Heterogeneity and continuum of multiple sclerosis phenotypes in Japanese according to the results of the fourth nationwide survey
Introduction
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). MS is rare in Asians, but when it appears, involvement of the optic nerve and spinal cord is destructive [1]. There are two distinct subtypes of MS in Asians: the optic-spinal form (OSMS), which shows selective involvement of the optic nerve and spinal cord, and the conventional form (CMS), which affects multiple sites of the central nervous system (CNS), including the cerebrum and cerebellum [2]. The two subtypes have distinct clinical and neuroimaging features. OSMS is characterized by a higher age at onset, greater female preponderance and higher Kurtzke's Expanded Disability Status Scale (EDSS) score [3] compared with CMS [1], [2]. Longitudinally extensive spinal cord lesions (LESCLs) extending over three or more vertebral segments are more commonly found in patients with OSMS than CMS patients [1]. However, reflecting the pronounced spinal cord damage seen in Asians, one-fourth of CMS patients also have such LESCLs [4], [5].
In Japan, nationwide surveys of MS were conducted in 1972, 1982, 1989 and 2004 using essentially identical criteria [6], [7], [8]. In the fourth survey, we disclosed a four-fold increase in the estimated number of clinically definite MS patients (9900; crude MS prevalence, 7.7/100,000) in 2003 compared with 1972, and a shift in the peak age at onset from early 30 s in 1989 to early 20 s in 2003 [8], suggesting an increase in susceptibility to this disease among the younger generation. In this study, a successive decrease in optic-spinal involvement in clinically definite MS patients was also revealed, while the absolute numbers of CMS patients and those with MS-like brain lesions fulfilling the Barkhof criteria were found to increase rapidly with advancing year of birth. Also, the frequency of LESCLs was found to be significantly higher in OSMS patients than in CMS patients in this nationwide survey.
We recently reported that there are distinct subtypes of MS according to clinical and MRI findings using our institutional series of MS patients [9], [10]. Therefore, in the present study, we aimed to clarify the characteristic features of each MS phenotype classified according to the clinically estimated sites of involvement and MRI findings unique to Asian MS patients, such as the presence or absence of LESCLs, using collated MS cases from the fourth nationwide survey of MS in Japan.
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Survey procedures
The fourth nationwide survey of MS was conducted by the Research Committees of Neuroimmunological Diseases and of Epidemiology of Intractable Diseases, sponsored by the Ministry of Health, Labor and Welfare, Japan. The study was approved by the Kyushu University Ethics Committee. The survey was undertaken in two steps: first, a preliminary survey was undertaken to ascertain the approximate number of MS patients in Japan, and second, a survey was conducted using a questionnaire sheet for each
Demographic features of each MS subtype
Based on the MRI findings, MS patients were subdivided into those with OSMS with or without LESCLs and those with CMS with or without LESCLs (Table 1). The proportion of females was significantly greater among OSMS or CMS patients with LESCLs than among CMS patients without LESCLs (Pcorr < 0.05 in OSMS with LESCLs and Pcorr < 0.05 in CMS with LESCLs). Age at onset was significantly higher in OSMS patients with LESCLs than in other patient groups (Pcorr < 0.05). The peak age at onset was early 20 s
Discussion
In the present study, using MS cases collated in the fourth nationwide survey in Japan, we disclose that distinct demographic features vary not only with clinical phenotype, such as OSMS and CMS, but also with the characteristic MRI findings, such as LESCLs and Barkhof brain lesions.
The present study had some limitations, primarily because the response rate in the second survey was not high. Concerning the relatively low response rate to this type of nationwide epidemiological survey in Japan,
Acknowledgments
This work was supported in part by grants from the Research Committees of Neuroimmunological Diseases and of Epidemiology of Intractable Diseases, the Ministry of Health, Labour and Welfare, Japan.
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These authors contributed equally to this work.