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Test Code DMS2 Dementia, Autoimmune Evaluation, Serum


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 prior to initiation of immunosuppressant medication.

2. This test should not be requested in 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.

3. Patient should have no general anesthetic or muscle-relaxant drugs in the previous 24 hours.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL


Secondary ID

92114

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 (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
GANG AChR Ganglionic Neuronal Ab, 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
DPPIS DPPX Ab IFA, 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
IG5IS IgLON5 IFA, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
GL1IS mGluR1 Ab IFA, S No Yes
NIFIS NIF IFA, S No Yes
NMDCS NMDA-R Ab CBA, S No Yes
CCN N-Type Calcium Channel Ab No Yes
CCPQ P/Q-Type Calcium Channel Ab No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
ARBI ACh Receptor (Muscle) Binding Ab Yes No
ARMO ACh Receptor (Muscle) Modulating Ab No No
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
DPPCS DPPX Ab CBA, S No 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
IG5CS IgLON5 CBA, 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
PC1BS PCA-1 Immunoblot, S No No
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No
PCTBS PCA-Tr Immunoblot, S 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 client requests or if IFA patterns suggest CRMP-5-IgG, then CRMP-5-IgG Western blot, ACh receptor (muscle) binding antibody, and ACh receptor (muscle) modulating antibody are 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 IF titer assay is performed at an additional charge.

 

If AMPA-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, ACh receptor (muscle) binding antibody, and ACh receptor (muscle) modulating antibody are performed at an additional charge.

 

If CASPR2-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, ACh receptor (muscle) binding antibody, and ACh receptor (muscle) modulating antibody are performed at an additional charge.

 

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

 

If IFA pattern suggests GFAP antibody, 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 IF titer assay is performed at an additional charge.

 

If IFA patterns suggest PCA-1, then Purkinje cell cytoplasmic antibody type 1 (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 IFA pattern suggests DPPX antibody, then DPPX antibody CBA and DPPX titer are performed at an additional charge.

 

If IFA pattern suggests mGluR1 antibody, then mGluR1 antibody CBA and mGluR1 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-Serum in Special Instructions.

Method Name

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

AGN1S, AMPHS, AMPIS, ANN1S, ANN2S, ANN3S, CRMS, DPPIS, DPPTS, GABIS, GFAIS, GFATS, GL1IS, GL1TS, IG5IS, IG5TS, NIFIS, NIFTS, NMDIS, PCAB2, PCABP, PCATR: Indirect Immunofluorescence Assay (IFA)

ARBI, CCN, CCPQ, GANG, GD65S: Radioimmunoassay (RIA)

ARMO: Live Cell Assay (LCA)

CRMWS: Western Blot (WB)

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)

Reporting Name

Dementia Autoimmune Eval, 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

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

GANG

AChR Ganglionic Neuronal Ab, S

Radioimmunoassay (RIA)

≤0.02 nmol/L

AMPCS

AMPA-R Ab CBA, S

Cell-binding assay (CBA)

Negative

AMPHS

Amphiphysin Ab, S

Indirect immunofluorescence assay (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

DPPIS

DPPX Ab IFA, S

IFA

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

IG5IS

IgLON5 IFA, S

IFA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

NIFIS

NIF IFA, S

IFA

Negative

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

CCN

N-Type Calcium Channel Ab

RIA

≤0.03 nmol/L

CCPQ

P/Q-Type Calcium Channel Ab

RIA

≤0.02 nmol/L

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:240

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

 

Reflex Information:

Test ID

Reporting name

Methodology

Reference value

ARBI

ACh Receptor (Muscle) Binding Ab

RIA

≤0.02

ARMO

ACh Receptor (Muscle) Modulating Ab

Live-cell assay

0-20% (reported as __% loss of AChR)

AGNBS

AGNA-1 Immunoblot, S

Immunoblot (IB)

Negative

AINCS

Alpha Internexin CBA, S

CBA

Negative

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

AMIBS

Amphiphysin Immunoblot, S

IB

Negative

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

CRMWS

CRMP-5-IgG Western Blot, S

Western blot

Negative

DPPCS

DPPX Ab CBA, S

CBA

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

IG5CS

IgLON5 CBA, S

CBA

Negative

IG5TS

IgLON5 IFA Titer, S

IFA

<1:240

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1TS

mGluR1 Ab 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

<1:120

PC1BS

PCA-1 Immunoblot, S

IB

Negative

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:240

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

 

