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Test Code ENC1 Encephalopathy, Autoimmune Evaluation, Spinal Fluid

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 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+ 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

Test ID Reporting Name Available Separately Always Performed
AEECI Encephalopathy, Interpretation, CSF No Yes
NMDCC NMDA-R Ab CBA, CSF No Yes
VGKCC VGKC-complex Ab IPA, CSF No Yes
LG1CC LGI1-IgG CBA, CSF No Yes
CS2CC CASPR2-IgG CBA, CSF No Yes
GD65C GAD65 Ab Assay, CSF Yes Yes
GABCC GABA-B-R Ab CBA, CSF No Yes
AMPCC AMPA-R Ab CBA, CSF 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
AGN1C Anti-Glial Nuclear Ab, Type 1 No Yes
PCA1C Purkinje Cell Cytoplasmic Ab Type 1 No Yes
PCA2C Purkinje Cell Cytoplasmic Ab Type 2 No Yes
PCTRC Purkinje Cell Cytoplasmc Ab Type Tr No Yes
AMPHC Amphiphysin Ab, CSF No Yes
CRMC CRMP-5-IgG, CSF No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
WBNC Paraneoplas Autoantibody WBlot,CSF No No
CRMWC CRMP-5-IgG Western Blot, CSF Yes No
ABLTC Amphiphysin Western Blot, CSF No No
NMOFC NMO/AQP4 FACS, CSF Yes No
NMOTC NMO/AQP4 FACS Titer, CSF No No
AMPIC AMPA-R Ab IF Titer Assay, CSF No No
GABIC GABA-B-R Ab IF Titer Assay, CSF No No
NMDIC NMDA-R Ab IF Titer Assay, CSF No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) (ANN1C, ANN2C, ANN3C, AGN1C, PCA2C, PCTRC, AMPHC, CRMC) is indeterminate, then WBNC is performed at an additional charge.

 

If client requests or if IFA patterns suggest CRMP-5-IgG, then CRMWC is performed at an additional charge.

 

If IFA pattern suggest amphiphysin antibody, then ABLTC is performed at an additional charge.

 

If IFA pattern suggest NMO/AQP4-IgG, then NMOFC is performed at an additional charge.

 

If NMO/AQP4-IgG FACS screen assay requires further investigation, then NMO/AQP4-IgG FACS titration assay is performed at an additional charge.

 

If IFA pattern suggest AMPA-R Ab and AMPCC is positive, then AMPIC is performed at an additional charge.

 

If IFA pattern suggest GABA-B-R Ab and GABCC is positive, then GABIC is performed at an additional charge.

 

If IFA pattern suggest NMDA-R Ab and NMDCC is positive, then NMDIC is performed at an additional charge.

 

See Encephalopathy Autoimmune Evaluation Algorithm, Spinal Fluid in Special Instructions

Method Name

ANN1C, ANN2C, ANN3C, AGN1C, PCA1C, PCA2C, PCTRC, AMPHC, CRMC, AMPIC, GABIC, NMDIC: Indirect Immunofluorescence Assay (IFA)

AMPCC, GABCC, NMDCC, LG1CC, CS2CC: Cell-Binding Assay (CBA)

GD65C: Immunoprecipitation Assay

VGKCC: Radioimmunoassay (RIA)

WBNC, ABLTC: Western Blot

AEECI: Interpretive Comments

Reporting Name

Encephalopathy-Autoimmune Eval, CSF
Seattle Children's Hospital Note:

Clinical System Name: Autoimmune Encephalopathy Panel, CSF

Specimen Type

CSF


Necessary Information


Include name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.



