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26477 Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum

Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Test Code: ENS2SO
Synonyms/Keywords

​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_

Useful For

​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 (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

Specimen Requirements
Fasting RequiredSpecimen TypePreferred Container/TubeAcceptable Container/TubeSpecimen VolumeSpecimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum​Red Top Tube (RTT)​Serum Separator Tube (SST)​4 mL​2.5 mL
Collection Processing Instructions

Necessary Information:

Provide the following information:

-Relevant clinical information

-Ordering provider name, phone number, mailing address, and e-mail address

 

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 Mayo Clinic 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.

Specimen Stability Information
Specimen TypeTemperatureTime
​Serum ​ ​​Refrigerated (preferred)​28 Days
​Frozen​28 Days
​Ambient​72 Hours
Rejection Criteria
Gross HemolysisReject
​Gross Lipemia​Reject
​Gross Icterus​Reject
Interference

​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.

Performing Laboratory Information
Performing LocationDay(s) Test PerformedAnalytical TimeMethodology/Instrumentation
​Mayo Clinic Laboratories​Monday through Sunday​10-13 Days

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)

Reference Lab
Test Information

​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: 1) neurotransmitter receptors and ion channels such as neuronal voltage-gated potassium channels (and interacting synaptic and axonal proteins, leucine-rich glioma inactivated protein: LGI1 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; 2) 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), and 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 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 Range Information
Performing LocationReference Range
​Mayo Clinic Laboratories​An interpretive report will be provided
Interpretation

​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

Outreach CPTs
CPTModifier
(if needed)
QuantityDescriptionComments
86255​​19
​86341​1
​84182​7​if appropriate
​83519​1​if appropriate
​86255​7​if appropriate
​86256​8​if appropriate
Synonyms/Keywords

​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_

Ordering Applications
Ordering ApplicationDescription
​COM​Encephalopathy, Autoimmune Eval (ENS2)
​Cerner​Encepalopathy, Autoimmune Evaluation, Serum (ENS2)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Fasting RequiredSpecimen TypePreferred Container/TubeAcceptable Container/TubeSpecimen VolumeSpecimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
​Serum​Red Top Tube (RTT)​Serum Separator Tube (SST)​4 mL​2.5 mL
Collection Processing

Necessary Information:

Provide the following information:

-Relevant clinical information

-Ordering provider name, phone number, mailing address, and e-mail address

 

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 Mayo Clinic 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.

Specimen Stability Information
Specimen TypeTemperatureTime
​Serum ​ ​​Refrigerated (preferred)​28 Days
​Frozen​28 Days
​Ambient​72 Hours
Rejection Criteria
Gross HemolysisReject
​Gross Lipemia​Reject
​Gross Icterus​Reject
Interference

​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.

Useful For

​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 (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

Reference Range Information
Performing LocationReference Range
​Mayo Clinic Laboratories​An interpretive report will be provided
Interpretation

​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

For more information visit:
Performing Laboratory Information
Performing LocationDay(s) Test PerformedAnalytical TimeMethodology/Instrumentation
​Mayo Clinic Laboratories​Monday through Sunday​10-13 Days

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)

Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPTModifier
(if needed)
QuantityDescriptionComments
86255​​19
​86341​1
​84182​7​if appropriate
​83519​1​if appropriate
​86255​7​if appropriate
​86256​8​if appropriate
For most current information refer to the Marshfield Laboratory online reference manual.