Extended Window of Treatment in Acute Stroke Is Not
for All—Brain Imaging Is Critical
By Ryan Hakimi, DO, MS (Division of Neurology, Department of Medicine, University of South Carolina-Greenville Health System, Greenville,
SC) on behalf of the American Society of Neuroimaging; David S Liebeskind, MD (Department of Neurology, David Geffen School of Medicine,
UCLA, Los Angeles, CA); Tatjana Rundek, MD, PhD (Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL); and
Andrei V. Alexandrov, MD (Department of Neurology, University of Tennessee Health Science Center, Memphis, TN)
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.
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