ARTICLE IN BRIEF
✓ MRI scans showed that patients who had a large area of damage — three hours after stroke — were less likely to benefit from tPA and were at greater risk for ICH.
MRI can help determine whether a stroke patient would benefit from the clot-busting drug tissue plasminogen activator (tPA), or risk intracerebral hemorrhage (ICH), according to a new study in Stroke, published online before print on June 14.
tPA is the only federally approved drug for acute stroke, yet only 5 percent of patients ever receive it. Early studies indicated that it is most effective and carries less risk of side effects if given within three hours of the onset of symptoms.
Now, doctors are trying to determine whether patients benefit from tPA if the delay could be extended to six hours. The main fear is ICH, a risk that seems to increase as time goes on.
Gregory W. Albers, MD, Maarten G. Lansberg, MD, PhD, and colleagues at Stanford University gave tPA to 74 stroke patients who arrived at the hospital more than three hours after symptom-onset. When they signed on for the study, the patients agreed to have a MRI diffusion-weighted imaging scan as well as a perfusion-weighted imaging scan before and immediately after intravenous tPA.
Seven patients, or 10 percent, had a hemorrhage. The before and after scans allowed the doctors to figure out who was most at risk for ICH — from a minor brain bleed to a fatal one.
Patients with diffuse tissue damage were the ones who should not have been given intravenous tPA. “The horse was out of the barn already,” said Dr. Albers, director of the Stanford Stroke Center and professor of neurology and neurosciences at Stanford University. “Those with a large area of damage would not benefit from tPA.”
When the clot-busting drug worked to restore blood to the oxygen-starved tissue, it made things worse for those patients with the largest lesions, Dr. Albers added.
“Reperfusion damage to the ischemic vessels may contribute to symptomatic intracerebral hemorrhage,” the authors wrote. In fact, three of the four patients with the largest tissue damage who responded to tPA actually had the most severe bleeds and died as a result, Dr. Albers said.
Those who did best had a mismatch of their scans: Patients with a small area of infarction as measured by diffusion imaging and those with a large area perfusion (meaning tPA did the job of opening the blocked vessel) did well. However, those with a large infarct who did not respond to the clot-busting drug fared better, leaving the blocked vessel unaltered.
“If you see a large lesion, it might not be a good idea to give tPA,” Dr. Albers said. While the risk for hemorrhage was 10 percent, the risk was close to 50 percent in those with large lesions and tPA opened the vessel.
“MRI can identify people who benefit from tPA between three to six hours,” said Dr. Albers. “And it helps predict who is at high risk for a brain hemorrhage.”
Traditionally, CT is performed in the early post-stroke hours. MRI would take too long if the window is three hours after stroke, Dr. Albers said, but if tPA is considered during hours three to six, MRI should be done to ensure that the damaged tissue can withstand a return of blood flow.
“Restoring blood flow can be dangerous if the tissue damage during the stroke has already broken down,” said George C. Newman, MD, PhD, chairman of neurosensory sciences and director of the Stroke Center at Albert Einstein Medical Center in Philadelphia. “When there is ongoing necrosis, successful re-perfusion is likely to cause a cerebral hemorrhage. Albers and his colleagues have figured out how to select out this high-risk group and that is important.”
S. Claiborne Johnston, MD, director of the Stroke Center at the University of California-San Francisco, agreed. “There is a suggestion that tPA is effective beyond three hours. But the risk for stroke is greater,” said Dr. Johnston. “Having a simple tool like MRI would be useful. However, we need confirmatory evidence from randomized trials.”
If doctors are pushing the envelope, a scan could be used to identify those who would not qualify for the treatment in the three- to six-hour extended window, and those who might, Dr. Johnston added. Dr. Albers agreed replication of the findings is needed.
In stroke, timing is critical. The longer the delay between symptom-onset and treatment, the less effective is tPA, Dr. Lansberg said. “When overall efficacy is less, it is important to know who is at high risk of bleeding.”
Dr. Newman added that high blood sugar is another risk factor for hemorrhage. “It's important to get a blood sugar reading immediately after the blood vessel is opened.”
• Lansberg MG, Thijs VN, Albers GW, et al., for the DEFUSE investigators. Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke. Stroke 2007; E-pub 10 June 2007.