Test Id : ENC2
Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid
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 using spinal fluid 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 or more pack-years) or other cancer risk factors
-Inflammatory cerebrospinal fluid (or isolated protein elevation)
-Neuroimaging signs suggesting inflammation
Evaluating limbic encephalitis (noninfectious)
Directing a focused search for cancer
Investigating encephalopathy appearing during or after 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 |
---|---|---|---|
AEECI | Encephalopathy, Interpretation, CSF | No | Yes |
AMPCC | AMPA-R Ab CBA, CSF | No | Yes |
AMPHC | Amphiphysin Ab, CSF | No | Yes |
AGN1C | Anti-Glial Nuclear Ab, Type 1 | 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 |
CS2CC | CASPR2-IgG CBA, CSF | No | Yes |
CRMC | CRMP-5-IgG, CSF | No | Yes |
DPPCC | DPPX Ab CBA, CSF | No | Yes |
GABCC | GABA-B-R Ab CBA, CSF | No | Yes |
GD65C | GAD65 Ab Assay, CSF | Yes | Yes |
GFAIC | GFAP IFA, CSF | No | Yes |
GL1IC | mGluR1 Ab IFA, CSF | No | Yes |
IG5CC | IgLON5 CBA, CSF | No | Yes |
LG1CC | LGI1-IgG CBA, CSF | No | Yes |
NCDIC | Neurochondrin IFA, CSF | No | Yes |
NIFIC | NIF IFA, CSF | No | Yes |
NMDCC | NMDA-R Ab CBA, CSF | No | Yes |
PCTRC | Purkinje Cell Cytoplasmc Ab Type Tr | No | Yes |
PCA1C | Purkinje Cell Cytoplasmic Ab Type 1 | No | Yes |
PCA2C | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
PDEIC | PDE10A Ab IFA, CSF | No | Yes |
SP7IC | Septin-7 IFA, CSF | No | Yes |
T46IC | TRIM46 Ab IFA, CSF | 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 |
---|---|---|---|
AGNBC | AGNA-1 Immunoblot, CSF | No | No |
AINCC | Alpha Internexin CBA, CSF | No | No |
AMPIC | AMPA-R Ab IF Titer Assay, CSF | No | No |
AMIBC | Amphiphysin Immunoblot, CSF | No | No |
AN1BC | ANNA-1 Immunoblot, CSF | No | No |
AN2BC | ANNA-2 Immunoblot, CSF | No | No |
CRMWC | CRMP-5-IgG Western Blot, CSF | Yes | No |
DPPTC | DPPX Ab IFA Titer, CSF | No | No |
GABIC | GABA-B-R Ab IF Titer Assay, CSF | No | No |
GFACC | GFAP CBA, CSF | No | No |
GFATC | GFAP IFA Titer, CSF | No | No |
IG5TC | IgLON5 IFA Titer, CSF | No | No |
GL1CC | mGluR1 Ab CBA, CSF | No | No |
GL1TC | mGluR1 Ab IFA Titer, CSF | No | No |
NFHCC | NIF Heavy Chain CBA, CSF | No | No |
NIFTC | NIF IFA Titer, CSF | No | No |
NFLCC | NIF Light Chain CBA, CSF | No | No |
NMDIC | NMDA-R Ab IF Titer Assay, CSF | No | No |
PC1BC | PCA-1 Immunoblot, CSF | No | No |
PCTBC | PCA-Tr Immunoblot, CSF | No | No |
AGNTC | AGNA-1 Titer, CSF | No | No |
AN1TC | ANNA-1 Titer, CSF | No | No |
AN2TC | ANNA-2 Titer, CSF | No | No |
AN3TC | ANNA-3 Titer, CSF | No | No |
APHTC | Amphiphysin Ab Titer, CSF | No | No |
CRMTC | CRMP-5-IgG Titer, CSF | No | No |
NCDCC | Neurochondrin CBA, CSF | No | No |
NCDTC | Neurochondrin IFA Titer, CSF | No | No |
PC1TC | PCA-1 Titer, CSF | No | No |
PC2TC | PCA-2 Titer, CSF | No | No |
PCTTC | PCA-Tr Titer, CSF | No | No |
PDETC | PDE10A Ab IFA Titer, CSF | No | No |
SP7CC | Septin-7 CBA, CSF | No | No |
SP7TC | Septin-7 IFA Titer, CSF | No | No |
T46CC | TRIM46 Ab CBA, CSF | No | No |
T46TC | TRIM46 Ab IFA Titer, CSF | No | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
To determine the necessity of laboratory testing for patients with suspected autoimmune encephalitis, epilepsy or dementia, see the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scorecard.
