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Test Code DMS1 Dementia, Autoimmune Evaluation, Serum

Secondary ID

48402

Useful For

Investigating new onset dementia and cognitive impairment plus 1 or more of the following:

-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 cerebral spinal fluid

-Neuroimaging findings atypical for degenerative etiology

Profile Information

Test ID Reporting Name Available Separately Always Performed
ADMSI Dementia, Interpretation, S No Yes
NMDCS NMDA-R Ab CBA, S No Yes
VGKC Neuronal (V-G) K+ Channel Ab, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
CS2CS CASPR2-IgG CBA, S No Yes
GD65S GAD65 Ab Assay, S Yes Yes
GABCS GABA-B-R Ab CBA, S No Yes
AMPCS AMPA-R Ab CBA, S 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
AGN1S Anti-Glial Nuclear Ab, Type 1 No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No Yes
AMPHS Amphiphysin Ab, S No Yes
CCN N-Type Calcium Channel Ab No Yes
CCPQ P/Q-Type Calcium Channel Ab No Yes
ARBI ACh Receptor (Muscle) Binding Ab No Yes
GANG AChR Ganglionic Neuronal Ab, S No Yes
CRMS CRMP-5-IgG, S No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
WBN Paraneoplastic Autoantibody WBlot,S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No
ABLOT Amphiphysin Western Blot, S No No
NMOFS NMO/AQP4 FACS, S Yes No
NMOTS NMO/AQP4 FACS Titer, S No No
AMPIS AMPA-R Ab IF Titer Assay, S No No
GABIS GABA-B-R Ab IF Titer Assay, S No No
NMDIS NMDA-R Ab IF Titer Assay, S No No
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) (ANNA-1, ANNA-2, ANNA-3, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, AGNA-1)) is indeterminate, paraneoplastic autoantibody Western blot is performed at an additional charge.

 

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

 

If IFA patterns suggest amphiphysin antibody, amphiphysin Western blot is performed at an additional charge.

 

If IFA pattern suggest NMO/AQP4-IgG, NMO/AQP4-IgG FACS is performed at an additional charge.

 

If NMO/AQP4-IgG FACS screen assay requires further investigation, then NMO/AQP4-IgG FACS titration assay is performed at an additional charge.

 

If IFA pattern suggest AMPA-Receptor antibody and AMPA-Receptor antibody CBA is positive, AMPA-Receptor antibody IF titer assay is performed at an additional charge.

 

If IFA pattern suggest GABA-B-Receptor antibody and GABA-B-R Receptor Ab antibody is positive, GABA-B-R Receptor Ab antibody IF titer assay is performed at an additional charge.

 

If IFA pattern suggest NMDA-Receptor antibody and NMDA-Receptor Ab antibody CBA is positive, NMDA-Receptor Ab antibody IF titer assay is performed at an additional charge.

 

If IFA patterns suggest PCA-1, Purkinje Cell Cytoplasmic antibody Type 1 assay is performed at an additional charge.

 

See Dementia Autoimmune Evaluation Algorithm, Serum in Special Instructions

Method Name

ANN1S, ANN2S, ANN3S, AGN1S, PCAB2, PCATR, AMPHS, CRMS, PCABP, NMDIS, AMPIS, GABIS: Indirect Immunofluorescence Assay (IFA)

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

WBN, ABLOT: Western Blot

AMPCS, GABCS, NMDCS, LG1CS, CS2CS: Cell Binding Assay (CBA)

NMOTS: Flow Cytometry

Reporting Name

Dementia Autoimmune Eval, S

Specimen Type

Serum


Necessary Information


Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.



Specimen Required


Container/Tube: 

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

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

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

NA

Other

NA

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 cerebral spinal 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, neuronal voltage-gated potassium channel (VGKC) antibodies were initially considered to be specific for autoimmune limbic encephalitis or disorders of peripheral nervous hyperexcitability, but over time other presentations have been reported, including a rapidly progressive course of cognitive decline mimicking frontotemporal dementia and Creutzfeldt-Jakob disease.

 

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 muscle acetylcholine receptor (AChR) binding, alpha 3 ganglionic AChR, and CRMP 5 IgG, those 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. However, simultaneous testing of serum and CSF is recommended for NMDA-R antibody, because CSF is usually more informative.

