Test Catalog

Test Id : CDS1

CNS Demyelinating Disease Evaluation, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of inflammatory demyelinating diseases (IDDs) with similar phenotype to neuromyelitis optica spectrum disorder (NMOSD), including optic neuritis (single or bilateral) and transverse myelitis

 

Diagnosis of autoimmune myelin oligodendrocyte glycoprotein (MOG)-opathy

 

Diagnosis of neuromyelitis optica (NMO)

 

Distinguishing NMOSD, acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis from multiple sclerosis early in the course of disease

 

Diagnosis of ADEM

 

Prediction of a relapsing disease course

Highlights

Myelin oligodendrocyte glycoprotein (MOG)-IgG with an NMO spectrum disorder like phenotype is now recognized as a sensitive and specific diagnostic antibody biomarker of inflammatory demyelinating disorders (IDDs).

 

Approximately 80% of patients fulfilling 2006 Wingerchuk criteria for neuromyelitis optica are seropositive for aquaporin-4 (AQP4)-IgG. Of the remaining 20%, one-third harbor MOG-IgG. Seropositivity predicts a relapsing phenotype and warrants immunosuppressive therapy. Patients only rarely harbor both antibodies.

 

There is currently no biomarker specific for MS (multiple sclerosis). Patients seropositive for MOG-IgG are commonly misdiagnosed as MS. Detection of MOG-IgG implies an inflammatory demyelinating disorder distinct from MS. MS therapies may worsen MOG-IgG associated IDDs, so correct diagnosis is important.

 

Seropositivity for MOG-IgG, in NMOSD like disorders, including optic neuritis (OT), transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM), predicts relapse and warrants consideration for maintenance immunosuppression.

 

Seropositivity for MOG-IgG in the setting of a severe relapse of central nervous system (CNS) demyelination warrants aggressive therapy with intravenous methylprednisolone or plasmapheresis.

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
CSI1 CNS Demyelinating Disease Interp, S No Yes
NMOFS NMO/AQP4 FACS, S Yes Yes
MOGFS MOG FACS, S Yes 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
NMOTS NMO/AQP4 FACS Titer, S No No
MOGTS MOG FACS Titer, S No No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When the results of this assay require further evaluation of myelin oligodendrocyte glycoprotein (MOG-IgG1), the MOG-IgG1 titer will be performed at an additional charge.

 

When the results of this assay require further evaluation of neuromyelitis optica (NMO)/Aquaporin-4-IgG, the neuromyelitis optica (NMO)/aquaporin-4-IgG titer will be performed at an additional charge.

 

See CNS Demylenating Evaluation Algorithm-Serum in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Flow Cytometry

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CNS Demyelinating Disease Eval, S

Aliases
Lists additional common names for a test, as an aid in searching

ADEM

AQP4

Aquaporin

Devic's Antibody

NMO (Neruomyelitis Optica)

NMO-IgG

Optic Neuritis Antibody

Transverse Myelitis Antibody

Vision Loss Antibody

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When the results of this assay require further evaluation of myelin oligodendrocyte glycoprotein (MOG-IgG1), the MOG-IgG1 titer will be performed at an additional charge.

 

When the results of this assay require further evaluation of neuromyelitis optica (NMO)/Aquaporin-4-IgG, the neuromyelitis optica (NMO)/aquaporin-4-IgG titer will be performed at an additional charge.

 

See CNS Demylenating Evaluation Algorithm-Serum in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Serum

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: For optimal antibody detection, we recommend blood drawing the specimen before initiation of immunosuppressant medication.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 3 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

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
Serum Refrigerated (preferred) 28 days
Frozen 28 days
Ambient 72 hours

Useful For
Suggests clinical disorders or settings where the test may be helpful

Diagnosis of inflammatory demyelinating diseases (IDDs) with similar phenotype to neuromyelitis optica spectrum disorder (NMOSD), including optic neuritis (single or bilateral) and transverse myelitis

 

Diagnosis of autoimmune myelin oligodendrocyte glycoprotein (MOG)-opathy

 

Diagnosis of neuromyelitis optica (NMO)

 

Distinguishing NMOSD, acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis from multiple sclerosis early in the course of disease

 

Diagnosis of ADEM

 

Prediction of a relapsing disease course

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When the results of this assay require further evaluation of myelin oligodendrocyte glycoprotein (MOG-IgG1), the MOG-IgG1 titer will be performed at an additional charge.

 

When the results of this assay require further evaluation of neuromyelitis optica (NMO)/Aquaporin-4-IgG, the neuromyelitis optica (NMO)/aquaporin-4-IgG titer will be performed at an additional charge.