If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then the amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.
If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then the AGNA-1 IFA titer and AGNA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then the ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the client requests or the IFA pattern suggests ANNA-3 antibodies, then the ANNA-3 titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then the PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then the PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then the PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.
If the IgLON5 antibody cell binding assay (CBA) result is positive, then the IgLON5 IFA titer will be performed at an additional charge.
If the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA result is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.
If the gamma-aminobutyric acid B (GABA-B) receptor antibody CBA result is positive, then the GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.
If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP IFA titer and GFAP CBA will be performed at an additional charge.
If the N-methyl-D-aspartate (NMDA) receptor antibody CBA result is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.
If the dipeptidyl-peptidase-like protein-6 (DPPX) antibody CBA result is positive, then the DPPX IFA titer will be performed at an additional charge.
If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then the mGluR1 antibody CBA and mGluR1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then the alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer will be performed at an additional charge.
If the IFA pattern suggests neurochondrin antibody, then the neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.
If the IFA pattern suggests septin-7 antibody, then the septin-7 antibody CBA and septin-7 IFA titer will be performed at an additional charge.
If the IFA pattern suggests tripartite motif-containing protein 46 (TRIM46) antibody, then the TRIM46 antibody CBA and TRIM46 IFA titer will be performed at an additional charge.
If the IFA pattern suggests phosphodiesterase 10A (PDE10A) antibody, then the PDE10A antibody IFA titer will be performed at an additional charge.
For more information, see the following algorithms:
-Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
-Central Nervous System Demyelinating Disease Diagnostic Algorithm
Method Name
A short description of the method used to perform the test
AEECI: Medical Interpretation
AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPTC, GABIC, GFAIC, GFATC, IG5TC, GL1IC, GL1TC, NCDIC, NCDTC, NIFIC, NIFTC, NMDIC, PCA1C, PC1TC, PCA2C, PC2TC, PCTRC, PCTTC, PDEIC, PDETC, SP7IC, SP7TC, T46IC, T26TC: Indirect Immunofluorescence Assay (IFA)
AMPCC, CS2CC, DPPCC, GABCC, GFACC, IG5CC, LG1CC, GL1CC, NCDCC, AINCC, NFLCC, NFHCC, NMDCC, SP7CC, T46CC: Cell Binding Assay (CBA)
CRMWC: Western Blot (WB)
AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Immunoblot (IB)
GD65C: Radioimmunoassay (RIA)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
AMPA-R Antibody CBA
Amphiphysin Antibody
Anti-Glial Nuclear Antibody, Type 1
Anti-Neuronal Nuclear Antibody, Type 1
Anti-Neuronal Nuclear Antibody, Type 2
Anti-Neuronal Nuclear Antibody, Type 3
Behavioral Change
CASPR2-IgG
Confusion
Contactin-Associated Protein-Like-2 (CASPR2)-IgG
CRMP-5-IgG
DPPX
dipeptidyl aminopeptidase-like protein 6
ENCEC
Encephalitis
GABA-B-R Antibody CBA
Glutamic Acid Decarboxylase (GAD65)
Leucine-Rich Glioma Inactivated Protein-1 IgG
LGI1-IgG
metabotropic glutamate receptor 1
mGluR1
NMDA-R Antibody CBA
Psychosis
Purkinje Cell Cytoplasmic Antibody, Type 1
Purkinje Cell Cytoplasmic Antibody, Type 2
Purkinje Cell Cytoplasmic Antibody, Type Tr
Limbic encephalitis
Neurochondrin
Septin-7
Phosphodiesterase 10A (PDE10A)
Tripartite Motif-Containing Protein 46 (TRIM46)
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
To determine the necessity of laboratory testing for patients with suspected autoimmune encephalitis, epilepsy or dementia, see the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scorecard.
