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MRI analysis could prevent brain
damage from stroke, Stanford study finds
Stanford, CA, November 1: A stroke victim
arrives in the emergency room and, within minutes, the doctor must make a
decision: Should drugs be administered to open up the blocked blood vessel and
prevent further brain damage? Or is this patient at high risk for suffering a
brain hemorrhage if the blocked vessel is opened?
Greg Albers, MD, director of the Stanford Stroke
Center, and his team report in the November issue of Annals of Neurology that
new magnetic resonance imaging techniques can discriminate between stroke
patients who are likely to benefit from a stroke medication - even when
administered beyond the currently approved three-hour time window - and those
for whom treatment is unlikely to be beneficial and may cause harm.
For years, Albers, professor of neurology and
neurological sciences at the
Stanford University School of Medicine, has been using new MRI techniques to
visualize the damage from stroke while it is actually happening. His goal is to
differentiate brain tissue that is potentially salvageable from tissue that is
already irreversibly injured by a stroke. As his group accumulated MRI scans of
stroke patients, they noticed patterns that seemed to identify which patients
were most likely to benefit from opening up blocked blood vessels.
"One of the criticisms was that these detailed
brain images looked beautiful and interesting, but there was no proof that they
should be used to influence treatment or that they would result in improved
outcomes," said Albers. "How do you know that these MRI patterns can predict
whether the therapy is likely to be beneficial?"
To answer these questions, Albers and his
colleagues designed a study to see if obtaining an MRI profile from stroke
patients before beginning treatment could identify which patients would benefit
from clot-dissolving drugs administered between three and six hours after stroke
onset and which patients were unlikely to benefit, or potentially might be
harmed. Albers was the principal investigator of the three-year study, which was
funded by National Institutes of Health and included sites in the United States,
Canada and Belgium.
Strokes result from decreased blood flow to an
area of the brain. Once brain cells are deprived of oxygen and nutrients carried
in the blood, they begin to malfunction. Symptoms of a stroke include weakness,
paralysis or numbness on one side of the body, problems speaking or loss of
vision.
About 85 percent of strokes are caused by clots
blocking blood vessels in the neck or brain. In 1996, the clot-busting drug tPA
was approved by the U.S. Food and Drug Administration. The drug can restore
blood flow to regions of the brain injured by stroke. The study that led to its
approval indicated that tPA should be used only in patients who were treated
within three hours of the onset of stroke symptoms and who also had a CT scan
indicating there was no bleeding in the brain.
Despite the need for early intervention, less
than a quarter of stroke patients make it to a hospital within three hours.
Albers has been trying to pin down what factors might allow the tPA treatment
window to remain open longer.
In the late 1990s, Albers was one of the
principal investigators of a study that attempted to extend the time window for
this therapy to six hours based on the CT scan approach. Unfortunately, this
study failed. The researchers suspected that this failure occurred because CT
scans were unable to differentiate patients who could benefit at three to six
hours from those who did not benefit.
"CT scans do not demonstrate how much brain
tissue is still salvageable and how much is irreversibly injured," said Albers.
"Therefore, with only the CT image it is difficult to know for any given patient
whether opening the blocked vessel is going to be a good thing, a bad thing or
have no effect. If there is already a large area of severely injured tissue,
opening up a blocked vessel can result in serious, even fatal, brain
hemorrhage."
Standard CT scans can differentiate strokes
caused by ruptured blood vessels from ones caused by blocked vessels, but the
location and extent of the brain injury is typically not evident for at least
eight hours after symptoms begin. An MRI can immediately demonstrate areas of
brain injury, outline areas of critically reduced blood flow and clarify which
blood vessel is blocked. These subtleties can determine whether opening the
vessel is likely to be beneficial, Albers said.
Patients with radically different situations in
their brains can have identical symptoms when brought into the emergency room.
Two study participants, for example, were both unable to speak and were
paralyzed on their right side. Although their CT scans looked the same, their
MRI patterns were completely different; one revealed minimal, irreversible
injury but considerable tissue at risk while the other revealed that extensive,
severe injury had already occurred.
The study's original hypothesis was that MRI
patterns would allow the patients to be divided into subgroups based on how much
brain tissue was already damaged and how much had insufficient blood flow.
Patients whose scans indicated substantial areas of insufficient blood flow but
little permanent damage were predicted to benefit most from tPA administration.
The drug does not repair existing damage.
The team enrolled 74 consecutive stroke cases
that met various criteria, including having the treatment administered between
three and six hours of symptoms onset. The team obtained MRI scans for each
patient immediately before, and approximately four hours after, administration
of intravenous tPA. No other study has performed these advanced MRI techniques
immediately before and so soon after treatment.
In this study, the MRI results were not used to
make treatment decisions. The scans were analyzed later at Stanford and the
pre-treatment MRI patterns were compared to how the patients fared three months
later.
During the trial, the researchers discovered a
significant twist to their hypothesis. Three patients developed fatal cerebral
hemorrhage after tPA treatment. All three had a unique MRI pattern prior to
treatment and the successful opening of their blocked blood vessel after
treatment. This finding led the investigators to define a new profile that
predicts a high risk of dangerous bleeding in the brain following tPA therapy
for that subset of patients.
Still, for those patients who had a pattern
indicating that a favorable response to tPA was likely, the benefits of opening
the blocked vessel were dramatic. "Sixty-seven percent of these patients had a
major improvement in neurological function," Albers said. "This often meant the
difference between inability to speak with paralysis of one side of the body and
a complete, or nearly complete, recovery."
This is the first study to show that certain MRI
patterns predict a very good response upon opening the blood vessel and that for
other patterns, opening the vessel may have no beneficial effect or can even
cause harm. A 20-minute MRI scan has the potential to indicate who is likely to
benefit and who is not. "By having this additional information available, we
should be able to make a much more sophisticated decision about which therapies
are optimal for an individual patient, especially as you get into the longer
time windows," said Albers.
Albers is currently working with a team of
radiologists, physicists and programmers to optimize the software to analyze the
MRI blood flow scans. The goal is to broaden the technique so that it can
eventually be used in any hospital with an MRI machine, delivering prognostic
information in real time, so that "we won't have to treat stroke by a stopwatch
any longer," said Albers.
In addition to Albers, there were nine
researchers from Stanford involved in the study: Roland Bammer, PhD, assistant
professor of radiology; Anna Finley, MD, clinical assistant professor of
neurology; Wataru Kakuda, MD, visiting research associate in neurology;
Stephanie Kemp, social science research assistant in neurology; Maarten Lansberg,
MD, instructor in neurology; Michael Marks, MD, professor of radiology and chief
of interventional neuroradiology; Michael Moseley, PhD, professor of radiology;
Neil Schwartz, MD, professor of radiology, and Christine Wijman, MD, assistant
professor of neurology and neurological sciences.
Stanford University Medical Center integrates
research, medical education and patient care at its three institutions -
Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile
Packard Children's Hospital at Stanford. For more information, please visit the
Web site of the medical center's Office of Communication & Public Affairs at
http://mednews.stanford.edu.
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