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.
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