CNS DEMYELINATING DISEASES (AQP4 AND MOG)TESTING TO DISTINGUISH A SPECTRUM OF DEMYELINATING DISEASES FROM MS

N E U R O L O G Y A T M A Y O C L I N I C

M A Y O M E D I C A L L A B O R A T O R I E S . C O M / N M O

OVERLAP OF PHENOTYPES

NEUROLOGICAL MANIFESTATION

FREQUENCY OF AQP4

FREQUENCY OF MOG

NMO 80% 7%

Recurrent Longitudinally Extensive Transverse

Myelitis (LETM)60–80% <5%

Single Occurrence of LETM 40% 20%

Recurrent Optic Neuritis 15% 25%

Chronic relapsing inflammatory optic

neuropathy (CRION)<5% 25%

Single Occurrence of Optic Neuritis

<5% <5%

Intractable Vomiting/ Area Postrema Syndrome

<5% <5%

Acute Disseminated Encephalomyelitis (ADEM),

Posterior Reversible Encephalopathy

Syndrome (PRES)

<5% 40%

DISTINGUISHING A SPECTRUM OF AUTOIMMUNE DEMYELINATING DISEASES FROM MSNEUROMYELITIS OPTICA SPECTRUM DISORDERSNeuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. NMO is characterized by severe relapsing attacks of optic neuritis and transverse myelitis. Unlike the attacks associated with multiple sclerosis (MS), NMO attacks commonly spare the brain in the early stages.

The spectrum of NMO was traditionally restricted to the optic nerves and the spinal cord. However, Mayo Clinic physician/scientist Vanda Lennon, M.D., Ph.D., discovered an antibody that targets aquaporin-4, the water channel on astrocytes, and it is a sensitive and specific biomarker for NMO. Since that discovery, a much broader category called “NMO spectrum disorders” (NMOSD) has evolved.

MYELIN OLIGODENDROCYTE GLYCOPROTEIN (MOG)-OPATHYDetection of MOG-IgG1 is diagnostic of central nervous system (CNS) inflammatory demyelination, where the clinical phenotype (NMO, optic neuritis, transverse myelitis, acute disseminated encephalomyelitis [ADEM]) may be similar, but the immunopathology (astrocytopathy vs. oligodendrogliopathy) and clinical outcome (worse vs. better) are different.1 Detection of MOG-IgG1 also predicts disease relapse.2

More importantly, MOG-IgG1 seropositive inflammatory demyelinating diseases (IDDs) are distinct from MS and are treated differently, and these MS treatments have been reported to worsen MOG-IgG1 seropositive IDDs.1,3

WHY TEST FOR AQP4 AND MOG?TO DISTINGUISH NMOSD AND MOG-OPATHIES FROM MSAlthough NMOSD and MOG-opathies can have very similar clinical and radiologic characteristics to MS, the diseases are treated very differently:

A majority of NMO patients, typically women, are initially misdiagnosed with MS.

While NMO and MOG-opathies are treated by immunosuppressant therapy, MS is treated by immunomodulation therapy, which may worsen NMO.

EARLY DIAGNOSIS AND TREATMENT MAY PREVENT FURTHER ATTACKS IN NMOSDUnlike MS, the neurological disability caused by NMO spectrum disorders and MOG-opathies is based on the number of attacks rather than a progressive phase of the illness:

Initiating therapy early in the course to eliminate recurrence of attacks will minimize patient disability.

If not treated appropriately, within five years, 50% of NMO patients lose functional vision in at least one eye or are unable to walk. Recent data suggests that patients with MOG-opathy may have less disability.

C N S D E M Y E L I N A T I N G D I S E A S E ( A Q P 4 A N D M O G )

WHICH TESTS SHOULD I ORDER? CNS Demyelinating Disease Evaluation, Serum (Mayo ID: CDS1) TAT: 7 Days

Neuromyelitis Optica (NMO)/Aquaporin-4-IgG Fluorescence-Activated Cell Sorting (FACS) Assay, Serum (Mayo ID: NMOFS) TAT: 5 Days

Myelin Oligodendrocyte Glycoprotein (MOG-IgG1) Fluorescence-Activated Cell Sorting (FACS) Assay, Serum (Mayo ID: MOGFS) TAT: 5 Days

C U S T O M E R S E R V I C E F O R C L I N I C A L S P E C I A L I S T S / 8 5 5 - 5 1 6 - 8 4 0 4 O R + 1 - 8 5 5 - 3 7 9 - 3 1 1 5 ( I N T ’ L )

WHEN SHOULD I ORDER THE CNS DEMYELINATING DISEASE EVALUATION?

