Test ID EPIES Epilepsy, Autoimmune Evaluation, Serum
Useful For
Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of <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 |
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 | Yes | 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 |
NMOCS | NMO/AQP4-IgG CBA, S | Yes | 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 CBA 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
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, CRMWS, ABLOT: Western Blot
AMPCS, GABCS, NMDCS: Cell Binding Assay (CBA)
Reporting Name
Epilepsy-Autoimmune Evaluation, SSpecimen Type
SerumContainer/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 4 mL
Additional Information: Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.
Forms: If not ordering electronically, complete, print, and send a Neurology Test Request Form (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)
Specimen Minimum Volume
2 mL
Specimen Stability Information
Specimen Type | Temperature | Time |
---|---|---|
Serum | 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 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
NMO/AQP4-IgG
Negative
Cautions
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.
Day(s) Performed
ANN1S, ANN2S, ANN3S, AGN1S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AMPIS, GABIS, NMDIS: Monday through Friday; 11 a.m.
AMPCS, GABCS, NMDCS: Monday through Friday; 8 a.m.
Paraneoplastic autoantibody Western blot confirmation, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday through Friday; 8 a.m.
ARBI: Monday through Saturday; 5 p.m.
CCPQ, CCN: Monday thought Friday; 6 a.m.
GANG, VGKC, GD65S: Sunday through Thursday
Report Available
4 days if negative/7 days if positivePerforming Laboratory

Test Classification
See Individual ComponentsCPT 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
86256-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 CBA (if appropriate)
86256-AMPAR-Ab titer (if appropriate)
86256-GABAR-Ab titer (if appropriate)
86256-NMDAR-Ab titer (if appropriate)