Genetic Studies to Identify Stroke Subtypes and Outcome

Background: In the United States, stroke is the third most common cause of death and the leading cause of adult disability. Despite the many efforts to find effective treatment for stroke there is at present only one acute stroke therapy. A major fact that has hindered stroke diagnosis and treatment is the lack of understanding about the pathophysiology of acute stroke. The advent of new brain imaging techniques has allowed the identification of further pathophysiological insights. To date, however, there has been a lack of genetic and molecular information, in part because the brain is not amenable to biopsy unlike other organs in the body. One new approach to studying the processes involved in the evolution of stroke and stroke recovery is the use of gene chip technology. The attraction of this technology is that it may allow differentiation of neurological conditions by non-invasive peripheral blood sampling. Objectives: The objective of this study will be to determine if the gene expression profile in white blood cells can be used to fingerprint different stroke subtypes and outcome. Study Design: Microarrays will be examined in a loop design allowing isolation of the gene effect from confounding variables by analysis of variance. Samples will be acquired from 200 control volunteers and 640 patients with various stroke subtypes. The stroke patients will have sequential samples taken at the time of stroke and during stroke recovery. Individual gene up-regulation and down-regulation will be defined by a univariate t-test comparison with the control population. These isolated gene effects will then be compared by the use of Hamming distances to define global statistical differences and graph analysis for inter-structure distances. Outcome Measures: Groups of genes with significantly altered expression in relation to stroke compared to controls allowing further examination of gene classes activity as potential stroke and stroke recovery fingerprints.