International Stroke Conference Digest - February 20, 2008 - (Page 6)

2008 isc digest | New Orleans | februAry 20 Symposium to examine relationship between sickle cell and stroke the connection between sickle cell disease and stroke, as well as ongoing research into ways to predict and prevent stroke in patients with sickle cell disease, will be explored this morning during a symposium on the first day of the 2008 International Stroke Conference. The session, titled “Stroke in Sickle Cell Disease: Recent Successes and Ongoing Challenges,” will begin at 9:10 a.m. in Hall B 2-2. The first of the symposium’s four speakers, Heather J. Fullerton, MD, a pediatric neurologist at the University of California, San Francisco, will address the changing demographics of stroke in sickle cell disease. Session moderator Robert J. Adams, MS, MD, Professor of Neuroscience and Director of the Stroke Center at the Medical University of South Carolina, Charleston, said Dr. Fullerton’s presentation will educate attendees on how current practices and research have influenced the demographics of stroke in sickle cell disease and also look at the interplay between pediatric stroke and stroke in older patients with sickle cells disease. “The problem of stroke and sickle cell disease begins at a very early age,” Dr. Adams said. “However, it may change in important ways in adults, and that’s one of the things we are trying to understand. The treatment approaches may also change. The treatment algorithm we developed with the STOP I and STOP II trials is in children.” As the symposium’s second presenter, Dr. Adams will discuss lessons learned in the Stroke Prevention in Sickle Cell Anemia (STOP) trials. The treatment algorithm he and his colleagues developed for the trials began with screening of sickle cell patients by transcranial Doppler ultrasound to detect a high-risk state and then using chronic blood transfusion to prevent stroke in children with sickle cell disease. “It’s not clear how that algorithm will apply to adults. I’ll talk about the design and results of the two STOP trials and reinforce the role of transcranial Doppler in selecting patients for prophylactic treatment. I’ll explain the results in terms of what we were able to do in preventing first strokes,” Dr. Adams explained. “To prevent stroke, we need to look at high-risk subsets to understand who might be at greater risk than others,” he continued. “The second STOP study examined the question of whether a lower risk subset of patients who have been transfused for 30 or more months can safely be removed from transfusion. That trial showed that while there may be some patients who can tolerate removal, 50 percent of patients are back on transfusion within the first year, either because they had symptoms of stroke or their Doppler results reverted to a high-risk category. “The bottom line message is that the transfusion program reduces risk by altering the environment in the short term but does not appear to change the fundamental characteristics of the patients that lead them to be at high risk. Therefore, the next trial most likely will have an active treatment arm to determine whether hydroxyurea is able to maintain a reduced stroke risk state after some initial period of transfusion,” Dr. Adams said. The session’s third speaker, Michael DeBaun, MD, MPH, Professor of Pediatrics, Biostatistics, and Neurology at Washington University in St. Louis, will discuss the challenge of small vessel stroke in patients with sickle cell disease. “Small, silent infarcts usually escape clinical detection but show up on MRI and are associated with adverse performance on neuropsych testing,” Dr. Adams said. “Dr. DeBaun will talk about how they relate to large vessel disease. He is conducting a trial of patients with a positive MRI for small vessel stroke, no history of stroke, and a negative transcranial Doppler exam. He is examining the impact of chronic transfusion on patients with small vessel disease.” Finally, James F. Meschia, MD, FAHA, a neurologist at the Mayo Clinic in Jacksonville, Florida, will discuss what is known about genetic predictors of stroke in patients with sickle cell disease. “There has been a lot of progress in genetic research in stroke, and sickle cell is one of the first molecular diseases that has been understood for a very long time on a genetic level,” Dr. Adams said. “One of the questions looked at recently is that in addition to the hemoglobin S mutation, are there other genetic abnormalities that will help determine which patients have the highest risk of stroke?” intervention this session will also motivate physicians to look more carefully at the clinical trials they are asked to participate in. “They should be excited to participate in these trials, but also they should think a little more carefully about what’s behind the trial,” he said. “They can be real participants by asking, ‘What’s the basic information here? Why should I participate in this trial?’” Also during today’s session, Victor Marder, MD, will discuss the pros and cons of using plasmin directly and how to deliver it. Dr. Marder is the Director of the Vascular Medicine Program at Los Angeles Orthopaedic Hospital, and a faculty member at the David Geffen School of Medicine at UCLA. He is CoDirector of the Hematology/ Medical Oncology Training Program and directs the NIHfunded “Training for Academic Hematology.” Mark Fisher, MD, will discuss his pre-clinical laboratory research on endothe- continued from page 1 tion of clotting. The session’s co-moderator, John Hallenbeck, MD, will present an overview of his laboratory research on immunomodulation in stroke. Dr. Hallenbeck is a senior investiis currently in pre-clinical animal testing. Dr. Hallenbeck said the first subjects to receive nasal installations of E-selectin were extremely hypertensive, stroke-prone rats. “Doing this really suppressed the strokes even though we didn’t treat the hypertension,” Dr. Hallenbeck said. “It robustly suppressed ischemic strokes and eliminated intraparenchymal hemorrhages in the brain.” Dr. Hallenbeck said his lab has developed other models and has found that in addition to reducing infarct volume, this immunomodulation suppresses damage to white matter in a model of vascular cognitive impairment. Dr. Hallenbeck ’s lab is starting the toxicology studies required to file for an IND, and hopes this preventive treatment can be studied in humans. “It’s a completely different mechanism than the agents that are currently used,” Dr. Hallenbeck said. lial cell anticoagulant properties and how these can be dealt with in clinical patients as potential therapies. Dr. Fisher is Professor and Chair of Neurology, Professor of Anatomy and Neurobiology, International Stroke Conference 2009 Call for Science submit session ideas Suggested Session Submitter Opens: Monday, Feb. 18, 2008 Suggested Session Submitter Closes: Monday, Mar. 17, 2008 submit Abstracts Submission Opens: Monday, June 16, 2008 Submission Closes: Monday, Aug. 11, 2008 Gregory del Zoppo, MD and Professor of Political Science at the University of California, Irvine. Activated protein C will be the focus of a presentation by Berislav Zlokovic, MD, PhD. He’ll discuss using the compound to reduce injury volume in the brain and other potential positive affects on the brain beyond the preven- John Hallenbeck, MD gator for the NINDS at NIH. Dr. Hallenbeck is developing an approach to stroke prevention that involves immunologically tolerizing subjects to E-selectin, an antigen specific to activated endothelium, in order to target regulatory T cells to vessel segments that are vulnerable to thrombosis or hemorrhage. The research submit late-breaking science and ongoing clinical trials Abstracts Submission Opens: Monday, Oct. 6, 2008 Submission Closes: Monday, Nov. 3, 2008

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International Stroke Conference Digest - February 20, 2008

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