If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then the amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.
If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then the AGNA-1 IFA titer and AGNA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then the ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the client requests or the IFA pattern suggests ANNA-3 antibodies, then the ANNA-3 titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then the PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then the PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then the PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.
If the IgLON5 antibody cell binding assay (CBA) result is positive, then the IgLON5 IFA titer will be performed at an additional charge.
If the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA result is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.
If the gamma-aminobutyric acid B (GABA-B) receptor antibody CBA result is positive, then the GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.
If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP IFA titer and GFAP CBA will be performed at an additional charge.
If the N-methyl-D-aspartate (NMDA) receptor antibody CBA result is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.
If the dipeptidyl-peptidase-like protein-6 (DPPX) antibody CBA result is positive, then the DPPX IFA titer will be performed at an additional charge.
If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then the mGluR1 antibody CBA and mGluR1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then the alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer will be performed at an additional charge.
If the IFA pattern suggests neurochondrin antibody, then the neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.
If the IFA pattern suggests septin-7 antibody, then the septin-7 antibody CBA and septin-7 IFA titer will be performed at an additional charge.
If the IFA pattern suggests tripartite motif-containing protein 46 (TRIM46) antibody, then the TRIM46 antibody CBA and TRIM46 IFA titer will be performed at an additional charge.
If the IFA pattern suggests phosphodiesterase 10A (PDE10A) antibody, then the PDE10A antibody IFA titer will be performed at an additional charge.
For more information, see the following algorithms:
-Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
-Central Nervous System Demyelinating Disease Diagnostic Algorithm
Specimen Type
Describes the specimen type validated for testing
CSF
Ordering Guidance
Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, see Autoimmune Neurology Test Ordering Guide.
When more than one evaluation is ordered on the same order number, the duplicate test will be canceled.
For a list of antibodies performed with each evaluation, see Autoimmune Neurology Antibody Matrix.
This test is intended to be ordered for adult patients. If this test is ordered for a patient younger than 18 years, it will be canceled and automatically reordered by the laboratory as PCDEC / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Spinal Fluid. The pediatric autoimmune CNS disorders evaluation is part of an evolving approach to testing for autoimmune neurological disorders using phenotypic-specific evaluations that include multiple antibodies known for their disease association.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering healthcare professional's 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
Container/Tube: Sterile vial
Preferred: Collection vial number 1
Acceptable: Any collection vial
Specimen Volume: 4 mL
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
If not ordering electronically, complete, print, and send 1 of the following with the specimen:
-Neurology Specialty Testing Client Test Request (T732)
-General Test Request (T239)
-Microbiology Test Request (T244)
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
2 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 |
---|---|---|---|
CSF | Refrigerated (preferred) | 28 days | |
Ambient | 72 hours | ||
Frozen | 28 days |
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 using spinal fluid 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 or more pack-years) or other cancer risk factors
-Inflammatory cerebrospinal fluid (or isolated protein elevation)
-Neuroimaging signs suggesting inflammation
Evaluating limbic encephalitis (noninfectious)
Directing a focused search for cancer
Investigating encephalopathy appearing during or after 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.
To determine the necessity of laboratory testing for patients with suspected autoimmune encephalitis, epilepsy or dementia, see the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scorecard.
If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then the amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.
If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then the AGNA-1 IFA titer and AGNA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then the ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the client requests or the IFA pattern suggests ANNA-3 antibodies, then the ANNA-3 titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then the PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then the PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then the PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.
If the IgLON5 antibody cell binding assay (CBA) result is positive, then the IgLON5 IFA titer will be performed at an additional charge.
If the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA result is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.
If the gamma-aminobutyric acid B (GABA-B) receptor antibody CBA result is positive, then the GABA-B-receptor antibody IFA titer assay will be performed at an additional charge.
