Myelopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid - Mayo Clinic Laboratories

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.

Necessary Information

Provide the following information:

-Relevant clinical information

-Ordering healthcare professional's name, phone number, mailing address, and email 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

Evaluating patients with suspected autoimmune myelopathy, myelitis, and paraneoplastic myelopathy using spinal fluid specimens

Profile Information

Test ID	Reporting Name	Available Separately	Always Performed
MCI1	Autoimmune Myelopathy Interp, 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
APBIC	AP3B2 IFA, CSF	No	Yes
CRMWC	CRMP-5-IgG Western Blot, CSF	Yes	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
GL1IC	mGluR1 Ab IFA, CSF	No	Yes
NCDIC	Neurochondrin IFA, CSF	No	Yes
NIFIC	NIF IFA, CSF	No	Yes
NMOFC	NMO/AQP4 FACS, CSF	Yes	Yes
PCA1C	Purkinje Cell Cytoplasmic Ab Type 1	No	Yes
PCA2C	Purkinje Cell Cytoplasmic Ab Type 2	No	Yes
SP7IC	Septin-7 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
AINCC	Alpha Internexin CBA, CSF	No	No
AMIBC	Amphiphysin Immunoblot, CSF	No	No
AN1BC	ANNA-1 Immunoblot, CSF	No	No
AN2BC	ANNA-2 Immunoblot, CSF	No	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
NFHCC	NIF Heavy Chain CBA, CSF	No	No
NIFTC	NIF IFA Titer, CSF	No	No
NFLCC	NIF Light Chain CBA, CSF	No	No
NMOTC	NMO/AQP4 FACS Titer, CSF	No	No
PC1BC	PCA-1 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
APBCC	AP3B2 CBA, CSF	No	No
APBTC	AP3B2 IFA 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
PC1TC	PCA-1 Titer, CSF	No	No
PC2TC	PCA-2 Titer, CSF	No	No
SP7CC	Septin-7 CBA, CSF	No	No
SP7TC	Septin-7 IFA Titer, CSF	No	No
T46CC	TRIM46 Ab CBA, CSF	No	No
T46TC	TRIM46 Ab IFA Titer, CSF	No	No

Testing Algorithm

If the indirect immunofluorescence assay (IFA) pattern suggests anti-glial 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 amphiphysin antibody, then the amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.

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

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

If the IFA pattern suggests adaptor protein 3 beta 2 (AP3B2) antibodies, then the AP3BC cell-binding assay (CBA) and AP3BC IFA titer will be performed at an additional charge.

If the collapsin response-mediator protein 5 (CRMP-5)-IgG Western blot is positive, then the CRMP-5-IgG IFA titer will be performed at an additional charge.

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

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

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

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

If the neuromyelitis optica/aquaporin-4-IgG (NMO/AQP4-IgG) fluorescence-activated cell sorting (FACS) screen assay requires further investigation, then the NMO/AQP4-IgG FACS titration assay 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 antibody 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 septin 7 antibody, then the septin 7 CBA and septin 7 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.

For more information see:

Autoimmune/Paraneoplastic Myelopathy Evaluation Algorithm-Spinal Fluid

Central Nervous System Demyelinating Disease Diagnostic Algorithm

Method Name

MCI1: Medical Interpretation

AGN1C, AGNTC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, APBIC, APBTC, CRMTC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, NCDIC, NCDTC, NIFIC, NIFTC, PCA1C, PC1TC, PCA2C, PC2TC, SP7IC, SP7TC, T46IC, T46TC: Indirect Immunofluorescence Assay (IFA)

GD65C: Radioimmunoassay (RIA)

CRMWC: Western Blot (WB)

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC: Immunoblot (IB)

NMOFC, NMOTC: Flow Cytometry (FCM)

APBCC, DPPCC, GABCC, GFACC, GL1CC, NCDCC, AINCC, NFLCC, NFHCC, SP7CC, T46CC: Cell-Binding Assay (CBA)

Reporting Name

Myelopathy, 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

Clinical Information

Patients with autoimmune myelopathy present with subacute onset and rapid progression of spinal cord symptoms with one or more of the following: weakness, gait difficulties, loss of sensation, neuropathic pain, and bowel and bladder dysfunction. Clinical history and examination, spinal cord magnetic resonance imaging, and cerebrospinal fluid (CSF) testing may provide clues to an autoimmune diagnosis. Autoimmune myelopathy evaluation of both serum and CSF can assist in the diagnosis (paraneoplastic or idiopathic autoimmune) and aid distinction from other causes of myelopathy (multiple sclerosis, sarcoidosis, vascular disease). Early testing may assist in early diagnosis of occult cancer, prompt initiation of immune therapies, or both.

