed. 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

NEURONAL NUCLEAR ANTIBODIES

Antineuronal Nuclear Antibody-Type 1 (ANNA-1)

<1:2

Antineuronal Nuclear Antibody-Type 2 (ANNA-2)

<1:2

Antineuronal Nuclear Antibody-Type 3 (ANNA-3)

<1:2

Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)

<1:2

 

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES

Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)

<1:2      

Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)

<1:2    

Purkinje Cell Cytoplasmic Antibody, Type TR (PCA-TR)

<1:2

Amphiphysin Antibody

<1:2

Collapsin Response-Mediator Protein-5 Neuronal (CRMP-5-IGG)

<1:2

 

ISLET CELL ANTIBODIES

Glutamic Acid Decarboxylase (GAD65) Antibody Assay

≤0.02 nmol/L

 

AMPA-Receptor Antibody By CBA

CBA: Negative

IFA: <1:2

GABA-B-Receptor Antibody By CBA

CBA: Negative

IFA: <1:2

NMDA-Receptor Antibody By CBA

CBA: Negative

IFA: <1:2

 

Neuronal Voltage-Gated Potassium Channel-Complex Autoantibody

≤0.02 nmol/L

 

WESTERN BLOT

Paraneoplastic Autoantibody, Western Blot Confirmation

Negative

Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot

Negative

Amphiphysin Antibody Western Blot

Negative

LGI1-IgG CBA: Negative

CASPR2-IgG CBA: Negative

 

Neuromyelitis Optica (NMO)/Aquaporin-4-Igg FACS Assay

Negative

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) and Time(s) Performed

ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, AMPIC, GABIC, NMDIC:

Monday through Friday; 11:30 a.m. and 8:00 p.m.; Saturday and Sunday 8:00 a.m.

 

AMPCC, GABCC, NMDCC, LG1CC, CS2CC: Monday through Friday; 6 a.m.

Paraneoplastic autoantibody Western blot confirmation, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday, Wednesday, Friday; 8 a.m.

GAD65: Monday to Friday; 6:00 a.m. and 4:00 p.m.

VGKC: Monday through Friday 11:00 a.m. and 6:00 p.m.; Saturday 6:00 a.m.; Sunday 6:00 a.m.

Analytic Time

3 days if negative/5 days if positive

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

See individual test IDs

CPT Code Information

83519-Neuronal VGKC autoantibody

86255-AGNA-1

86255-Amphiphysin

86255-ANNA-1

86255-ANNA-2

86255-ANNA-3

86255-CRMP-5-IgG

86255-PCA-2

86255-PCA-Tr

86255-AMPAR-Ab

86255-GABAR-Ab

86255-NMDAR-Ab

86341-GAD65

86255-LG1CC

86255-CS2CC

 

86255-PCA-1 (if appropriate)

84182-Amphiphysin Western blot (if appropriate)

84182-CRMP-5 Western blot confirmation (if appropriate)

84182-Paraneoplastic autoantibody Western blot confirmation (if appropriate)

86255-NMO/AQP4-IgG FACS (if appropriate)

86256-AMPAR-Ab titer (if appropriate)

86256-GABAR-Ab titer (if appropriate)

86256-NMDAR-Ab titer (if appropriate)

86256- NMO/AQP4-IgG FACS titer (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
EPC1 Epilepsy-Autoimmune Evaluation, CSF In Process

 

Result ID Test Result Name Result LOINC Value
61513 NMDA-R Ab CBA, CSF No LOINC Needed
61514 AMPA-R Ab CBA, CSF No LOINC Needed
61515 GABA-B-R Ab CBA, CSF No LOINC Needed
34258 Epilepsy, Interpretation, CSF 69048-7
61729 VGKC-complex Ab IPA, CSF 68913-3
64280 LGI1-IgG CBA, CSF In Process
64282 CASPR2-IgG CBA, CSF In Process
89079 AGNA-1, CSF 53714-2
5906 Amphiphysin Ab, CSF 56531-7
3852 ANNA-1, CSF 24400-4
7472 ANNA-2, CSF 24401-2
21633 ANNA-3, CSF 35144-5
21650 CRMP-5-IgG, CSF 35385-4
21632 PCA-2, CSF 35143-7
21631 PCA-Tr, CSF 51748-2
21702 GAD65 Ab Assay, CSF 53708-4
36429 Reflex Added No LOINC Needed

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)