Approximately 60 Principal Investigators, and several Post Docs, both basic science/laboratory and clinical researchers, work within the Research Institute and the Medical Center.
California Pacific Medical Center physicians from many different disciplines engage in active research. Take a look at our Clinical Trials section for some of these projects.
Joey English, M.D.: Pioneering neurointerventional approaches to treating cerebrovascular diseases
Speed and precision is critical in treating acute ischemic stroke (AIS), a condition impacting almost one million Americans annually in which blood flow to the brain is severely limited after abrupt occlusion of an intracranial artery—and which can cause irreparable brain damage within hours.
Timely interventions to restore blood flow during an AIS event determine the degree of resulting neurological deficits and quality of outcome for the patient.
“We are pursuing the latest in research and medical approaches to advance the treatment of acute ischemic strokes,” says Joey English (M.D., Ph.D.), a neurointerventional surgeon and Medical Director of Neurointerventional Services at California Pacific Medical Center (CPMC). Dr. English specializes in the diagnosis and minimally invasive treatment of vascular disease of the brain and spine such as AIS, hemorrhagic stroke, brain aneurysms, cerebral arteriovenous malformations and dural arteriovenous fistulas.
He explains that large-vessel occlusions (LVOs)—a typically embolic acute blockage of a proximal great vessel or of its distal cortical branches—are particularly challenging to treat because they respond only modestly to intravenous tissue plasminogen activator (tPA).
“Large-vessel occlusion-related AIS are more common, clinically more severe than small vessel stroke syndromes, and significantly reduce the likelihood of good long-term functional outcomes,” says Dr. English. “However, it’s encouraging that significant data show that successful, timely restoration of blood flow to the occluded vessel markedly improves the chance of favorable long-term functional outcomes.”
Using endovascular therapies for acute large-vessel occlusions
Dr. English notes that the rationale underlying the development of endovascular therapy has been driven by the principle that any treatment improving timely revascularization of an LVO can significantly improve a patient’s chance for favorable neurological outcomes.
Recent advances in endovascular AIS treatment have occurred through the development of mechanical thrombectomy devices, which engage and physically remove the clot from the target intracranial artery.
“The use of stent retriever devices has dramatically improved our ability to quickly and safely achieve successful recanalization of AIS patients presenting with a large-vessel occlusion,” says Dr. English, referring to some of the newer self-expanding non-detachable stents that physically remove a clot from a large intracranial artery. Preliminary data from CPMC and other centers suggest significant improvements in long-term clinical outcomes for patients with LVOs.
Identifying patients most likely to benefit from endovascular therapy
Imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) perfusion imaging can identify which patients will benefit most from endovascular therapy, and Dr. English and colleagues at CPMC are pursing the latest research in this area.
“The main challenges in treating patients with acute ischemic stroke lie in identifying areas of brain tissue that are salvageable,” says Dr. English. “CT scans are fairly ‘insensitive’, however with newer technologies such as perfusion imaging, we can better predict tissue that can be saved with timely interventions.”
Advances in image-based patient selection (with perfusion imaging) allow physicians to offer endovascular therapy beyond the typical six-to-eight hour time window.
The use of stent retrievers and image-based patient selection is being studied in clinical trials at CPMC and other large centers with acute stroke programs.
One of these studies is the DAWN (DWI and CTP Assessment in the Triage of Wake-up and Late Presenting Strokes Undergoing Neurointervention) trial, a phase 3 interventional trial to study the safety and efficacy of endovascular treatment in MR or CT perfusion-selected patients suffering from AIS. Inclusion criteria include patients who present at least eight hours after the ischemic event. DAWN, which will begin enrollment later this year, involves nationwide, major stroke referral centers. CPMC is the only site from Northern California involved in the study.
Treating hemorrhagic strokes
Deadly and destructive, the acute rupture of a cerebral blood vessel—resulting in hemorrhagic stroke—represents only a small subset of all strokes but leaves 50% of survivors with permanent disability.
When clinical and radiologic findings confirm intracranial hemorrhage and suggest an underlying cerebrovascular lesion, immediate high-level care at a certified stroke care center such as CPMC can significantly increase a patient’s chance for survival and improve long-term outcomes. Early steps are crucial to manage intracranial bleeding, control intracranial pressure and cerebral edema, prevent respiratory failure, and treat the seizures sometimes resulting from hemorrhage.
“Using our advanced non-invasive technologies, we can diagnose even a small 2-3 millimeter aneurysm or other hemorrhagic lesion,” says Dr. English. “Our neurointerventional suite can detect even the subtlest cerebrovascular pathology to provide detailed views for treatment planning.”
Dr. English and colleagues including Warren Kim (M.D., Ph.D.) work to clearly define a ruptured aneurysm’s anatomy with a catheter angiogram, which determines its size, shape, location and relationship to the parent vessel. “We can make immediate decisions about how best to treat the aneurysms, since many have a high likelihood of re-bleeding and prompt decisions about therapy are critical,” says Dr. English. Most likely, treatment involves minimally invasive endovascular treatment or open microvascular neurosurgery. For both techniques, Drs. English and Kim are investigating new approaches to optimize patient outcomes.
Endovascular treatment of hemorrhagic stroke involves inserting a microcatheter through the blood vessels into the aneurysm, and then packing tiny platinum coils within the aneurysm sac until it clots and closes. Sometimes small balloons or stents are temporarily inflated to help position the coils.
For smaller, wide-based aneurysms, Drs. Kim and English perform microvascular surgeries to close a surgical clip around the neck of the aneurysm, occluding its connection with the parent vessel.
Each year in the U.S., approximately 750,000 people experience an acute ischemic stroke (AIS), which account for 85% of all strokes (with the remaining being related to rupture of a cerebral blood vessel, giving a hemorrhagic stroke). AIS is the third leading cause of death and the leading cause of adult disability.
Nationally, fewer than 5% of patients with AIS receive lifesaving thrombolysis (clot-busting drugs), the most effective known treatment. At CPMC—home to one of the best stroke care and research programs in the U.S.—that rate averages over 25%, one of the highest rates nationwide.
Typically, the treatment window closes at around 4.5 hours post-stroke, but most people can’t access treatment in time. CPMC’s stroke team is conducting new research to find ways for administering treatments upwards of twelve hours, in part by using advanced imaging techniques that measure brain activity (which might suggest that thrombolysis will still help).
- Peggy Cawthon, PhD, MPH
- Stewart Cooper, MD
- Steven Cummings, MD
- Shanaz Dairkee, PhD
- Robert Debs, MD
- Pierre Desprez, PhD
- Dan Evans, PhD
- Gantt Galloway, PharmD
- Mohammed Kashani-Sabet, MD
- Sean D. McAllister, PhD
- John Mendelson, MD
- John Muschler, PhD
- Karin L. Petersen, MD
- Michael C. Rowbotham, MD
- Liliana Soroceanu, MD, PhD
- Katie Stone, PhD
- Gregory James Tranah, PhD
- Cassandra Vieten, PhD
- Esther Wei, ScD
- Li Xi Yang, MD, PhD
- Garret L. Yount, PhD