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Neuromyelitis optica (NMO) is characterised by severe optic neuritis and transverse myelitis. In contrast to multiple sclerosis (MS), there have been few large-scale epidemiological surveys of NMO. The worldwide prevalence of NMO is estimated to be 1 in 100 000. NMO may be more prevalent in Asia, Africa and Latin America than in Europe and North America. NMO has been well recognised following the discovery of anti-aquaporin 4 (AQP4) antibody, and highly sensitive and specific cell-based assays using AQP4 antibody are widely available in Japan. Based on previous literature, we planned and performed the first-ever nationwide epidemiological study of NMO in Japan, which has a population of about 130 million. An advantage of performing a nationwide survey in Japan is that the Japanese archipelago stretches for 3500 km from north to south (45°−24° N). As the north–south gradient for the prevalence of MS is an important epidemiological finding reported in Japan and other countries, Japan is an ideal country to study potential differences in the prevalence of NMO associated with changes in latitude.
We conducted a nationwide survey on NMO in clinical departments using established epidemiological methods in 20111. The survey was performed at departments of neurology, internal medicine, paediatrics, neurosurgery, orthopaedics, ophthalmology and psychiatry based on random selection using a stratified sampling method. Although the diagnostic criteria for NMO were renewed in 2015, clinical diagnosis of definite NMO in this study was based on the 2006 Wingerchuk diagnostic criteria,2 as they were the standard criteria used in 2011. Patients with NMO had to fulfil both absolute criteria (category 1). Patients with NMO spectrum disorder (NMOsd) were classified into three groups (categories 2, 3 and 4). Patients in category 2 had no spinal cord lesions (with predominant optic nerve involvement), those in category 3 had no optic nerve lesions (with predominant spinal cord involvement) and those in category 4 had positive results in the anti-AQP4 antibody test but were not categorised as category 2 or 3.
The survey consisted of two questionnaires (primary and secondary surveys) directly sent to the selected departments, as in previous Japanese nationwide surveys of intractable diseases.1 The first questionnaire was an inquiry regarding the number of patients with NMO or NMOsd (NMO/NMOsd) who satisfied the above-mentioned criteria. The secondary survey requested more detailed clinical information on patients identified in the primary survey. The number of patients treated for NMO/NMOsd in Japan in 2011 was estimated based on the assumption that responses to the survey were independent of the number of patients treated in a specific department. Formulas used to estimate the total number of patients and the 95% CIs are described elsewhere in detail.1 Data from the 2011 Japanese census were used to determine the crude prevalence rate. We examined differences in the prevalence of NMO in Japan associated with north–south geographic location by dividing the country at the 37° N parallel, as in a previous nationwide study of MS in Japan.3
Responses to the primary survey were obtained from 3796 institutes (52.6% recovery). The estimated number of patients satisfying the study criteria was 2093 (95% CI 1740 to 2240) for category 1 (NMO); 883 (95% CI 760 to 1020) for category 2 (NMOsd without spinal cord lesion); 1031 (95% CI 840 to 1190) for category 3 (NMOsd without optic nerve lesion); and 370 (95% CI 230 to 520) for category 4 (anti-AQP4 antibody-positive not in categories 1–3). We estimated the total number of patients with NMO/NMOsd in Japan in 2011 to be 4377 (95% CI 3570 to 4970) by adding the numbers of patients in each category. The prevalence of NMO was 1.64 (category 1) and that for NMO/NMOsd was 3.42 in 100 000 (categories 1–4). The prevalences of definite NMO and NMOsd were significantly higher in Southern Japan than in Northern Japan (3.54 vs 3.20, P<0.001, table 1).
We obtained responses to the second questionnaire for 1194 patients. After excluding ineligible cases, 1042 cases were analysed. Table 1 shows the basic data obtained using the second questionnaire. Most patients with NMO/NMOsd were women (86.5%). The mean age at disease onset was 42.2 years, and the mean disease duration was 9.8 years.
The estimated number of patients with NMO was 2093 and that of patients with NMO/NMOsd was 4377 in Japan in 2011. The number of registered patients affected by MS was 16 140 in 2011. As this number would have included patients with NMO/NMOsd, it can be estimated that NMO and NMO/NMOsd, respectively, account for 13% and 27% of patients registered as having MS in this database. Although the prevalence of MS was found to be significantly higher in Northern Japan in a previous study,3 the prevalence of NMO had a regional pattern opposite to that of MS in the present survey. Japanese residents in the southern part of the country had a significantly higher prevalence of NMO/NMOsd than those in the northern part of the country. Reasons for this regional difference in NMO prevalence should be investigated in future studies.
A comparative population-based study of the prevalence of NMO/NMOsd in Olmsted County, USA (82% Caucasian), and Martinique (90% Afro-Caribbean) revealed that the prevalence of NMO/NMOsd in Martinique was higher than that in Olmsted County (10 vs 3.9 per 100 000).4 The prevalence of NMOsd in Australia and New Zealand is estimated to be 0.70 per 100 000. NMOsd was three times more common in Asians (1.57 per 100 000) than in non-Asians (0.57 per 100 000) in a previous study. The latitudinal gradient evident for MS has not been observed for NMOsd.5 Japan is ethnically highly homogeneous and consists of a mainly Asian population. Our results indicate that NMO/NMOsd has a prevalence of 3.42 in 100 000 in Japan, similar to that found in Olmsted County. Our study is the first national epidemiological survey on NMO in Japan. Continuous surveys are required to investigate whether the prevalence of NMO is increasing. Such investigations may provide us with more insight into the pathogenetic mechanisms and potential prophylactic approaches for this intractable disease.
The authors would like to thank Wakaba Fukushima and Yoshio Hirota for their assistance in data management.
Contributors SK planned the study. All authors contributed to data acquisition. NK and AT analysed the data. KM wrote the first draft; all authors revised the draft paper.
Funding This work was supported in part by Health Sciences Research Grants (Comprehensive Research on Disability Health and Welfare and Research on Intractable Diseases) from the Ministry of Health, Labor and Welfare of Japan (H23-017).
Competing interests None declared.
Ethics approval Kindai University Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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