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SUMMARY:Mechanism-based therapy of stroke - Professor Jean-Claude Baron\, 
 Department of Clinical Neurosciences\, Cambridge
DTSTART:20090930T101500Z
DTEND:20090930T104500Z
UID:TALK18698@talks.cam.ac.uk
CONTACT:Hannah Critchlow
DESCRIPTION:This talk is part of the Cambridge Clinical Neuroscience and M
 ental Health Symposium\, 29th - 30th September 2009 at West Road Concert H
 all. This event is free to attend for cambridge neuroscientists although r
 egistration is required. To register\, and for further information\, pleas
 e visit: http://www.neuroscience.cam.ac.uk/cnmhs/\n\nAbstract: Preventing 
 death and limiting handicap from stroke are major goals that can be achiev
 ed only if the pathophysiology of early infarct expansion is properly unde
 rstood. Seminal primate studies showed that following occlusion of the mid
 dle cerebral artery (MCA) - the most frequent stroke subtype -\, local tis
 sue fate depends on the severity of hypoperfusion and duration of occlusio
 n\, with the MCA territory being initially in a functionally impaired but 
 viable\, i.e.\, “penumbral”\, state which inexorably progresses to inf
 arction unless reperfused early enough.. \n\nPhysiological imaging has tra
 nslated this knowledge in man and confirmed the presence of extensive penu
 mbra early after stroke. These observations underpinned key trials of thro
 mbolysis\, now approved in clinical routine up to 3hrs after stroke onset 
 – hopefully soon to be extended to 4.5hrs.  However\, only patients who 
 are likely to benefit should ideally be exposed to its risks. Imaging has 
 shown considerable pathophysiological heterogeneity from patient to patien
 t\, largely unpredictable from elapsed time or clinical presentation. Acco
 rdingly\, imaging-based diagnosis is rapidly becoming an essential compone
 nt of stroke assessment\, replacing the clock by individually customized m
 anagement. For instance\, diffusion- and perfusion-MR and CT-based perfusi
 on imaging are increasingly being used\, and have undergone formal validat
 ion against established but clinically non-accessible quantitative techniq
 ues. Their clinical utility is currently being tested in controlled trials
 . As penumbra can be present up to 16hrs after onset in some patients\, ap
 propriate patients who may still benefit from treatment may be identified 
 by imaging beyond currently accepted time limits.   \n\nSecondary physiolo
 gical disturbances such as hypotension\, hyperglycaemia and hypoxia may al
 so cause infarct expansion\, and clinical benefits from preventing them is
  currently emerging\, underpinning the established benefit from early admi
 ssion to acute stroke units. Early brain swelling may expose to “maligna
 nt” MCA infarction\, which causes death in over 80% of the cases and sev
 ere disability in the survivors. By raising intracranial pressure\, vasoge
 nic edema is a major cause of secondary drops in cerebral perfusion pressu
 re and hence perfusion in situation of persistent occlusion. Based on this
 \, early surgical brain decompression has been shown in RCTs to markedly r
 educe mortality\, but also disability in the survivors. Finally\, there is
  currently no place for neuroprotection in the clinical setting as all RCT
 s have so far failed\, which may in part reflect the inclusion of heteroge
 neous samples instead of targeting subsets matching the drug’s presumed 
 mode of action. \n\nSuggested reading:\n1.	Muir KW\, Buchan AM\, von Kumme
 r R\, Rother J\, Baron JC. Imaging of Acute Stroke. Lancet Neurol.\, 2006\
 ; 5: 755-768.\n2.	Moustafa RR\, Baron JC. Pathophysiology of Ischaemic Str
 oke: Insights from Imaging and Implications for Therapy and Drug Discovery
 . Brit. J. Pharmacol. 2008\; 153(S1):S44-S54.\n3.	Donnan GA\, Baron JC\, M
 a H\, Davis SM. Penumbral selection for trials of acute stroke therapy. La
 ncet Neurol.\, 2009\; 8: 261–69.\n\nBiosketch: Jean-Claude Baron receive
 d his medical education and trained in Medical Physics and Neurology at th
 e University of Paris. He was research fellow at Harvard University in 197
 6-77\, Head of Neurosciences research at CEA Orsay in 1978-1988\, and Head
  of the INSERM Neuroscience Unit and Scientific Director of the PET labora
 tory at the University of Caen\, France in 1988-2000. In 2000 he was appoi
 nted Chair of Stroke Medicine\, Dept of Clinical Neurosciences\, Universit
 y of Cambridge\, and Neurology Consultant at Addenbrooke's Hospital\, Camb
 ridge\, UK. He is member of the Executive Committee and Chair of the PET U
 sers Group of the Wolfson Brain Imaging Centre\, University of Cambridge. 
 His main area of research is the pathophysiology of stroke and the mechani
 sms of functional recovery\, assessed mainly with imaging methods. His wor
 k is mainly supported by MRC\, the Stroke Association and the EU.\n\n
LOCATION:West Road Concert Hall
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