If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP IFA titer and GFAP CBA will be performed at an additional charge.
If the N-methyl-D-aspartate (NMDA) receptor antibody CBA result is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.
If the dipeptidyl-peptidase-like protein-6 (DPPX) antibody CBA result is positive, then the DPPX IFA titer will be performed at an additional charge.
If the IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then the mGluR1 antibody CBA and mGluR1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then the alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer will be performed at an additional charge.
If the IFA pattern suggests neurochondrin antibody, then the neurochondrin antibody CBA and neurochondrin IFA titer will be performed at an additional charge.
If the IFA pattern suggests septin-7 antibody, then the septin-7 antibody CBA and septin-7 IFA titer will be performed at an additional charge.
If the IFA pattern suggests tripartite motif-containing protein 46 (TRIM46) antibody, then the TRIM46 antibody CBA and TRIM46 IFA titer will be performed at an additional charge.
If the IFA pattern suggests phosphodiesterase 10A (PDE10A) antibody, then the PDE10A antibody IFA titer will be performed at an additional charge.
For more information, see the following algorithms:
-Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
-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 based on the 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, 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 testing 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 (eg, NMDA-R antibody and glial fibrillary acidic protein [GFAP]-IgG) because CSF testing is 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 |
AEECI | Encephalopathy, Interpretation, CSF | Medical interpretation | Interpretive report |
AMPCC | AMPA-R Ab CBA, CSF | CBA | Negative |
AMPHC | Amphiphysin Ab, CSF | IFA | Negative |
AGN1C | Anti-Glial Nuclear Ab, Type 1 | IFA | Negative |
ANN1C | Anti-Neuronal Nuclear Ab, Type 1 | IFA | Negative |
ANN2C | Anti-Neuronal Nuclear Ab, Type 2 | IFA | Negative |
ANN3C | Anti-Neuronal Nuclear Ab, Type 3 | IFA | Negative |
CS2CC | CASPR2-IgG CBA, CSF | CBA | Negative |
CRMC | CRMP-5-IgG, CSF | IFA | Negative |
DPPCC | DPPX Ab CBA, CSF | CBA | Negative |
GABCC | GABA-B-R Ab CBA, CSF | CBA | Negative |
GD65C | GAD65 Ab Assay, CSF | RIA | < or =0.02 nmol/L Reference values apply to all ages. |
GFAIC | GFAP IFA, CSF | IFA | Negative |
GL1IC | mGluR1 Ab IFA, CSF | IFA | Negative |
IG5CC | IgLON5 CBA, CSF | CBA | Negative |
LG1CC | LGI1-IgG CBA, CSF | CBA | Negative |
NCDIC | Neurochondrin IFA, CSF | IFA | Negative |
NIFIC | NIF IFA, CSF | IFA | Negative |
NMDCC | NMDA-R Ab CBA, CSF | CBA | Negative |
PCTRC | Purkinje Cell Cytoplasmc Ab Type Tr | IFA | Negative |
PCA1C | Purkinje Cell Cytoplasmic Ab Type 1 | IFA | Negative |
PCA2C | Purkinje Cell Cytoplasmic Ab Type 2 | IFA | Negative |
PDEIC | PDE10A Ab IFA, CSF | IFA | Negative |
SP7IC | Septin-7 IFA, CSF | IFA | Negative |
T46IC | TRIM46 IFA, CSF | IFA | Negative |
Reflex Information:
Test ID | Reporting name | Methodology* | Reference value |
AGNBC | AGNA-1 Immunoblot, CSF | IB | Negative |
AGNTC | AGNA-1 Titer, CSF | IFA | <1:2 |
AINCC | Alpha Internexin CBA, CSF | CBA | Negative |
AMPIC | AMPA-R Ab IF Titer Assay, CSF | IFA | <1:2 |
AMIBC | Amphiphysin Immunoblot, CSF | IB | Negative |
AN1BC | ANNA-1 Immunoblot, CSF | IB | Negative |
AN1TC | ANNA-1 Titer, CSF | IFA | <1:2 |
AN2BC | ANNA-2 Immunoblot, CSF | IB | Negative |
AN2TC | ANNA-2 Titer, CSF | IFA | <1:2 |
AN3TC | ANNA-3 Titer, CSF | IFA | <1:2 |
APHTC | Amphiphysin Ab Titer, CSF | IFA | <1:2 |
CRMTC | CRMP-5-IgG Titer, CSF | IFA | <1:2 |
CRMWC | CRMP-5-IgG Western Blot, CSF | WB | Negative |
DPPTC | DPPX Ab IFA Titer, CSF | IFA | <1:2 |
GABIC | GABA-B-R Ab IF Titer Assay, CSF | IFA | <1:2 |
GFACC | GFAP CBA, CSF | CBA | Negative |
GFATC | GFAP IFA Titer, CSF | IFA | <1:2 |
IG5TC | IgLON5 IFA Titer, CSF | IFA | <1:2 |
