Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum - MU Health Care Laboratory Test Catalog

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 test will be canceled.

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

This test is intended to be ordered for adult patients. If this test is ordered for a patient younger than 18 years of age, it will be canceled and automatically reordered by the laboratory as PCDES / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Serum. The pediatric autoimmune CNS disorders evaluation is part of an evolving approach to testing for autoimmune neurological disorders using phenotypic-specific evaluations that include multiple antibodies known for their disease association.

This test should not be requested for patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed or canceled if radioactivity remains.

Necessary Information

Provide the following information:

-Relevant clinical information

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

Specimen Required

Patient Preparation: For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 4 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Forms

If not ordering electronically, complete, print, and send 1 of the following with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-General Test Request (T239)

Secondary ID

92116

Useful For

Evaluating new onset encephalopathy (noninfectious or metabolic) comprising confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, sensory or motor complaints, seizures, dyssomnias, ataxias, nausea, vomiting, inappropriate antidiuresis, coma, dysautonomias, or hypoventilation using serum specimens

The following accompaniments should increase of suspicion for autoimmune encephalopathy:

-Headache

-Autoimmune stigmata (personal or family history or signs of diabetes mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)

-History of cancer

-Smoking history (20 or more pack-years) or other cancer risk factors

-Inflammatory cerebral spinal fluid (or isolated protein elevation)

-Neuroimaging signs suggesting inflammation

Evaluating limbic encephalitis (noninfectious)

Directing a focused search for cancer

Investigating encephalopathy appearing during or after cancer therapy and not explainable by metastasis or drug effect

Profile Information

Test ID	Reporting Name	Available Separately	Always Performed
AEESI	Encephalopathy, Interpretation, S	No	Yes
AMPCS	AMPA-R Ab CBA, S	No	Yes
AMPHS	Amphiphysin Ab, S	No	Yes
AGN1S	Anti-Glial Nuclear Ab, Type 1	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
CS2CS	CASPR2-IgG CBA, S	No	Yes
CRMS	CRMP-5-IgG, S	No	Yes
DPPCS	DPPX Ab CBA, S	No	Yes
GABCS	GABA-B-R Ab CBA, S	No	Yes
GD65S	GAD65 Ab Assay, S	Yes	Yes
GFAIS	GFAP IFA, S	No	Yes
GL1IS	mGluR1 Ab IFA, S	No	Yes
IG5CS	IgLON5 CBA, S	No	Yes
LG1CS	LGI1-IgG CBA, S	No	Yes
NCDIS	Neurochondrin IFA, S	No	Yes
NIFIS	NIF IFA, S	No	Yes
NMDCS	NMDA-R Ab CBA, S	No	Yes
PCABP	Purkinje Cell Cytoplasmic Ab Type 1	No	Yes
PCAB2	Purkinje Cell Cytoplasmic Ab Type 2	No	Yes
PCATR	Purkinje Cell Cytoplasmic Ab Type Tr	No	Yes
PDEIS	PDE10A Ab IFA, S	No	Yes
SP7IS	Septin-7 IFA, S	No	Yes
T46IS	TRIM46 Ab IFA, S	No	Yes

