Test Catalog

Test Id : ENS2

Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum

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

Evaluating new onset encephalopathy (noninfectious or metabolic) comprising confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, sensory or motor complaints, seizures, dyssomnias, ataxias, nausea, vomiting, inappropriate antidiuresis, coma, dysautonomias, or hypoventilation in serum specimens

 

The following accompaniments should increase of suspicion for autoimmune encephalopathy:

-Headache

-Autoimmune stigmata (personal or family history or signs of diabetes mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)

-History of cancer

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

-Inflammatory cerebral spinal fluid (or isolated protein elevation)

-Neuroimaging signs suggesting inflammation

 

Evaluating limbic encephalitis (noninfectious)

 

Directing a focused search for cancer

 

Investigating encephalopathy appearing in the course or wake of cancer therapy and not explainable by metastasis or drug effect

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
AEESI Encephalopathy, Interpretation, 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
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr 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
ARBI ACh Receptor (Muscle) Binding Ab Yes 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
PCTBS PCA-Tr Immunoblot, S No No

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

If client requests or if immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

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

 

If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, 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 Purkinje cytoplasmic antibody (PCA)-1, 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 IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) 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 CBA is positive, then AMPA-receptor antibody IFA titer assay is performed at an additional charge.

 

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

 

If contactin-associated protein-like-2 (CASPR2)-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B (GABA-B)-receptor antibody, and GABA-B-receptor antibody 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 titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1 antibody CBA and mGluR1 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 titer are performed at an additional charge.

 

For more information, see the following algorithms:

Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Serum

Central Nervous System Demyelinating Disease Diagnostic Algorithm

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

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)

 

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

 

CRMWS: Western Blot (WB)

 

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

 

ARBI, GD65S: 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

Encephalopathy, Autoimm/Paraneo, S

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

ACh Receptor (Muscle) Binding Ab

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

Behavioral change

CASPR2-IgG

Confusion

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

CRMP-5-IgG

Encephalitis

GABA-B-R Ab CBA

Glutamic Acid Decarboxylase (GAD65)

Leucine-Rich Glioma Inactived Protein-1 IgG

LGI1-IgG

Limbic encephalitis

NMDA-R Ab CBA

Psychosis

Purkinje Cell Cytoplasmc Ab Type Tr

Purkinje Cell Cytoplasmic Ab Type 1

Purkinje Cell Cytoplasmic Ab Type 2

GFAP

IGLON5

NIF

ENCES_

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

If client requests or if immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

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

 

If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, 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 Purkinje cytoplasmic antibody (PCA)-1, 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 IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) 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 CBA is positive, then AMPA-receptor antibody IFA titer assay is performed at an additional charge.

 

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

 

If contactin-associated protein-like-2 (CASPR2)-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B (GABA-B)-receptor antibody, and GABA-B-receptor antibody 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 titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1 antibody CBA and mGluR1 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 titer are performed at an additional charge.

 

For more information, see the following algorithms:

Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Serum

Central Nervous System Demyelinating Disease Diagnostic Algorithm

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

Multiple neuroimmunology profile tests are available. For testing that is performed with each profile, see Autoimmune Neurology Antibody Matrix.

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

Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

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 Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic 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

2.5 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
Serum Refrigerated (preferred) 28 days
Frozen 28 days
Ambient 72 hours

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

Evaluating new onset encephalopathy (noninfectious or metabolic) comprising confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, sensory or motor complaints, seizures, dyssomnias, ataxias, nausea, vomiting, inappropriate antidiuresis, coma, dysautonomias, or hypoventilation in serum specimens

 

The following accompaniments should increase of suspicion for autoimmune encephalopathy:

-Headache

-Autoimmune stigmata (personal or family history or signs of diabetes mellitus, thyroid disorder, vitiligo, poliosis [premature graying], myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)

-History of cancer

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

-Inflammatory cerebral spinal fluid (or isolated protein elevation)

-Neuroimaging signs suggesting inflammation

 

Evaluating limbic encephalitis (noninfectious)

 

Directing a focused search for cancer

 

Investigating encephalopathy appearing in the course or wake of cancer therapy and not explainable by metastasis or drug effect

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

If client requests or if immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

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

 

If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, 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 Purkinje cytoplasmic antibody (PCA)-1, 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 IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) 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 CBA is positive, then AMPA-receptor antibody IFA titer assay is performed at an additional charge.

