Diseases of the Vestibular System

描述(由申请人提供)：我们建议对前庭系统疾病的患者进行一项多学科的临床研究。虽然眩晕和失衡是患者最常见的主诉之一，但大多数前庭系统障碍的病因和病理生理学尚不清楚。人们认识到许多不同的临床症状，但这些疾病背后的细胞和分子机制才刚刚开始解决。遗传学和分子生物学的最新进展提高了人们对几种常见前庭综合征的理解的希望。在项目1中，研究人员将通过应用选择性刺激对特定的前庭感觉器官或大脑区域进行新的测试，由于其短暂的性质，可以将前庭反应与非迷路代偿机制分开。项目2的研究人员将研究典型的遗传性通道病综合征-发作性共济失调2型-目的是了解不同的突变如何导致临床症状和体征的谱。他们将识别新的突变，并使用电生理学技术对突变基因产物进行表征。 最后，项目3的研究人员将在全基因组范围内搜索与家族性良性复发性眩晕相关的一个或多个基因。在我们的数据库中有大量患有这种综合征的家庭，初步的模拟研究表明很有可能找到显著的联系。临床核心A是所有研究的患者来源，技术核心B为所有项目提供硬件和软件支持。我们的总体目标是通过汇聚一个多学科的研究团队来弥合目前实验室和床边之间存在的差距，从而改善对头晕和失衡患者的诊断和治疗。

DESCRIPTION (provided by applicant): We propose a multidisciplinary clinical study of patients with diseases of the vestibular system. Although vertigo and imbalance are among the most frequent complaints of patients visiting their physician, the etiology and pathophysiology of most vestibular system disorders are poorly understood. Many different clinical syndromes are recognized, but the cellular and molecular mechanisms underlying these disorders are only beginning to be addressed. Recent advances in genetics and molecular biology raise hopes for improved understanding of several common vestibular syndromes. In Project 1, investigators will develop new tests of specific vestibular sensory organs or brain regions through application of selective stimuli that by their transient nature can isolate vestibular responses from nonlabyrinthine compensatory mechanisms. Investigators in Project 2 will study the prototypical inherited channelopathy syndrome - episodic ataxia type 2 - with the goal of understanding how different mutations lead to the spectrum of clinical symptoms and signs. They will identify new mutations and characterize the mutant gene products using electrophysiologic techniques. Finally, investigators in Project 3 will perform a genome-wide search for the gene or genes associated with familial benign recurrent vertigo. There is a large collection of families with this syndrome in our database and initial simulation studies indicate there is a good likelihood of finding a significant linkage. Clinical Core A is the patient source for all studies and the technical Core B provides hardware and software support for all projects. Our overall goal is to improve the diagnosis and treatment of patients with dizziness and imbalance by bringing together a multidisciplinary research team to bridge the gap that currently exists between the laboratory and the bedside.