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Test Code DMC2 Dementia, 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 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


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

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)

Reporting Name

Dementia, Autoimm/Paraneo, CSF

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

Clinical Information

The rapid identification of subacute cognitive decline as autoimmune dementia facilitates optimum treatment with immunotherapy and an expedited search for a limited stage of cancer in some patients. Traditionally, neurologists have been reluctant to consider a diagnosis of an autoimmune cognitive disorder in the absence of delirium. However, some recent case series and clinical-serologic observations have suggested a growing appreciation for autoimmune neurologic disorders presenting with features of a rapidly progressive dementia rather than delirium. These disorders can affect all age groups.

 

Unfortunately, these potentially reversible conditions may be misdiagnosed as being progressive neurodegenerative (currently irreversible) disorders with devastating consequences for the patient. In the evaluation of a patient with cognitive decline, clinicians should consider the possibility of an autoimmune etiology on their list of differential diagnoses. The importance of not overlooking this possibility rests in the experience that these patients have a potentially immunotherapy-responsive, reversible disorder. The development and widespread availability of neural antibody marker testing has changed this perspective so that other presenting symptoms, such as personality change, executive dysfunction, and psychiatric symptoms, are increasingly recognized in an autoimmune context.

 

Clues that are helpful in identifying patients with an autoimmune dementia can be summarized as a triad of:

-Suspicious clinical features (a subacute onset of symptoms, a rapidly progressive course, and fluctuating symptoms) and radiological findings

-Detection of cerebrospinal fluid (CSF) or serological biomarkers of autoimmunity

-Response to immunotherapy

 

Detection of neural autoantibodies in serum or CSF serves 2 purposes; to inform the physician of a likely autoimmune etiology and to raise suspicion for a paraneoplastic cause. The neurological associations of neural autoantibodies tend to be diverse and multifocal, although certain syndromic associations may apply. For example, LGI1 (leucine-rich, glioma inactivated 1) antibody was initially considered to be specific for autoimmune limbic encephalitis, but, over time, other presentations have been reported, including rapidly progressive course of cognitive decline mimicking neurodegenerative dementia.

 

Since neurological presentations are often multifocal and diverse, comprehensive antibody testing is usually more informative than testing for 1 or 2 selected antibodies. Some of the antibodies are highly predictive of an unsuspected underlying cancer. For example, small-cell lung carcinoma (antineuronal nuclear antibody-type 1 [ANNA-1]; collapsin response-mediator protein-5 neuronal [CRMP-5-IgG]), ovarian teratoma (N-methyl-D-aspartate receptor: NMDA-R), and thymoma (CRMP-5 IgG).

 

Also, a profile of seropositivity for multiple autoantibodies may be informative for cancer type. For example, in a patient presenting with a rapidly progressive dementia who has CRMP-5-IgG, and subsequent testing reveals muscle acetylcholine receptor (AChR) binding antibody, the findings should raise a high suspicion for thymoma. If an associated tumor is found, its resection or ablation optimizes the neurological outcome.

 

Antibody testing on CSF is additionally helpful particularly 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.

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.

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 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)