GL1CC | mGluR1 Ab CBA, CSF | CBA | Negative |
GL1TC | mGluR1 Ab IFA Titer, CSF | IFA | <1:2 |
NCDCC | Neurochondrin CBA, CSF | CBA | Negative |
NCDTC | Neurochondrin IFA Titer, CSF | IFA | <1:2 |
NFLCC | NIF Light Chain CBA, CSF | CBA | Negative |
NFHCC | NIF Heavy Chain CBA, CSF | CBA | Negative |
NIFTC | NIF IFA Titer, CSF | IFA | <1:2 |
NMDIC | NMDA-R Ab IF Titer Assay, CSF | IFA | <1:2 |
PC1BC | PCA-1 Immunoblot, CSF | IB | Negative |
PC1TC | PCA-1 Titer, CSF | IFA | <1:2 |
PC2TC | PCA-2 Titer, CSF | IFA | <1:2 |
PCTBC | PCA-Tr Immunoblot, CSF | IB | Negative |
PCTTC | PCA-Tr Titer, CSF | IFA | <1:2 |
PDETC | PDE10A Ab IFA Titer, CSF | IFA | <1:2 |
SP7CC | Septin-7 CBA, CSF | CBA | Negative |
SP7IC | Septin-7 IFA Titer, CSF | IFA | <1:2 |
T46CC | TRIM46 CBA, CSF | CBA | Negative |
T46TC | TRIM46 IFA Titer, CSF | IFA | <1:2 |
*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, ANNA-3, 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 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (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: These are all potential effectors of neurological dysfunction: 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 acetylcholine receptor.
-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), collapsin response-mediator protein-5 (CRMP-5), or glutamic acid decarboxylase (GAD65).
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 (also known as 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.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Orozco E, Valencia-Sanchez C, Britton J, et al. Autoimmune encephalitis criteria in clinical practice. Neurol Clin Pract. 2023;13(3):e200151. doi:10.1212/CPJ.0000000000200151
2. Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30-39. doi:10.1001/jamaneurol.2022.4251
3. Budhram A, Dubey D, Sechi E, et al. Neural Antibody Testing in Patients with Suspected Autoimmune Encephalitis. Clin Chem. 2020;66(12):1496-1509. doi:10.1093/clinchem/hvaa254
4. Abboud H, Probasco JC, Irani S, et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry. 2021;92(7):757-768. doi:10.1136/jnnp-2020-325300
5. Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166-177. doi:10.1002/ana.25131
Method Description
Describes how the test is performed and provides a method-specific reference
Cell-Binding Assay:
Patient specimen is applied to a composite slide containing transfected and nontransfected EU90 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, 02/25/2019)
Indirect Immunofluorescence Assay:
The patient's sample is tested by a standardized indirect immunofluorescence 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. Neurol Neuroimmunol Neuroinflamm. 2017;4[5]:e385. doi:10.1212/NXI.0000000000000385)
Radioimmunoassay:
(125)I-labeled recombinant human antigens or labeled receptors are incubated with patient specimen. After incubation, anti-human IgG is added to form an immunoprecipitate. The amount of (125)I-labeled antigen in the immunoprecipitate is measured using a gamma-counter. The amount of gamma emission in the precipitate is proportional to the amount of antigen-specific IgG in the specimen. Results are reported as units of precipitated antigen (nmol) per liter of patient sample.(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. 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;72[11]:1304-1312. doi:10.1001/jamaneurol.2015.2378)
Immunoblot:
All steps are performed at ambient temperature (18 to 28 degrees C) utilizing the EUROBlot One instrument. Diluted patient serum (1:12.5) 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 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;6[3]:e552. doi:10.1212/NXI.0000000000000552)
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, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al. Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019;93(20):e1873-e1880. doi:10.1212/WNL.0000000000008472)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
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. It 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.
