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Research

Johns Hopkins Bayview Stroke Intervention Clinic (BaSIC)

Led by Elisabeth Marsh, M.D., assistant professor of medicine

The Johns Hopkins Bayview Stroke Intervention Clinic (BaSIC) is a multidisciplinary outpatient clinic for patients who recently have suffered a stroke. Patients are seen within four to six weeks of their discharge from the neurology service, so that key follow-up issues, such as post-stroke depression and fatigue, can be addressed, persistent symptoms can be managed, and medications can be reconciled. Patients and families have the opportunity to see their stroke using neuro-imaging, with the goal of truly understanding why the stroke occurred and the best way to decrease the chance of a future event.

Our multidisciplinary approach allows for those with continued needs to be directly linked to our rehabilitation services. The program has already led to higher post-discharge follow-up rates, better adherence to risk factor modification strategies, and decreased rates of re-hospitalization.

In addition to patient care, BaSIC also serves as a clinical research environment focused on stroke outcomes. Together, we are identifying critical gaps in the knowledge of stroke recovery. Our long-term goal is to enhance post-stroke care by improving both symptomatic recovery and patient-centered outcomes. We are currently investigating factors related to cognitive decline post-stroke, and the influence of post-stroke depression, fatigue, and persistent symptoms on long-term recovery and quality of life for both patients and their families.
 

Predicting Intracranial Hemorrhage: The HeRS score

Led by Elisabeth Marsh, M.D., assistant professor of medicine

Intracranial hemorrhage (ICH) is a devastating neurologic event. One form of ICH is hemorrhagic transformation of ischemic stroke (HT), which typically occurs in the days immediately following the infarct. HT 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 HT and ICH is important to clinicians, particularly when considering treatment with anticoagulation, a common occurrence given the increasing frequency of patients with atrial fibrillation, blood clots, and mechanical valves. Anticoagulation itself likely increases risk of HT, making this group a potentially high-risk patient population. Until recently, no clinical tool existed to accurately estimate risk.

Using a retrospective cohort of inpatients with acute stroke with an indication for anticoagulation, we found that age, infarct volume, and renal impairment are important predictors of HT. We created a Hemorrhage Risk Stratification (HeRS) 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. The HeRS score has been prospectively validated in a unique prospectively recruited inpatient cohort.

In collaboration with information technologist Peter Dziedzic, we have created an application available on iTunes that allows for quick and easy calculation of a patient’s HeRS score. The score provides a clinically useful and quantifiable risk estimate for hemorrhagic transformation in patients warranting anticoagulation, and may be used to guide treatment decisions when the need for anticoagulation is less clear.
  

Treating Superficial Siderosis

Led by Rafael Llinas, M.D., associate professor of medicine

Superficial siderosis (SS) is a neurodegenerative condition caused by hemosiderin deposition on the surface of the brain, cranial nerves, and spinal cord. Superficial siderosis is an exceptionally rare condition characterized by a triad of hearing loss, ataxia, and myelopathy. The most common etiologies are trauma, previous surgical procedures, dural tears, and tumors of the central nervous system. We have demonstrated the efficacy of deferiprone (Ferriprox), a lipid-soluble iron chelator, for reducing hemosiderin deposition through MR imaging in a series of 10 patients with SS using 30 mg/kg/day of deferiprone.

With approval of deferiprone by the US Food and Drug Administration in October 2011, we have launched an observational trial to characterize the potential clinical benefit of hemosiderin chelation (www.clinicaltrials.gov, identifier: NCT01284127).
 

Cognitive Impacts of Stroke and Other Vascular Disease

Led by Rebecca Gottesman, M.D., associate professor of neurology

Dr. Gottesman's lab work focuses on the cognitive impacts of stroke and other vascular disease, both in the short-term and the long-term, and on the association between vascular disease and dementia (including Alzheimer's disease). She evaluates this in large community-based populations, as well as smaller hospital-based studies, and has particular interest in neuroimaging as a way to evaluate cerebrovascular changes in the brain, as well as neurodegenerative changes in the brain, such as those due to Alzheimer's disease.

