Test Catalog

Test ID: EPC1    
Epilepsy, Autoimmune Evaluation, Spinal Fluid

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

 

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

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

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.

 

The following algorithms are available in Special Instructions:

-Epilepsy Autoimmune Evaluation Algorithm, Spinal Fluid

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

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

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 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.

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

< or =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

< or =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 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 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.

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 evaluation 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.

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

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

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