Environmental Epidemiology of Essential Tremor

特发性震颤(ET)是人类最常见的震颤原因，但其病因尚不清楚。 环境毒物可能是其病因之一。这些因素被认为起着重要的作用 在其他神经退行性疾病中的作用，但它们在ET中的作用受到的关注较少。在过去的八年里 多年来(2000-2008年)，我们研究了几种推定的毒物。哈曼(1-甲基-9H-吡啶并[3，4-b]吲哚)是 在寻找ET的环境风险因素方面最有希望的早期候选者。在过去三年中 在2005-2008年间，我们研究了几种可能导致血压升高的潜在机制。 我们在纽约以临床为基础的ET病例样本中的浓度。这些研究表明，饮食因素 可能会起到一定作用。在这些研究的同时，我们继续在纽约采集血液样本 约克市。展望未来，我们的目标是现在明确地建立这种神经毒素和ET之间的联系。这是一个 五年竞争续期，我们在其中建议解决四个相互关联的问题。首先，尽管 在ET病例中观察到哈马林浓度升高，在血液中，脑中这一浓度 神经毒素还没有被研究过。ET是一种脑部疾病，大脑是其假定的靶器官 神经毒素。在ET脑中Harmane浓度是否升高(特定目标1)？第二，我们的发现是 来源于对主要来自纽约一个三级转诊中心的ET病例的单一研究。如果有人要 对一组以完全不同的方式(即，基于社区)确定的ET病例进行中途抽样 在世界各地，人们会发现血液中的有害物质浓度升高(具体目标2)吗？第三，我们的发现 哈曼浓度升高是一项横断面观察，在单个时间点采集血液样本。 目前尚不清楚这些同样的ET病例是否会持续表现出血液哈马斯升高 如果在几年后的第二个时间点重新评估浓度(具体目标3)？最后，一项研究 发现帕金森氏症患者血液中Harmane浓度升高，这引发了一个问题，即 血压升高与ET有特定的联系，或者仅仅是一个更普遍的、全球性的标志 神经系统疾病(具体目标4)？大约50%的ET病例是非家族性的。鉴于它的人口 在40岁的人群中患病率为4.0%，那么2.0%的40岁人群中有非家族性 虽然这是外星人的一种形式，但这种震颤的环境基础才刚刚开始被探索。鉴定 了解这些毒物是预防进行性神经系统疾病的第一步 治疗方案。

Essential tremor (ET) is the most common cause of tremor in humans yet its etiology remains unclear. Environmental toxicants are likely to contribute to its etiology. Such factors are thought to play an important role in other neuro-degenerative diseases,but their role in ET has received less attention. During the last eight years (2000 - 2008), we have studied several putative toxicants. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is the most promising early candidate in the search for environmental risk factors for ET. During the past three years (2005 - 2008), we studied several potential mechanisms that could underlie elevated blood harmane concentrations in our clinic-based sample of ET cases in New York. These studies suggest that dietary factors might play a role. In tandem with these studies, we have continued to collect blood harmane samples in New York. Moving forward, our goal is to now definitely establish the links between this neurotoxin and ET. This is a five-year competitive renewal in which we propose to address four inter-related questions. First, although elevated harmane concentrations have been observed in ET cases in blood, brain concentrations of this neurotoxin have not been investigated. ET is a brain disease and the brain is the presumed target organ of this neurotoxin. Are harmane concentrations elevated in the ET brain (Specific Aim 1)? Second, our finding was derived from a single study of ET cases primarily from one tertiary referral center in New York. If one were to sample a group of ET cases ascertained in a completely different manner (i.e., community-based) half-way around the world, would one find an elevated blood harmane concentration (Specific Aim 2)? Third, our finding of an elevated harmane concentration was a cross-sectional observation, sampling blood at a single time point. It is not clear whether these same ET cases would persist in demonstrating elevated blood harmane concentrations if re-assessed at a second time point several years later (Specific Aim 3)? Finally, one study found elevated blood harmane concentrations in Parkinson's disease, raising the question as to whether elevated blood harmane is specifically linked with ET or is merely a more general, global marker of neurological illness (Specific Aim 4)? Approximately 50% of ET cases are non-familial. Given its population prevalence of 4.0% in persons age > 40 years, then 2.0% of the population aged > 40 years has a non-familial form of ET, yet the environmental underpinnings for this tremor are just beginning to be explored. Identification and understanding of these toxicants is the first step in preventing a progressive neurological disease with few treatment options.