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Neuromyelitis Optica Autoantibody

Neuromyelitis Optica Spectrum Disorder (NMOSD), also known as Devic's disease or optic spinal multiple sclerosis, is a severe autoimmune inflammatory demyelinating disease that selectively affects optic nerves and the spinal cord. This disorder has a prevalence of 0.5 to 10 persons per 100,000 population. There are approximately 17,000 patients with NMOSD in the United States. Women are affected nine times more often than men. Black and Asian populations have a two to three-fold higher incidence than Caucasians. The average age of onset is 40 years.

NMOSD has three clinical presentations:

  • 35% present with partial vision loss due to optic neuritis
  • 50% present with transverse myelitis that transcends 3 spinal segments
  • 5% present with brainstem syndrome or area postrema symptoms

Within 5 years, approximately 30% of patients lose vision in at least 1 eye and 20% are unable to walk independently. 

Patients with NMO produce an antibody to aquaporin-4, a water channel protein expressed on the foot processes of astrocytes in the central nervous system. NMO is now classified as an autoimmune AQP4 channelopathy. Anti-AQP4 antibodies are produced by plasma cells in peripheral lymphoid tissue and cross the blood brain barrier. AQP4 IgG binding to astrocytes activates the complement cascade and formation of the membrane attack complex, which leads to cell death. Astrocyte death leads to loss of oligodendrocytes and then neurons. 

AQP4 IgG antibodies are detectable in 65 to 88% of patients with NMOSD. Seropositivity for aquaporin4 IgG allows early diagnosis of NMO. Specificity is 99.9%, meaning the false positive rate is 0.1%. 

Many patients with NMO are misdiagnosed as having multiple sclerosis. Aquaporin4 IgG is uniformly negative in patients with classical multiple sclerosis. A positive value is consistent with an NMO spectrum disorder and justifies initiation of early immunosuppressive therapy to prevent severe disability. Accurate diagnosis is important because prognosis and treatment for the two diseases differ. NMO attacks are often severe resulting in early onset of blindness and paraplegia. NMO is treated with immunosuppression while multiple sclerosis is treated with immunomodulation. FDA has approved three medications for treatment of NMOSD: inebilizumab, satrilizumab, and eculizumab. Plasmapheresis is more beneficial for patients with acute attacks of NMO than for those with multiple sclerosis. 

Seropositive patients are much more likely to relapse or progress within 2 years than seronegative patients. Seronegativity does not exclude the diagnosis of NMO. Patients already treated with immunosuppressive therapy may not have detectable antibody.  

Since aquaporin4 IgG autoantibody is synthesized by peripheral lymphoid tissues and not intrathecally, serum autoantibody must reach a significant concentration before autoantibody is detected in cerebrospinal fluid. The optimal specimen for detection of aquaporin4 IgG is serum and not cerebrospinal fluid. Followup testing is recommended within 3 to 6 months after initiation of therapy. 

The preferred method for detecting Aquaporin-4 IgG is a fluorescence activated cell sorting assay. Reference value is negative. If antibody is detected, serum is diluted to endpoint and the highest titer is reported. 

Preferred specimen is a red top tube of blood. 


  1. Wingerchuk DM, Lennon VA, Pittock SJ, et al:  Revised diagnostic criteria for neuromyelitis optica. Neurol 2006;66:1485-1489. 
  1. Kerr DA:  The lumping and splitting of inflammatory CNS diseases, Neurol 2006;66:1466-1467
  1. 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
  1. 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 
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