By John Fauber
Milwaukee Journal Sentinel
Copyright 2008 Journal Sentinel Inc.
MILWAUKEE — As her car raced to the hospital, Elizabeth Weiler lay in the back seat unable to move or talk.
No one knew what was wrong with her. At age 25 she seemed too young to be having a stroke.
As Jim Cody, 69, lay in his hospital bed recovering from knee replacement surgery, a tiny fat particle traveled to his brain. Soon he was unable to move or talk.
What Cody and Weiler didn’t know was that they were about to become the latest remarkable cases in a burgeoning field of medicine that holds great promise. Stroke treatments have been limited, and strokes persist as the No. 1 cause of severe long-term disability and No. 3 cause of death in the country.
Weiler and Cody also would be patients whose strokes would be treated using novel but unproven devices that go directly into the brain to eliminate clots and restore blood flow.
Convinced by a growing number of miraculous anecdotal accounts and limited research, more doctors are using the devices. But rigorous evidence proving that patients are more likely to survive or regain everyday function such as speaking or walking has yet to be established.
“We are a little nervous about what is going on,” said Walter Koroshetz, a physician with the National Institutes of Health. “These are invasive procedures. The field is a bit struck now with new devices coming out more rapidly than we can learn how to use them to benefit patients.”
Yet doctors often are faced with an intolerable dilemma: Do nothing and let the patient die or suffer serious disability, or use an unproven treatment that might help, but also might do no good, or might make things worse.
Doctors say they have used the devices to open arteries in patients who could not talk and moments later they began speaking on the table.
“You can’t turn away from them,” said Cameron McDougall, a stroke researcher and chief of endovascular neurosurgery at Barrow Neurological Institute in Phoenix.
Lots of research
Just three years ago there were few tools to treat a stroke in its early stages. Today, doctors reach for out any number of devices that can be threaded up to the brain to eliminate a clot.
The devices have emerged, in part, because they extend the limited treatment window for the standard therapy - the intravenous clot-dissolving drug tPA. Less than 5% of people having strokes get to the hospital within the mandatory three hours in which tPA can be used as an IV infusion.
In a crude sense, these new devices mimic everyday activities:
* One uses suction to remove the clot like a vacuum.
* Another has a corkscrew shape to pull out the clot like a cork from a wine bottle.
* Still another special probe uses ultrasound to help break the clot up into smaller, harmless pieces.
Another technique soon to be tried in Milwaukee and around the country is the use of a catheter to deliver synthetic snake venom directly to the brain in patients who get to the hospital after three hours.
At the same time, doctors also are using catheters to go into the brain and deliver tPA, which works like a drain cleaner, clearing the plumbing of the brain.
“Every (medical) company I know has a device they are working on,” said Beverly Aagaard-Kienitz, an assistant professor of neuroradiology at the University of Wisconsin-Madison. The UW Hospital has performed about 25 inside-the-artery stroke procedures in the last three years.
The U.S. Food and Drug Administration approves drugs and devices in different ways.
For drugs to be approved, randomized clinical trials must show that the agents are safe and effective; the drugs must improve outcomes in patients, said Koroshetz, deputy director of the National Institute of Neurologic Disorders and Stroke.
Devices also must be proven safe and effective, but approval can be granted merely by showing that the device performs a task such as removing a clot. And removing a clot doesn’t always mean the patient will do better, especially if it is accomplished after the brain has been damaged.
And in some instances, restoring blood flow to dead areas of the brain can cause bleeding or swelling, Koroshetz said.
“It can kill you,” he said
In an effort to find the most effective treatments, NIH now is funding a 900-patient nationwide trial.
The trial will test standard intravenous tPA against different inside-the-brain methods plus standard IV drug treatment. Disability will be a main measure of the trial.
Froedtert Hospital is one of the centers in the trial.
The hospital also recently took part in a small trial of the Penumbra System, which uses suction to remove the clot. The device can be used up to eight hours after the onset of symptoms.
Last month, research involving 125 patients treated with Penumbra showed that blood flow was restored in 82 percent of blood vessels treated with the device. The research was presented at the American Stroke Association annual meeting.
Serious side effects, including two deaths, occurred, although none of the events was due to the device itself, said researcher McDougall, of the Barrow Neurological Institute.
“This device isn’t perfect,” he said. “It’s progress. We are getting tantalizingly close.”
Experiment that worked
On April 18 last year, Jim Cody was lying in his bed at Columbia St. Mary’s Hospital Columbia recovering from knee replacement surgery. He had just finished breakfast when he lost the ability to speak or move.