LONG SPINAL CORD

LESION

CONSIDER ORDERING

DEFINITELY ORDER

SHORT SPINAL CORD

LESION

MULTIPLE EPISODES OF

OPTIC NEURITIS

SINGLE EPISODE OF

OPTIC NEURITIS

NERVE OR SPINAL CORD INVOLVEMENT SYMPTOMS OUTSIDE OPTIC NERVE OR SPINAL CORD

DEFINITELY ORDER When any of the symptoms below are present

in combination with either a single episode of optic neuritis or short spinal cord lesions.

When ADEM is suspected.

CONSIDER ORDERING Area postrema syndrome: episode of otherwise

unexplained hiccups or nausea and vomiting.

Acute brainstem syndrome.

Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions.

Symptomatic cerebral syndrome with NMOSD-typical brain lesions.

FACS: A SUPERIOR METHOD OF TESTING

The likelihood of having a false-positive result with ELISA methodology is at least 5x greater when compared with the Mayo Clinic cell-binding assay.5

5x

SENSITIVITY5 SPECIFICITY

FACS LIVE CELL-BINDING ASSAY

>80% >99%

ELISA 60–65% 99%

INDIRECT IMMUNOFLUORESCENCE

50–55% >99%

Mayo Clinic has developed the only fluorescence-activated cell sorting (FACS) live cell-binding assay that is currently available in the U.S. for antibody detection of AQP4 and MOG. FACS is recommended by international leaders in neuroimmunology for its increased sensitivity and specificity.

MC2775-80rev1117

@mayocliniclabs/mayocliniclabsnews.mayomedicallaboratories.commayomedicallaboratories.com

FOR MORE INFORMATION ABOUT AUTOIMMUNE NEUROLOGY TESTING, VISIT US AT:

mayomedicallaboratories.com/nmo

LABORATORY DIRECTORS1 SEAN PITTOCK, M.D.2 ANDREW MCKEON, M.D.3 JOHN R. MILLS, PH.D.

CONSULTANTS4 EOIN FLANAGAN, M.B., B.CH.5 CHRISTOPHER KLEIN, M.D.6 DANIEL LACHANCE, M.D.

1 2

5 64

MAYO CLINIC DISCOVERY AND ASSAY PERFORMANCE PUBLICATIONS FOR NMODISCOVERY OF ANTIBODY MARKER FOR NMOLennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106-2112.

IDENTIFICATION OF AQUAPORIN-4 AS ANTIBODY TARGETLennon VA, Kryzer TJ, Pittock SJ, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202(4):473-477.

AQP4-IGG FACS ASSAY SUPERIOR PERFORMANCEFryer JP, Lennon VA, Pittock SJ, et al. AQP4 autoantibody assay performance in clinical laboratory service. Neurol Neuroimmunol Neuroinflamm. 2014;1(1):e11.

CITATIONS1. Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving

spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann N Y Acad Sci. 2016;1366(1):20-39.

2. Hyun JW, Woodhall MR, Kim SH, et al. Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry. 2017;88(10):811-817.

3. Peschl P, Bradl M, Hoftberger R, et al. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol. 2017;8:529.

4. 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.

5. 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.

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A HISTORY OF INNOVATION AND DISCOVERY Recognized as a world leader in the diagnosis and treatment of autoimmune neurologic disorders and demyelinating diseases, Mayo Clinic mounts unmatched resources for uncovering novel syndromes, developing new diagnostic biomarkers and unique laboratory tests.

COLLEGIAL ACCESS TO MAYO CLINIC NEUROLOGISTS Neurologists are available for consultation and assistance in the interpretation of autoantibody evaluations. These conversations enable the best diagnosis and treatment approach, as they provide our neurologists the opportunity to ask additional clinical information, as well as address the questions of the ordering neurologist.CONTACT US AT 855-516-8404 OR +1-855-379-3115 (INT’L).