 

See CNS Demylenating Evaluation Algorithm-Serum in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Neuromyelitis optica (NMO), sometimes called Devic disease or opticospinal multiple sclerosis (MS) is a severe, relapsing, autoimmune, inflammatory and demyelinating central nervous system disease (IDD) that predominantly affects optic nerves and spinal cord.(1) The disorder is now recognized as a spectrum of autoimmunity (termed NMO spectrum disorders: NMOSD).(1-3) Brain lesions are observed in more than 60% of patients with NMOSD and approximately 10% will be MS-like.(4) Children tend to have greater brain involvement than adults, and brain lesions are more symptomatic than is typical for adult patients.(3) The clinical course is characterized by relapses of optic neuritis or transverse myelitis, or both. Some patients may present with acute disseminated encephalomyelitis (ADEM). Many patients with NMOSD are misdiagnosed as having MS. More effective treatments combined with earlier and more accurate diagnosis has led to improved outcomes.

 

Approximately 80% of patients with NMO are seropositive for aquaporin-4 (AQP4)-IgG.(5-7) In the remaining 20% of patients, myelin oligodendrocyte glycoprotein (MOG)-IgG is detected in up to a third.(8) The pathogenic target for the remaining patients remains unknown. Detection of MOG-IgG is diagnostic of central nervous system (CNS) inflammatory demyelination, where the clinical phenotype (NMOSD, optic neuritis, transverse myelitis, ADEM) may be similar, but the immunopathology (astrocytopathy vs oligodendrogyopathy) and clinical outcome (worse vs better) is different.(9) Detection of MOG-IgG also predicts relapse.(10) More importantly, however, is that MOG-IgG seropositive IDDs are distinct from MS and treated differently.(8, 9) Treatments for IDDs seropositive for MOG-IgG include corticosteroids and plasmapheresis for acute attacks and mycophenolate mofetil, azathioprine, and rituximab for relapse prevention. Disease modifying agents, treatments promoted for MS, have been reported to exacerbate MOG-IgG1 seropositive IDDS. Therefore, early diagnosis and initiation of appropriate immunosuppressant treatment is important to optimize the clinical outcome by preventing further attacks. In 2015, Waters and colleagues (11) from Oxford University established a novel cell based assay for the measurement of IgG1 MOG antibodies based on previous findings that MOG antibodies are almost exclusively of the IgG1 subclass. They showed that their MOG-IgG1 flow cytometry assay eliminated false-positives without losing true-positives with low titers. The detection of MOG-IgG1 allowed non MS demyelinating diseases (ADEM, AQp4-IgG negative neuromyelitis optica spectrum disorder: including ON,TM) to be distinguished from MS.(12)

 

Using a similar assay to our MOG-IgG1 flow cytometry assay, Wingerchuk et al demonstrated high specificity of their MOG-IgG1 assay in which 49 patients with MS, 13 healthy control sera, and 37 AQP4-seropositive serum samples were all negative at a dilution of 1:20. Of 58 patients fulfilling 2006 Wingerchuk criteria for NMO, 21 (36%) tested negative for AQP4-IgG MOG-IgG1 was detected by cell based assay in 8 (38%) of these cases. (13)

 

Testing of 1,109 consecutive sera sent for AQP4-IgG testing,(11) revealed 40 AQP4-IgG and 65 MOG-IgG1 positive cases. None were positive for both. The clinical diagnoses obtained in 33 MOG-IgG1 positive patients included 4 NMO, 1 ADEM and 11 optic neuritis (n = 11). All 7 patients with probable MS were MOG-IgG1 negative. This study provides Class II evidence that the presence of serum MOG-IgG1 distinguishes non-MS central nervous system (CNS) demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%-45%; specificity 100%, 95% CI 88%-100%).

 

The assay validated here, was developed using the MOG construct provided by Dr Waters(11) and the validation was based on a blinded comparison with the Oxford assay. Comparison was also made with the Euroimmun fixed cell-based kit assay.(14)

 

A recent longitudinal analysis with 2 year follow-up suggested that persistence of MOG-IgG is associated with relapses thus warranting relapse preventing.(10) Detection of MOG-IgG1 allows distinction from MS and is generally indicative of a relapsing disease, mandating initiation of immunosuppression, even after the first attack in some, thereby reducing attack frequency and disability in the future.

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.

MOG FACS, S

Negative

Reference values apply to all ages.

 

NMO/AQP4 FACS, S

Negative

Reference values apply to all ages.

Interpretation
Provides information to assist in interpretation of the test results

A positive value for aquaporin-4 (AQP4)-IgG is consistent with an autoimmune astrocytopathy/neuromyelitis optica spectrum disorder (NMOSD) and justifies initiation of appropriate immunosuppressive therapy at the earliest possible time. This allows early initiation and maintenance of optimal therapy. Recommend follow-up in 3 to 6 months if NMOSD is suspected.

