Summer 2009

Extending Treatment Window for Acute Ischemic Stroke

In spring 2006, after a stroke caused dense right hemiparesis, paramedics rushed a 67-year-old woman to a local emergency room, where physicians administered standard tissue plasminogen activator (tPA) treatment within the prescribed three-hour window. But when her symptoms did not dissipate, her physicians had the woman airlifted to the Neurovascular Disease and Stroke Center at UCSF Medical Center.

"Images at five hours revealed a large territory of her brain was still at risk," says neurointensivist Wade Smith, M.D., Ph.D., director of the UCSF Neurovascular Service. "We were worried about loss of language and possibly losing the whole brain."

At that point, a team of neurologists and neurointerventional radiologists — pioneers in the use of the Merci (mechanical embolus removal in cerebral ischemia) Retriever — moved the patient to the catheter lab, where the radiologists removed the clot. Hours later, the woman regained full movement on her right side. Postintervention imaging revealed a healthy cortex, and on her third day, she was transferred back to her local referring hospital. Today, she is improved and has no troubles with communication.

Two Factors Change the Treatment Equation

Smith says that the treatment path for this patient was ideal. Stroke patients should always go first to the closest emergency room for standard treatment, but if symptoms persist, physicians should consider transfer to a Joint Commission Primary Stroke Center like the one at UCSF Medical Center. There, patients find a dedicated, 29-bed Neuro ICU and a team of stroke experts that is available 24/7. "Patient outcomes for stroke are better when patients are treated in dedicated units," says Smith.

Smith says mechanical embolectomies are typically done after tPA has failed, though they also do the procedure when the risks of tPA are too high. In both cases, the UCSF team follows American Stroke Association guidelines, including completion of all appropriate exams and imaging, before moving forward within an eight-hour window.

Two factors appear to play a major role in successful outcomes for mechanical embolectomies. "Advanced imaging and experience reading the images is certainly one key," says Smith. "We believe we can extend the treatment window if we have a good profile."

Either MRI or a CT scan can provide that profile, but Smith currently prefers a multidetector CT scan, using IV contrast. "CT angiography is available in practically every emergency room, so physicians can obtain these images locally and make a decision about whether to transfer the patient for potential embolectomy," says Smith.

The second factor — experience with the Merci Retriever — is limited to primary stroke centers, in part because while the FDA approved the technique in 2004, many still view mechanical embolectomy as experimental. At UCSF Medical Center, however, Smith is lead investigator in the new international, multicenter RETRIEVE trial, and three neurointerventional radiologists — Christopher Dowd, M.D., Van Halbach, M.D., and Randall Higashida, M.D. — have completed multiple procedures with the Retriever.

With stroke remaining a prominent cause of death and disability worldwide, the value of mechanical embolectomies when standard treatment fails is becoming clearer. Smith's new trial will help determine who specifically benefits from the device. "Future research into extending the treatment window beyond eight hours is necessary as well," he says.

Prevention Angle: Stratifying Post-TIA Risk

"We consider TIA (transient ischemic attack) an emergency because numerous studies have shown that the risk of stroke after  TIA is 10 to 15 percent in the ensuing 90 days, with half of those strokes occurring in the first two days," says S. Claiborne Johnston, M.D.,  director of the UCSF Neurovascular Disease and Stroke Center.

Johnston's own research efforts were instrumental in the development of the ABCD2, an important addition to clinical decision making when treating TIAs. The score is calculated by adding up points for the presence of independent risk factors; higher scores are associated with higher risk of stroke after TIA.

"Especially when paired with advanced imaging, these scores can help save lives. If the clot is in a large artery — and if you have a team available — you can fix the problem with medical or surgical techniques," says Smith. Though it's not yet firmly established that stratification and aggressive treatment of the most at-risk TIA patients prevent stroke, Smith believes that "this can be the Holy Grail because it can save lives and be cost-effective."

Age ≥60  1 point
Blood pressure ≥140/90mmHg  1 point
Clinical Symptoms
Unilateral weakness
Speech impairment without weakness

 2 points
 1 point
≥60 minutes
10–59 minutes

 2 points
 1 point
Diabetes  1 point
Total Score 0–7

For more information, contact S. Claiborne Johnston, M.D., at (415) 476–2477 or Wade Smith, M.D., Ph.D., at (415) 353–1489.

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