The Past, Present, and Future of Multiple Sclerosis Clinical Research in Japan

Although it was once thought that multiple sclerosis (MS) was extremely rare in Japan, it has now been estimated that as many as 18 000 individuals with MS are currently residing in Japan—still a much lower proportion of the country's population compared to those in Western countries. Another concern about MS in Japan over the past 20 years has been with regard to the clinical type of MS. Most of the cases of the form of MS, which is a more frequent and more severe involvement of optic nerves and spinal cord and had been classified as 'optic-spinal form MS,' are now considered as a neuromyelitis optica spectrum disorder (NMOSD). Clinical research in Japan regarding MS did not advance significantly in the past, probably due to the country's low prevalence of MS. However, interesting research data that appear to be unique to Japan have been obtained in studies of the clinical characteristics of Japanese individuals with MS. For example, several investigations have indicated that cerebellar lesions are relatively uncommon in Japanese patients with MS, which suggests that there is ample justification for conducting clinical research concerning MS that is unique to Japan. In the invited review articles in this issue of Clinical and Experimental Neuroimmunology, the history of MS research in Japan and recent topics in Japan are discussed from three perspectives: epidemiology, MRI data, and the cognitive function and quality of life (QOL) of individuals with MS. Nationwide epidemiological surveys (including those for MS) have been conducted in Japan for over 50 years. Few other countries in Asia have conducted such surveys of MS over such a long period. In this issue of Clinical and Experimental Neuroimmunology, Dr. Watanabe gives a historical overview of epidemiological studies on MS in Japan, which have shown increasing trends in the prevalence and delineated clinical features of MS in the Japanese population 1. The reasons for the differences in the prevalence of MS among ethnicities and regions worldwide are of significant interest, and Watanabe discusses the genetic and environmental risk factors in Japan as well as the disease burden. The importance of epidemiological data will continue to grow as they accumulate over time. By synthesizing Japan's epidemiological research to date, Watanabe's review may well suggest the future direction of epidemiological research in Japan. MRI was first applied to diagnose MS in the 2001 criteria presented by McDonald et al. 2, and the description of the usefulness of MRI in studies of MS is further increased in the revised 2024 McDonald criteria 3. The application of MRI is significantly higher in Japan than in other countries; access to MRI in Japan is relatively easy. Dr. Yokote reviews the evolution of MS research that applied MRI findings across five distinct phases of MS, highlighting contributions from Japan within a global context 4. He notes that over the nearly five decades since the first MRI studies of MS were published, the advances in imaging technology have been remarkable and have steadily brought us closer to the core mechanisms underlying the pathophysiology of MS. Yokote's review is expected to serve as a useful reference for considering future directions in MRI research regarding MS. The prevalence of cognitive dysfunction among individuals with MS has been historically underestimated due to the difficulty in detecting cognitive impairment during brief office visits without a formal neuropsychological assessment. Approximately 40%–65% of individuals with MS have shown cognitive impairment in neuropsychological studies, with prominent involvements of memory, sustained attention, and information-processing-speed impairment. However, studies of cognition and QOL in MS have not been a research focus in Japan, despite the importance of these factors in the daily lives of people with MS. Drs. Okuda and Fujimori recently reviewed and discussed the extant studies of cognitive function and health-related QOL in people with MS in Japan 5, but the research on cognitive function and QOL in MS in Japan is still in its infancy. It is clearly necessary to further expand research in this field, examining Japanese individuals in studies conducted in Japan. Observations that will help uncover these less visible symptoms are expected. Fortunately, the progress of clinical studies of MS in Japan has been remarkable, as the authors of the three reviews 1, 4, 5 explain. The data that have already been obtained in various MS research fields in Japan have contributed to a broader understanding of MS, and the research will continue. Numerous clinical challenges regarding MS in Japan remain that cannot be addressed in this editorial. The three articles of the current review series shed light on the past, present, and future of clinical research concerning MS in Japan, contributing to further advances in MS clinical research. I would like to thank all authors who agreed to contribute to the Focused Review Series. The author has nothing to report. The author declares no conflicts of interest. Masaaki Niino is a Guest Editor of Clinical and Experimental Neuroimmunology. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.