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

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

Clinical Information

Antiepileptic drugs (AED) 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 (CSF) 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 most informative for autoimmune epilepsies include leucine-rich glioma inactivated protein-1 (LGI1), glutamic acid decarboxylase-65 (GAD65), N-methyl-D-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPA-R), and gamma-aminobutyric acid type B receptor (GABA-B-R)Â 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), 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 CSF and serum for neural autoantibodies. Selective testing for individual autoantibodies is not advised because each is individually rare, and a timely diagnosis is critical. Collectively, the antibodies tested for in the autoimmune epilepsy evaluations represent a broad spectrum of treatable disorders, some of which are associated with occult cancer. Testing of CSF for autoantibodies is particularly helpful when serum testing is negative, although, in some circumstances, testing both serum and CSF simultaneously is pertinent. Testing of CSF is recommended for some antibodies (eg, NMDA-R antibody and glial fibrillary acidic protein [GFAP]-IgG) because CSF testing is more sensitive and specific. In contrast, serum testing for LGI1 antibody is more sensitive than CSF testing. 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

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.

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

8 to 12 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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