Test ID: NMOER
Neuromyelitis Optica (NMO) Evaluation with Reflex, Serum
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Establishing the diagnosis of an neuromyelitis optica spectrum disorder and distinguishing one of these disorders from multiple sclerosis early in the course of disease, allowing early initiation, and maintenance, of optimal therapy
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 |
|---|---|---|---|
| PAINT | Interpretive Comments | No | Yes |
| AQP4E | NMO/AQP4-IgG ELISA, S | No | Yes |
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| NMOS | NMO-IgG, Serum | No | No |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
If NMO/APQ4 ELISA results are indeterminate (> or =1.6 and < or =4.9 U/mL), NMO-IgG will be performed at an additional charge.
Method Name A short description of the method used to perform the test
AQP4E/60795: Enzyme-Linked Immunosorbent Assay (ELISA)
NMOS/83185: Indirect Immunofluorescence
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
AQP4
AQP4 ELISA
Aquaporin
Devic's Antibody
Neuromyelitis Optica (NMO)
NMO (Neuromyelitis Optica)
NMO-IgG
Optic Neuritix Antibody
Optic-Spinal MS Antibody
Transverse Myelitis Antibody
Vision Loss Antibody
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 2 mL
Additional Information: Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | Mild OK; Gross reject |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 14 days |
| Ambient | 72 hours | |
| Frozen | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Neuromyelitis optica (NMO, sometimes called Devic disease) is a severe, relapsing, autoimmune, inflammatory and demyelinating central nervous system disease that predominantly affects optic nerves and the spinal cord. The disorder is now recognized as a spectrum of autoimmunity targeting the astrocytic water channel aquaporin-4 (AQP4). NMO spectrum disorders (NMOSD) may involve the brain and brainstem with symptoms of encephalopathy (particularly in children). The initial symptoms may be bouts of intractable nausea and vomiting. Magnetic resonance imaging typically reveals large inflammatory spinal cord lesions involving 3 or more vertebral segments. During acute attacks, the cerebrospinal fluid contains inflammatory cells, but usually lacks evidence of intrathecal IgG synthesis. The clinical course is characterized by relapses of optic neuritis or transverse myelitis, or both.
Prior to introducing a serological biomarker for NMO, the disorder was thought to be confined exclusively to the optic nerves and spinal cord, that the clinical course was monophasic and that NMO was a subset of multiple sclerosis (MS). The discovery of a highly specific disease marker for NMO (NMO-IgG/AQP4-IgG) helped to define the full clinical spectrum of NMOSD and to distinguish these disorders from MS. Attacks are often severe resulting in a rapid accumulation of disability (blindness and paraplegia). Within 5 years, 50% of patients lose functional vision in at least 1 eye or are unable to walk independently. Many patients with NMOSD are misdiagnosed as having MS. Importantly, the prognosis and optimal treatments for the 2 diseases differ. NMOSD typically has a worse natural history than MS, with frequent and early relapses. Treatments for NMOSD include corticosteroids and plasmapheresis for acute attacks and mycophenolate mofetil, azathioprine and rituximab for relapse prevention. Beta-interferon, a treatment promoted for MS, exacerbates NMOSD. Therefore, early diagnosis and initiation of NMO-appropriate immunosuppressant treatment is important to optimize the clinical outcome by preventing further attacks.
Detection of AQP4-IgG by enzyme-linked immunosorbent assay allows distinction of NMOSD (65%-77% are positive) from MS (0% positive), and is indicative of a relapsing disease, mandating initiation of immunosuppression, even after the first attack, 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.
NMO/AQP4-IgG: <1.6 U/mL
Interpretation Provides information to assist in interpretation of the test results
A positive value is consistent with a neuromyelitis optica (NMO) spectrum disorder and justifies initiation of appropriate immunosuppressive therapy at the earliest possible time. Positive AQP4-IgG enzyme-linked immunosorbent assay results are > or =5 units/mL. Negative results are <1.6 units/mL. Sera yielding indeterminate results (1.6-4.9 units/mL) will be reflexed to NMO-IgG indirect immunofluorescence testing for confirmation of positivity. NMO-IgG indirect immunofluorescence is positive if an NMO-specific immunostaining pattern is detected at a dilution of > or =1:60.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Seronegativity does not exclude the diagnosis of a neuromyelitis optica spectrum disorder (current seronegativity rate is 23%).
Seronegativity may reflect immunosuppressant therapy.
Supportive Data
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Hinson SR, McKeon A, Lennon VA: Neurological autoimmunity targeting aquaporin-4. Neuroscience 2010;281:1009-1018
2. Wingerchuk DM, Lennon VA, Pittock SJ, et al: Revised diagnostic criteria for neuromyelitis optica. Neurol 2006;66:1485-1489
3. Wingerchuk DM, Lennon VA, Lucchinetti CF, et al: The spectrum of neuromyelitis optica. Lancet Neurol 2007;6:805-815
4. Lennon VA, Kryzer TJ, Pittock SJ, et al: IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 channel. J Exp Med 2005;202:473-477
5. Lennon VA, Wingerchuk DM, Kryzer TJ, et al: A serum autoantibody marker of neuromyelitis optica; distinction from multiple sclerosis. Lancet 2004;364:2106-2112
6. Lennon VA, Kryzer TJ, Pittock SJ, et al: IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 channel. J Exp Med 2005;202:473-477
7. McKeon A, Chen S, Pittock SJ, et al: Comparison of optimized immunohistochemical assay with a novel aquaporin-4-specific ELISA for Detection of NMO-IgG. Ann Neurol 2009; 66:S37
Method Description Describes how the test is performed and provides a method-specific reference
NMO/AQP4-IgG Enzyme-Linked Immunosorbent Assay:
A 50 microL aliquot of undiluted serum, is added to AQP4 coated plate wells in duplicate. Then, 25 microL of AQP4-biotin is added to each well. Plates are incubated with shaking for 2 hours at ambient temperature. After aspiration and wash, 100-microL Streptavidin-peroxidase is added to each well. Plates are incubated further with shaking for 20 minutes at ambient temperature. After aspiration and wash, 100-microL peroxidase substrate (tetramethylbenzidine) is added. Plates are further incubated (in the dark) for 20 minutes at ambient temperature. At that time, 50 microL of Stop Solution (0.5 mol/L H2S04) is added to each well. Absorbance is measured at 450nm. (McKeon A, Chen S, Pittock SJ, et al: Comparison of optimized immunohistochemical assay with a novel aquaporin-4-specific ELISA for detection of NMO-IgG. Ann Neurol 2009;66:S37).
Indirect Immunofluorescence:
The substrate is a frozen composite block of mouse kidney, gut, and cerebellum. Bound IgG is detected by a fluorescein-conjugated goat IgG reactive with human IgG. To eliminate staining by nonorgan-specific IgG, each serum is preabsorbed at 1:60 dilution with liver powder. Results are reported as positive or negative. (Lennon VA, Wingerchuk DM, Kryzer TJ, et al: A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-2112)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 9 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83520-Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified
86255-Fluorescent noninfectious agent antibody screen (if appropriate)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 60795 | NMO/AQP4-IgG ELISA, S | In Process |
| 29347 | Interpretive Comments | In Process |
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