Cognition in Individuals Hospitalized with Congestive Heart Failure
Congestive heart failure (CHF) is a growing epidemic in this country, as the population ages. Prior studies have demonstrated that CHF patients may be at particular risk for not only stroke, but also for impaired cognition. This may be due to reduced perfusion to the brain in individuals with low cardiac function, or may be due to other factors such as circulating inflammatory markers or reduced oxygenation during a heart failure exacerbation. Little is understood about how cognition in CHF patients is related to “typical” markers of CHF worsening, such as edema or shortness of breath, or whether cognition improves as these other symptoms improve. In this study, we are recruiting hospitalized patients with acute worsening of their CHF, and performing cognitive testing at one or two time points during their hospital stays. We hypothesize specifically that level of cognitive performance will be improved after the other symptoms typically associated with CHF, such as edema and shortness of breath, improve.

Stroke and Cognition After Coronary Artery Bypass Graft Surgery
The goal of this study is to evaluate factors that contribute to stroke and short-term cognitive problems after coronary artery bypass graft (CABG) surgery. Specifically, we are interested in the importance of changes in blood pressure during surgery and how these relate to the development of different types of stroke postoperatively. Individuals enrolled in this study are recruited preoperatively, and undergo preoperative and postoperative cognitive testing, as well as postoperative brain imaging. The major hypothesis is that a larger decrease in blood pressure will be associated with more postoperative strokes, and that this will be especially true in individuals with large-vessel stenosis as seen on postoperative magnetic resonance angiography (MRA). The study is funded by the American Heart Association.

The ARIC-PET Amyloid Imaging Study
This study is an ancillary study to the larger Atherosclerosis Risk in Communities (ARIC) study and the ARIC-Neurocognitive (ARIC-NCS) studies. The ARIC study is a large, community-based cohort study from 4 community sites across the U.S. (http://drupal.cscc.unc.edu/aric/) designed to evaluate the natural history of atherosclerosis and its risk factors. The ARIC-NCS study is designed to evaluate the relationship between these vascular risk factors and cognitive impairment and dementia. The ARIC-PET study, for which Dr. Gottesman is the PI, is designed to evaluate the contribution of these vascular risk factors specifically to the deposition of amyloid in the brain, measured using PET scanning with 18F-AV-45 (florbetapir). Some existing studies suggest that vascular risk factors, such as hypertension, actually cause deposition of amyloid (the protein felt to be responsible for the development of Alzheimer’s disease) in the brain, but others suggest that these risk factors are only related to Alzheimer’s because the combination of Alzheimer’s neuropathology and vascular neuropathology make an individual more likely to experience cognitive impairment. This study, conducted at the Comstock center in Hagerstown, MD, and also at the University of Mississippi Medical Center in Jackson, MS, is designed to evaluate both of these possibilities in this existing ARIC cohort. It's funded by NIH/ NIA.

Clinical Trials

Carotid Stenting versus Endarterectomy versus Medical Management: CREST II
Carotid endarterectomy (CEA) is the currently accepted treatment for patients with significant symptomatic carotid artery stenosis. However, carotid artery stenting (CAS) has also emerged as a less invasive alternative procedure after the SAPPHIRE (2004, NEJM) and CREST (2010, Stroke) trials suggested that stenting was equivalent to CEA, and in some cases superior (i.e., in patients at high risk for complications due to general anesthesia). The treatment of asymptomatic disease is less clear, as better medical management with dual antiplatelet therapy and statins have decreased the risk of cerebrovascular complications. In CREST II, CEA and CAS are compared to medical management in a large patient population with asymptomatic significant carotid artery disease. Enrollment currently is underway at Johns Hopkins Bayview Medical Center.

SAIL-ON: Safety of Intravenous Thrombolytics in Stroke on Awakening
This study is a Phase 2, one arm, open label study. The aim is to test the safety of IV rt-PA in stroke upon awakening. Enrollment currently is underway at both Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center.

Major inclusion criteria:

  • At least 18 years old
  • Ability to provide informed consent
  • Diagnosis of acute ischemic stroke by history and physical exam
  • Patients will have woken up with stroke symptoms and present to the ED within 4.5 hours of awakening
  • Able to receive t-PA within 4.5 hours of awakening
  • Pre-morbid modified Rankin Score of 0 or 1
  • MRI or CT scan with no hemorrhage and no major hypodensity or edema

Major exclusion criteria:

  • All the current exclusion criteria for the use of rt-PA in acute stroke within three hours of onset
  • Pregnant or lactating women
  • Inability to provide informed consent

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