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Test Code LAB8675 Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

Additional Codes

DMC2


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 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


Secondary ID

92115

Useful For

Investigating new onset dementia and cognitive impairment plus 1 or more of the following accompaniments using cerebrospinal fluid specimens:

-Rapid onset and progression

-Fluctuating course

-Psychiatric accompaniments (psychosis, hallucinations)

-Movement disorder (myoclonus, tremor, dyskinesias)

-Headache

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

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

-History of cancer

-Inflammatory cerebrospinal fluid

-Neuroimaging findings atypical for degenerative etiology

Profile Information

Test ID Reporting Name Available Separately Always Performed
ADMCI Dementia, 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
IG5CC IgLON5 CBA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
GL1IC mGluR1 Ab IFA, CSF No Yes
NCDIC Neurochondrin IFA, CSF No Yes
NIFIC NIF 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
AINCC Alpha Internexin CBA, 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
IG5TC IgLON5 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
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
PCTTC PCA-Tr Titer, CSF No No
PC2TC PCA-2 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 indirect immunofluorescence assay (IFA) pattern suggests antiglial nuclear antibody (AGNA)-1 antibody, then AGNA-1 immunoblot and AGNA-1 titer will be performed at an additional charge.

 

If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then 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 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 antibody, then ANNA-3 titer will be performed at an additional charge.

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

If IgLON5 antibody CBA is positive, then  IgLON5 IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then 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 neurochondrin antibody, then 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 Dementia Evaluation Algorithm-Spinal Fluid.

Method Name

AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPTC, GABIC, GFAIC, GFATC, IG5TC, GL1IC, GL1TC, NCDIC, NCDTC, NIFIC, NIFTC, NMDIC, PCA2C, PC2TC, PCTRC, PCTTC, PDEIC, PDETC, T46IC, T46TC: Indirect Immunofluorescence Assay (IFA)

 

AMPCC, CS2CC, DPPCC, GABCC, GFACC, IG5CC, LG1CC, GL1CC, NCDCC, AINCC, NFLCC, NFHCC, NMDCC, T46CC: Cell Binding Assay (CBA)

 

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

 

CRMWC: Western Blot (WB)

 

GD65C: Radioimmunoassay (RIA)

Specimen Type

CSF

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
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

ADMCI

Dementia, 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

IG5CC

IgLON5 CBA, CSF

CBA

Negative

LG1CC

LGI1-IgG CBA, CSF

CBA

Negative

NCDIC

Neurochondrin IFA, CSF

IFA

Negative

GL1IC

mGluR1 Ab IFA, CSF

IFA

Negative

NIFIC

NIF IFA, CSF

IFA

Negative

NMDCC

NMDA-R Ab CBA, CSF

CBA

Negative

PCTRC

Purkinje Cell Cytoplasmc Ab Type Tr

IFA

Negative

PCA2C

Purkinje Cell Cytoplasmic Ab Type 2

IFA

Negative

PDEIC

PDE10A Ab 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

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 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

IG5TC

IgLON5 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

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 CBA, CSF

CBA

Negative

T46TC

TRIM46 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, CRMP-5-IgG, 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 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (held 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.

Interpretation

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 dementia:

-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).

Method Description

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, 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)

 

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)

 

Immunoblot:

All steps are performed at room 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 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)

 

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)

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

8 to 12 days

Specimen Retention Time

28 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

86255 x 21

86341

84182-AGNBC (if appropriate)

86256 AGNTC (if appropriate)

86255-AINCC (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)

86256-IG5TC (if appropriate)

86255 NCDCC (if appropriate)

86256 NCDTC (if appropriate)

86255-GL1CC (if appropriate)

86256-GL1TC (if appropriate)

86255-NFHCC (if appropriate)

86256-NIFTC (if appropriate)

86255-NFLCC (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)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMC2 Dementia, Autoimm/Paraneo, CSF 94707-7

 

Result ID Test Result Name Result LOINC Value
61513 NMDA-R Ab CBA, CSF 93502-3
61514 AMPA-R Ab CBA, CSF 93491-9
61515 GABA-B-R Ab CBA, CSF 93426-5
34254 Dementia, Interpretation, CSF 69048-7
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
21650 CRMP-5-IgG, CSF 63216-6
21632 PCA-2, CSF 90843-4
21631 PCA-Tr, CSF 90845-9
21702 GAD65 Ab Assay, CSF 94359-7
64280 LGI1-IgG CBA, CSF 94288-8
64282 CASPR2-IgG CBA, CSF 94286-2
64927 mGluR1 Ab IFA, CSF 94361-3
64934 DPPX Ab CBA, CSF 94283-9
605156 GFAP IFA, CSF 94360-5
606965 NIF IFA, CSF 96490-8
606951 IgLON5 CBA, CSF 96481-7
615866 Neurochondrin IFA, CSF 101451-3
620067 PDE10A Ab IFA, CSF 103842-1
616446 TRIM46 Ab IFA, CSF 103843-9
618893 IFA Notes 48767-8