Neuromyelitis optica in western countries: Establishing diagnostic criteria and characterization of the spectrum

Neuromyelitis optica (NMO) can be distinguished from MS by clinical, radiological and serological findings, especially the tendency for spinal cord lesions to be longer than 3 vertebral segments during acute attacks and the presence of aquaporin-4 autoantibodies in NMO. The spectrum of NMO is broader than previously realized and includes recurrent myelitis, recurrent optic neuritis, certain cerebral presentations, including intractable vomiting and posterior reversible encephalopathy. It may coexist with other systemic autoimmune diseases, including systemic lupus erythematosus and Sjogren’s syndrome. Whether NMO has a predilection for individuals of Asian ancestry or whether there are differences between NMO and Asian optic-spinal MS other than arbitrary definitions remains to be clarified. Further epidemiological studies using comparable diagnostic criteria, radiological studies and serological tests are required. Neurology Asia 2008; 13 : 161 – 166 Just a decade ago, there was controversy about the distinctness of neuromyelitis optica (NMO) from multiple sclerosis (MS). Over the past three years, investigators worldwide have accepted that these diseases are distinct clinically, radiologically, pathologically, prognostically and in their responsiveness to MS diseasemodifying therapies. Questionably, the major factor responsible for this acceptance was the discovery of an IgG biomarker with moderate, but variable among different investigative teams, sensitivity for NMO.1,2 However, the uniformly high specificity of this IgG biomarker2, that has been termed NMO-IgG, has reassured most about its significance. Virtually every relevant control group that has been studied, including other fulminant demyelinating diseases, systemic autoimmune disease and other neurological diseases, has shown that only in those with typical symptoms of NMO is the test positive. Initial efforts to characterize the specificity of this marker required independent clinical and serological characterization of suspected cases to avoid the pitfall of “circular argument” wherein the biomarker being evaluated influenced the clinical diagnosis with which an association was being explored.1 However, having established the specificity of the marker beyond doubt2, it seemed reasonable to use this marker as a probe to explore disorders with credible clinical relatedness (limited syndromes, such as isolated or recurrent transverse myelitis or optic neuritis; optic-myelitic syndromes associated with other comorbidities such as systemic autoimmune disorders that raised question about the relationship to NMO; atypical manifestations such as brain syndromes, that occur with unusually high frequency in patients with NMO). While the potential pitfalls of circular reasoning might still raise concerns among some, the alternative of failing to utilize this marker to probe the spectrum of NMO was to ignore the existence of definable syndromes that might be related to NMO and benefit from similar therapeutic strategies as were being developed for clinically definite NMO. A point of continuing controversy is the relationship of NMO to optic-spinal MS in Asian countries and elsewhere. Final consensus on this issue has yet to be reached, but an analysis of the issues in this debate is now possible that can frame the necessary studies to resolve persisting controversies. In this review, I will outline the nature of NMO spectrum disorders that are now being recognized and diagnosed in individuals in western countries, and address the issue of similarity and differences between Asian optic-spinal forms of MS and NMO. I will also compare and contrast the recently proposed consensus criteria of the National Multiple Sclerosis Society task force on the diagnosis of MS with the Wingerchuk et al (2006) Mayo Clinic criteria for NMO and their implications. Neurology Asia December 2008 162 NEW MANIFESTATIONS OF NEUROMYELITIS OPTICA SPECTRUM