Cody’s stroke was caused by a fat particle that had traveled from his leg to the left middle cerebral artery.
Cody’s wife, Judy, said doctors at the hospital told her they could not treat his stroke there. But when it was learned that Froedtert was doing a clinical trial with the Penumbra device, he was transferred there.
Doctors at Froedtert warned that the treatment was experimental and had risks. Still, she signed the approval.
“It was either take the risk or have Jim become a vegetable or die,” she said. “We had nothing left to lose.”
Since the treatment, he has regained use of much of the right side of his body, although his arm and leg remain weak.
He can speak, but he talks slowly and his words are slurred.
“I have to talk slow,” he said. “If I talk fast garbage comes out.”
Cody, of Greenfield, works out regularly at his health club and is hoping to play golf this spring.
His eyes tear up when he talks about the treatment.
“Thank God,” he said. “I’d be dead.”
Between 50% and 80% of those who have a blockage in the middle cerebral artery will die if it is not reopened, said Brian-Fred Fitzsimmonds, the interventional and vascular neurologist who treated Cody at Froedtert.
Though Cody survived, he still suffered some brain damage because the procedure did not start until five or six hours after his symptoms began.
If the treatment had been started three hours earlier, there would have been little disability, said Fitzsimmonds, an assistant professor of neurology and neurosurgery at the Medical College of Wisconsin.
Over the last two years, doctors at Froedtert have used inside-the-brain treatments on more than 75 patients, Fitzsimmonds said.
“It’s good that these devices are being expedited to market, but the downside is once they are approved the companies lose interest in proving they improve outcomes (in patients),” Fitzsimmonds said.
A stroke at 25
Elizabeth Weiler doesn’t remember much from the day she had her stroke in August 2006.
She fell to floor in the living room of her New Berlin home.
The left side of her face was moving up and down.
Weiler’s sister, Jeanne Weiler, asked how she could do that.
“She didn’t answer me,” Jeanne Weiler said.
Jeanne Weiler and her boyfriend put Elizabeth in the back of her car and drove to the Wheaton Franciscan Healthcare Urgent Care Center in Wauwatosa.
At first, emergency medical personnel thought she was on drugs, Jeanne Weiler said.
Her sister then was transferred to Froedtert by ambulance.
Doctors there immediately began IV tPA and a couple of hours later threaded a catheter to her brain and began administering the drug at the site of the clot and also began delivering ultrasound energy into the clot.
“It took us about two hours and it opened,” said Osama Zaidat, director of the neuro interventional program at Froedtert.
There is about an 80% death rate in people Weiler’s age who have that kind of stroke, said Zaidat, an associate professor of neurology and neurosurgery at the Medical College.
It is believed that Weiler’s stroke was caused by several factors, including smoking, taking birth control pills, which is a known stroke risk, and having a congenital heart condition that can increase stroke risk in some people. Weiler, who now has a 5-month-old son, has since quit smoking and gone off the pill.
Snake venom in trial
In the coming weeks, doctors at Aurora St. Luke’s Medical Center expect to push the stroke treatment effort even further.
The hospital is part of a national clinical trial that will use synthetic snake venom to treat stroke patients who get to the hospital more than three hours after their symptoms occur. The drug, Alfimeprase, first isolated from the venom of the southern copperhead snake, now is made synthetically. It will be administered at the site of the clot using a catheter.
Unlike tPA, which can cause serious bleeding in the brain in some patients, it is believed that Alfimeprase will dissolve clots and then become inactivated after it moves down the bloodstream, thereby reducing the risk of bleeding in the brain.
St. Luke’s expects to treat up to 10 patients with the drug, said Arvind Ahuja, a neurosurgeon and director of the stroke center at the hospital.
In 1999, Ahuja was co-author of one of the few studies showing that going into the brain to deliver a clot-dissolving drug up to six hours after the onset of symptoms could significantly reduce disability in stroke patients.
“When I started we didn’t have all the toys,” he said.
Doctors still don’t have the ultimate solution for treating strokes, but, he said, he is convinced that the devices and drugs that now are available are saving lives and reducing disability.
“My approach is to say, ‘If it was my brother or father, what would I do?’ If there was a chance, I would do it.”
Seven years ago he got a chance to put that philosophy into action when his father-in-law, P.K. Lahiri, also a doctor, suffered a stroke.
Ahuja delivered tPA at the site of the clot.
His father-in-law, who could not speak or move his right side, improved dramatically, Ahuja said.
“He worked for another five years,” he said.
His father-in-law, 70, now is retired, and leads an active life.
“He drives our kids to school,” Ahuja said. “He plays tennis every Sunday.”