Order Code EPC2 Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

Ordering Guidance

Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, see Autoimmune Neurology Test Ordering Guide.

When more than one evaluation is ordered on the same order number the duplicate will be canceled.

For a list of antibodies performed with each evaluation, see Autoimmune Neurology Antibody Matrix.

Necessary Information

Provide the following information:

-Relevant clinical information

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

Specimen Required

Container/Tube: Sterile vial

Preferred: Collection vial number 1

Acceptable: Any collection vial

Specimen Volume: 4 mL

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Useful For

Investigating new onset cryptogenic epilepsy with incomplete seizure control and duration of fewer 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 or more pack-years) or other cancer risk factors

-Investigating seizures occurring within the context of a subacute multifocal neurological disorder without an obvious cause, especially in a patient with a 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
DPPCC	DPPX Ab CBA, 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
NCDIC	Neurochondrin 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
PDEIC	PDE10A Ab IFA, CSF	No	Yes
T46IC	TRIM46 Ab IFA, CSF	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
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
PCTBC	PCA-Tr Immunoblot, CSF	No	No
AGNTC	AGNA-1 Titer, CSF	No	No
AN1TC	ANNA-1 Titer, CSF	No	No
AN2TC	ANNA-2 Titer, CSF	No	No
AN3TC	ANNA-3 Titer, CSF	No	No
APHTC	Amphiphysin Ab Titer, CSF	No	No
CRMTC	CRMP-5-IgG Titer, CSF	No	No
NCDCC	Neurochondrin CBA, CSF	No	No
NCDTC	Neurochondrin IFA Titer, CSF	No	No
PC2TC	PCA-2 Titer, CSF	No	No
PCTTC	PCA-Tr Titer, CSF	No	No
PDETC	PDE10A Ab IFA Titer, CSF	No	No
T46CC	TRIM46 Ab CBA, CSF	No	No
T46TC	TRIM46 Ab IFA Titer, CSF	No	No

Testing Algorithm

If the client requests or if the indirect immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.

If the IFA patterns suggest amphiphysin antibody, then the amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.

If the IFA pattern suggests antiglial nuclear antibody (AGNA)-1, then the AGNA-1 immunoblot and AGNA-1 IFA titer will be performed at an additional charge.

If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.

If the IFA pattern suggests ANNA-2 antibody, then the ANNA-2 IFA titer, ANNA-2 immunoblot, and ANNA-1 immunoblot will be performed at an additional charge.

If the client requests or the IFA pattern suggests ANNA-3 antibody, then the ANNA-3 IFA titer will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 2 (PCA-2), then the PCA-2 IFA titer will be performed at an additional charge.

If the IFA pattern suggests PCA-Tr antibody, then the PCA-Tr immunoblot and PCA-Tr IFA titer will be performed at an additional charge.

If the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-receptor antibody cell-binding assay (CBA) result is positive, then the AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

If the gamma-aminobutyric acid B (GABA-B)-receptor antibody CBA result is positive, then the GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.

If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP IFA titer and GFAP CBA will be performed at an additional charge.

If the N-methyl-D-aspartate (NMDA) receptor antibody CBA result is positive, then the NMDA-receptor antibody IFA titer assay will be performed at an additional charge.

If the dipeptidyl-peptidase-like protein-6 (DPPX) antibody CBA result is positive, then the DPPX IFA titer will be performed at an additional charge.

If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then the mGluR1 antibody CBA and mGluR1 IFA titer will be performed at an additional charge.

If the IFA pattern suggests neurochondrin antibody, then the neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.

If the IFA pattern suggests tripartite motif-containing protein 46 (TRIM46) antibody, then the TRIM46 antibody CBA and TRIM46 IFA titer will be performed at an additional charge.

If the IFA pattern suggests phosphodiesterase 10A (PDE10A) antibody, then the PDE10A antibody IFA titer will be performed at an additional charge.

For more information see Autoimmune/Paraneoplastic Epilepsy Evaluation Algorithm-Spinal Fluid.

