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Test Code DMS2 Dementia, Autoimmune/Paraneoplastic Evaluation, Serum


Ordering Guidance


Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, refer to 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 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:

1. For optimal antibody detection, specimen collection is recommended before initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

2. For 24 hours before specimen collection, patient should not receive general anesthetic or take muscle-relaxant drugs.

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.


Useful For

Investigating new onset dementia and cognitive impairment plus 1 or more of the following using serum 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 (over 20 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
ADMSI Dementia, 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
IG5CS IgLON5 CBA, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
GL1IS mGluR1 Ab IFA, S No Yes
NCDIS Neurochondrin IFA, S No Yes
NIFIS NIF IFA, S No Yes
NMDCS NMDA-R Ab CBA, S 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
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
PCTBS PCA-Tr Immunoblot, S No No
AN1TS ANNA-1 Titer, S No No
AN2TS ANNA-2 Titer, S No No
AN3TS ANNA-3 Titer, S No No
APHTS Amphiphysin Ab 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
PC2TS PCA-2 Titer, S No No
PCTTS PCA-Tr Titer, S No No
AGNTS AGNA-1 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 the indirect immunofluorescence assay (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 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 client requests or if 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 amphiphysin antibody, then the amphiphysin immunoblot and amphiphysin 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 the CRMP-5-IgG Western blot and CRMP-5-IgG IFA titer will be performed at an additional charge.

 

If the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 9) receptor antibody cell-binding assay (CBA) result is positive, then the AMPA receptor antibody IFA titer will be performed at an additional charge.

 

If the contactin-associated protein-like-2 (CASPR2)-receptor antibody CBA result is positive, then the CRMP-5-IgG Western blot 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 IF titer will be performed at an additional charge.

 

If 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 NMDA receptor antibody IF 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 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 IgLON5 antibody CBA result is positive, then the IgLON5 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 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 Dementia Evaluation Algorithm-Serum.

Method Name

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

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

GD65S: Radioimmunoassay (RIA)

CRMWS: Western Blot (WB)

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

Reporting Name

Dementia, Autoimm/Paraneo, S

Specimen Type

Serum

Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Reference Values

Test ID

Reporting name

Methodology

Reference value

ADMSI

Dementia, Interpretation, S

Medical interpretation

Interpretive report

AMPCS

AMPA-R Ab CBA, S

CBA

Negative

AMPHS

Amphiphysin Ab, S

IFA

<1:240

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

<1:240

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

<1:240

ANN2S

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:240

ANN3S

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:240

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMS

CRMP-5-IgG, S

IFA

<1:240

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

IG5CS

IgLON5 CBA, S

CBA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

NCDIS

Neurochondrin IFA, S

IFA

Negative

NIFIS

NIF IFA, S

IFA

Negative

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:240

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

PDEIS

PDE10A Ab 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

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

APHTS

Amphiphysin Ab 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

PC2TS

PCA-2 Titer, S

IFA

<1:240

PCTTS

PCA-Tr Titer, S

IFA

<1:240

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

PDETS

PDE10A Ab IFA Titer, S

IFA

<1:240

T46CS

TRIM46 CBA, S

CBA

Negative

T46TS

TRIM46 IFA Titer, S

IFA

<1:240

 

*Methodology abbreviations used:

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-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.

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).

Clinical Reference

1. Sechi E, Flanagan EP. Diagnosis and management of autoimmune dementia. Curr Treat Options Neurol. 2019;21(3):11. Published 2019 Feb 27. doi:10.1007/s11940-019-0550-9

2. Bastiaansen AEM, van Steenhoven RW, de Bruijn MAAM, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1039. Published 2021 Aug 2. doi:10.1212/NXI.0000000000001039

3. Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30-39. doi:10.1001/jamaneurol.2022.4251

4. Orozco E, Valencia-Sanchez C, Britton J, et al. Autoimmune encephalitis criteria in clinical practice. Neurol Clin Pract. 2023;13(3):e200151. doi:10.1212/CPJ.0000000000200151

5. Bastiaansen AEM, van Steenhoven RW, Te Vaarwerk ES, et al. Antibodies associated with autoimmune encephalitis in patients with presumed neurodegenerative dementia. Neurol Neuroimmunol Neuroinflamm. 2023;10(5):e200137. Published 2023 Jun 13. doi:10.1212/NXI.0000000000200137

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 21

86341

84182-AGNBS (if appropriate)

86256 AGNTS (if appropriate)

86255-AINCS (if appropriate)

86256-AMPIS (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-APHTS (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)

86256-PC2TS (if appropriate)

84182-PCTBS (if appropriate)

86256-PCTTS (if appropriate)

86256 PDETS (if appropriate)

86255 T46CS (if appropriate)

86256 T46TS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMS2 Dementia, Autoimm/Paraneo, S 94696-2

 

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
616445 TRIM46 Ab IFA, S 103843-9
620068 PDE10A Ab IFA, S 103842-1
34255 Dementia, 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
83076 PCA-Tr, S 84926-5
618894 IFA Notes 48767-8