Reflex Tests

Test ID	Reporting Name	Available Separately	Always Performed
AGNBS	AGNA-1 Immunoblot, S	No	No
AINCS	Alpha Internexin CBA, S	No	No
AMPIS	AMPA-R Ab IF Titer Assay, S	No	No
AMIBS	Amphiphysin Immunoblot, S	No	No
AN1BS	ANNA-1 Immunoblot, S	No	No
AN2BS	ANNA-2 Immunoblot, S	No	No
CRMWS	CRMP-5-IgG Western Blot, S	Yes	No
DPPTS	DPPX Ab IFA Titer, S	No	No
GABIS	GABA-B-R Ab IF Titer Assay, S	No	No
GFACS	GFAP CBA, S	No	No
GFATS	GFAP IFA Titer, S	No	No
IG5TS	IgLON5 IFA Titer, S	No	No
GL1CS	mGluR1 Ab CBA, S	No	No
GL1TS	mGluR1 Ab IFA Titer, S	No	No
NFHCS	NIF Heavy Chain CBA, S	No	No
NIFTS	NIF IFA Titer, S	No	No
NFLCS	NIF Light Chain CBA, S	No	No
NMDIS	NMDA-R Ab IF Titer Assay, S	No	No
PC1BS	PCA-1 Immunoblot, S	No	No
PCTBS	PCA-Tr Immunoblot, S	No	No
AGNTS	AGNA-1 Titer, S	No	No
APHTS	Amphiphysin Ab Titer, S	No	No
AN1TS	ANNA-1 Titer, S	No	No
AN2TS	ANNA-2 Titer, S	No	No
AN3TS	ANNA-3 Titer, S	No	No
CRMTS	CRMP-5-IgG Titer, S	No	No
NCDCS	Neurochondrin CBA, S	No	No
NCDTS	Neurochondrin IFA Titer, S	No	No
PC1TS	PCA-1 Titer, S	No	No
PC2TS	PCA-2 Titer, S	No	No
PCTTS	PCA-Tr Titer, S	No	No
SP7CS	Septin-7 CBA, S	No	No
SP7TS	Septin-7 IFA Titer, S	No	No
PDETS	PDE10A Ab IFA Titer, S	No	No
T46CS	TRIM46 Ab CBA, S	No	No
T46TS	TRIM46 Ab IFA Titer, S	No	No

Testing Algorithm

If client requests or if the immunofluorescence (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 IFA titer and amphiphysin immunoblot will be performed at an additional charge.

If the IFA pattern suggests antiglial nuclear antibody (AGNA)-1, then the AGNA-1 IFA titer and AGNA-1 immunoblot 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 antibodies, then the ANNA-3 titer will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then the PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.

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

If the IgLON5 antibody cell binding assay (CBA) result is positive, then the IgLON5 IFA titer will be performed at an additional charge.

If the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody 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 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 neuronal intermediate filament (NIF) antibody, then the alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF 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 the following algorithms:

-Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Serum

-Central Nervous System Demyelinating Disease Diagnostic Algorithm

Special Instructions

Method Name

AEESI: Medical Interpretation

AGN1S, AGNTS, AMPHS, APHTS, AMPIS, ANN1S, AN1TS, ANN2S, AN2TS, AN3TS, ANN3S, CRMS, CRMTS, DPPTS, GABIS, GFAIS, GFATS, IG5TS, GL1IS, GL1TS, NCDIS, NCDTS, NIFIS, NIFTS, NMDIS, PCABP, PC1TS, PCAB2, PC2TS, PCATR, PCTTS, PDEIS, PDETS, SP7IS, SP7TS, T46IS, T46TS: Indirect Immunofluorescence Assay (IFA)

AMPCS, CS2CS, DPPCS, GABCS, GFACS, IG5CS, LG1CS, GL1CS, NCDCS, AINCS, NFLCS, NFHCS, NMDCS, SP7CS, T46CS: Cell Binding Assay (CBA)

CRMWS: Western Blot (WB)

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)

GD65S: Radioimmunoassay (RIA)