 

A positive value for myelin oligodendrocyte glycoprotein (MOG)-IgG is consistent with an neuromyelitis optica (NMO)-like phenotype, and in the setting of acute disseminated encephalomyelitis (ADEM), optic neuritis (ON) and transverse myelitis (TM) indicates an autoimmune oligodendrogliopathy with potential for relapsing course. Identification of MOG-IgG allows distinction from multiple sclerosis (MS) and may justify initiation of appropriate immunosuppressive therapy (not MS disease-modifying agents) at the earliest possible time. This allows early initiation and maintenance of optimal therapy. Recommend follow-up in 3 to 6 months as persistence of MOG-IgG seropositivity predicts a relapsing course.

 

Detection of both antibodies is rare and unusual.

 

AQP4-IgG and MOG-IgG are not found in MS or healthy subjects.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Aquaporin-4 (AQP4)-IgG and myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies may drop below detectable levels in setting of therapies for acute attack (IV methylprednisolone or plasmapheresis) or attack prevention (immunosuppressants).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Wingerchuk DM, Lennon VA, Lucchinetti CF, et al: The spectrum of neuromyelitis optica. Lancet Neurol 2007;6(9):805-815

2. Apiwattanakul M, Popescu BF, Matiello M, et al: Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol 2010;68(5):757-761

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

4. Pittock SJ, Weinshenker BG, Lucchinetti CF, et al: Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006;63(7):964-968

5. Fryer JP, Lennon VA, Pittock SJ, et al: AQP4 autoantibody assay performance in clinical laboratory service. Neurol Neuroimmunol Neuroinflamm 2014;1(1):e11

6. Waters PJ, McKeon A, Leite MI, et al: Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology 2012;78(9):665-671; discussion 669

7. Lennon VA, Wingerchuk DM, Kryzer TJ, et al: A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364(9451):2106-2112

8. Peschl P, Bradl M, Hoftberger R, et al: Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases. Front Immunol 2017;8:529

9. Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann N Y Acad Sci 2015

10. Hyun JW, Woodhall MR, Kim SH, et al: Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry 2017

11. Waters P, Woodhall M, O'Connor KC, et al: MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm 2015;2(3):e89

12. Reindl M, Jarius S, Rostasy K, Berger T: Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they? Curr Opin Neurol 2017;30(3):295-301

13. Wingerchuk DM, Banwell B, Bennett JL, et al: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85(2):177-189

14. Jarius S, Ruprecht K, Kleiter I, et al: MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation 2016;13(1):279

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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 (AcGFP) and AQP4-M1. After 36 hours, a mixed population of cells (transfected expressing AQP4 on the surface and AcGFP in the cytoplasm and nontransfected lacking AQP4 and AcGFP) are lifted and resuspended in live cell-binding buffer. Cells are incubated with patient serum and an AlexaFluor 647-labeled secondary antibody is added. Two populations are gated on the basis of AcGFP expression: positive (high AQP4 expression) and negative (low or no AQP4 expression). Positivity is based on the ratio (Positive >2.0) of the average MFI of each cell population (MFI GFP positive:MFI GFP negative).(Unpublished Mayo method)

 

If AQP4 cell based flow cytometry (FACS) assay is positive at screening dilution, AQP4 FACS Titer Assay is performed at an additional charge.

 

MOG-IgG1 Fluorescence-Activated Cell Sorting Assay (FACS)

Human embryonic kidney cells (HEK 293) are transfected transiently with a DNA plasmid that allows coexpression of both a reporter fluorescent protein (green fluorescent protein [AcGFP]) and full-length MOG. After 36 hours, a mixed population of cells (transfected expressing MOG on the surface and AcGFP in the cytoplasm and nontransfected lacking MOG and AcGFP) are lifted and resuspended in live cell-binding buffer. Cells are incubated with patient serum and an AlexaFluor 647 labeled secondary antibody is added. Two populations are gated on the basis of AcGFP expression: positive (high MOG expression) and negative (low or no MOG expression). Positivity is based on the ratio (Positive >2.5) of the average MFI of each cell population (MFI GFP positive:MFI GFP negative).(Unpublished Mayo method)

 

If MOG-IgG1 cell based flow cytometry (FACS) assay is positive at screening dilution, the MOG-IgG1 flow cytometry titer assay is performed at an additional charge.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

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.

Monday, Tuesday, Thursday

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.

7 to 10 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

28 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

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 Regional Manager. 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. This test 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.

86053

86363

86053-Titer (if appropriate)

86363-Titer (if appropriate)

LOINC® Information

Test Id Test Order Name Order LOINC Value
CDS1 CNS Demyelinating Disease Eval, S In Process
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip

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.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

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.

SI Normal Reports | SI Abnormal Reports