Method Name

AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, NCDIC, NCDTC, NMDIC, PCA2C, PC2TC, PCTRC, PCTTC, PDEIC, PDETC, T46IC, T46TC: Indirect Immunofluorescence Assay (IFA)

AMPCC, CS2CS, DPPCC, GABCC, GFACC, LG1CC, GL1CC, NCDCC, NMDCC, T46CC: Cell Binding Assay (CBA)

CRMWC: Western Blot (WB)

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

GD65C: Radioimmunoassay (RIA)

Reporting Name

Epilepsy, Autoimm/Paraneo, CSF

Specimen Type

CSF

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

Gross hemolysis	Reject
Gross lipemia	Reject
Gross icterus	Reject

Reference Values

Test ID	Reporting Name	Methodology*	Reference Value
AEPCI	Epilepsy, Interpretation, CSF	Medical interpretation	Interpretive report
AMPCC	AMPA-R Ab CBA, CSF	CBA	Negative
AMPHC	Amphiphysin Ab, CSF	IFA	Negative
AGN1C	Anti-Glial Nuclear Ab, Type 1	IFA	Negative
ANN1C	Anti-Neuronal Nuclear Ab, Type 1	IFA	Negative
ANN2C	Anti-Neuronal Nuclear Ab, Type 2	IFA	Negative
ANN3C	Anti-Neuronal Nuclear Ab, Type 3	IFA	Negative
CS2CC	CASPR2-IgG CBA, CSF	CBA	Negative
CRMC	CRMP-5-IgG, CSF	IFA	Negative
DPPCC	DPPX Ab CBA, CSF	CBA	Negative
GABCC	GABA-B-R Ab CBA, CSF	CBA	Negative
GD65C	GAD65 Ab Assay, CSF	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
NCDIC	Neurochondrin IFA, CSF	IFA	Negative
NMDCC	NMDA-R Ab CBA, CSF	CBA	Negative
PCTRC	Purkinje Cell Cytoplasmic Ab Type Tr	IFA	Negative
PCA2C	Purkinje Cell Cytoplasmic Ab Type 2	IFA	Negative
PDEIC	PDE10A Ab IFA, CSF	IFA	Negative
T46IC	TRIM46 Ab IFA, CSF	IFA	Negative

Reflex Information:

Test ID	Reporting Name	Methodology*	Reference Value
AGNBC	AGNA-1 Immunoblot, CSF	IB	Negative
AGNTC	AGNA-1 Titer, CSF	IFA	<1:2
AMPIC	AMPA-R Ab IF Titer Assay, CSF	IFA	<1:2
AMIBC	Amphiphysin Immunoblot, CSF	IB	Negative
AN1BC	ANNA-1 Immunoblot, CSF	IB	Negative
AN1TC	ANNA-1 Titer, CSF	IFA	<1:2
AN2BC	ANNA-2 Immunoblot, CSF	IB	Negative
AN2TC	ANNA-2 Titer, CSF	IFA	<1:2
AN3TC	ANNA-3 Titer, CSF	IFA	<1:2
APHTC	Amphiphysin Ab Titer, CSF	IFA	<1:2
CRMTC	CRMP-5-IgG Titer, CSF	IFA	<1:2
CRMWC	CRMP-5-IgG Western Blot, CSF	WB	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
NCDCC	Neurochondrin CBA, CSF	CBA	Negative
NCDTC	Neurochondrin IFA Titer, CSF	IFA	<1:2
NMDIC	NMDA-R Ab IF Titer Assay, CSF	IFA	<1:2
PC2TC	PCA-2 Titer, CSF	IFA	<1:2
PCTBC	PCA-Tr Immunoblot, CSF	IB	Negative
PCTTC	PCA-Tr Titer, CSF	IFA	<1:2
PDETC	PDE10A Ab IFA Titer, CSF	IFA	<1:2
T46CC	TRIM46 Ab CBA, CSF	CBA	Negative
T46TC	TRIM46 Ab IFA Titer, CSF	IFA	<1:2

*Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Western blot (WB)

Radioimmunoassay (RIA)

Immunoblot (IB)

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, ANNA-3, PCA-2, or PCA-Tr may be reported as "unclassified antineuronal IgG." Complex patterns that include non-neuronal 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 for 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.