Reporting Name

Encephalopathy, Autoimm/Paraneo, S

Specimen Type

Serum

Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type	Temperature	Time
Serum	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
AEESI	Encephalopathy, Interpretation, S	Medical interpretation	Interpretive report
AMPCS	AMPA-R Ab CBA, S	CBA	Negative
AMPHS	Amphiphysin Ab, S	IFA	Negative
AGN1S	Anti-Glial Nuclear Ab, Type 1	IFA	Negative
ANN1S	Anti-Neuronal Nuclear Ab, Type 1	IFA	Negative
ANN2S	Anti-Neuronal Nuclear Ab, Type 2	IFA	Negative
ANN3S	Anti-Neuronal Nuclear Ab, Type 3	IFA	Negative
CS2CS	CASPR2-IgG CBA, S	CBA	Negative
CRMS	CRMP-5-IgG, S	IFA	Negative
DPPCS	DPPX Ab CBA, S	CBA	Negative
GABCS	GABA-B-R Ab CBA, S	CBA	Negative
GD65S	GAD65 Ab Assay, S	RIA	≤0.02 nmol/L Reference values apply to all ages.
GFAIS	GFAP IFA, S	IFA	Negative
GL1IS	mGluR1 Ab IFA, S	IFA	Negative
IG5CS	IgLON5 CBA, S	CBA	Negative
LG1CS	LGI1-IgG CBA, S	CBA	Negative
NCDIS	Neurochondrin IFA, S	IFA	Negative
NIFIS	NIF IFA, S	IFA	Negative
NMDCS	NMDA-R Ab CBA, S	CBA	Negative
PCABP	Purkinje Cell Cytoplasmic Ab Type 1	IFA	Negative
PCAB2	Purkinje Cell Cytoplasmic Ab Type 2	IFA	Negative
PCATR	Purkinje Cell Cytoplasmic Ab Type Tr	IFA	Negative
PDEIS	PDE10A Ab IFA, S	IFA	Negative
SP7IS	Septin-7 IFA, S	IFA	Negative
T46IS	TRIM46 IFA, S	IFA	Negative

Reflex Information:

Test ID	Reporting name	Methodology*	Reference value
AGNBS	AGNA-1 Immunoblot, S	IB	Negative
AGNTS	AGNA-1 Titer, S	IFA	<1:240
AINCS	Alpha Internexin CBA, S	CBA	Negative
AMPIS	AMPA-R Ab IF Titer Assay, S	IFA	<1:240
APHTS	Amphiphysin Ab Titer, S	IFA	<1:240
AMIBS	Amphiphysin Immunoblot, S	IB	Negative
AN1BS	ANNA-1 Immunoblot, S	IB	Negative
AN1TS	ANNA-1 Titer, S	IFA	<1:240
AN2BS	ANNA-2 Immunoblot, S	IB	Negative
AN2TS	ANNA-2 Titer, S	IFA	<1:240
AN3TS	ANNA-3 Titer, S	IFA	<1:240
CRMTS	CRMP-5-IgG Titer, S	IFA	<1:240
CRMWS	CRMP-5-IgG Western Blot, S	WB	Negative
DPPTS	DPPX Ab IFA Titer, S	IFA	<1:240
GABIS	GABA-B-R Ab IF Titer Assay, S	IFA	<1:240
GFACS	GFAP CBA, S	CBA	Negative
GFATS	GFAP IFA Titer, S	IFA	<1:240
IG5TS	IgLON5 IFA Titer, S	IFA	<1:240
GL1CS	mGluR1 Ab CBA, S	CBA	Negative
GL1TS	mGluR1 Ab IFA Titer, S	IFA	<1:240
NCDCS	Neurochondrin CBA, S	CBA	Negative
NCDTS	Neurochondrin IFA Titer, S	IFA	<1:240
NFHCS	NIF Heavy Chain CBA, S	CBA	Negative
NIFTS	NIF IFA Titer, S	IFA	<1:240
NFLCS	NIF Light Chain CBA, S	CBA	Negative
NMDIS	NMDA-R Ab IF Titer Assay, S	IFA	<1:240
PC1BS	PCA-1 Immunoblot, S	IB	Negative
PC1TS	PCA-1 Titer, S	IFA	<1:240
PC2TS	PCA-2 Titer, S	IFA	<1:240
PCTBS	PCA-Tr Immunoblot, S	IB	Negative
PCTTS	PCA-Tr Titer, S	IFA	<1:240
PDETS	PDE10A Ab IFA Titer, S	IFA	<1:240
SP7CS	Septin-7 CBA, S	CBA	Negative
SP7TS	Septin-7 IFA Titer, S	IFA	<1:240
T46CS	TRIM46 CBA, S	CBA	Negative
T46TS	TRIM46 IFA Titer, S	IFA	<1:240

