The role of anti-aquaporin-4 antibody in Asian patients with multiple sclerosis: Confusions and controversies

Neuromyelitis optica (NMO) was first described as a severe monophasic syndrome of acute bilateral optic neuritis and transverse myelitis. Whether it is a form of multiple sclerosis (MS) or a separate disease entity has been continually debated since the beginning of last century. The redefinition of NMO as a relapsing disease, the wider use of magnetic resonance imaging showing longer spinal cord lesion, and the recently discovered anti-aquaporin-4 (AQP4) water channel antibody, or NMO-IgG, has rekindled this controversy. The many recent publications including the abstracts published in this issue of Neurology Asia have shown that anti-AQP4 antibody is of variable sensitivity in different populations. It appears to be associated mainly with longitudinal extensive spinal cord lesions and frequent relapses. The site of pathology of NMO also do not co-localize with the widespread expression of AQP4 in the body, throwing doubts on the suggestion that the anti-AQP4 antibody plays primary role in the pathogenesis of NMO. In the day-to-day clinical practice in Asia, anti-AQP4 antibody remains a research investigatory test. As for optic-spinal MS, which is closely similar to NMO based on recently revised criteria, interferon should remain the treatment of first choice. HISTORICAL DEVELOPMENT OF NEUROMYELITIS OPTICA Neuromyelitis optica (NMO) was first described by Allbutt in 1870. Sporadic case reports and small pathological studies were published in the years that followed, but it was in 1894 when Devic and his student Gault described 17 patients who had a severe monophasic syndrome of acute transverse myelitis with bilateral optic neuritis that the name NMO was given.1,2 Many cases of the early reports had pathological changes in the brainstem and cerebrum, which in retrospect probably included a variety of conditions such as acute disseminated encephalomyelitis and multiple sclerosis (MS), and perhaps even infections, such as syphilis.2 The debate of whether NMO is a form of MS first started nearly 80 years ago. As early as 1927, pathological studies showed that the inflammation in NMO was more severe and was not only associated with demyelinating plaques, but also with cavitation, necrosis and acute axonal pathology in both the grey and white matter.2-4 However, pathological reports since 1882 had also reported similar findings in MS, and these had been confirmed in many subsequent studies.2 As early as 1942 patients who initially diagnosed as NMO were reported to develop other neurological signs consistent with MS later.2 MULTIPLE SCLEROSIS IN ASIA Studies in Asia in the 1970s, especially in Japan, showed that the clinical features in a proportion of Asian patients with MS were dissimilar from that seen in Western countries. These patients had recurrent optic neuritis and transverse myelitis and, apart from minor brainstem signs and symptoms, had little evidence of disease elsewhere and the term optic-spinal form of MS was used to describe them. In Asia, the term Devic disease or NMO was used to refer to a monophasic disease with bilateral optic neuritis and severe transverse myelitis, as defined by Shibasaki, McDonald and Kuroiwa in 1981.5 The difference between optic-spinal MS and NMO then was that the latter is a monophasic disease and the former, a recurrent one.2 Other significant Address correspondence to: Dr HT Chong, Neurology Laboratory, University Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia. E-mail: hengtchong@