Extended Window of Treatment in Acute Stroke Is Not for All—Brain Imaging Is Critical
Published on: March 29, 2018
The mortality rate associated with stroke has markedly declined over the past two decades from the second to the fifth most common cause of death in the U.S. Much of this improvement has been attributed to improvements in stroke systems of care, which have centered on reducing time to neurological evaluation and treatment including increasing community awareness, reduced EMS transport time, reduced time to acute brain imaging, and reduced time to administration of IV tPA when patients present in the zero to 4.5 hour time window. Since the introduction of tPA as an acute stroke therapy in 1995, several clinical trials in acute stroke yielded negative or mixed results, including in the area of endovascular thrombectomy (EVT). This was the landscape of acute ischemic stroke therapy until 2015.
After the success of five recent EVT trials within the first six hours from symptom onset, The DAWN and the DEFUSE 3 trials demonstrated the benefits of EVT in the six to 24 hour time window when patients were carefully selected utilizing additional imaging to identify individuals who have a large vessel occlusion (LVO) with small core infarction in the presence of a larger region at-risk of ischemic injury. These two studies fueled changes in the recent AHA/ASA Ischemic Stroke Guidelines. More importantly, the studies have led to questions regarding one of the central tenets of acute stroke care, namely “time is brain.” This is evident in the comments made by Gregory Albers, MD, professor of neurology at Stanford University Medical Center in a recent Washington Post article wherein he asserts, “while some brain tissue dies quickly after a stroke begins, in most patients, collateral blood vessels usually take over feeding a larger area of the brain that is also starved for blood and oxygen, giving doctors many more hours to save that tissue than they previously believed.”
The relationship between the time duration from symptom onset to irreversible ischemic injury in the brain and the resulting time window for individual treatment is complex, largely depending on the pre-ischemia status of cerebral collateral circulation and its capacity to rapidly react to ischemia. Cerebral collateral status, therefore, must be determined as fast as possible, and the only way to determine it is from imaging, which should always be obtained. The recent media statement potentially risks inadvertently reversing all of the efforts of the stroke community, which for decades, have strived to reduce the time to evaluation and treatment by now giving providers a reduced sense of urgency due to the expanded treatment window. What these two pivotal trials highlight is that ischemic stroke indeed is a heterogeneous disease comprised of primarily two cohorts, those in whom evolution of stroke is rapidly time dependent and are dependent on revascularization with IV tPA and those likely to be minority in whom stroke progression is much slower due to the presence of functional collaterals in whom the revascularization window is much longer. However, this information is rarely known a priori and thus there needs to be a continued focus on reducing the time to arrival to hospitals providing IV tPA treatment and capable of imaging determining tissue at risk in those unfortunate to arrive late. The suggestion that the sense of urgency can be reduced is misleading and dangerous because it may reverse the positive impact of acute stroke care of the past two decades.