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Research by: Elisabeth B. Marsh, MD
Intracranial hemorrhage (ICH) is a devastating neurologic event that can occur on a micro- or macrovascular scale. Microbleeds in the general population may be associated with cognitive decline and increased risk of symptomatic ICH. Hemorrhagic transformation of ischemic stroke often results in neurologic deficits, long term disability, or death. It is unknown whether all types of ICH share common risk factors. The ability to predict who is at highest risk for ICH is important to clinicians, particularly when considering treatment with anticoagulation. Currently no clinical tool exists to accurately estimate risk in either group. We have acquired preliminary data from a small, retrospective cohort of inpatients to suggest that ICH is likely a multifactorial event. Age, infarct volume, and renal impairment are important predictors of hemorrhagic transformation. We have created a Hemorrhage Risk Score using these factors, specifically for the inpatient population, to allow physicians to quickly and accurately predict their patient’s individual risk of hemorrhagic conversion. This is useful not only to inform the clinical team and the patient of the expected risk, but also to guide treatment decisions.
We are currently working to validate our hemorrhage risk model in a prospective inpatient cohort, and have expanded the study to investigate risk factors for spontaneous hemorrhage in the general population as part of the Atherosclerosis Risk in Communities (ARIC) study. With the addition of a community-based cohort, our findings have the potential not only to directly impact patient care, but to identify an ‘at risk’ population who have yet to experience a neurologically devastating hemorrhage. In collaboration with Dr. Josef Coresh, a nephrologist and one of the principal investigators in the ARIC study, and Dr. Nauder Faraday, an expert in platelet dysfunction who runs a molecular lab at Johns Hopkins, we are also working to prospectively determine the underlying mechanisms by which renal failure results in increased likelihood of ICH, focusing specifically on platelet dysfunction and the potentiation of a chronic inflammatory state leading to breakdown of the blood brain barrier.
Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by a mutation in the tumor suppressor gene NF1. Characterized by nerve sheath neurofibromas and other neoplasms, the syndrome also results in a vasculopathy, leading to an increased incidence of heart disease and stroke. Despite being the most common neurocutaneous disorder, occurring in approximately 1 in 3,000 births, the vasculopathy of NF1 is poorly characterized and not well understood, with no large population-based studies. Several small studies have examined the prevalence and spectrum of cerebrovascular disease in children with NF1 and found that moyamoya syndrome is fairly common (3-5% of those imaged). Through collaboration with Dr. Jaishri Blakeley of the Johns Hopkins Neurofibromatosis Center, we are working to characterize the extent and underlying etiology of vascular malformations in both children and adults with NF1.