Neuromyelitis Optica (NMO) Autoantibody, IgG, Spinal Fluid
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Neuromyelitis optica (NMO, also known as Devic's disease and optic-spinal multiple sclerosis) is a severe idiopathic inflammatory demyelinating disease that selectively affects optic nerves and the spinal cord, typically spares the brain, and generally follows a relapsing course. Within 5 years, 50% of patients lose functional vision in at least 1 eye or are unable to walk independently. In North America, the proportion of nonwhite individuals is higher among patients with NMO than among those with classic multiple sclerosis. During acute attacks, the cerebrospinal fluid contains inflammatory cells, but often lacks evidence of intrathecal IgG synthesis.
Many patients with NMO are misdiagnosed as having multiple sclerosis, due to earlier misconceptions that NMO was a monophasic disorder, and was not associated with brain imaging abnormalities. Importantly the prognosis and optimal treatments for the 2 diseases differ. NMO typically has a worse outcome than multiple sclerosis, with frequent and early relapses. Plasmapheresis is more beneficial for patients with NMO than for those with multiple sclerosis. Early diagnosis and treatment are important to reduce the morbidity of NMO.
Seropositivity for NMO autoantibody IgG (NMO-IgG) allows early diagnostic distinction between NMO (73% positive; 91% specific) and multiple sclerosis (0% positive). NMO-IgG is uniformly negative in patients with classical multiple sclerosis, for which no biomarker is currently recognized. This distinction is important both prognostically and therapeutically, because optimal treatments differ for NMO (immunosuppression) and multiple sclerosis (immunomodulation with beta-IFN or glatiramer acetate).
Establishing the diagnosis of neuromyelitis optica (NMO) and related disorders (eg, relapsing transverse myelitis or relapsing optic neuritis), predicting with 60% probability, relapse or progression to NMO in patients presenting with an initial episode of longitudinally extensive transverse myelitis. Seropositivity distinguishes these disorders from multiple sclerosis early in the course of disease. This allows initiation and maintenance of optimal therapy.
Serum is the preferred specimen for detection of NMO-IgG (see NMOER/60796 Neuromyelitis Optica (NMO) Evaluation with Reflex, Serum); cerebrospinal fluid is usually less informative.
A positive value is consistent with neuromyelitis optica (NMO) or a related disorder, and justifies initiation of appropriate immunosuppressive therapy at the earliest possible time.
Our prospective studies have revealed that 40% of adult patients with longitudinally-extensive transverse myelitis are seropositive and, of that group, 60% relapse or progress to NMO within 2 years. No seronegative patient relapsed in up to 7 years of follow-up.
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 NMO (current seronegativity rate is 27%).
Immunosuppressive therapy may result in negative results.
High levels of nonorgan-specific autoantibodies (which are frequent in patients with NMO) may preclude interpretation of a positive immunofluorescence pattern.
Serum (NMOER/60796 Neuromyelitis Optica [NMO] Evaluation with Reflex, Serum) is the preferred specimen. Cerebrospinal (CSF) is usually less informative than serum for detection of NMO-IgG. However, testing of accompanying CSF for CRMP-5-IgG (CRMWC/21747 Collapsin Response-Mediator Protein-5-IgG [CRMP-5-IgG] Western Blot, Spinal Fluid) is recommended as a sensitive assay for paraneoplastic myelitis and optic neuritis.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Wingerchuk DM, Lennon VA, Pittock SJ, et al: Revised diagnostic criteria for neuromyelitis optica. Neurol 2006;66:1485-1489
2. Kerr DA: The lumping and splitting of inflammatory CNS diseases. Neurol 2006;66:1466-1467
3. Luccinnetti CF, Mandler RN, McGavern D, et al: A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 2002;125:1450-1461
3. Cross SA, Salomao DR, Parisi JE, et al: Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003;54:38-50
5. Cross SA, Salomao DR, Parisi JE, et al: Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Am J Ophthalmol 2003;136(6):1200 (abstract)