W D Heiss1, A Thiel, M Grond, R Graf. 1. Max Planck Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Köln, Germany.
Abstract
BACKGROUND: The efficiency of various strategies of neuroprotection is well documented in animal experiments but is thus far disappointing in ischemic stroke, for which only early reperfusion induced by thrombolysis has improved clinical outcome. This discrepancy between expectation from experimental research and clinical reality may be related to differences in the pathogenetic factors contributing to infarction. SUMMARY OF COMMENT: Positron emission tomography cerebral blood flow studies within 3 hours of onset were used to identify the various compartments of the infarct outlined on MRI 2 to 3 weeks after a hemispheric stroke in 10 patients. Critical hypoperfusion below the viability threshold accounted for the largest proportion (mean, 70%) of the final infarct, whereas penumbral tissue (18%) and initially sufficiently perfused tissue (12%) were responsible for considerably smaller portions of the final infarct. CONCLUSIONS: These results indicate that early critical flow disturbance leading to rapid cell damage is the predominant cause of infarction, while secondary and delayed pathobiochemical processes in borderline or initially sufficiently perfused regions contribute only little to the final infarct. Therefore, emerging therapeutic strategies should be targeted to the initially critically perfused tissue subcompartments. Clinical drug trials might benefit from stratification of patients for target tissue compartments applying functional imaging.
BACKGROUND: The efficiency of various strategies of neuroprotection is well documented in animal experiments but is thus far disappointing in ischemic stroke, for which only early reperfusion induced by thrombolysis has improved clinical outcome. This discrepancy between expectation from experimental research and clinical reality may be related to differences in the pathogenetic factors contributing to infarction. SUMMARY OF COMMENT: Positron emission tomography cerebral blood flow studies within 3 hours of onset were used to identify the various compartments of the infarct outlined on MRI 2 to 3 weeks after a hemispheric stroke in 10 patients. Critical hypoperfusion below the viability threshold accounted for the largest proportion (mean, 70%) of the final infarct, whereas penumbral tissue (18%) and initially sufficiently perfused tissue (12%) were responsible for considerably smaller portions of the final infarct. CONCLUSIONS: These results indicate that early critical flow disturbance leading to rapid cell damage is the predominant cause of infarction, while secondary and delayed pathobiochemical processes in borderline or initially sufficiently perfused regions contribute only little to the final infarct. Therefore, emerging therapeutic strategies should be targeted to the initially critically perfused tissue subcompartments. Clinical drug trials might benefit from stratification of patients for target tissue compartments applying functional imaging.
Authors: Victoria E O'Collins; Malcolm R Macleod; Susan F Cox; Leena Van Raay; Elena Aleksoska; Geoffrey A Donnan; David W Howells Journal: J Cereb Blood Flow Metab Date: 2010-10-27 Impact factor: 6.200
Authors: Reinoud P H Bokkers; Daymara A Hernandez; José G Merino; Raymond V Mirasol; Matthias J van Osch; Jeroen Hendrikse; Steven Warach; Lawrence L Latour Journal: Stroke Date: 2012-03-15 Impact factor: 7.914
Authors: Daymara A Hernandez; Reinoud P H Bokkers; Raymond V Mirasol; Marie Luby; Erica C Henning; José G Merino; Steven Warach; Lawrence L Latour Journal: Stroke Date: 2012-02-16 Impact factor: 7.914
Authors: Nora Sandu; Jan Cornelius; Andreas Filis; Belachew Arasho; Miguel Perez-Pinzon; Bernhard Schaller Journal: Expert Rev Cardiovasc Ther Date: 2009-10