Vessel occlusion, penumbra, and reperfusion – translating theory to practice

Read it and weep, for our doctors still have no idea what is going on with stroke or how to treat it.
http://journal.frontiersin.org/Journal/10.3389/fneur.2014.00194/full?utm_source=newsletter&utm_medium=email&
Bruce C. V. Campbell^1,2*, 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.