TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: DMS2    
Dementia, Autoimmune Evaluation, Serum

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 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

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 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.

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 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 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

GANG

AChR Ganglionic Neuronal Ab, S

Radioimmunoassay (RIA)

< or =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

< or =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

< or =0.03 nmol/L

CCPQ

P/Q-Type Calcium Channel Ab

RIA

< or =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

< or =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 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 test 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;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

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