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Iuliu Hatieganu University of Medicine and Pharmacy Doctoral SchooL Neuroscience P r o g r a m 2015-2016 Section 1 February 5 th, 2016 1

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PhD Neuroscience Program Coordinator Dafin F. Mureşanu President of the Romanian Society of Neurology Professor of Neurology, Chairman Department of Neurosciences Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania President of the Society for the Study of Neuroprotection and Neuroplasticity (SSNN) International Guest Lecturer Natan M. Bornstein Professor of Neurology at the Tel-Aviv University Sackler Faculty of Medicine, Israel Vice President of the World Stroke Organization (WSO) Head of Stroke Unit at the Tel-Aviv Medical Center Chairman of the Israeli Neurological Association Doctor honoris causa, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania 3

PhD Neuroscience Program Faculty 2015-2016 Natan Bornstein /Israel Michael Brainin /Austria Anca Buzoianu /Romania Michael Chopp /USA László Csiba /Hungary Antonio Federico /Italy Marc Fisher /USA Ștefan Florian /Romania Wolf Dieter Heiss /Germany Maurizio Leone /Italy Dafin F. Mureșanu /Romania Lăcrămioara Perju Dumbrava /Romania Maura Pugliatti /Italy Johannes Vester /Germany ORGANIZERS University of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca, Romania www.umfcluj.ro 4

International Guest Lecturer 5

NATAN BORNSTEIN israel EDUCATION 1970-73 University of Sienna, Medicine, Sienna, Italy 1973-79 Technion Medical School, Hifa, Medicine, MD, 1979 Date of receiving specialixation certificate: 11 September, 1984 Title of Doctoral dissertation: Dextran 40 in acute ischemic stroke Name of Supervisor: Dr. Jacob Vardi FURTHER EDUCATION 1978-83 Tel-Aviv University, Sackler Faculty of Medicine, neurology (residence), Israeli Board certified in Neurology, 1983 1979-83 Tel-Aviv University, Sackler Faculty of Medicine, Post graduate studies in Neurology 1984-87 Sunnybrook Medical Center, University of Toronto, M.R.C stroke, Fellowship ACADEMIC AND PROFESSIONAL EXPERIENCE 1982-1995 Tel-Aviv University, Neurology, instructor 1991-present European stroke Conference (ESC), Executive committee 1995-1999 Tel-Aviv University, Neurology, Senior lecturer 1995 Eliprodil CVD 715 clinical trial, Steering Committee 1995-1997 International Stroke Study (IST), Steering Committee 1995-1999 American Academy of Neurology, Member of the International Affairs Committee 1996 Asymptomatic Carotid Stenosis and Risk of Stroke(ACSRS), Advisory Committee 1996-present The Mediterranean Stroke Society (MSS), President 1996-2002 EFNS, Management Committee 1997-2009 Israeli Neurological Association, Secretary 1999-present Tel-Aviv University, Neurology, Associated Professor 2001- present European Society Neurosonology and Cerebral Hemodynamics (ESNCH) Executive committee 2005-present Neurosonolgy Research Group, Executive committee 2006-present European Master in Stroke Medicine, Member of faculty 2006-2008 NEST II clinical Trial, Steering Committee 2006-present SENTIS clinical Trial, Steering Committee 2006-present CASTA Trial, Steering Committee 2006-present Brainsgate clinical Trial, Steering Committee 2008- present World Stroke Association (WSO), Vice president 2009-present Israeli Neurological Association, Chairman 2009-present European Stroke Organization (ESO), Member on the board of directors 2010- NEST III clinical Trial, Steering Committee 6

