Reversing Stroke in the 2010s

Marc Fisher MD Kennedy Lees MD Section Editors: Only months from now, another decade will dawn on stroke research with a dearth of therapeutic innovations developed to reverse the devastating effects of acute ischemic stroke. Despite generations of academic research investigators and associated industry collaborations, our clinical trials have marked each decade by successive eras of failed treatments with only a few exceptions. The recent publication of results from the Desmoteplase In Acute ischemic Stroke (DIAS)-2 trial provides important lessons that may hold the clues to reversing stroke in the 2010s.1 DIAS-2 was undoubtedly a landmark study, incorporating sophisticated trial design with the latest innovations in CT and MRI techniques to confirm benefit of a novel fibrinolytic agent to treat acute ischemic stroke up to 9 hours after symptom onset. The potential for another stroke therapy in clinical practice was replaced by collective introspection on the determinants of yet another negative trial after earlier positive results.2 Once again, an article starts by underscoring the limited treatment options for stroke, details the saga of an elaborate yet negative clinical trial, and ends by noting that the “criteria to optimize the selection and treatment outcomes” remain elusive. The perpetual motion of academia echoes the familiar chorus that further studies are indicated, but perhaps this philosophical juncture provides an opportunity to heed important lessons learned. An endless list of reasons can be cited for failure, like in the litany of articles on neuroprotective trials or the thoughtful considerations of Stroke Therapy Academic Industry Roundtable (STAIR),3,4 yet most are difficult to prove or easily remedy without a comprehensive overhaul. Overall, DIAS-2 teaches us that the traditional approaches to stroke therapy may require revision of our currently engrained textbook approach to key variables such as time, imaging of the penumbra, ischemic pathophysiology, …