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, 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. McKeon A, Lennon, VA, Pittock, SJ: Immunotherapy Responsive Dementias and Encephalopathies. Continuum (Minneap Minn). 2010;16(2):80-101. doi: 10.1212/01.CON.0000368213.63964.34

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

GL1CS, IG5CS:

Monday, Thursday; 6 p.m.

 

AGN1S, AMPHS, AMPIS, ANN1S, ANN2S, ANN3S, CRMS, DPPIS, DPPTS, GABIS, GFAIS, GFATS, GL1IS, GL1TS, IG5IS, IG5TS, NIFIS, NIFTS, NMDIS, PCAB2, PCABP, PCATR:

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

Saturday, Sunday; 6 a.m.

 

AMPCS, CS2CS, DPPCS, GABCS, LG1CS, NMDCS:

Monday through Friday; 10 p.m.

Sunday; 10 p.m.

 

GFACS:

Monday, Wednesday, Friday; 6 p.m.

 

ARMO:

Monday through Thursday; 1 p.m.

Saturday; 8 a.m.

 

ARBI:

Monday through Friday; 11 a.m., 6 p.m., 10 p.m.

Saturday; 6 a.m.

Sunday; 6 a.m., 10 a.m.

 

CCN, CCPQ, GANG:

Monday through Friday; 6 a.m., 8 a.m., 6 p.m.

Saturday, Sunday; 7 a.m.

 

GD65S:

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

Saturday, Sunday; 7 a.m.

 

CRMWS:

Monday through Thursday; 8 a.m.

 

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS:

Monday through Friday; 6 p.m.

 

AINCS, NFHCS, NFLCS:

Tuesday, Thursday; 6 p.m.

Analytic Time

10 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

83519 x 3

86255 x18

86341 x 1

83519 ARBI (if appropriate)

83519 ARMO (if appropriate)

84182 AGNBS (if appropriate)

86255 AINCS (if appropriate)

86256 AMPIS (if appropriate)

84182 AMIBS (if appropriate)

84182 AN1BS (if appropriate)

84182 AN2BS (if appropriate)

84182 CRMWS (if appropriate)

86255 DPPCS (if appropriate)

86256 DPPTS (if appropriate)

86256 GABIS (if appropriate)

86255 GFACS (if appropriate)

86256 GFATS (if appropriate)

86255 IG5CS (if appropriate)

86256 IG5TS (if appropriate)

86255 GL1CS (if appropriate)

86256 GL1TS (if appropriate)

86255 NFHCS (if appropriate)

86256 NIFTS (if appropriate)

86255 NFLCS (if appropriate)

86256 NMDIS (if appropriate)

84182 PC1BS (if appropriate)

86255 PCABP (if appropriate)

84182 PCTBS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMS2 Dementia Autoimmune Eval, 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
34255 Dementia, Interpretation, S 69048-7
64279 LGI1-IgG CBA, S 94287-0
64281 CASPR2-IgG CBA, S 94285-4
64930 DPPX Ab IFA, S 82976-2
64928 mGluR1 Ab IFA, S 94347-2
605155 GFAP IFA, S 94346-4
606946 IgLON5 IFA, S In Process
606964 NIF IFA, S In Process
80776 ANNA-2, S 94343-1
83137 ANNA-3, S 94344-9
81184 N-Type Calcium Channel Ab 94348-0
81185 P/Q-Type Calcium Channel Ab 94349-8
83077 CRMP-5-IgG, S 94815-8
84321 AChR Ganglionic Neuronal Ab, S 94694-7
81596 GAD65 Ab Assay, S 94345-6
83138 PCA-2, S 94351-4
83076 PCA-Tr, S 94352-2
89080 AGNA-1, S 94341-5
81722 Amphiphysin Ab, S 94340-7
80150 ANNA-1, S 94342-3
36349 Reflex Added 77202-0