Reference Values

NEURONAL NUCLEAR ANTIBODIES

Antineuronal Nuclear Ab, Type 1 (ANNA-1)

<1:240

Antineuronal Nuclear Ab, Type 2 (ANNA-2)

<1:240

Antineuronal Nuclear Ab, Type 3 (ANNA-3)

<1:240

Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1)

<1:240

 

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES

Purkinje Cell Cytoplasmic Ab, Type1 (PCA-1)

<1:240

Purkinje Cell Cytoplasmic Ab, Type 2 (PCA-2)

<1:240

Purkinje Cell Cytoplasmic Ab, Type Tr (PCA-Tr)

<1:240

Amphiphysin Antibody

<1:240

CRMP-5-IgG

<1:240

 

WESTERN BLOT

Paraneoplastic Western Blot

Negative

CRMP-5-IgG Western Blot

Negative

Amphiphysin Western Blot

Negative

 

ISLET CELL ANTIBODIES

Glutamic Acid Decarboxylase (GAD65) Antibody

≤0.02 nmol/L

 

CATION CHANNEL ANTIBODIES

N-Type Calcium Channel Antibody

≤0.03 nmol/L

P/Q-Type Calcium Channel Antibody

≤0.02 nmol/L

AChR Ganglionic Neuronal Antibody

≤0.02 nmol/L

Neuronal VGKC Autoantibody

≤0.02 nmol/L

 

ACHR RECEPTOR ANTIBODIES

ACh Receptor (Muscle) Binding Antibody

≤0.02 nmol/L

 

N-Methyl-D-aspartate receptor (NMDA-R) CBA

Negative

IFA: <1:120

2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor (AMPA-R) CBA

Negative

IFA: <1:120

Gamma-Amino Butyric acid-type B receptor (GABA-B-R) CBA

Negative

IFA: <1:120

Neuromyelitis Optica (NMO)/Aquaporin-4-IgG FACS Assay

Negative

LGI1-IgG CBA: Negative

CASPR2-IgG CBA: Negative

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 Lifelong Learning 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 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

ANN1S, ANN2S, ANN3S, AGN1S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AMPIS, GABIS, NMDIS:

Monday through Friday; 11:30 a.m. and 8:00 p.m.; Saturday and Sunday 8:00 a.m.

 

AMPCS, GABCS, NMDCS, LG1CS, CS2CS: Monday through Friday; 6 a.m.

Paraneoplastic autoantibody Western blot confirmation, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday, Wednesday, Friday; 8 a.m.

ARBI: Monday through Friday 11:00 a.m., 6:00 p.m., and 10:00 p.m.; Saturday 6:00 a.m.; Sunday 6:00 a.m. and 10:00 a.m.

CCPQ, CCN, GANG, VGKC: Monday through Friday 11:00 a.m. and 6:00 p.m.; Saturday 6:00 a.m.; Sunday 6:00 a.m.

GD65S: Monday to Friday; 6:00 a.m. and 4:00 p.m.

Analytic Time

4 days if negative/ 7 days if positive

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

See Individual Test IDs

CPT Code Information

83519-ACh receptor (muscle) binding antibody

83519-AChR ganglionic neuronal antibody

83519-Neuronal VGKC autoantibody

83519-N-type calcium channel antibody

83519-P/Q-type calcium channel antibody

86255-AGNA-1

86255-Amphiphysin

86255-ANNA-1

86255-ANNA-2

86255-ANNA-3

86255-CRMP-5-IgG

86255-PCA-2

86255-PCA-Tr

86255-AMPAR-Ab

86255-GABAR-Ab

86255-NMDAR-Ab

86341-GAD65

86255-LG1CS

86255- CS2CS

 

86255-PCA-1 (if appropriate)

84182-Amphiphysin Western blot (if appropriate)

84182-CRMP-5 Western blot confirmation (if appropriate)

84182-Paraneoplastic autoantibody Western blot confirmation (if appropriate)

86255-NMO/AQP4-IgG FACS (if appropriate)

86256-AMPAR-Ab titer (if appropriate)

86256-GABAR-Ab titer (if appropriate)

86256-NMDAR-Ab titer (if appropriate)

86256- NMO/AQP4-IgG FACS titer (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMS1 Dementia Autoimmune Eval, S In Process

 

Result ID Test Result Name Result LOINC Value
61516 NMDA-R Ab CBA, S No LOINC Needed
61518 AMPA-R Ab CBA, S No LOINC Needed
61519 GABA-B-R Ab CBA, S No LOINC Needed
34255 Dementia, Interpretation, S 69048-7
64279 LGI1-IgG CBA, S In Process
64281 CASPR2-IgG CBA, S In Process
89080 AGNA-1, S 53709-2
81722 Amphiphysin Ab, S 33927-5
80150 ANNA-1, S 13997-2
80776 ANNA-2, S 43188-2
83137 ANNA-3, S 33924-2
8338 ACh Receptor (Muscle) Binding Ab 11034-6
81184 N-Type Calcium Channel Ab 33979-6
81185 P/Q-Type Calcium Channel Ab 33980-4
83077 CRMP-5-IgG, S 35386-2
84321 AChR Ganglionic Neuronal Ab, S 42233-7
81596 GAD65 Ab Assay, S 30347-9
83138 PCA-2, S 33925-9
83076 PCA-Tr, S 33926-7
89165 Neuronal (V-G) K+ Channel Ab, S 41871-5
36349 Reflex Added No LOINC Needed

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)