Method Description

Cell-Binding Assay:

Patient specimen is applied to a composite slide containing transfected and nontransfected HEK-293 cells. After incubation and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the presence of patient IgG binding.(Package insert: IIFT: Neurology Mosaics, Instructions for the indirect immunofluorescence test. EUROIMMUN; FA_112d-1_A_UK_C13, 02/2019)

Indirect Immunofluorescence Assay:

The patient's sample is tested by a standardized immunofluorescence assay that uses a composite frozen section of mouse cerebellum, kidney, and gut tissues. After incubation with sample and washing, fluorescein-conjugated goat-antihuman IgG is applied. Neuron-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Samples that are scored positive for any neuronal nuclear or cytoplasmic autoantibody are titrated to an endpoint. Interference by coexisting non-neuron-specific autoantibodies can usually be eliminated by serologic absorption.(Honorat JA, Komorowski L, Josephs KA, et al. IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm 2017;4(5):e385. doi:10.1212/NXI.0000000000000385)

Radioimmunoassay:

(125)I-labeled recombinant human antigens or labeled receptors are incubated with patient specimen. After incubation, anti-human IgG is added to form an immunoprecipitate. The amount of (125)I-labeled antigen in the immunoprecipitate is measured using a gamma-counter. The amount of gamma emission in the precipitate is proportional to the amount of antigen-specific IgG in the specimen. Results are reported as units of precipitated antigen (nmol) per liter of patient sample.(Griesmann GE, Kryzer TJ, Lennon VA. Autoantibody profiles of myasthenia gravis and Lambert-Eaton myasthenic syndrome. In: NR Rose, RG Hamilton, eds. Manual of Clinical and Laboratory Immunology. 6th ed. ASM Press; 2002:1005-1012; Walikonis JE, Lennon VA. Radioimmunoassay for glutamic acid decarboxylase [GAD65] autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc. 1998;73[12]:1161-1166; Jones AL, Flanagan EP, Pittock SJ, et al. Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol. 2015;72[11]:1304-1312. doi:10.1001/jamaneurol.2015.2378)

Immunoblot:

All steps are performed at ambient temperature (18-28° C) utilizing the EUROBlot One instrument. Diluted patient specimen (1:12.5) is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive specimens will bind to the purified recombinant antigen and negative specimens will not bind. Strips are washed to remove unbound antibodies and then incubated with antihuman IgG antibodies (alkaline phosphatase-labeled) for 30 minutes. The strips are again washed to remove unbound antihuman IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produce a black band. Strips are digitized via picture capture on the EUROBlot One instrument and evaluated with the EUROLineScan software.(O'Connor K, Waters P, Komorowski L, et al. GABAA receptor autoimmunity: A multicenter experience. Neurol Neuroimmunol Neuroinflamm. 2019;6[3]:e552 doi:10.1212/NXI.0000000000000552)

Western Blot:

Neuronal antigens extracted aqueously from adult rat cerebellum, full-length recombinant human collapsin response-mediator protein-5 (CRMP-5), or full-length recombinant human amphiphysin protein is denatured, reduced, and separated by electrophoresis on 10% polyacrylamide gel. IgG is detected autoradiographically by enhanced chemiluminescence.(Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al. Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019;93[20]:e1873-e1880. doi:10.1212/WNL.0000000000008472)

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

86255 x 19

86341 x 1

84182-AGNBC (if appropriate)

86256-AGNTC (if appropriate)

86256-AMPIC (if appropriate)

84182-AMIBC (if appropriate)

84182-AN1BC (if appropriate)

86256 AN1TC (if appropriate)

84182-AN2BC (if appropriate)

86256-AN2TC (if appropriate)

86256-AN3TC (if appropriate)

86256-APHTC (if appropriate)

86256-CRMTC (if appropriate)

84182-CRMWC (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)

86255-NCDCC (if appropriate)

86256-NCDTC (if appropriate)

86256-NMDIC (if appropriate)

86256-PC2TC (if appropriate)

84182-PCTBC (if appropriate)

86256-PCTTC (if appropriate)

86256-PDETC (if appropriate)

86255-T46CC (if appropriate)

86256-T46TC (if appropriate)

Special Instructions

Autoimmune/Paraneoplastic Epilepsy Evaluation Algorithm-Spinal Fluid

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