http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00194/full?utm_source=newsletter&utm_medium=email&
Bruce C. V. Campbell1,2*, Geoffrey A. Donnan2 and Stephen M. Davis1
- 1Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
- 2Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
The management of ischemic stroke is at a critical
juncture. Administration of intravenous tPA is currently restricted to
within 4.5 h from stroke onset with several trials in longer time
windows proving neutral (1, 2). Revascularization success with tPA in major vessel occlusion is widely recognized as suboptimal (3).
Alternative thrombolytic agents with theoretical efficacy advantages
such as tenecteplase and desmoteplase are yet to show benefit in phase 3
trials. The promise of endovascular therapy has also yet to translate
into positive randomized trials (4–6),
although a new generation of devices is currently being studied. While
it is possible that these therapeutic approaches are simply ineffective,
the heterogeneity of stroke pathophysiology is likely to be
contributing to the neutral results we often observe.
Imaging selection has been proposed as a means of
reducing heterogeneity by identifying patients with the potential to
benefit from revascularization and therefore enhancing the probability
of success in trials of new therapies. However, whether it is sufficient
to demonstrate an occluded artery as the target or to also require
evidence of salvageable downstream tissue has been debated. The recent
announcement of neutral results in DIAS 3 (7),
a trial that compared desmoteplase versus placebo 3–9 h after stroke
onset in patients with vessel occlusion, without reference to downstream
tissue status other than what was visible on non-contrast CT, will no
doubt further stimulate this discussion. It is, therefore, salient to
consider the current methods to identify salvageable ischemic penumbra
and the potential value of commonly used surrogates for clinical
outcome, chiefly reperfusion, recanalization, and infarct growth.
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