ArticlesA serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis
Introduction
Neuromyelitis optica (Devic's syndrome) is a severe idiopathic inflammatory demyelinating disease that selectively affects optic nerves and spinal cord, typically spares the brain, and generally follows a relapsing course.1, 2, 3, 4 Within 5 years, 50% of patients lose functional vision in at least one eye or are unable to walk independently. In North America, the proportion of non-white individuals is higher among patients with neuromyelitis optica than among those with classic multiple sclerosis.3, 4 In Asia, an optic-spinal form of multiple sclerosis is a common inflammatory demyelinating disease. It accounts for 15–40% of multiple sclerosis cases in Japan.5, 6 Is the Asian optic-spinal form of multiple sclerosis the same entity as neuromyelitis optica seen in western populations?
When fully developed, neuromyelitis optica can be distinguished from multiple sclerosis by a combination of clinical, neuroimaging, and spinal-fluid findings.3 Characteristics typical of neuromyelitis optica include episodic myelitis—commonly severe and frequently accompanied by paroxysmal tonic spasms—with longitudinally extensive spinal-cord lesions spanning three or more vertebral segments, absence of clinical evidence of brain involvement, and usually lack of multiple-sclerosis-type lesions on MRI of the brain.7 During acute attacks, the spinal fluid contains inflammatory cells but there is no evidence of intrathecal IgG synthesis (panel). However, many patients showing initial symptoms of neuromyelitis optica are diagnosed with multiple sclerosis. Neither disorder has a specific diagnostic marker, but the prognosis and optimum treatments for the two diseases differ. Immunosuppressive drugs (eg, azathioprine and corticosteroids) are regarded as the best treatment for neuromyelitis optica,8 whereas immunomodulatory treatments (eg, interferon beta and glatiramer acetate) are presently recommended for early treatment of multiple sclerosis.9 When severe exacerbations of myelitis do not respond to corticosteroid therapy, plasmapheresis is more beneficial for patients with neuromyelitis optica than for those with multiple sclerosis10.
Early diagnosis and treatment are very important to reduce the morbidity of neuromyelitis optica. Early use of appropriate immunosuppressive therapy would be justified if this disorder could be reliably distinguished from multiple sclerosis at the initial onset of optic neuritis or transverse myelitis, before progression and fulfilment of all clinical diagnostic criteria. We describe a newly identified IgG autoantibody (NMO-IgG) that localises to the blood-brain barrier and seems to be a specific serological marker for neuromyelitis optica. We have assessed the diagnostic accuracy of this autoantibody for neuromyelitis optica and other high-risk syndromes that could lead to a diagnosis of the disorder (eg, longitudinally extensive transverse myelitis or recurrent optic neuritis).
Section snippets
Patients
Our study included 124 clinically ascertained patients (figure 1) and 75 additional control patients (figure 2) with classic multiple sclerosis (19) and miscellaneous neurological disorders (56). The study was approved by the institutional review boards of the Mayo Clinic, Rochester, MN, USA, and Tohoku University School of Medicine, Sendai, Japan. Patients gave spoken consent for testing. All serum specimens were assayed and scored as positive or negative without knowledge of clinical
Results
We identified a serum IgG that seems to be specific for patients with neuromyelitis optica or a high-risk syndrome. NMO-IgG yielded a characteristic immunohistochemical pattern of binding in mouse CNS tissues (Figure 3, Figure 4). It was prominent in pia and subpia, and outlined the Virchow-Robin space and microvessels in white and grey matter of the cerebellum, midbrain, and spinal cord. It also bound to subependymal white matter and the subpial layer of midbrain in a mesh pattern. No staining
Discussion
We describe an IgG autoantibody (NMO-IgG) that has high specificity for neuromyelitis optica. No biomarker has previously been described to aid diagnosis of this disorder. Our assay detected NMO-IgG in almost three-quarters of patients with this diagnosis, in nearly half of those at high risk of developing neuromyelitis optica, and in about a tenth of those showing optic neuritis or myelitis as the initial manifestation of multiple sclerosis. As yet we have not detected NMO IgG in any patient
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