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Test Code DMC2 Dementia, Autoimmune Evaluation, Spinal Fluid


Necessary Information


Provide the following information:

-Relevant clinical information

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



Specimen Required


Collection Container/Tube: Sterile 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+ 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
DPPIC DPPX Ab IFA, 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
IG5IC IgLON5 IFA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
GL1IC mGluR1 Ab 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

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
DPPCC DPPX Ab CBA, 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
IG5CC IgLON5 CBA, 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
PC1BC PCA-1 Immunoblot, CSF No No
PCTBC PCA-Tr Immunoblot, CSF No No
PCA1C Purkinje Cell Cytoplasmic Ab Type 1 No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) pattern suggests AGNA-1 antibody, then AGNA-1 immunoblot is performed at an additional charge.

 

If IFA pattern suggests ANNA-1 antibody, then ANNA-1 immunoblot is performed at an additional charge.

 

If IFA pattern suggests ANNA-2 antibody, then ANNA-2 immunoblot is performed at an additional charge.

 

If IFA pattern suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge,

 

If IFA pattern suggest PCA-1 antibody, then PCA-1 immunoblot is performed at an additional charge,

 

If IFA pattern suggest PCA-Tr antibody, then PCA-Tr immunoblot is performed at an additional charge,

 

If client requests or if IFA patterns suggest CRMP-5-IgG, then CRMP-5-IgG Western blot is performed at an additional charge.

 

If IFA pattern suggests AMPA-receptor antibody, and AMPA-receptor antibody cell-binding assay (CBA) is positive, then AMPA-receptor antibody IFA titer assay is performed at an additional charge.

 

If IFA pattern suggests GABA-B-receptor antibody, and GABA-B-receptor antibody CBA is positive, then GABA-B-receptor antibody IFA titer assay is performed at an additional charge.

 

If IFA pattern suggests GFAP antibody, then GFAP IFA titer and GFAP CBA are performed at an additional charge.

 

If IFA pattern suggests NMDA-receptor antibody, and NMDA-receptor antibody CBA is positive, then NMDA-receptor antibody IFA titer assay is performed at an additional charge.

 

If IFA pattern suggests DPPX antibody, then DPPX antibody CBA and DPPX antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests mGluR1 antibody, then mGluR1 antibody CBA and mGluR1 antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests IgLON5 antibody, then IgLON5 antibody CBA and IgLON5 IFA titer are performed at an additional charge.

 

If IFA pattern suggests NIF antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer are performed at an additional charge.

 

See Dementia Autoimmune Evaluation Algorithm-Spinal Fluid in Special Instructions.

Method Name

AGN1C, AMPHC, AMPIC, ANN1C, ANN2C, ANN3C, CRMC, DPPIC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, IG5IC, IG5TC, NIFIC, NIFTC, NMDIC, PCA1C, PCA2C, PCTRC: Indirect Immunofluorescence Assay (IFA)

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

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Immunoblot

CRMWC: Western Blot (WB)

GD65C: Radioimmunoassay (RIA)

Reporting Name

Dementia-Autoimmune Evaluation, 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 within a triad of: 1) suspicious clinical features (a subacute onset of symptoms, a rapidly progressive course, and fluctuating symptoms) and radiological findings, 2) the detection of cerebrospinal fluid (CSF) or serological biomarkers of autoimmunity and 3) a 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 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 reflex 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, though in some circumstances testing both serum and CSF simultaneously is pertinent. Testing of CSF is recommended for some antibodies in particular (such as NMDA-R antibody and GFAP-IgG) because CSF testing is both more sensitive and specific.

Reference Values

Test ID

Reporting name

Methodology

Reference value

AMPCC

AMPA-R Ab CBA, CSF

Cell-binding assay (CBA)

Negative

AMPHC

Amphiphysin Ab, CSF

Indirect immunofluorescence assay (IFA)

<1:2

AGN1C

Anti-Glial Nuclear Ab, Type 1

IFA

<1:2

ANN1C

Anti-Neuronal Nuclear Ab, Type 1

IFA

<1:2

ANN2C

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:2

ANN3C

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:2

CS2CC

CASPR2-IgG CBA, CSF

CBA

Negative

CRMC

CRMP-5-IgG, CSF

IFA

<1:2

DPPIC

DPPX Ab IFA, CSF

IFA

Negative

GABCC

GABA-B-R Ab CBA, CSF

CBA

Negative

GD65C

GAD65 Ab Assay, CSF

Radioimmunoassay (RIA)

≤0.02 nmol/L

Reference values apply to all ages.