 

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

 

If contactin-associated protein-like-2 (CASPR2)-receptor antibody CBA is positive, then CRMP-5-IgG Western blot, and ACh receptor (muscle) binding antibody are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B (GABA-B)-receptor antibody, and GABA-B-receptor antibody 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 titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1 antibody CBA and mGluR1 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 titer are performed at an additional charge.

 

For more information, see the following algorithms:

Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Serum

Central Nervous System Demyelinating Disease Diagnostic Algorithm

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

Autoimmune encephalopathies extend beyond the classically recognized clinical and radiological spectrum of "limbic encephalitis." They encompass a diversity of neurological presentations with subacute or insidious onset, including confusional states, psychosis, delirium, memory loss, hallucinations, movement disorders, sensory or motor complaints, seizures, dyssomnias, ataxias, eye movement problems, nausea, vomiting, inappropriate antidiuresis, coma, dysautonomias, or hypoventilation. A diagnosis of autoimmune encephalopathy should be suspected on the basis of clinical course, coexisting autoimmune disorder (eg, thyroiditis, diabetes), serological evidence of autoimmunity, spinal fluid evidence of intrathecal inflammation, neuroimaging or electroencephalographic abnormalities, and favorable response to trial of immunotherapy. 

 

Detection of one or more neural autoantibodies aids the diagnosis of autoimmune encephalopathy and may guide a search for cancer. Pertinent autoantibody specificities include:

-Neurotransmitter receptors and ion channels such as neuronal voltage-gated potassium channels (and interacting synaptic and axonal proteins, leucine-rich glioma inactivated 1 [LGI1] protein and contactin associated protein 2 [CASPR2]), ionotropic glutamate receptors (N-methyl-D-aspartate receptor [NMDA] and 2-amino-3-[5-methyl-3-oxo-1,2- oxazol-4-yl] propanoic acid [AMPA]), metabotropic gamma-aminobutyric acid (GABA)-B receptors

-Enzymes, signaling molecules, and RNA-regulatory proteins in the cytoplasm and nucleus of neurons (glutamic acid decarboxylase 65 [GAD65], collapsin response-mediator protein-5 neuronal [CRMP-5], antineuronal nuclear antibody-type 1 [ANNA-1], and ANNA-2) 

 

Importantly, autoimmune encephalopathies are reversible. Misdiagnosis as a progressive (currently irreversible) neurodegenerative condition is not uncommon and has devastating consequences for the patient. Clinicians must consider the possibility of an autoimmune etiology in the differential diagnoses of encephalopathy. For example, a potentially reversible disorder justifies a trial of immunotherapy for the detection of neural autoantibodies in patients presenting with symptoms of personality change, executive dysfunction, and psychiatric manifestations. 

 

A triad of clues helps to identify patients with an autoimmune encephalopathy:

1) Clinical presentation (subacute symptoms, onset rapidly progressive course, and fluctuating symptoms) and radiological findings consistent with inflammation

2) Detection of neural autoantibodies in serum or cerebrospinal fluid (CSF)

3) Favorable response to a trial of immunotherapy

 

Detection of neural autoantibodies in serum or CSF informs the physician of a likely autoimmune etiology, and may heighten suspicion for a paraneoplastic basis and guide the search for cancer. Neurological accompaniments of neural autoantibodies are generally not syndromic, but diverse and multifocal. 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. Comprehensive antibody testing is more informative than selective testing for 1 or 2 neural antibodies. Some antibodies strongly predict an underlying cancer. For example, small-cell lung carcinoma (ANNA-1, CRMP-5-IgG), ovarian teratoma (NMDA-R), and thymoma (CRMP-5 IgG). 

