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Stroke: Every Second Counts

A blockage in a tiny artery. A rip in a blood vessel wall. Stroke begins in small, silent ways — with potentially  life-shattering consequences. Suddenly, millions of neurons and billions of brain-cell connections are at risk. Memories can be lost, speech fraught and the ability to walk impaired. No wonder “brain attacks” are America’s fifth-leading cause of death and a major cause of serious disability. Yet many of the 795,000 Americans who have a stroke each year arrive at the hospital too late to receive advanced, brain-saving treatments.

Fast action — by those at the scene when someone is having a stroke and by hospital health care practitioners — makes all the difference. Just ask Prad Sabharwal, 58, who arrived at the hospital minutes after the first signs of stroke struck on a November morning in 2015. “My right hand went numb, then my right arm and leg stopped working,” recalls Sabharwal, an investment banker who lives with his family in a historic neighborhood in St. Louis. “It was such a weird feeling — no pain or confusion, but I couldn’t control my limbs.”

He fumbled for the phone, managing to call his wife, Kelly. “As soon as I heard his voice I knew something was wrong,” she says. “I called 9-1-1 and headed home. The right side of Prad’s face was drooping, and his speech was slurred. He couldn’t even squeeze my hand.” Within minutes, Sabharwal was in an ambulance headed to Barnes-Jewish Hospital.

According to the Centers for Disease Control and Prevention, stroke kills more than 6,000 people each year in Missouri and Illinois alone.

“In stroke, time equals brain,” explains emergency-medicine specialist Peter Panagos, MD, FACEP, FAHA, co-director of the Washington University and Barnes-Jewish Hospital Stroke Network — a collaboration of St. Louis-area hospitals and emergency-medicine responders aimed at streamlining and improving stroke care. “Call 9-1-1 if you suspect that you or someone near you is having a stroke,” Panagos says. “Don’t hesitate, and don’t drive to the hospital yourself. You are wasting valuable time. Paramedics begin preparations for stroke evaluation in the ambulance, and they call ahead to the hospital so the stroke team is ready. That makes a big difference.”

Sabharwal’s case is a prime example of the importance of fast action.

As the ambulance driver negotiated traffic, paramedics assessed Sabharwal’s condition and alerted the stroke-care team at Barnes-Jewish Hospital. Bypassing the assigned bed in the emergency department, the normal destination for most arrivals by ambulance, first responders wheeled Sabharwal directly to one of the hospital’s computed tomography (CT) scanners, where a team of doctors, nurses and technicians simultaneously scanned his brain, took his vital signs, gathered data about his symptoms, drew and tested his blood, and prepared him for treatment. Within minutes of his arrival at the hospital, Sabharwal received a drug that broke up the clot impeding blood flow to his brain. Then a neurointerventionalist removed the pieces of the clot by threading a very small tool through blood vessels from Sabharwal’s groin to the stroke’s epicenter in his brain. “In less than two hours, Prad was out of surgery and talking to me,” Kelly says. “He could squeeze my hand. Today, he has no after-effects.”

Door to needle — and beyond

Every day, stroke specialists at academic medical centers across the U.S. push the boundaries of medicine to improve treatment of ischemic strokes, which involve a blocked blood vessel and account for 87 percent of all strokes, and hemorrhagic strokes, in which a blood vessel leaks or ruptures. At Barnes-Jewish Hospital, one notable advance stands out: The stroke team has applied the automobile industry’s lean manufacturing principles to streamline its door-to-needle time — the gold-standard measure of how fast people with ischemic strokes receive the medication needed to break up blood clots.

The potential benefits of this drug, called tPA, include decreased neurological damage and disability, and a faster recovery. But tPA must be given within four and a half hours of the onset of ischemic stroke symptoms to be effective. In a widely cited 2012 study published in the journal Stroke, Washington University physician-researchers demonstrated how they reduced median door-to-needle time from 60 to 39 minutes. The team employed process changes such as having paramedics deliver people with stroke directly to the CT scanner and having health care practitioners perform tests and evaluations of a stroke patient in parallel, rather than one at a time.

“We are always looking for ways to improve. Our door-to-needle time is now under 30 minutes for many patients and as low as 10 minutes in some cases,” says neurologist Jin-Moo Lee, MD, PhD, a Washington University physician at Barnes-Jewish Hospital who specializes in ischemic stroke and intracerebral hemorrhage. “As our times improve, more patients receive tPA who might otherwise have arrived at the hospital too late to be evaluated and treated before the treatment window closes. And more people with ischemic strokes involving large blood clots can undergo endovascular thrombectomy to remove the clot.”

Before prescribing tPA, physicians must first rule out other potential causes of stroke-like symptoms, including low blood sugar or a brain tumor or brain bleed. “There are probably 100 things that have to be done before we can determine if someone is eligible for tPA,” says neurologist Andria Ford, MD, MSCI, director of the Barnes-Jewish Hospital emergency department’s acute stroke service.  To help facilitate this decision-making process, Ford says, “we take assessment and treatment to patients instead of moving them around in the emergency department.” By way of example, she notes, “We brought in a machine to analyze blood instead of sending samples to the central hospital lab. We’ve recruited the emergency-department pharmacist to prepare tPA, and we have an emergency-department social worker available to talk with the family to learn when stroke symptoms began.”

