Essential tremor (ET) is one of the most prevalent adult neurological disorders. Despite this, several fundamental clinical and genetic issues remain unknown: (1) The extent of familial aggregation is not known. (2) There are few quantitative data on the natural progression of disease, and the associations between disease progression, tremor distribution and tremor severity are not known. (3) There are few data on whether the degree of familial aggregation of ET is greater for certain subtypes of ET than for others (genetic heterogeneity). (4) Data on the mode of inheritance are almost exclusively derived from service or clinic-based studies, which may be biased towards an apparent autosomal dominant mode of inheritance. Additionally, all studies of this question have examined ethnically-homogeneous populations. The study proposal is the first with a case-control community-based shielded (blinded) design, and has the following aims: (1) to determine the extent of familial aggregation of ET, (2) to analyze the natural history of ET, and associations between different clinically-defined subtypes of ET (subtypes will be based on clinical features such as tremor distribution, severity, and age of onset), (3) to compare different clinically-defined subtypes of ET in terms of the extent of increased risk of ET within families, and (4) to test genetic and nongenetic models that could explain the familial distribution of ET. In families with three or more affected cases, blood specimens will be drawn from study subjects for future linkage analysis. Subjects will be selected from a community-based study of neurological disease in a multiethnic community in Washington Heights-Inwood, northern Manhattan, New York (NIH Grant # PO-1-AG07232-06, R. Mayeux, P.I.). Thirty-seven cases with ET, 37 matched controls, and 666 relatives of these cases and controls will be interviewed, examined, and videotaped using a standardized protocol. Data on disease characteristics and progression will be collected. Diagnoses will be assigned by two neurologists using a diagnostic protocol utilized in our previous study. Electrophysiological studies (tremor analysis) will be used to validate a proportion of all diagnoses. This applicant is trained as an academic clinical neurologist with specialization in clinical movement disorders and neuroepidemiology. This grant will enable him to develop an academic career in neurology and genetic epidemiology by allowing him (1) to collaborate with neurologists and genetic epidemiologists in the Sergievsky Center, (2) to learn methods of genetic epidemiology. including segregation analysis and eventually. linkage analysis, (3) to continue courses in the Columbia University School of Public Health. Drs. W. Allen Hauser, Ruth Ottman, Richard Mayeux and Stanley Fahn, all internationally recognized either within the areas of Neuroepidemiology or Movement Disorders, will provide invaluable guidance in these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001863-04
Application #
2796979
Study Section
NST-2 Subcommittee (NST)
Program Officer
Oliver, Eugene J
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1998-09-30
Budget End
1999-08-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Louis, Elan D; Ford, Blair; Frucht, Steven (2003) Factors associated with increased risk of head tremor in essential tremor: a community-based study in northern Manhattan. Mov Disord 18:432-6
Pappert, E J; Goetz, C G; Louis, E D et al. (2003) Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology 61:936-40
Brennan, Kevin C; Jurewicz, Eva C; Ford, Blair et al. (2002) Is essential tremor predominantly a kinetic or a postural tremor? A clinical and electrophysiological study. Mov Disord 17:313-6
Schneier, F R; Barnes, L F; Albert, S M et al. (2001) Characteristics of social phobia among persons with essential tremor. J Clin Psychiatry 62:367-72
Louis, E D; Ford, B; Frucht, S et al. (2001) Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study. Ann Neurol 49:761-9
Louis, E D; Ford, B; Frucht, S et al. (2001) Evidence for familial aggregation of tremor in normal individuals. Neurology 57:110-4
Louis, E D; Barnes, L; Albert, S M et al. (2001) Correlates of functional disability in essential tremor. Mov Disord 16:914-20
Louis, E D; Barnes, L F; Ford, B et al. (2001) Family history information on essential tremor: potential biases related to the source of the cases. Mov Disord 16:320-4
Louis, E D; Ford, B; Frucht, S et al. (2001) Mild tremor in relatives of patients with essential tremor: what does this tell us about the penetrance of the disease? Arch Neurol 58:1584-9
Louis, E D; Barnes, L; Wendt, K J et al. (2001) A teaching videotape for the assessment of essential tremor. Mov Disord 16:89-93

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