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Test Code DMC1 Dementia, Autoimmune Evaluation, Spinal Fluid

Secondary ID

48405

Useful For

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

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
ADMCI Dementia, Interpretation, CSF No Yes
NMDCC NMDA-R Ab CBA, CSF No Yes
VGKCC VGKC-complex Ab IPA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
CS2CC CASPR2-IgG CBA, CSF No Yes
GD65C GAD65 Ab Assay, CSF Yes Yes
GABCC GABA-B-R Ab CBA, CSF No Yes
AMPCC AMPA-R Ab CBA, CSF 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
AGN1C Anti-Glial Nuclear Ab, Type 1 No Yes
PCA2C Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCTRC Purkinje Cell Cytoplasmc Ab Type Tr No Yes
AMPHC Amphiphysin Ab, CSF No Yes
CRMC CRMP-5-IgG, CSF No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
WBNC Paraneoplas Autoantibody WBlot,CSF No No
CRMWC CRMP-5-IgG Western Blot, CSF Yes No
ABLTC Amphiphysin Western Blot, CSF No No
NMOFC NMO/AQP4 FACS, CSF Yes No
NMOTC NMO/AQP4 FACS Titer, CSF No No
AMPIC AMPA-R Ab IF Titer Assay, CSF No No
GABIC GABA-B-R Ab IF Titer Assay, CSF No No
NMDIC NMDA-R Ab IF Titer Assay, CSF No No
PCA1C 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, Spinal Fluid in Special Instructions

Method Name

ANN1C, ANN2C, ANN3C, AGN1C, PCA1C, PCA2C, PCTRC, AMPHC, CRMC, AMPIC, GABIC, NMDIC: Indirect Immunofluorescence Assay (IFA)

AMPCC, GABCC, NMDCC, LG1CC, CS2CC: Cell-Binding Assay (CBA)

GD65C: Immunoprecipitation Assay

VGKCC: Radioimmunoassay Assay (RIA)

WBNC, ABLTC: Western Blot

Reporting Name

Dementia-Autoimmune Evaluation, CSF

Specimen Type

CSF


Necessary Information


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



Specimen Required


Container/Tube: Sterile vial

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

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

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

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 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, 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. However, simultaneous testing on serum and CSF is recommended for some (such as NMDA-R antibody testing, since CSF is usually more informative).

Reference Values

Anti-neuronal Nuclear Ab, Type 1 (ANNA-1), CSF: <1:2     

Anti-neuronal Nuclear Ab, Type 2 (ANNA-2), CSF: <1:2                             

Anti-neuronal Nuclear Ab, Type 3 (ANNA-3), CSF: <1:2

Purkinje Cell Cytoplasmic Ab, Type1 (PCA-1), CSF: <1:2

Purkinje Cell Cytoplasmic Ab, Type 2 (PCA-2), CSF: <1:2         

Purkinje Cell Cytoplasmic Ab, Type Tr (PCA-Tr), CSF: <1:2     

Amphiphysin Ab, CSF: <1:2                                                                       

CRMP-5-IgG Ab, CSF: <1:2

Paraneoplastic Western Blot, CSF: Negative

CRMP-5-IgG Western Blot, CSF: Negative

Amphiphysin Western Blot, CSF: Negative                                                          

Glutamic Acid Decarboxylase-65 (GAD65), CSF: ≤0.02 nmol/L

Neuronal Voltage-Gated Potassium Channel-Complex Autoantibody, Spinal Fluid: ≤0.02 nmol/L

N-Methyl-D-aspartate receptor (NMDA-R), CSF

CBA: Negative

IFA: <1:2

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

CBA: Negative

IFA: <1:2

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

CBA: Negative

IFA: <1:2                     

Anti-Glial/Neuronal Nuclear Ab, Type 1 (AGNA-1), CSF: <1:2

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

Negative

LGI1-IgG CBA, CSF: Negative

CASPR2-IgG CBA, CSF: 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

ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, AMPIC, GABIC, NMDIC: Monday through Friday; 11:30 a.m. and 8:00 p.m.; Saturday and Sunday 8:00 a.m.

AMPCC, GABCC, NMDCC, LG1CC, CS2CC: Monday through Friday; 6:00 a.m.

Paraneoplastic autoantibody Western blot confirmation, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday, Wednesday, Friday; 6:00 a.m.

GAD65: Monday to Friday; 6:00 a.m. and 4:00 p.m.

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

Analytic Time

3 days if negative/5 days if positive

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

See Individual Test IDs

CPT Code Information

83519-Neuronal VGKC autoantibody

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-LG1CC

86255- CS2CC

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)

86255-PCA-1 (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
DMC1 Dementia-Autoimmune Evaluation, CSF In Process

 

Result ID Test Result Name Result LOINC Value
61513 NMDA-R Ab CBA, CSF No LOINC Needed
61514 AMPA-R Ab CBA, CSF No LOINC Needed
61515 GABA-B-R Ab CBA, CSF No LOINC Needed
34254 Dementia, Interpretation, CSF 69048-7
61729 VGKC-complex Ab IPA, CSF 68913-3
64280 LGI1-IgG CBA, CSF In Process
64282 CASPR2-IgG CBA, CSF In Process
89079 AGNA-1, CSF 53714-2
5906 Amphiphysin Ab, CSF 56531-7
3852 ANNA-1, CSF 24400-4
7472 ANNA-2, CSF 24401-2
21633 ANNA-3, CSF 35144-5
21650 CRMP-5-IgG, CSF 35385-4
21632 PCA-2, CSF 35143-7
21631 PCA-Tr, CSF 51748-2
21702 GAD65 Ab Assay, CSF 53708-4
36429 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)