CPT codes are provided by the performing laboratory.
86255 x23
86341 x1
84182 AGNBC (if appropriate)
86256 AGNTC (if appropriate)
86255 AINCC (if appropriate)
86256 AMPIC (if appropriate)
84182 AMIBC (if appropriate)
84182 AN1BC (if appropriate)
86256 AN1TC (if appropriate)
84182 AN2BC (if appropriate)
86256 AN2TC (if appropriate)
86256 AN3TC (if appropriate)
86256 APHTC (if appropriate)
86256 CRMTC (if appropriate)
84182 CRMWC (if appropriate)
86256 DPPTC (if appropriate)
86256 GABIC (if appropriate)
86255 GFACC (if appropriate)
86256 GFATC (if appropriate)
86256 IG5TC (if appropriate)
86255 GL1CC (if appropriate)
86256 GL1TC (if appropriate)
86255 NCDCC (if appropriate)
86256 NCDTC (if appropriate)
86255 NFHCC (if appropriate)
86256 NIFTC (if appropriate)
86255 NFLCC (if appropriate)
86256 NMDIC (if appropriate)
84182 PC1BC (if appropriate)
86256 PC1TC (if appropriate)
86256 PC2TC (if appropriate)
84182 PCTBC (if appropriate)
86256 PCTTC (if appropriate)
86256 PDETC (if appropriate)
86255 SP7CC (if appropriate)
86256 SP7TC (if appropriate)
86255 T46CC (if appropriate)
86256 T46TC (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 |
---|---|---|
ENC2 | Enceph, Autoimm/Paraneo, CSF | 94708-5 |
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.
|
---|---|---|
89079 | AGNA-1, CSF | 90827-7 |
5906 | Amphiphysin Ab, CSF | 90815-2 |
3852 | ANNA-1, CSF | 44768-0 |
7472 | ANNA-2, CSF | 56959-0 |
21633 | ANNA-3, CSF | 90836-8 |
21650 | CRMP-5-IgG, CSF | 63216-6 |
3988 | PCA-1, CSF | 90841-8 |
21632 | PCA-2, CSF | 90843-4 |
21631 | PCA-Tr, CSF | 90845-9 |
21702 | GAD65 Ab Assay, CSF | 94359-7 |
61513 | NMDA-R Ab CBA, CSF | 93502-3 |
61514 | AMPA-R Ab CBA, CSF | 93491-9 |
61515 | GABA-B-R Ab CBA, CSF | 93426-5 |
34256 | Encephalopathy, Interpretation, CSF | 69048-7 |
618895 | IFA Notes | 48767-8 |
64280 | LGI1-IgG CBA, CSF | 94288-8 |
64282 | CASPR2-IgG CBA, CSF | 94286-2 |
64927 | mGluR1 Ab IFA, CSF | 94361-3 |
64934 | DPPX Ab CBA, CSF | 94283-9 |
605156 | GFAP IFA, CSF | 94360-5 |
606965 | NIF IFA, CSF | 96490-8 |
606951 | IgLON5 CBA, CSF | 96481-7 |
615866 | Neurochondrin IFA, CSF | 101451-3 |
615874 | Septin-7 IFA, CSF | 101464-6 |
620067 | PDE10A Ab IFA, CSF | 103842-1 |
616446 | TRIM46 Ab IFA, CSF | 103843-9 |
Test Setup Resources
Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.
Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.
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.
Test Update Resources
Change Type | Effective Date |
---|---|
File Definition - Algorithm | 2024-06-04 |