Specimen Required


Container/Tube: Sterile vial

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time
CSF Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

NA

Other

NA

Reference Values

NEURONAL NUCLEAR ANTIBODIES

Antineuronal Nuclear Antibody-Type 1 (ANNA-1)

<1:2

Antineuronal Nuclear Antibody-Type 2 (ANNA-2)

<1:2

Antineuronal Nuclear Antibody-Type 3 (ANNA-3)

<1:2

Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)

<1:2

 

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES

Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)

<1:2    

Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)

<1:2    

Purkinje Cell Cytoplasmic Antibody, Type TR (PCA-TR)

<1:2

Amphiphysin Antibody

<1:2

Collapsin Response-Mediator Protein-5 Neuronal (CRMP-5-IGG)

<1:2

 

ISLET CELL ANTIBODIES

Glutamic Acid Decarboxylase (GAD65) Antibody Assay

≤0.02 nmol/L

 

AMPA-RECEPTOR ANTIBODY BY CBA

CBA: Negative

IFA: <1:2

GABA-B-RECEPTOR ANTIBODY BY CBA

CBA: Negative

IFA: <1:2

NMDA-RECEPTOR ANTIBODY BY CBA

CBA: Negative

IFA: <1:2

LGI1-IgG CBA: Negative

CASPR2-IgG CBA: Negative

 

Neuronal Voltage-Gated Potassium Channel-Complex Autoantibody

≤0.02 nmol/L

 

WESTERN BLOT

Paraneoplastic Autoantibody, Western Blot Confirmation

Negative

Collapsin Response-Mediator Protein-5-IGG (CRMP-5-IGG) Western Blot

Negative

Amphiphysin Antibody Western Blot

Negative

 

Neuromyelitis Optica (NMO)/Aquaporin-4-Igg FACS Assay

Negative

Method Description

Indirect Immunofluorescence Assay (IFA):

Before testing, patient's serum is preabsorbed with liver powder to remove nonorgan-specific autoantibodies. After applying to a composite substrate of frozen mouse tissues (brain, kidney, and gut) and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the distribution and pattern of patient IgG binding.(Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004;56:715-719)

 

Radioimmunoprecipitation (RIA):

Goat-antihuman IgG and IgM is used as precipitant in all assays. Cation channel protein ntigens are solubilized from neuronal or muscle membrane, in non-ionic detergent, and complexed with a selective high-affinity ligand labeled with (125)I. (125)I-labelled recombinant human GAD65 antigen is used to confirm GAD65 autoantibody (when suspected from immunofluorescent staining pattern).(Griesmann GE, Kryzer TJ, Lennon VA: Autoantibody profiles of myasthenia gravis and Lambert-Eaton myasthenic syndrome. In Manual of Clinical and Laboratory Immunology, Sixth edition. Edited by NR Rose, RG Hamilton, et al. Washington, DC, ASM Press, 2002, pp 1005-1012; Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid decarboxylase [GAD65] autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998;73[12]:1161-1166)

 

Cell-Binding Assay (CBA):

Patient serum 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: EUROIMMUN AG. Stocker W, et al. Differenzierte Autoantikorper-Diagnostik mit BIOCHIP-Mosaiken. U Conrad, K. (Hrsg) Autoantikorper. Pabst-Verlag [1998] 78-99)

 

Western Blot (WB):

WB is performed when IFA screening for ANNA-1 is not interpretable due to interfering autoantibodies. A mixture of neuronal antigens extracted aqueously from adult rat cerebellum is denatured, reduced, and separated by electrophoresis on 10% polyacrylamide gel. Full-length recombinant human CRMP-5 antigen is used to confirm CRMP-5-IgG.(Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001;49[2]:145-154)

 

NMO-IgG Fluorescence-Activated Cell Sorting Assay (FACS):

