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Test ID PCDEC Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Spinal Fluid


Ordering Guidance


Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, refer to 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.



Necessary Information


Provide the following information:

-Relevant clinical information

-Ordering healthcare professional's name, phone number, mailing address, and email address



Specimen Required


Container/Tube: Sterile vial

Preferred: Collection vial number 1

Acceptable: Any collection vial

Specimen Volume: 4 mL


Useful For

Evaluating children with autoimmune central nervous system disorders using spinal fluid specimens

Profile Information

Test ID Reporting Name Available Separately Always Performed
PCCI Peds Autoimmune CNS Interp, CSF No Yes
AMPCC AMPA-R Ab CBA, CSF No Yes
ANN1C Anti-Neuronal Nuclear Ab, Type 1 No Yes
CS2CC CASPR2-IgG CBA, 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
LG1CC LGI1-IgG CBA, CSF No Yes
GL1IC mGluR1 Ab IFA, CSF No Yes
NCDIC Neurochondrin IFA, CSF No Yes
NMDCC NMDA-R Ab CBA, CSF No Yes
NMOFC NMO/AQP4 FACS, CSF Yes Yes
PCTRC Purkinje Cell Cytoplasmc Ab Type Tr No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AMPIC AMPA-R Ab IF Titer Assay, CSF No No
AN1BC ANNA-1 Immunoblot, CSF No No
AN2BC ANNA-2 Immunoblot, CSF No 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
GL1CC mGluR1 Ab CBA, CSF No No
GL1TC mGluR1 Ab IFA Titer, CSF No No
NMDIC NMDA-R Ab IF Titer Assay, CSF No No
NMOTC NMO/AQP4 FACS Titer, CSF No No
PCTBC PCA-Tr Immunoblot, CSF No No
AN1TC ANNA-1 Titer, CSF No No
NCDCC Neurochondrin CBA, CSF No No
NCDTC Neurochondrin IFA Titer, CSF No No
PCTTC PCA-Tr Titer, CSF No No

Testing Algorithm

If the indirect immunofluorescence assay (IFA) pattern suggests antineuronal nuclear antibodies (ANNA)-1, then the ANNA-1 immunoblot, ANNA-1 IFA titer and ANNA-2 immunoblot will be performed at an additional charge.

 

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

 

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

 

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

 

If the neuromyelitis optica/aquaporin-4-IgG (NMO/AQP4-IgG) fluorescence-activated cell sorting (FACS) screen assay requires further investigation, then the NMO/AQP4-IgG FACS titration assay 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 alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA)-receptor antibody CBA result is positive, then AMPA-receptor antibody IFA titer assay will be performed at an additional charge.

 

For more information, see the following:

Pediatric Autoimmune Encephalopathy/Central Nervous System Disorders Evaluation Algorithm-Spinal Fluid

Pediatric Autoimmune Central Nervous System Demyelinating Disease Diagnostic Algorithm

Method Name

AMPCC, CS2CC, DPPCC, GABCC, GFACC, LG1CC, GL1CC, NCDCC, NMDCC: Cell-Binding Assay (CBA)

 

NMOFC, NMOTC: Flow Cytometry

 

AMPIC, ANN1C, AN1TC, DPPTC, GABIC, GFAIC, GFATC, GL1IC, GL1TC, NCDIC, NCDTC, NMDIC, PCTRC, PCTTC: Indirect Immunofluorescence Assay (IFA)

 

GD65C: Radioimmunoassay (RIA)

 

AN1BC, AN2BC, PCTBC: Immunoblot (IB)

 

PCCI: Medical Interpretation

Reporting Name

Peds Autoimm Enceph CNS, CSF

Specimen Type

CSF

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

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Clinical Information

Autoimmune encephalitis and myelitis is increasingly recognized as a cause of central nervous system disease in children and adolescents. N-methyl-D-aspartate receptor antibody (NMDA-R) encephalitis and myelin oligodendrocyte glycoprotein (MOG) autoimmunity are most common, although other entities, including aquaporin-4 autoimmunity, contactin-associated protein-like 2 (CASPR2) autoimmunity, autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, and paraneoplastic encephalomyelopathies, may also occur in children.

Reference Values

Test ID

Reporting name

Methodology

Reference value

PCCI

Peds Autoimmune CNS Interp, CSF

Medical interpretation

Interpretive report

AMPCC

AMPA-R Ab CBA, CSF

CBA

Negative

ANN1C

Anti-Neuronal Nuclear Ab, Type 1

IFA

Negative

CS2CC

CASPR2-IgG CBA, CSF

CBA

Negative

DPPCC

DPPX Ab CBA, CSF

CBA

Negative

GABCC

GABA-B-R Ab CBA, CSF

CBA

Negative

GD65C

GAD65 Ab Assay, CSF

RIA

≤0.02 nmol/L

Reference values apply to all ages.

