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Which targets are relevant for therapy of acute ischemic stroke?
1Max Planck Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Köln, Germany.
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.
Insights
Early critical blood flow reduction causes most ischemic stroke infarcts, not delayed processes. Therapeutic strategies should target this initial hypoperfusion for better outcomes.
Area of Science:
- Neurology
- Neuroscience
- Medical Imaging
Background:
- Neuroprotection strategies show promise in animal models but yield disappointing results in human ischemic stroke.
- Early reperfusion via thrombolysis is the only current strategy to improve clinical outcomes in ischemic stroke.
- Discrepancies between experimental and clinical findings may stem from differing pathogenetic factors in infarction.
Purpose of the Study:
- To identify the specific tissue compartments contributing to final infarct volume in hemispheric stroke.
- To correlate early cerebral blood flow with final infarct size and composition.
- To inform the development of targeted neuroprotective therapies for ischemic stroke.
Main Methods:
- Positron emission tomography (PET) cerebral blood flow studies were performed within 3 hours of stroke onset.
- Magnetic resonance imaging (MRI) was used to delineate infarcts 2-3 weeks post-stroke in 10 patients.
- Analysis identified contributions of hypoperfused, penumbral, and initially perfused tissues to the final infarct.
Main Results:
- Critical hypoperfusion below the viability threshold constituted the largest proportion (mean, 70%) of the final infarct.
- Penumbral tissue contributed 18% and initially sufficiently perfused tissue 12% to the final infarct size.
- Early, severe hypoperfusion is the primary driver of rapid cell damage and infarction.
Conclusions:
- Early critical flow disturbance is the predominant cause of ischemic stroke infarction.
- Secondary pathobiochemical processes in less affected areas contribute minimally to the final infarct.
- Future therapies should target initially critically perfused tissue; functional imaging can aid patient stratification in clinical trials.