*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, CRMP-5-IgG, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

Note: CRMP-5 titers lower than 1:240 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored serum (held 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: Rose NR, Hamilton RG, et al, eds. Manual of Clinical and Laboratory Immunology. 6th ed. ASM Press; 2002:1005-1012; 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 room temperature (18 to 28° C) utilizing the EUROBlot One instrument. Diluted patient serum (1:101) 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 serum antibodies and then incubated with anti-human IgG antibodies (alkaline phosphatase-labelled) for 30 minutes. The strips are again washed to remove unbound anti-human IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolylphosphate (NBT/BCIP) substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produces 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, Kim K, Benarroch EE, Lennon VA. 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

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 23

86341 x 1

84182-AGNBS (if appropriate)

86256 AGNTS (if appropriate)

86255-AINCS (if appropriate)

86256-AMPIS (if appropriate)

86256 APHTS (if appropriate)

84182-AMIBS (if appropriate)

84182-AN1BS (if appropriate)

86256 AN1TS (if appropriate)

84182-AN2BS (if appropriate)

86256 AN2TS (if appropriate)

86256 AN3TS (if appropriate)

86256 CRMTS (if appropriate)

84182-CRMWS (if appropriate)

86256-DPPTS (if appropriate)

86256-GABIS (if appropriate)

86255-GFACS (if appropriate)

86256-GFATS (if appropriate)

86256-IG5TS (if appropriate)

86255-GL1CS (if appropriate)

86256-GL1TS (if appropriate)

86255 NCDCS (if appropriate)

86256 NCDTS (if appropriate)

86255-NFHCS (if appropriate)

86256-NIFTS (if appropriate)

86255-NFLCS (if appropriate)

86256-NMDIS (if appropriate)

84182-PC1BS (if appropriate)

86256 PC1TS (if appropriate)

86256 PC2TS (if appropriate)

84182-PCTBS (if appropriate)

86256 PCTTS (if appropriate)

86256 PDETCS (if appropriate)

86255 SP7CS (if appropriate)

86256 SP7TS (if appropriate)

86255 T46CS (if appropriate)

86256 T46TS (if appropriate)

LOINC Code Information

Test ID	Test Order Name	Order LOINC Value
ENS2	Encephalopathy, Autoimm/Paraneo, S	94697-0

Result ID	Test Result Name	Result LOINC Value
61516	NMDA-R Ab CBA, S	93503-1
61518	AMPA-R Ab CBA, S	93489-3
61519	GABA-B-R Ab CBA, S	93428-1
606950	IgLON5 CBA, S	96478-3
615867	Neurochondrin IFA, S	101452-1
615875	Septin-7 IFA, S	101465-3
616445	TRIM46 Ab IFA, S	103843-9
620068	PDE10A Ab IFA, S	103842-1
34257	Encephalopathy, Interpretation, S	69048-7
64279	LGI1-IgG CBA, S	94287-0
64281	CASPR2-IgG CBA, S	94285-4
64933	DPPX Ab CBA, S	94676-4
64928	mGluR1 Ab IFA, S	94347-2
605155	GFAP IFA, S	94346-4
606964	NIF IFA, S	96486-6
89080	AGNA-1, S	84927-3
81722	Amphiphysin Ab, S	72327-0
80150	ANNA-1, S	33615-6
80776	ANNA-2, S	43187-4
83137	ANNA-3, S	43102-3
83077	CRMP-5-IgG, S	72504-4
81596	GAD65 Ab Assay, S	30347-9
83138	PCA-2, S	84925-7
9477	PCA-1, S	84924-0
83076	PCA-Tr, S	84926-5
618896	IFA Notes	48767-8

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Test Code ENS2 Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum