Elsevier

The Lancet Neurology

Volume 6, Issue 9, September 2007, Pages 805-815
The Lancet Neurology

Review
The spectrum of neuromyelitis optica

https://doi.org/10.1016/S1474-4422(07)70216-8Get rights and content

Summary

Neuromyelitis optica (also known as Devic's disease) is an idiopathic, severe, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. Neuromyelitis optica has a worldwide distribution, poor prognosis, and has long been thought of as a variant of multiple sclerosis; however, clinical, laboratory, immunological, and pathological characteristics that distinguish it from multiple sclerosis are now recognised. The presence of a highly specific serum autoantibody marker (NMO-IgG) further differentiates neuromyelitis optica from multiple sclerosis and has helped to define a neuromyelitis optica spectrum of disorders. NMO-IgG reacts with the water channel aquaporin 4. Data suggest that autoantibodies to aquaporin 4 derived from peripheral B cells cause the activation of complement, inflammatory demyelination, and necrosis that is seen in neuromyelitis optica. The knowledge gained from further assessment of the exact role of NMO-IgG in the pathogenesis of neuromyelitis optica will provide a foundation for rational therapeutic trials for this rapidly disabling disease.

Introduction

Inflammatory demyelinating diseases of the central nervous system occur throughout the world and are the foremost reason for non-traumatic neurological disability in young, white adults;1 multiple sclerosis is the most common of these disorders. The diagnosis of multiple sclerosis requires confirmation that the symptoms and signs of CNS white-matter involvement are disseminated in time and space, supportive evidence from magnetic resonance imaging and cerebrospinal fluid analysis, if needed, and the exclusion of other diagnoses (table).2 Multiple sclerosis is not associated with a specific biomarker, and although intrathecal synthesis of oligoclonal IgGs is characteristic of multiple sclerosis, no target antigen has been defined;3 therefore, any relapsing idiopathic demyelinating disease of the central nervous system has, until recently, been diagnosed as multiple sclerosis.4

Neuromyelitis optica (Devic's disease) is an inflammatory, demyelinating syndrome of the central nervous system that is characterised by severe attacks of optic neuritis and myelitis, which, unlike the attacks in multiple sclerosis, commonly spare the brain in the early stages.5 In developed nations, neuromyelitis optica disproportionately strikes non-white populations, in which multiple sclerosis is rare. Whether neuromyelitis optica is a variant of multiple sclerosis or a separate disease has been long debated: optic neuritis, myelitis, and inflammatory demyelination are features of both disorders.6, 7, 8 The traditional concept of neuromyelitis optica was that it is a monophasic disorder, in which near-simultaneous bilateral optic neuritis and transverse myelitis arise. Nowadays, neuromyelitis optica is recognised as a discrete, relapsing, demyelinating disease, with clinical, neuroimaging, and laboratory findings that can distinguish it from multiple sclerosis (table).5, 9 Moreover, the detection of neuromyelitis optica immunoglobulin G (NMO-IgG), an autoantibody, in the serum of patients with neuromyelitis optica, distinguishes neuromyelitis optica from other demyelinating disorders.10 NMO-IgG binds to aquaporin 4,11 which is the main channel that regulates water homoeostasis in the central nervous system.12 NMO-IgG is also detected in the serum of patients with disorders related to neuromyelitis optica, including Asian optic-spinal multiple sclerosis, recurrent myelitis associated with longitudinally extensive spinal cord lesions, recurrent isolated optic neuritis, and optic neuritis or myelitis in the context of certain organ-specific and non-organ-specific autoimmune diseases (panel 1).

Section snippets

Clinical features and definition

In 1894, Devic and Gault described the sine qua non clinical characteristics of neuromyelitis optica: optic neuritis and acute transverse myelitis. The patients described by Devic and Gault had monophasic or relapsing courses of neuromyelitis optica.13, 14 Various antecedents or coexisting infections, vaccinations, and systemic autoimmune diseases have been linked to neuromyelitis optica, but the cause of the disease is unknown.6, 8, 15

The definition of neuromyelitis optica developed from the

Epidemiology

Neuromyelitis optica is up to nine times more prevalent in women than it is in men (table).5, 16, 34, 35 The median age of onset (39 years) is older than the median age of onset of multiple sclerosis (29 years);4 however, neuromyelitis optica also occurs in children and elderly people.5, 36, 37 Despite over-representation of east Asians and other non-white populations worldwide, compared with multiple sclerosis, most patients with neuromyelitis optica in the developed world are white.5, 16

Disease course and prognosis

80–90% of patients with neuromyelitis optica have relapsing episodes of optic neuritis and myelitis, rather than a monophasic course.5, 16, 17 Relapse occurs within 1 year in 60% of patients and within 3 years in 90%.5 Monophasic neuromyelitis optica is difficult to diagnose because relapses can happen decades after the index event; however, patients with nearly simultaneous bilateral optic neuritis and myelitis are less likely to relapse than patients who have index events that are several

Immunopathology

Demyelination in neuromyelitis optica extends across multiple sections of the spinal cord, and the necrosis and cavitation affect the grey matter and the white matter in spinal cord and optic nerve lesions.33, 59, 60 Unlike in multiple sclerosis, eosinophils and neutrophils are commonly found in the inflammatory infiltrates of active lesions of neuromyelitis optica,38, 60 and the penetrating spinal vessels are frequently thickened and hyalinised.33, 60, 61 Post-mortem studies confirm that brain

Revised diagnostic criteria for neuromyelitis optica

Diagnostic criteria before 2006 have helped the distinction of neuromyelitis optica from multiple sclerosis in people in disparate geographic regions and ethnic groups,25, 34, 35 and in patients who first present with a clinically isolated syndrome (eg, optic neuritis or myelitis).87 However, these criteria did not include patients who have brain lesions on MRI (usually asymptomatic) but a disease course that is otherwise indicative of neuromyelitis optica. Conversely, patients who present with

Treatment

Intravenous corticosteroid therapy is commonly the initial treatment for acute attacks of optic neuritis or myelitis. Patients who did not respond promptly to corticosteroid treatment benefited from seven treatments of plasmapheresis (1·0 to 1·5 plasma volume per exchange) over a period of 2 weeks in a randomised, controlled, crossover trial of patients with acute, severe demyelinating disease, which included patients with neuromyelitis optica and acute transverse myelitis.110 In a recent

Conclusion

The heterogeneity of idiopathic inflammatory demyelinating diseases of the central nervous system is one of the main factors that confound epidemiological, genetic, and therapeutic studies of multiple sclerosis. Neuromyelitis optica is a homogeneous disorder that can be identified from within this group of demyelinating diseases by a combination of clinical, neuroimaging, serological, and pathological characteristics.120 The use of these characteristics to distinguish neuromyelitis optica from

Search strategy and selection criteria

References for this review were identified by searches of Ovid Medline from 1966 to June, 2007 with the terms “neuromyelitis optica”, “Devic's syndrome”, “Devic's disease”, “opticospinal”, and “multiple sclerosis”. The authors also identified articles through searches of their own files and by reviewing original papers published in English, translations of relevant papers published in French and Spanish, and abstracts published in Japanese.

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