 

An individual patient's profile autoantibody may be informative for a specific cancer type. For example, in a patient presenting with encephalitis who has CRMP 5 IgG, and subsequent reflex reveals muscle acetylcholine receptor (AChR) binding antibody, the findings should raise a high suspicion for thymoma. Testing of CSF for autoantibodies is particularly helpful 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. In contrast, serum testing for LGI1 antibody is more sensitive than CSF testing.

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

AEESI

Encephalopathy, Interpretation, S

Medical interpretation

NA

AMPCS

AMPA-R Ab CBA, S

CBA

Negative

AMPHS

Amphiphysin Ab, S

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

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:240

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 nmol/L

AGNBS

AGNA-1 Immunoblot, S

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

WB

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

<1:120

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

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

 

*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, 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

Neuronal, glial, and muscle autoantibodies are valuable serological markers of autoimmune encephalopathy and of a patient's immune response to cancer. These autoantibodies are usually accompanied by subacute neurological symptoms and signs are not found in healthy subjects. It is not uncommon for more than 1 of the following autoantibody specificities to be detected in patients with an autoimmune encephalopathy:

-Plasma membrane autoantibodies: 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; neuronal ACh receptor. These are all potential effectors of neurological dysfunction.

-Neuronal nuclear autoantibodies, type 1 (ANNA-1), type 2 (ANNA-2), or type 3 (ANNA-3)

-Neuronal or muscle cytoplasmic antibodies: amphiphysin, Purkinje cell antibodies (PCA-1) and PCA-2, CRMP-5, GAD65, or striational

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 encephalopathy or cancer.

 

This test does not detect Ma1 or Ma2 antibodies (alias MaTa), which are sometimes associated with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advised for men who present with unexplained subacute encephalitis.

 

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

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 Dementia):80-101

2. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1 anti-neuronal nuclear autoantibodies. Neurology. 1998;50:652-657

3. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc. 2006 Sep;81(9):1207-1214

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:

The patient's sample is tested by a standardized indirect immunofluorescence assay (IFA) that uses a composite frozen section of mouse cerebellum, kidney, and gut tissues. After incubation with sample and washing, fluorescein-conjugated goat-antihuman IgG is applied. Neuron-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Samples that are scored positive for any neuronal nuclear or cytoplasmic autoantibody are titrated to an endpoint. Interference by coexisting non-neuron-specific autoantibodies can usually be eliminated by serologic absorption.(Honorat JA, Komorowski L, Josephs KA, et al: IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients. Neruol Neruoimmunol Neruoinflamm. 2017 Jul 18;4(5):e385. doi: 10.1212/NXI.0000000000000385)

 

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 Nov 12;93(20):e1873-e1880. doi: 10.1212/WNL.0000000000008472)

 

Immunoblot:

All steps are performed at room temperature (18 to 28 degrees C) utilizing the EUROBlot One instrument. Diluted patient serum (1:101) 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 serum 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)

 

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, et al, eds. Manual of Clinical and Laboratory Immunology. 6th ed. Washington, DC, ASM Press; 2002:1005-1012; 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)

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.

10 to 13 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
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  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
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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 19

86341 x 1

83519-ARBI (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)

84182-PCTBS (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
ENS2 Encephalopathy, Autoimm/Paraneo, S 94697-0
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.
89080 AGNA-1, S 94341-5
81722 Amphiphysin Ab, S 94340-7
80150 ANNA-1, S 94342-3
36349 Reflex Added 77202-0
80776 ANNA-2, S 94343-1
83137 ANNA-3, S 94344-9
83077 CRMP-5-IgG, S 94815-8
81596 GAD65 Ab Assay, S 94345-6
83138 PCA-2, S 94351-4
9477 PCA-1, S 94350-6
83076 PCA-Tr, S 94352-2
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
34257 Encephalopathy, 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 96476-7
606964 NIF IFA, S 96486-6

Test Setup Resources

Setup Files
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Sample Reports
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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