Human embryonic kidney cells (HEK 293) are transfected transiently with a plasmid (pIRES2-Aequorea coerulescens green fluorescent protein [AcGFP]) encoding both green fluorescent protein (GFP) and AQP4-M1. After 36 hours, the mixed population of cells (transfected expressing AQP4 on the surface and GFP in the cytoplasm and nontransfected lacking AQP4 and GFP) are harvested with short exposure to trypsin. Patient CSF is then added to cells at a 1 in 2 screening dilution. After incubation and washing, the cells are resuspended with AlexaFluor 647-conjugated goat-antihuman IgG-gamma specific secondary antibody (Southern Biotech catalog No. 2040-31, 1:2000 in LCBB), held on ice, washed, fixed with 4% paraformaldehyde, and examined with flow cytometry (BD FACSCanto; Becton, Dickinson and Co). Two populations are gated on the basis of GFP expression: positive (high AQP4 expression) and negative (low or no AQP4 expression). The median Alexafluor 647 fluorescence intensity (MFI) for the AcGFP-positive population indicates relative abundance of human IgG potentially bound to AQP4 surface epitopes; MFI for the GFP-negative population indicated nonspecifically-bound IgG. The IgG binding index was calculated as the ratio of the average MFI for duplicate aliquots of each cell population: (MFI GFP positive/MFI GFP negative). We established conservative cutoff IgG binding index values of 2.00 for M1-FACS.

 

If FACS assay is positive at screening dilution, FACS Titer Assay is performed at an additional charge. The patient CSF is titrated to endpoint. The dilution where the IgG binding index is greater than or equal to 2, is considered the endpoint dilution. If a patient is positive at a 1:2 dilution, but negative at 1:4, the endpoint will be reported as 2.

Day(s) and Time(s) Performed

ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, AMPIC, GABIC, NMDIC:

Monday through Friday; 11:30 a.m. and 8:00 p.m.; Saturday and Sunday 8:00 a.m.

 

AMPCC, GABCC, NMDCC LG1CC, CS2CC: Monday through Friday; 6 a.m.

Paraneoplastic autoantibody Western blot confirmation, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday, Wednesday, Friday; 8 a.m.

GAD65: : Monday to Friday; 6:00 a.m. and 4:00 p.m.

VGKC: Monday through Friday 11:00 a.m. and 6:00 p.m.; Saturday 6:00 a.m.; Sunday 6:00 a.m.

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

See Individual Test IDs

CPT Code Information

83519-Neuronal VGKC autoantibody

86255-AGNA-1

86255-Amphiphysin

86255-ANNA-1

86255-ANNA-2

86255-ANNA-3

86255-CRMP-5-IgG

86255-PCA-1

86255-PCA-2

86255-PCA-Tr

86255-AMPAR-Ab

86255-GABAR-Ab

86255-NMDAR-Ab

86341-GAD65

86255-LG1CC

86255- CS2CC

84182-Amphiphysin Western blot (if appropriate)

84182-CRMP-5 Western blot confirmation (if appropriate)

84182-Paraneoplastic autoantibody Western blot confirmation (if appropriate)

86255-NMO/AQP4-IgG FACS (if appropriate)

86256-AMPAR-Ab titer (if appropriate)

86256-GABAR-Ab titer (if appropriate)

86256-NMDAR-Ab titer (if appropriate)

86256- NMO/AQP4-IgG FACS titer (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
ENC1 Encephalopathy-Autoimmune Eval, CSF In Process

 

Result ID Test Result Name Result LOINC Value
61513 NMDA-R Ab CBA, CSF No LOINC Needed
61514 AMPA-R Ab CBA, CSF No LOINC Needed
61515 GABA-B-R Ab CBA, CSF No LOINC Needed
34256 Encephalopathy, Interpretation, CSF 69048-7
61729 VGKC-complex Ab IPA, CSF 68913-3
64280 LGI1-IgG CBA, CSF In Process
64282 CASPR2-IgG CBA, CSF In Process
89079 AGNA-1, CSF 53714-2
5906 Amphiphysin Ab, CSF 56531-7
3852 ANNA-1, CSF 24400-4
7472 ANNA-2, CSF 24401-2
21633 ANNA-3, CSF 35144-5
21650 CRMP-5-IgG, CSF 35385-4
3988 PCA-1, CSF 14248-9
21632 PCA-2, CSF 35143-7
21631 PCA-Tr, CSF 51748-2
21702 GAD65 Ab Assay, CSF 53708-4
36429 Reflex Added No LOINC Needed

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)