PROFESSIONAL ACHIEVEMENTS- EDITORIAL BOARD 1991-present Neurological Research Journal, Guest Editor 1991-present STROKE, Member of the editorial board 1998-present European Journal of Neurology, Member of the editorial board 1999-present Journal of Cerebrovascular disease, Member of the editorial board 2000-present Journal of Annals of Medical Science, Consulting Editor 2001-present Journal of Neurological Science (Turkish), Member of the editorial board 2001-present Acta Clinica Croatica, Member of the editorial Counsil 2003-present Italian Heart Journal, International Scientific Board 2003-present Journal of Neurological Sciences, Guest Editor 2004-present Turkish Journal of Neurology, International Advisory Board 2005-present Archives of Medical Sciences (AMS), Member of the Editorial Board 2006-present Journal of Cardiovascular Medicine, International Scientific Board 2006-present International Journal of Stroke, Editorial Board 2006-present Acta Neurologica Scandinavica, Editorial Board 2009-present American Journal of Neuroprotection& Neurogeneration (AJNN) Member of the Editorial Board 2010 Neurosonology, International Editorial Board 2010 Frontiers in Stroke, Review Editor PROFESSIONAL ACHIEVEMENTS- REVIEWER 1998-present Lancet, Ad Hoc reviewer 1998-present Diabetes and its complications, Ad Hoc reviewer 1999-present Journal of Neuroimaging, Reviewer 1999-present Journal of Neurology, Ad Hoc reviewer 2000-present Neurology, Ad Hoc reviewer 2003-present Israeli Medical Association Journal (IMAJ), Reviewer 2003-present Acta Neurologica Scandinavica, Ad Hoc reviewer 2006-present Journal of Neurology, Neurosurgery & Psychiatry, Reviewer 2010- European Neurology, Ad Hoc reviewer MEMBERSHIP IN PROFESSIONAL SOCIETIES 1977-present Israeli Medical Association 1983-present The Israeli Neurological Association 1985-present Stroke Council of the American Heart Association (Fellow) 1986-present American Academy of Neurology 1986-present Neurosonology Research Group of the World Federation of Neurology 1987-present Stroke Research Group of the World Federation of Neurology 1990-2008 International Stroke Society 1995-2008 European Stroke Council 1995-present Mediterranean Stroke Society (MSS) 1998-present European Neurosonology Society 2005-present World Stroke Organization (WSO) 2008-present Fellow of the European Stroke organization (FESO) 7

8 COURSE PROGRAM

COURSE Program February 5 th, 2016 Multimedia Auditorium, Iuliu Hatieganu UMF Cluj-Napoca 8 Victor Babes Street CLUJ-NAPOCA ROMANIA 13:30-14:30 Management of symptomatic carotid stenosis CEA vs. Stent 14:30-15:30 Secondary stroke prevention 15:30-16:00 Coffee Break 16:00-17:00 Time is Brain, TIA as an emergency 17:00-18:00 Management of intracerebral hemorrhage - update 18:00-18:30 Coffee Break 18:30-19:30 What can we learn from National Stroke Registry - The Israeli model 9

10 ABSTRACTS

Management of symptomatic carotid stenosis. CEA vs. Stent NATAN BORNSTEIN Tel-Aviv University, Sackler Faculty of Medicine, Israel Stroke Unit at Tel-Aviv Medical Center, Israel Symptomatic severe carotid stenosis (>70%) carries a high risk of subsequent stroke of about ~ 30% over 2 years. Carotid endarterectomy (CEA) was proved to reduce the risk of stroke significantly, with Relative Risk Reduction (RRR) = 65% and Number Needed to Treat (NNT) = 6 if performed safely (perioperative S&D =5.8%) and should be executed within 2 weeks of TIA or minor stroke (NASCET & ECST). For carotid stenting to replace CEA we need to know the comparative safety, durability and efficacy of the procedure. Only a few randomized, controlled studies comparing CEA and stenting were conducted (CAVATAS, SAPPHIRE, EVA-3 and SPACE) with inconclusive results. There are still several ongoing studies (CREST in the USA and ICSS in Europe and Australia). Until more data will be available carotid stenting should be performed only in a selected group of patients with specific indications like: re-stenosis of the CEA, post neck radiation, inaccessible lesion for CEA and contra-indications for CEA. Secondary stroke prevention NATAN BORNSTEIN Tel-Aviv University, Sackler Faculty of Medicine, Israel Stroke Unit at Tel-Aviv Medical Center, Israel Patients with TIA or ischemic stroke carry a risk of recurrent stroke between 5 and 20% per year. In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs are able to decrease the risk of stroke by 11-15% and the risk of stroke, MI and vascular death by 15-22%. Aspirin is the most widely used drug. It is affordable and effective. Low doses of 50-325 mg aspirin are as effective as high doses and cause less gastrointestinal side effects. Severe bleeding complications are dose-dependent. The combination of aspirin with slow release dipyridamole is superior to aspirin alone for stroke prevention (ESPS-2 and ESPRIT1). Both studies have shown approximately 20%-24% relative risk reduction (RRR) of stroke and death. Clopidgrel is superior to aspirin in patients at high risk of recurrence by about 8.7% RRR (CAPRIE2). The combination of aspirin plus clopidogrel is not more effective than clopidogrel alone but carries a higher bleeding risk (MATCH3 and CHARISMA4). None of the antiplatelet agents is able to significantly reduce mortality. The recent results of the PRoFESS trial 5,6 showed no difference between clopidogrel and aspirin with slow release dipyridamole in secondary stroke prevention. References: 1. Lancet 2006;367:1665-73 2. Lancet 1996;348:1392-1339 3. Lancet 2004;364:331-337 4. N Eng J Med 2006;354(16):1744-6 5. Cerebrovasc Dis 2007;23:368-380 6. N Engl J Med 2008;359:1238-51 11

