Pathogenesis of Essential Tremor: Cerebellar Metabolism

特发性震颤（ET）是最常见的神经系统疾病之一，但它也是研究最少的疾病之一。几 药物治疗这种疾病，通常是渐进的。虽然它的流行程度是普通人的20倍， 帕金森？在我们最初申请的时候（2002年），我们注意到只有15个尸检，大多数是 这些都是前现代时期的因此，几乎没有关于ET的潜在病理学的知识。虽然 经常重申，没有病理学？在ET中，这不是基于严格的研究。自2003年以来，我们的目标是 建立特发性震颤集中式大脑知识库，以解决ET研究中的一个基本问题： 根据特定脑区的形态学变化确定潜在的病理学？经过密集收集 然后研究了46个ET大脑和32个对照大脑，我们发现，确实， ET大脑的变化：80.4%的ET大脑具有小脑退行性变化，其形式为 鱼雷和浦肯野细胞（PC）数量（）轻度减少，而19.6%的人有脑干路易体。 因此，在这一点上，我们已经描述了ET大脑中的几个基本变化。两者之间的临床差异 病理学鉴定的ET亚型尚未得到充分研究。我们现在希望超越我们最初的工作。 具体目的1是提高我们对小脑ET患者死后变化的认识（目的1A）， Lewy小体ET（Aim 1B）通过PC神经元形态学的详细研究。因为到目前为止我们的分析 由于我们只限于小脑半球的一个区域，我们将扩大我们的范围，包括其他每个区域 小脑的功能解剖区域（Aim 1C）。通过目标1，我们将测试一个假设（疾病模型）， ET的每种病理亚型。具体目标2是建立临床特征和尸检之间的基本联系 脑变化（临床-病理相关性）。我们2002年申请中的临床评价设计简单， 间接（电话和录像带）。现在，我们的目标是对175名患者进行全面的临床评估。 我们预计在这五年的建议期内，会有42名长者因感染ET而死亡。这样，我们就可以开始识别 表征具有ET的两种病理亚型中的每一种的患者的特定临床特征。我们的目标是 推进这一领域：（1）增加我们对ET病理解剖的理解，（2）锻造所需的 医生在活着的病人身上观察到的和我们在详细的死后研究中发现的之间的联系。

Essential tremor (ET) is one of the most common neurological diseases yet it is also among the least studied. Few medications treat the disorder, which is usually progressive. Although it is as much as twenty times more prevalent than Parkinson?s disease, at the time of our original application (2002), we noted that there were only 15 postmortems, most of which were from the pre-modern era. Hence, there was almost no knowledge of the underlying pathology of ET. Although often reiterated that ¿there is no pathology? in ET, this was not based on rigorous study. Since 2003, our goal has been to establish the Essential Tremor Centralized Brain Repository to address a fundamental question in ET research: can an underlying pathology be identified in terms of morphological changes in specific brain regions? After intensively collecting and then studying 46 ET brains and 32 control brains, we have discovered that, indeed, there are identifiable pathological changes in the ET brain: 80.4% of ET brains have cerebellar degenerative changes in the form of increased numbers of torpedoes and mild reduction in Purkinje cell (PC) number (¿cerebellar ET¿) whereas 19.6% have brainstem Lewy bodies. Hence, at this point, we have described several basic changes in the ET brain. Clinical differences between the two pathologically-identified subtypes of ET have not been well studied. We now wish to move beyond our initial work. SPECIFIC AIM 1 is to advance our knowledge of the postmortem changes in patients with cerebellar ET (Aim 1A) and Lewy body ET (Aim 1B) through detailed studies of PC neuronal morphology. Because our analyses have thus far been confined to a single region of one cerebellar hemisphere, we will broaden our scope to include each of the other functional-anatomic regions of the cerebellum (Aim 1C). Through Aim 1, we will test a hypothesis (disease model) for each pathological subtype of ET. SPECIFIC AIM 2 is to establish basic links between clinical features and postmortem brain changes (clinical-pathological correlation). The clinical evaluation in our 2002 application was, by design, brief and indirect (telephone and videotape). Now our aim is to conduct a comprehensive in-person clinical evaluation of 175 elderly ET cases, 42 of whom we expect to die during this five year proposal. In doing so, we can begin to identify the specific clinical features that characterize patients with each of the two pathological subtypes of ET. Our goal is to advance this field by: (1) increasing our understanding of the pathological anatomy of ET, and (2) forging the needed links between what physicians observe in living patients and what we uncover in detailed postmortem studies.