Test Catalog

Test Id : DMC2

Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

Useful For
Suggests clinical disorders or settings where the test may be helpful

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 (over 20 pack-years) or other cancer risk factors

-History of cancer

-Inflammatory cerebrospinal fluid

-Neuroimaging findings atypical for degenerative etiology

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

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
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial 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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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

 

If IFA pattern suggests antineuronal nuclear antibodies (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 suggests amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 immunoblot is performed at an additional charge.

 

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

 

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

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (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 gamma-aminobutyric acid (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 glial fibrillary acidic protein (GFAP) antibody, then GFAP IFA titer and GFAP CBA are performed at an additional charge.

 

If IFA pattern suggests N-methyl-D-aspartate (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 dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (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 neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer are performed at an additional charge.

 

For more information, see Autoimmune/Paraneoplastic Dementia Evaluation Algorithm-Spinal Fluid.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

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 (IB)

CRMWC: Western Blot (WB)

GD65C: Radioimmunoassay (RIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Dementia, Autoimm/Paraneo, CSF

Aliases
Lists additional common names for a test, as an aid in searching

AMPA-R Ab CBA

Amphiphysin Ab

Anti-Glial Nuclear Ab, Type 1

Anti-Neuronal Nuclear Ab, Type 1

Anti-Neuronal Nuclear Ab, Type 2

Anti-Neuronal Nuclear Ab, Type 3

CASPR2-IgG

Cognitive decline

Cognitive impairment

Contactin-Associated Protein-Like-2 (CASPR2)-IgG

CRMP-5-IgG

DEMEC

DPPX

dipeptidyl aminopeptidase-like protein 6

GABA-B-R Ab CBA

Glutamic Acid Decarboxylase (GAD65)

LGI1-IgG

NMDA-R Ab CBA

metabotropic glutamate receptor 1

mGluR1

Purkinje Cell Cytoplasmic Ab Type 2

GFAP

IgLON5

NIF

Leucine-Rich Glioma Inactivated Protein-1 IgG

Purkinje Cell Cytoplasmic Ab Type Tr

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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

 

If IFA pattern suggests antineuronal nuclear antibodies (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 suggests amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 immunoblot is performed at an additional charge.

 

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

 

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

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (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 gamma-aminobutyric acid (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 glial fibrillary acidic protein (GFAP) antibody, then GFAP IFA titer and GFAP CBA are performed at an additional charge.

 

If IFA pattern suggests N-methyl-D-aspartate (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 dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (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 neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer are performed at an additional charge.

 

For more information, see Autoimmune/Paraneoplastic Dementia Evaluation Algorithm-Spinal Fluid.

Specimen Type
Describes the specimen type validated for testing

CSF

Ordering Guidance

Necessary Information

Provide the following information:

-Relevant clinical information

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

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Collection Container/Tube: Sterile vial

Specimen Volume: 4 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

Useful For
Suggests clinical disorders or settings where the test may be helpful

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 (over 20 pack-years) or other cancer risk factors

-History of cancer

-Inflammatory cerebrospinal fluid

-Neuroimaging findings atypical for degenerative etiology

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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

 

If IFA pattern suggests antineuronal nuclear antibodies (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 suggests amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 immunoblot is performed at an additional charge.

 

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

 

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

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (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 gamma-aminobutyric acid (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 glial fibrillary acidic protein (GFAP) antibody, then GFAP IFA titer and GFAP CBA are performed at an additional charge.

 

If IFA pattern suggests N-methyl-D-aspartate (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 dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (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 neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer are performed at an additional charge.

 

For more information, see Autoimmune/Paraneoplastic Dementia Evaluation Algorithm-Spinal Fluid.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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 glial fibrillary acidic protein [GFAP]-IgG) because CSF testing is both more sensitive and specific.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Test ID

Reporting name

Methodology*

Reference value

ADMCI

Dementia, Interpretation, CSF

Medical interpretation

NA

AMPCC

AMPA-R Ab CBA, CSF

CBA

Negative

AMPHC

Amphiphysin Ab, CSF

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

RIA

< or =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

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

WB

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

*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-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
Provides information to assist in interpretation of the test results

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).

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Negative results do not exclude autoimmune dementia or cancer.

 

This evaluation does not detect Ma1 or Ma2 antibodies (alias: MaTa). Ma2 antibody has been described in patients with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advisable in men who present with unexplained subacute encephalitis.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. McKeon A, Lennon VA, Pittock SJ: Immunotherapy-responsive dementias and encephalopathies. Continuum (Minneap Minn). 2010 Apr;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 Jul 12;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 Feb;70(2):229-234

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Indirect Immunofluorescence Assay:

Before testing, patient's specimen is preabsorbed with liver powder to remove nonorgan-specific autoantibodies. After applying to a composite substrate of frozen mouse tissues (brain, kidney, and gut) and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the distribution and pattern of patient IgG binding.(Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov;56(5):715-719; Basal E, Zalewski N, Kryzer TJ, et al: Paraneoplastic neuronal intermediate filament autoimmunity. Neurology. 2018 Oct 30;91[18]:e1677-e1689)

 

Radioimmunoassay:

Duplicate aliquots of patient specimen are incubated with (125)I-labeled antigen. Immune complexes, formed by adding secondary (goat) antihuman immunoglobulin, are pelleted by centrifugation and washed. Gamma emission from the washed pellet is counted, and mean counts per minute (cpm) are compared with results yielded by high positive and negative control sera. Specimen yielding cpm higher than the background cpm yielded by normal human specimen are retested to confirm positivity and titrated as necessary to obtain a value in the linear range of the assay. The antigen binding capacity (nmol per liter) is calculated from the cpm precipitated at a dilution yielding a linear range value.(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 Dec;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 Nov;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 February;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al: Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019 Oct 17 pii: 10.1212/WNL.0000000000008472. doi: 10.1212/WNL.0000000000008472)

 

Immunoblot:

All steps are performed at room temperature (18-28 degrees 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 Apr 4;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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 11 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

28 Days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86255 x 18

86341

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® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
DMC2 Dementia, Autoimm/Paraneo, CSF 94707-7
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
89079 AGNA-1, CSF 94355-5
5906 Amphiphysin Ab, CSF 94354-8
3852 ANNA-1, CSF 94356-3
36429 Reflex Added 77202-0
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
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 96490-8
606947 IgLON5 IFA, CSF 96479-1

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports