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

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