ENC2 - Overview: Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid (2023)

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

If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then 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 amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.

If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then 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 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 ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.

If the IFA pattern suggests PCA-2 antibody, then PCA-2 IFA titer will be performed at an additional charge.

If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.

If the IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) will be performed at an additional charge.

If AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

If gamma-aminobutyric acid B (GABA-B) receptor antibody CBA is positive, then 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 GFAP IFA titer and GFAP CBA will be performed at an additional charge.

If N-methyl-D-aspartate (NMDA) receptor antibody CBA is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.

If the IFA pattern suggests dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX IFA titer will be performed at an additional charge.

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

If the IFA pattern suggests septin-7 antibody, then septin-7 antibody CBA and septin-7 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

• Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
• Central Nervous System Demyelinating Disease Diagnostic Algorithm

AGN1C, AGNTC, AMPIC, AMPHC, APHTC, ANN1C, AN1TC, ANN2C, AN2TC, ANN3C, AN3TC, CRMTC, CRMC, DPPIC, DPPTC, GABIC, GFAIC, GFATC, IG5IC, IG5TC, GL1IC, GL1TC, NCDIC, NCDTC, NIFIC, NIFTC, NMDIC, PCA1C, PC1TC, PCA2C, PC2TC, PCTRC, PCTTC, SP7IC, SP7TC: Indirect Immunofluorescence Assay (IFA)

AMPCC, CS2CC, DPPCC, GABCC, GFACC, IG5CC, LG1CC, GL1CC, NCDCC, AINCC, NFLCC, NFHCC, NMDCC, SP7CC: Cell Binding Assay (CBA)

CRMWC: Western Blot (WB)

AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Immunoblot (IB)

GD65C: Radioimmunoassay (RIA)

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

If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then 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 amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.

If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then 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 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 ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.

If the IFA pattern suggests PCA-2 antibody, then PCA-2 IFA titer will be performed at an additional charge.

If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.

If the IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) will be performed at an additional charge.

If AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

If gamma-aminobutyric acid B (GABA-B) receptor antibody CBA is positive, then 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 GFAP IFA titer and GFAP CBA will be performed at an additional charge.

If N-methyl-D-aspartate (NMDA) receptor antibody CBA is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.

If the IFA pattern suggests dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX IFA titer will be performed at an additional charge.

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

If the IFA pattern suggests septin-7 antibody, then septin-7 antibody CBA and septin-7 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

Multiple neuroimmunology profile tests are available. For testing that is performed with each profile, 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 of age, 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 knownfor their disease association.

Provide the following information:

-Relevant clinical information

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

Container/Tube: Sterile vial

Specimen Volume: 4 mL

• Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
• Central Nervous System Demyelinating Disease Diagnostic Algorithm

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)

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

If client requests or if the immunofluorescence (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then 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 amphiphysin IFA titer and amphiphysin immunoblot will be performed at an additional charge.

If the IFA pattern suggests antiglial nuclear antibody (AGNA-1), then 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 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 ANNA-2 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then PCA-1 IFA titer and PCA-1 immunoblot will be performed at an additional charge.

If the IFA pattern suggests PCA-2 antibody, then PCA-2 IFA titer will be performed at an additional charge.

If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr IFA titer and PCA-Tr immunoblot will be performed at an additional charge.

If the IFA pattern suggests IgLON5 antibody, then IgLON5 IFA titer and IgLON5 cell-binding assay (CBA) will be performed at an additional charge.

If AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor antibody CBA is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

If gamma-aminobutyric acid B (GABA-B) receptor antibody CBA is positive, then 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 GFAP IFA titer and GFAP CBA will be performed at an additional charge.

If N-methyl-D-aspartate (NMDA) receptor antibody CBA is positive, then NMDA-receptor antibody IFA titer assay will be performed at an additional charge.

If the IFA pattern suggests dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX IFA titer will be performed at an additional charge.

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

If the IFA pattern suggests septin-7 antibody, then septin-7 antibody CBA and septin-7 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

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 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.

Reflex Information:

*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.

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 ACh 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).

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.

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 Mar;50(3):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;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

• Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm-Spinal Fluid
• Central Nervous System Demyelinating Disease Diagnostic Algorithm

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)

Indirect Immunofluorescence Assay:

The patient's sample is tested by a standardized indirect immunofluorescence (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. Neurol Neuroimmunol Neuroinflamm 2017 Jul 18;4(5):e385. doi: 10.1212/NXI.0000000000000385

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. 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)

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 Apr 4;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, 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 Nov12;93(20) e1873-e1880. doi: 10.1212/WNL.0000000000008472)

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86255 x21

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)

86255 DPPCC (if appropriate)

86256 DPPTC (if appropriate)

86256 GABIC (if appropriate)

86255 GFACC (if appropriate)

86256 GFATC (if appropriate)

86255 IG5CC (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)

86255 SP7CC (if appropriate)

86256 SP7TC (if appropriate)

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