The long-term goal of our research is to develop more effective methods for the prevention and treatment of stroke. Our group uses clinical, neuroimaging and genetic characterization of patients with stroke in order to improve understanding of the risk and clinical course of cerebrovascular disease. In addition to our broad-based genetic studies, we continue to enroll patients with hemorrhagic and ischemic stroke in longitudinal studies of stroke outcome. All of our efforts involve collaborations with other groups, within the Department of Neurology, the Center for Human Genetic Research, the Broad Institute, and the Martinos Center for Biomedical Imaging, as well as within the International Stroke Genetics Consortium.

Genetic studies

Accumulating data suggest that genetic variation plays a substantial role in stroke risk. Research in our group is directed at discovering those so-called "culprit" genetic variants. A major thrust is the application of genome-wide association studies in patients with ischemic and hemorrhagic stroke. We are founding members of the International Stroke Genetics Consortium (www.strokegenetics.org), and our genome-wide association studies are all conducted in collaboration with Consortium members. An additional focus of our work is on the application of genetic discoveries to bedside decision-making, an ongoing collaboration with Mark Eckman at the University of Cincinnati and Brian Gage at Washington University.

White matter hyperintensity

The chronic small vessel diseases that lead to symptomatic stroke can also be detected as radiographic white matter hyperintensity (WMH). WMH, visible on CT scan and MRI, is the most common manifestation of cerebrovascular disease in the elderly. Twin, sibling and pedigree studies have consistently demonstrated a powerful genetic contribution to WMH. The volume of WMH measured on MRI strongly predicts risk of symptomatic stroke and cognitive decline as well as gait deterioration and late-life depression. Effective prevention of WMH progression therefore holds the promise of transforming the human aging process and markedly reducing age-related disability for future generations. Work in our group is directed at discovering the genetic variants that govern WMH severity in patients with stroke as well characterizing the role of WMH in the brain's response to ischemic stroke.

Intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the most devastating acute manifestation of chronic progressive diseases of the cerebral small vessels. It is fatal in up to 50% of patients, and leaves the majority of survivors with substantial life-long disability. In a long-standing cohort study of patients with ICH, we use data from neuroimaging, clinical and genetic analyses to investigate the biological underpinnings of ICH, identify those patients at greatest risk for ongoing hemorrhage and neurological deterioration in the Emergency Department, and improve the care currently provided to ICH patients.

Anticoagulation and ICH

As the most feared complication of chronic anticoagulation, ICH plays a major role in decision-making for those patients at high risk for thromboembolic stroke. Anticoagulation, while beneficial for preventing such strokes, increases the risk of ICH and worsens the severity of the hemorrhage when it occurs. Decision modeling suggests that an individual's risk for ICH powerfully affects the risk-benefit balance of anticoagulation. Work in our group seeks to clarify the risk factors for anticoagulant-related ICH, the effect of anticoagulation on ICH severity as well as identify ways to improve emergency care for anticoagulant-related ICH.