GFAIC

GFAP IFA, CSF

IFA

Negative

GL1IC

mGluR1 Ab IFA, CSF

IFA

Negative

LG1CC

LGI1-IgG CBA, CSF

CBA

Negative

NCDIC

Neurochondrin IFA, CSF

IFA

Negative

NMDCC

NMDA-R Ab CBA, CSF

CBA

Negative

NMOFC

NMO/AQP4 FACS, CSF

FACS

Negative

PCTRC

Purkinje Cell Cytoplasmc Ab Type Tr

IFA

Negative

 

Reflex Information:

Test ID

Reporting name

Methodology

Reference value

AMPIC

AMPA-R Ab IF Titer Assay, CSF

IFA

<1:2

AN1BC

ANNA-1 Immunoblot, CSF

IB

Negative

AN1TC

ANNA-1 Titer, CSF

IFA

<1:2

AN2BC

ANNA-2 Immunoblot, CSF

IB

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

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

NMDIC

NMDA-R Ab IF Titer Assay, CSF

IFA

<1:2

NMOTC

NMO/AQP4 FACS Titer, CSF

FACS

<1:2

PCTTC

PCA-Tr Titer, CSF

IFA

<1:2

PCTBC

PCA-Tr Immunoblot, CSF

IB

Negative

 

*Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Fluorescence activated cell sorting assay (FACS)

Radioimmunoassay (RIA)

Immunoblot (IB)

 

*Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1 or PCA-Tr may be reported as "unclassified antineuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

Interpretation

This profile is consistent with an autoimmune central nervous system disorder.

Cautions

Negative results do not exclude a diagnosis of an autoimmune central nervous system disorder.

Clinical Reference

1. Dubey D, Pittock SJ, Krecke KN, et al. Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol. 2019;76(3):301-309 doi:10.1001/jamaneurol.2018.4053

2. McKeon A, Lennon VA, Lotze T, et al. CNS aquaporin-4 autoimmunity in children. Neurology. 2008;71(2):93-100

3. Dubey D, Hinson SR, Jolliffe EA, et al. Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year. J Neuroimmunol. 2018;321:157-163

4. Philipps G, Alisanski SB, Pranzatelli M, et al. Purkinje cell cytoplasmic antibody type 1 (anti-Yo) autoimmunity in a child with Down syndrome. JAMA Neurol. 2014;71(3):347-349

5. Lopez-Chiriboga AS, Klein C, Zekeridou A, et al. LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol. 2018;84(3):473-480

6. Lopez-Chiriboga AS, Majed M, Fryer J, et al. Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol. 2018;75(11):1355-1363

7. Clardy SL, Lennon VA, Dalmau J. Childhood onset of stiff-man syndrome. JAMA Neurol. 2013;70(12):1531-1536

8. Banwell B, Tenembaum S, Lennon VA, et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology. 2008;70(5):344-352

Method Description

Cell-Binding Assay:

Patient sample 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)

 

Fluorescence-Activated Cell Sorting Assay:

Human embryonic kidney cells (HEK 293) are transfected transiently with a plasmid (pIRES2-Aequorea coerulescens green fluorescent protein [AcGFP]) encoding both green fluorescent protein (AcGFP) and AQP4-M1. After 36 hours, a mixed population of cells (transfected expressing AQP4 or MOG on the surface and AcGFP in the cytoplasm and nontransfected lacking AQP4 or MOG and AcGFP) are lifted and resuspended in live cell-binding buffer. Cells are incubated with patient sample and an AlexaFluor 647-labeled secondary antibody is added. Two populations are gated on the basis of AcGFP expression: positive (high AQP4 or MOG expression) and negative (low or no AQP4 or MOG expression). Positivity is based on the ratio (positive >2.0) of the average median fluorescence intensity (MFI) of each cell population (MFI GFP positive:MFI GFP negative).(Unpublished Mayo method)

 

Indirect Immunofluorescence Assay:

The patient's sample is tested by a standardized immunofluorescence assay 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 sample. 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 sample. 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; 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. 1983[12]:1161-1166; 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 (18-28° C) utilizing the EUROBlot One instrument. 

Diluted patient sample (1:101) is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive samples will bind to the purified recombinant antigen, and negative samples will not bind. Strips are washed to remove unbound antibodies and then incubated with antihuman IgG antibodies (alkaline phosphatase-labeled) for 30 minutes. The strips are again washed to remove unbound antihuman IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produce 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)

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

8 to 12 days

Test Classification

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

86255 x 11

86341

86053

86256 AMPIC (if appropriate)

84182 AN1BC (if appropriate)

86256 AN1TC (if appropriate)

84182 AN2BC (if appropriate)

86256 DPPTC (if appropriate)

86256 GABIC (if appropriate)

86255 GFACC (if appropriate)

86256 GFATC (if appropriate)

86255 GL1CC (if appropriate)

86256 GL1TC (if appropriate)

86255 NCDCC (if appropriate)

86256 NCDTC (if appropriate)

86256 NMDIC (if appropriate)

86053 NMOTC (if appropriate)

84182 PCTBC (if appropriate)

86256 PCTTC (if appropriate)

NY State Approved

Yes