Rinsho Shinkeigaku (Clinical Neurology)

The 48th Annual Meeting of the Japanese Society of Neurology

ALS-parkinsonism-dementia complex of the Kii peninsula of Japan (Muro disease). Historical review, epidemiology and concept

Shigeki Kuzuhara, M.D.

Department of Neurology, Mie University School of Medicine
National Center of Neurology and Psychiatry

The Muro district includes the southern coastal mountainous areas of the Kii peninsula of Japan where high incidence foci of ALS and parkinsonism-dementia complex (PDC) exist. "Muro disease" refers to the endemic ALS in Muro, and the oldest description is in a book published in 1689. Miura reported high prevalence of ALS in Muro in 1911, and the first epidemiological survey by Kimura and Yase in 1960s disclosed extremely high prevalence of ALS in Hohara and Kozagawa. The high incidence was, however, reported to have disappeared by early 1980s as in Guam. In 1990s we resurveyed and found not only continuous high ALS incidence but also neuropathologically-verified PDC in Hohara. ALS and PDC here frequently affected one individual simultaneously and members in a family. Neuropathological changes were common to ALS and PDC, showing a combination of ALS changes and many neurofibrillar tangles (NFTs) in the brainstem and cerebral cortex, suggesting ALS/PDC may be a single entity with different clinical manifestations, "ALS-parkinsonism-dementia complex". TDP-43-positive inclusions were confirmed in all cases examined. Age-adjusted incidence rates during 1950 and 2000 have showed that incidence of ALS gradually declined for 50 years while that of PDC rose up steeply in 1990s, suggesting changing pattern of ALS/PDC that had occurred in Guam in 1970s. Continuing high incidence of ALS/PDC and high familial occurrence suggest that primary cause of Kii ALS/PDC may be genetic rather than environmental.

(CLINICA NEUROL, 47: 962－965, 2007)
key words: amyotrophic lateral sclerosis, parkinsonism-dementia complex, Kii peninsula, epidemiology, history

(Received: 16-May-07)