The result? The median door-to-needle time at  Barnes-Jewish Hospital is now less than 37 minutes, among the fastest in the nation. The national average is as high as 96 minutes, according to the American Stroke Association. And 100 percent of people who arrive at Barnes-Jewish Hospital within two hours of the onset of an ischemic stroke receive tPA within the three-hour window, compared to 91 percent at other hospitals throughout Missouri.

Care for complex cases

Barnes-Jewish Hospital treats about 1,600 people with stroke per year, including approximately 150 people who require advanced endovascular neurointervention to restore the flow of oxygen-rich blood to brain cells by grabbing and removing those clots. Thanks to the stroke network, many people with large strokes arrive at  Barnes-Jewish after receiving tPA at other St. Louis-area hospitals that don’t offer endovascular procedures; others are transported by helicopter from communities up to  100 miles away.

“Endovascular thrombectomy allows the 20 to 30 percent of people whose ischemic strokes involve blockages in large blood vessels to return to normal or close to normal in many cases. These are people who in the past would have been completely disabled by large strokes, needing lifelong care,” says neurointerventional radiologist Akash Kansagra, MD, MS, co-director of the stroke center.

Specialists like Kansagra treat and even prevent stroke by working inside blood vessels. Guided by images on large screens above the operating table, Kansagra deftly guides wires and surgical tools along four to five feet of twisting, turning arteries thinner than strands of angel-hair pasta — starting in the femoral artery at the groin and moving up through the torso and neck before reaching his target within the skull. In addition to excising clots in this manner, neurointerventional radiologists can use the same technique to deliver tPA directly to a clot. And for a person with a cerebral aneurysm (a weakened, ballooning section of an artery in the brain), endovascular procedures are used to insert metal coils or other devices to prevent or stop bleeding. “Procedures may last 20 minutes or several hours,” Kansagra says. “We can navigate to almost any part of the brain using the arteries as conduits.”

The future of stroke care

Washington University researchers are involved in significant studies aimed at getting more women, men and children back to their everyday lives after stroke. Recent studies have focused on:

Clotbusting drugs for “wake-up” strokes: “About 30 percent of strokes happen when a person is asleep or alone,” Ford says. Some of these are known as wake-up strokes because symptoms aren’t obvious until the person wakens. “In these cases, no one knows exactly when stroke symptoms began, and that uncertainty can rule out the use of tPA.” Researchers at Washington University collaborated with scientists at 10 other medical centers in a study of 80 people with wake-up strokes who underwent magnetic resonance imaging, or MRI, to determine the true time of stroke onset. If the MRI showed the stroke had recent onset, just prior to awakening, then tPA was administered. According to results presented at the 2016 International Stroke Conference, this research indicated that tPA could be safely administered when MRI was used to determine stroke onset time in patients with wake-up strokes. “Studies underway in Europe are now looking at how effective tPA is in this population,” Ford says, “and this research could allow many more people with stroke to receive the benefits of tPA.”

The genetics of ischemic stroke: “In the first 24 hours after an ischemic stroke, some people improve rapidly, while others deteriorate,” Lee says. “We are working with collaborators around the world in an ongoing study of the genetic makeup of 5,000 stroke survivors to see if genes explain the differences.” Lee notes that this could lead to targeted therapies and perhaps even to the development of blood tests to help diagnose stroke, something not currently available.

Stroke prevention after a “mini stroke”: Every year, 250,000 or more Americans have transient ischemic attacks (TIAs): short-lived stroke symptoms that pass quickly but boost the risk for a bigger stroke in the future. Washington University researchers are collaborating with an international team of scientists to see whether the combination of clopidogrel, an antiplatelet medication, and aspirin, are more effective at lowering the risk of recurrent stroke after a TIA than aspirin alone.

Protecting fragile neurons: After a stroke, inflammation can damage brain cells even in people who receive tPA. Could an experimental IV drug known as 3K3A-APC, derived from a protein found naturally in the body, protect brain cells from damage? Washington University scientists are participating in an early, multicenter study to see if 3K3A-APC is safe; future research will assess effectiveness.

The power of rehab

Stroke care doesn’t end when the clot or bleed is fixed. Rehabilitation — involving physical, occupational and speech therapy, and more — begins in the hospital soon after a stroke, and it continues at home or in a rehab center after discharge. Rehab is the bridge between stroke and resuming one’s daily activities, a goal stroke survivors like Sabharwal strive to reach.

“The brain has an amazing ability to adapt to injury by rewiring itself,” Lee says. “To make that happen, you have to keep practicing the activities made difficult by stroke to force the brain to make repairs. Early rehab is the most important — there seems to be a special window of opportunity. Our rehab teams begin assessing survivors within a day or two of their arrival at the hospital, and then begin therapy.” This kind of intervention, he says, “makes all the difference.”

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