Kuzuhara Shigeki
Department of Medical Welfare, Faculty of Health Science, Suzuka University of Medical Science, Mie, Japan.
Brain Nerve. 2011 Feb;63(2):119-29.
Muro disease refers to the endemic amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) in the high incidence ALS focus in the Muro district of the Kii peninsula. Kii paralysis was first described in the 1680s in a folk literature, and as ALS in the medical literature by Kin-no-suke Miura in 1911. Two high-incidence ALS foci were discovered in 1960s by Kimura and Yase, and retro- and anterospective epidemiological surveys were started. Kii ALS was neuropathologically characterized by classical ALS pathology together with many neurofibrillary tangles (NFTs) in the brain, similar to Guamanian ALS. The incidence rates of ALS dramatically declined during the 1950s and 1980s, resulting in the disappearance of the high-incidence foci. In the early 1990s, however, Kuzuhara found existence of high-incidence of ALS in the region, and, in addition, of a high-incidence of PDC with abundant NFTs, similar to Guamanian PDC. The incidence rates of PDC dramatically rose during the 1980s and 1990s, and PDC replaced ALS. Unsuccessful attempts were made to identify cause and pathogenesis of the disease in minerals and environmental factors. More than 70% of patients in the endemic region had a family history of ALS or PDC; therefore, genetic factors were suspected as the cause. The authors analyzed the causative and risk candidate genes in the affected and unaffected family members, but failed to find genes related to ALS/PDC. The changing pattern of Muro disease from ALS with a younger onset and rapid progression to PDC with a later onset and longer survival suggests that some unknown environmental factor(s) might modulate the disease process, which basically might be programmed in the gene(s).
室户病是指纪伊半岛室户地区肌萎缩侧索硬化症（ALS）高发区的地方性肌萎缩侧索硬化症和帕金森痴呆综合征（PDC）。纪伊麻痹最早于17世纪80年代在一部民间文献中被描述，1911年三浦绢之助在医学文献中将其作为肌萎缩侧索硬化症进行了描述。20世纪60年代，木村和矢濑发现了两个肌萎缩侧索硬化症高发区，并开始进行回顾性和前瞻性流行病学调查。纪伊型肌萎缩侧索硬化症的神经病理学特征是典型的肌萎缩侧索硬化症病理学表现，同时大脑中存在许多神经原纤维缠结（NFTs），类似于关岛型肌萎缩侧索硬化症。20世纪50年代至80年代期间，肌萎缩侧索硬化症发病率急剧下降，导致高发区消失。然而，在20世纪90年代初，久原发现该地区存在肌萎缩侧索硬化症高发情况，此外，还存在帕金森痴呆综合征高发情况，且有大量神经原纤维缠结，类似于关岛型帕金森痴呆综合征。帕金森痴呆综合征的发病率在20世纪80年代和90年代急剧上升，帕金森痴呆综合征取代了肌萎缩侧索硬化症。人们曾试图从矿物质和环境因素中确定该疾病的病因和发病机制，但未成功。该流行地区70%以上的患者有肌萎缩侧索硬化症或帕金森痴呆综合征家族史；因此，怀疑遗传因素是病因。作者分析了患病和未患病家庭成员中的致病候选基因和风险候选基因，但未发现与肌萎缩侧索硬化症/帕金森痴呆综合征相关基因。室户病从发病较早、进展较快的肌萎缩侧索硬化症转变为发病较晚、存活时间较长的帕金森痴呆综合征，这一变化模式表明，某些未知的环境因素可能会调节疾病进程，而疾病进程基本上可能由基因编程。
