Neuromyelitis Optica (NMO) Evaluation with Reflex, Serum
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.
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
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.
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
Clinical References 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