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Test Code EPS1 Epilepsy, Autoimmune Evaluation, Serum

Secondary ID

48403

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

-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
NMDCS NMDA-R Ab CBA, S No Yes
VGKC Neuronal (V-G) K+ Channel Ab, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
CS2CS CASPR2-IgG CBA, S No Yes
GD65S GAD65 Ab Assay, S Yes Yes
GABCS GABA-B-R Ab CBA, S No Yes
AMPCS AMPA-R Ab CBA, S 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
AGN1S Anti-Glial Nuclear Ab, Type 1 No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No Yes
AMPHS Amphiphysin Ab, S No Yes
CCN N-Type Calcium Channel Ab No Yes
CCPQ P/Q-Type Calcium Channel Ab No Yes
ARBI ACh Receptor (Muscle) Binding Ab No Yes
GANG AChR Ganglionic Neuronal Ab, S No Yes
CRMS CRMP-5-IgG, S No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No
WBN Paraneoplastic Autoantibody WBlot,S No No
CRMWS CRMP-5-IgG Western Blot, S No No
ABLOT Amphiphysin Western Blot, S No No
NMOFS NMO/AQP4 FACS, S Yes No
NMOTS NMO/AQP4 FACS Titer, S No No
NMDIS NMDA-R Ab IF Titer Assay, S No No
AMPIS AMPA-R Ab IF Titer Assay, S No No
GABIS GABA-B-R Ab IF Titer Assay, S No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) patterns suggest PCA-1, then Purkinje cell cytoplasmic antibody type 1 is performed at an additional charge.

 

If IFA suggests ANN1S, ANN2S, ANN3S, PCAB2, PCATR, AMPHS, CRMS, AGN1S, or is indeterminate, then paraneoplastic autoantibody Western blot is performed at an additional charge.

 

If client requests, or 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 NMDA-R antibody and NMDA-R antibody CBA is positive, then NMDA-R titer is performed at an additional charge.

 

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

 

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

 

Confirmation of GAD65 antibodies when IF screening suggests GAD65 antibodies.

 

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

 

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, Serum in Special Instructions

Method Name

ANN1S, ANN2S, ANN3S, AGN1S, PCAB2, PCATR, AMPHS, CRMS, PCABP, NMDIS, AMPIS, GABIS: Indirect Immunofluorescence Assay (IFA)

VGKC, CCN, CCPQ, GANG, GD65S, ARBI: Radioimmunoassay (RIA)

WBN, ABLOT: Western Blot

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

Reporting Name

Epilepsy-Autoimmune Evaluation, S

Specimen Type

Serum


Necessary Information


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



Specimen Required


Container/Tube: 

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

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

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

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, CRMP 5-IgG, N-type voltage-gated calcium channel and muscle AChR) 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 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 Ab, Type 1 (ANNA-1)

<1:240

Antineuronal Nuclear Ab, Type 2 (ANNA-2)

<1:240

Antineuronal Nuclear Ab, Type 3 (ANNA-3)

<1:240

Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)

<1:240

 

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES

Purkinje Cell Cytoplasmic Ab, Type1 (PCA-1)

<1:240

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

<1:240

Purkinje Cell Cytoplasmic Ab, Type Tr (PCA-Tr)

<1:240

Amphiphysin Antibody

<1:240

CRMP-5-IgG

<1:240

 

WESTERN BLOT

Paraneoplastic Western Blot

Negative

CRMP-5-IgG Western Blot

Negative

Amphiphysin Western Blot

Negative

 

ISLET CELL ANTIBODIES

Glutamic Acid Decarboxylase (GAD65) Antibody

≤0.02 nmol/L

 

CATION CHANNEL ANTIBODIES

N-Type Calcium Channel Antibody

≤0.03 nmol/L

P/Q-Type Calcium Channel Antibody

≤0.02 nmol/L

AChR Ganglionic Neuronal Antibody

≤0.02 nmol/L

Neuronal VGKC Autoantibody

≤0.02 nmol/L

 

ACHR RECEPTOR ANTIBODIES

ACh Receptor (Muscle) Binding Antibody

≤0.02 nmol/L

 

N-Methyl-D-aspartate receptor (NMDA-R)

CBA: Negative

IFA: <1:120

2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor (AMPA-R)

CBA: Negative

IFA: <1:120

Gamma-Amino Butyric acid-type B receptor (GABA-B-R)

CBA: Negative

IFA: <1:120

LGI1-IgG CBA: Negative

CASPR2-IgG CBA: Negative         

 

Neuromyelitis Optica (NMO)/Aquaporin-4-IgG FACS Assay, S

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 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.

-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).

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, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 Feb;49(2):146-154 *Accompanying 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

ANN1S, ANN2S, ANN3S, AGN1S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AMPIS, GABIS, NMDIS:

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

AMPCS, GABCS, NMDCS, LG1CS, CS2CS: 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.

ARBI:

Monday through Friday 11:00 a.m., 6:00 p.m., and 10:00 p.m.; Saturday 6:00 a.m.; Sunday 6:00 a.m. and 10:00 a.m.

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

GD65S: Monday to Friday; 6:00 a.m. and 4:00 p.m.

Analytic Time

4 days if negative/7 days if positive

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

See Individual Test IDs

CPT Code Information

83519-ACh receptor (muscle) binding antibody

83519-AChR ganglionic neuronal antibody

83519-Neuronal VGKC autoantibody

83519-N-type calcium channel antibody

83519-P/Q-type calcium channel antibody

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-LG1CS

86255-CS2CS

 

 

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
EPS1 Epilepsy-Autoimmune Evaluation, S In Process

 

Result ID Test Result Name Result LOINC Value
61516 NMDA-R Ab CBA, S No LOINC Needed
61518 AMPA-R Ab CBA, S No LOINC Needed
61519 GABA-B-R Ab CBA, S No LOINC Needed
34259 Epilepsy, Interpretation, S 69048-7
64279 LGI1-IgG CBA, S In Process
64281 CASPR2-IgG CBA, S In Process
89080 AGNA-1, S 53709-2
81722 Amphiphysin Ab, S 33927-5
80150 ANNA-1, S 13997-2
80776 ANNA-2, S 43188-2
83137 ANNA-3, S 33924-2
8338 ACh Receptor (Muscle) Binding Ab 11034-6
81184 N-Type Calcium Channel Ab 33979-6
81185 P/Q-Type Calcium Channel Ab 33980-4
83077 CRMP-5-IgG, S 35386-2
84321 AChR Ganglionic Neuronal Ab, S 42233-7
81596 GAD65 Ab Assay, S 30347-9
83138 PCA-2, S 33925-9
83076 PCA-Tr, S 33926-7
89165 Neuronal (V-G) K+ Channel Ab, S 41871-5
36349 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)