Time is Brain, TIA as an Emergency NATAN BORNSTEIN Tel-Aviv University, Sackler Faculty of Medicine, Israel Stroke Unit at Tel-Aviv Medical Center, Israel Transient Ischemic Attack (TIA) should be considered as an emergency and work-up has to be done within 24 hours like acute unstable angina pectoris. It is known that about 23% of stroke are preceded by TIA.Several studies have shown that the risk of subsequent stroke in the first 2 weeks after a TIA is about 1% per day. In 2 published well conducted studies, EXPRESS (P. Rothwell) and SOS_TIA (P. Amarenco) it was shown that very early management in a TIA clinic will reduce the risk of subsequent stroke by 80% at 3 months. Therefore, workup evaluation has to be performed with in 24 hours in a dedicated organized structure. Several stroke registries reported that carotid stenosis is the cause of embolic stroke in about 25%-30% of all ischemic strokes. Current guidelines recommend immediate intervention either by carotid endarterectomy (CEA) or stenting (CAS) in patients with symptomatic carotid stenosis greater than 50%. Carotid duplex is a reliable, non-invasive, accessible tool for evaluation of carotid stenosis with very high level of accuracy. Therefore, carotid duplex should be the first line tool for rapid evaluation of every patient with TIA in order to detect a potential treatable carotid stenosis for stroke prevention. It is recommended to establish an Acute TIA clinic equipped with immediate accessible Duplex device to enable rapid evaluation of the carotid system in order to detect potential treatable carotid stenosis. Management of Intracerebral hemorrhage - update NATAN BORNSTEIN Tel-Aviv University, Sackler Faculty of Medicine, Israel Stroke Unit at Tel-Aviv Medical Center, Israel Intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes and is one of the major causes of strokerelated death and disability. After the initial hemorrhage, further bleeding and edema contribute to secondary damage and worsened outcomes. As such, goals of previous and ongoing trials are to prevent continued bleeding, as well as mitigate the impact of cerebral edema. Although no trials have shown a definite functional outcome benefit with a given intervention, much progress has been made recently. This review focuses on recent developments that inform the acute management of ICH. The lecture will review the progress made in the treatment of ICH and the new American Stroke Association guidelines( June 2015) 12

National Acute Stroke Israeli registry-nasis NATAN BORNSTEIN Tel-Aviv University, Sackler Faculty of Medicine, Israel Stroke Unit at Tel-Aviv Medical Center, Israel Stroke is a major cause of long-term adult disability, death and health care costs worldwide. This overwhelming burden on global health necessitates ongoing improvements in stroke management. Indeed, considerable progress in acute stroke care is evident nowadays thanks to urgent triage, multimodal CT or MRI based brain imaging, and endovascular reperfusion therapy. Randomized controlled trials (RCTs) have been rightly put in top of hierarchies of evidence for assessing the efficacy of therapeutic interventions. RCT, however, have also some inherent shortcomings that leave a clear need for complimentary registry research. While efficacy is best evaluated in RCTs, observational data collected in registries and including unselected patients populations are most useful for the appraisal of clinical effectiveness in heterogeneous populations of patients. Registries provide real-world views of clinical practice contributing to an ongoing process of quality improvement and education. They are useful for determining the presence of disparities in healthcare delivery among subpopulations, including racial and ethnic minorities. Trends in the utilization of novel technologies and quality of care can be easily assessed. In Israel, the National Acute Stroke Israeli (NASIS) registry founded in 2004 is conducted triennially during 2-month periods and includes all adult patients with acute stroke or TIA hospitalized in all medical centers nationwide. The NASIS registry is a valuable source of information which serves as the basis for research on specific areas of stroke and provides details on secular trends in risk factors, stroke characteristics, management and outcomes. 13

14 NOTES

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