Reference Values

Test ID	Reporting name	Methodology*	Reference value
MCI1	Autoimmune Myelopathy Interp, CSF	Medical interpretation	Interpretive report
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
APBIC	AP3B2 IFA, CSF	IFA	Negative
CRMWC	CRMP-5-IgG Western Blot, CSF	WB	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
GL1IC	mGluR1 Ab IFA, CSF	IFA	Negative
NCDIC	Neurochondrin IFA, CSF	IFA	Negative
NIFIC	NIF IFA, CSF	IFA	Negative
NMOFC	NMO/AQP4 FACS, CSF	FCM	Negative
PCA1C	Purkinje Cell Cytoplasmic Ab Type 1	IFA	Negative
PCA2C	Purkinje Cell Cytoplasmic Ab Type 2	IFA	Negative
SP7IC	Septin-7 IFA, CSF	IFA	Negative
T46IC	TRIM46 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
AINCC	Alpha Internexin CBA, CSF	CBA	Negative
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
APBCC	AP3B2 CBA, CSF	CBA	Negative
APBTC	AP3B2 IFA Titer, CSF	IFA	<1:2
APHTC	Amphiphysin Ab Titer, CSF	IFA	<1:2
CRMTC	CRMP-5-IgG Titer, CSF	IFA	<1:2
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
NFHCC	NIF Heavy Chain CBA, CSF	CBA	Negative
NIFTC	NIF IFA Titer, CSF	IFA	<1:2
NFLCC	NIF Light Chain CBA, CSF	CBA	Negative
NMOTC	NMO/AQP4 FACS Titer, CSF	FCM	<1:2
PC1BC	PCA-1 Immunoblot, CSF	IB	Negative
PC1TC	PCA-1 Titer, CSF	IFA	<1:2
PC2TC	PCA-2 Titer, CSF	IFA	<1:2
SP7CC	Septin-7 CBA, CSF	CBA	Negative
SP7TC	Septin-7 IFA Titer, CSF	IFA	<1:2
T46CC	TRIM46 CBA, CSF	CBA	Negative
T46TC	TRIM46 IFA Titer, CSF	IFA	<1:2

*Methodology Abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Flow cytometry (FCM)

Radioimmunoassay (RIA)

Immunoblot (IB)

Western blot (WB)

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, ANNA-3, CRMP-5-IgG, PCA-1, or PCA-2 may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

Interpretation

A positive result is consistent with a diagnosis of autoimmune myelopathy in the appropriate clinical context.

Clinical Reference

1. Dubey D, Pittock SJ, Krecke KN, et al. Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol. 2019;76(3):301-309. doi:10.1001/jamaneurol.2018.4053

2. Zalewski NL, Flanagan EP. Autoimmune and paraneoplastic myelopathies. Semin Neurol. 2018;38(3):278-289. doi:10.1055/s-0038-1660856

3. Flanagan EP, Hinson SR, Lennon VA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol. 2017;81(2):298-309. doi:10.1002/ana.24881

4. Keegan BM, Pittock SJ, Lennon VA. Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G. Ann Neurol. 2008;63(4):531-534. doi:10.1002/ana.21324

5. Weinshenker BG, Wingerchuk DM, Vukusic S, et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol. 2006;59(3):566-569. doi:10.1002/ana.20770

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

8 to 12 days

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 16

86053

86341

84182

84182 AGNBC (if appropriate)

86256 AGNTC (if appropriate)

86255 AINCC (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)

86255 APBCC (if appropriate)

86256 APBTC (if appropriate)

86256 APHTC (if appropriate)

86256 CRMTC (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)

86255 NFHCC (if appropriate)

86255 NFLCC (if appropriate)

86256 NIFTC (if appropriate)

86053 NMOTC (if appropriate)

84182 PC1BC (if appropriate)

86256 PC1TC (if appropriate)

86256 PC2TC (if appropriate)

86255 SP7CC (if appropriate)

86256 SP7TC (if appropriate)

86255 T46CC (if appropriate)

86256 T46TC (if appropriate)

LOINC Code Information

Test ID	Test Order Name	Order LOINC Value
MAC1	Myelopathy, Autoimm/Paraneo, CSF	94353-0

Result ID	Test Result Name	Result LOINC Value
61515	GABA-B-R Ab CBA, CSF	93426-5
38325	NMO/AQP4-IgG FACS, CSF	46718-3
64927	mGluR1 Ab IFA, CSF	94361-3
64934	DPPX Ab CBA, CSF	94283-9
605156	GFAP IFA, CSF	94360-5
605128	Autoimmune Myelopathy Interp, CSF	69048-7
606965	NIF IFA, CSF	96490-8
615862	AP3B2 IFA, CSF	101907-4
615866	Neurochondrin IFA, CSF	101451-3
615874	Septin-7 IFA, CSF	101464-6
616446	TRIM46 Ab IFA, CSF	103843-9
89079	AGNA-1, CSF	90827-7
5906	Amphiphysin Ab, CSF	90815-2
3852	ANNA-1, CSF	44768-0
7472	ANNA-2, CSF	56959-0
21633	ANNA-3, CSF	90836-8
3988	PCA-1, CSF	90841-8
21632	PCA-2, CSF	90843-4
21747	CRMP-5-IgG Western Blot, CSF	53707-6
21702	GAD65 Ab Assay, CSF	94359-7
618901	IFA Notes	48767-8

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Test ID: MAC1 Myelopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid