NEUROMYELITIS OPTICA (NMO) SPECTRUM DISORDERSINCREASED SENSITIVITY & SPECIFICITY WITH AQUAPORIN-4-IgG FACS LIVE CELL-BINDING ASSAYS

WHAT IS NEUROMYELITIS OPTICA (NMO)?Neuromyelitis 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 Vanda Lennon, M.D., Ph.D., discovered an antibody that targets aquaporin-4, the water channel on astrocytes and is a sensitive and specific biomarker for NMO. Since that discovery, a much broader category called “NMO spectrum disorders” (NMOSD) has evolved.

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

WHY TEST FOR NMO & NMOSD?TO DIFFERENTIATE BETWEEN NMO AND MULTIPLE SCLEROSIS.} Although NMO spectrum disorders 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 is treated by immunosuppressant therapy, MS is treated by immunomodulation therapy, which may worsen NMO.

NEUROLOGICAL MANIFESTATION FREQUENCY IN NMOSD

RECURRENT LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS (LETM)

60–80%

SINGLE OCCURRENCE LETM 40%

RECURRENT OPTIC NEURITIS 20%

SINGLE OCCURRENCE OF OPTIC NEURITIS

<5%

INTRACTABLE VOMITING <5%

ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM),POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

<5%

ENCEPHALOPATHY, SLEEP DISORDER, SIAD

<5%

HEARING LOSS <5%

ATAXIA, DIPLOPIA <5%

WHAT IS NMOSD?NMOSD includes patients who are seropositive for aquaporin-4-IgG but have more diverse neurological manifestations.

BECAUSE AN EARLY DIAGNOSIS CAN STOP THE DISABILITY.} Unlike MS, the neurological disability caused by

NMO spectrum disorders 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 5 years, 50% of NMO patients lose functional vision in at least 1 eye or are unable to walk.

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

FACS LIVE CELL-BINDING ASSAY

ELISAINDIRECT

IMMUNOFLUORESCENCE

SENSITIVITY1 >80% 60–65% 50–55%

SPECIFICITY >99% 99% >99%

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.5x

WHICH TESTS SHOULD I ORDER?

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

WHEN SHOULD I ORDER AQP4-IgG LIVE CELL-BINDING ASSAY?

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

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

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

* Serum is generally more sensitive than CSF for detection of NMO/

Aquaporin-4-IgG

} Neuromyelitis Optica (NMO)/Aquaporin-4-IgG Fluorescence-Activated Cell Sorting (FACS) Assay, Spinal Fluid (Mayo ID: NMOFC) TAT: 3 days

1. Waters PJ, McKeon A, Leite MI, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology. 2012 Feb 28;78(9):665-671.

MC2775-80rev0816

@mayocliniclabs/mayocliniclabsnews.mayomedicallaboratories.commayomedicallaboratories.com

TAP INTO THE EXPERTISE OF MAYO CLINIC

The Mayo Clinic Neuroimmunology Laboratory

was the first to introduce comprehensive

serological evaluations to aid the diagnosis

of neurological autoimmunity. The laboratory

continues to discover and clinically validate novel

autoantibody profiles that inform neurological

decision-making and guide the search for cancer.

The clinical and research activities of the Mayo

Clinic Neuroimmunology Laboratory focus on

autoimmunity affecting the brain, optic nerve,

retina, spinal cord, and autonomic and somatic

nerves and muscle. The Neuroimmunology

Laboratory complements Mayo Clinic’s

Autoimmune Neurology Clinic.

FOR MORE INFORMATION ABOUT AUTOIMMUNE NEUROLOGY TESTINGMayoMedicalLaboratories.com/NMO

LABORATORY DIRECTORS1 SEAN PITTOCK, M.D.2 ANDREW MCKEON, M.D.

CONSULTANTS3 EOIN FLANAGAN, M.B., B.CH.4 CHRISTOPHER KLEIN, M.D.5 DANIEL LACHANCE, M.D.

NEUROLOGISTS STAFFING THE CLINICAL LABORATORY ARE AVAILABLE FOR CONSULTATION AND ASSISTANCE IN THE INTERPRETATION OF AUTOANTIBODY EVALUATIONS

1 2

4 53

MAYO CLINIC DISCOVERY AND ASSAY PERFORMANCE PUBLICATIONS FOR NMO

Discovery 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;202:473–77.

AQP4-IgG FACS assay superior performanceFryer JP, Lennon VA, Pittock SJ, et al. AQP4 autoantibody assay performance in clinical laboratory service. Neurol Neuroimmunol Neuroinflammation. 2014;1:e11.