GFAIC

GFAP IFA, CSF

IFA

Negative

IG5IC

IgLON5 IFA, CSF

IFA

Negative

LG1CC

LGI1-IgG CBA, CSF

CBA

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

<1:2

PCA2C

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:2

 

Reflex Information:

Test ID

Reporting name

Methodology

Reference value

AGNBC

AGNA-1 Immunoblot, CSF

Immunoblot (IB)

Negative

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

AN2BC

ANNA-2 Immunoblot, CSF

IB

Negative

CRMWC

CRMP-5-IgG Western Blot, CSF

Western blot

Negative

DPPCC

DPPX Ab CBA, CSF

CBA

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

IG5CC

IgLON5 CBA, CSF

CBA

Negative

IG5TC

IgLON5 IFA Titer, CSF

IFA

<1:2

GL1CC

mGluR1 Ab CBA, CSF

CBA

Negative

GL1TC

mGluR1 Ab 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

PC1BC

PCA-1 Immunoblot, CSF

IB

Negative

PCTBC

PCA-Tr Immunoblot, CSF

IB

Negative

PCA1C

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:2

 

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 1:2 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).

Clinical Reference

1. McKeon A, Lennon, VA, Pittock, SJ: Immunotherapy Responsive Dementias and Encephalopathies. Continuum (Minneap Minn) 2010;16(2):80-101

2. Flanagan EP, McKeon A, Lennon VA, et al: Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc 2010 Oct;85(10):881-897

3. Geschwind MD, Tan KM, Lennon VA, et al: Voltage-gated potassium channel autoimmunity mimicking Creutzfeldt-Jakob disease. Arch Neurol 2008 Oct;65(10):1341-1346

4. Lancaster E, Martinez-Hernandez E, Dalmau J: Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77(2):179-189

5. Klein CJ, Lennon VA, Aston PA, et al: Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping. JAMA Neurol 2013;70(2):229-234

Day(s) and Time(s) Performed

GL1CC, IG5CC:

Monday, Thursday; 6 p.m.

 

AINCC, NFHCC, NFLCC:

Tuesday, Thursday; 6 p.m.

 

GFACC

Monday, Wednesday, Friday; 6 p.m.

 

CRMWC:

Monday through Thursday; 8 a.m.

 

GD65C:

Monday through Friday; 5 a.m., 2 p.m.

Saturday, Sunday; 7 a.m.

 

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC:

Monday through Friday; 6 p.m.

 

AGN1C, AMPHC, AMPIC, ANN1C, ANN2C, ANN3C, CRMC, DPPIC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, IG5IC, IG5TC, NIFIC, NIFTC, NMDIC, PCA1C, PCA2C, PCTRC:

Monday through Friday; 5 a.m., 7 a.m., 5 p.m.

Saturday, Sunday; 6 a.m.

 

AMPCC, CS2CC, DPPCC, GABCC, LG1CC, NMDCC:

Monday through Friday; 10 p.m.

Sunday; 10 p.m.

Analytic Time

8 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. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

86255 x18

86341 x1

84182 AGNBC (if appropriate)

86255 AINCC (if appropriate)

86256 AMPIC (if appropriate)

84182 AMIBC (if appropriate)

84182 AN1BC (if appropriate)

84182 AN2BC (if appropriate)

84182 CRMWC (if appropriate)

86255 DPPCC (if appropriate)

86256 DPPTC (if appropriate)

86256 GABIC (if appropriate)

86255 GFACC (if appropriate)

86256 GFATC (if appropriate)

86255 IG5CC (if appropriate)

86256 IG5TC (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)

84182 PC1BC (if appropriate)

84182 PCTBC (if appropriate)

86255 PCA1C (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMC2 Dementia-Autoimmune Evaluation, 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
64280 LGI1-IgG CBA, CSF 94288-8
64282 CASPR2-IgG CBA, CSF 94286-2
64929 DPPX Ab IFA, CSF 82989-5
64927 mGluR1 Ab IFA, CSF 94361-3
605156 GFAP IFA, CSF 94360-5
606965 NIF IFA, CSF In Process
606947 IgLON5 IFA, CSF In Process
89079 AGNA-1, CSF 94355-5
5906 Amphiphysin Ab, CSF 94354-8
3852 ANNA-1, CSF 94356-3
7472 ANNA-2, CSF 94357-1
21633 ANNA-3, CSF 94358-9
21650 CRMP-5-IgG, CSF 94706-9
21632 PCA-2, CSF 94364-7
21631 PCA-Tr, CSF 94362-1
21702 GAD65 Ab Assay, CSF 94359-7
36429 Reflex Added 77202-0