Stroke: a Q & A with our director of endovascular neurosurgery
Every year, more than 750,000 Americans suffer from a stroke, which occur either from a lack of blood flow to the brain, known as an ischemic stroke, or from bleeding within the brain, called a hemorrhagic stroke.
Past treatments were limited to clot-busting drugs such as aspirin or, in the immediate aftermath of a stroke, injections of tissue plasminogen activator (TPA). Now, specially trained doctors can provide a new catheter-based treatment or minimally-invasive neurosurgery for medical emergencies within the brain. Advocates say the technological advancement expands realistic hope for recovery beyond the typical three-hour window of TPA intervention.
We asked Alexander Khalessi, MD, director of endovascular neurosurgery at the UC San Diego Health System’s Comprehensive Stroke Center, about the latest developments and about what to do if a stroke appears to be happening.
First and foremost, he said, call 911 immediately. Don’t delay, even if you’re unsure. Prompt arrival at a hospital helps doctors better understand what’s happening, its cause and, if it is a stroke, to help prevent further occurrences.
Q: If I am having a stroke, will I know it?
A: Not necessarily. By attacking the brain, strokes often limit your insight into what is actually happening. Though you may feel normal, you may exhibit symptoms that include garbled speech, weakness or numbness on one side of the body. Worse still, you may be aware of the stroke, but unable to communicate because a particular part of the brain is affected.
Importantly, strokes can occur at night while a person is sleeping. If you or a loved one wake up to symptoms such as prolonged numbness or tingling on one side of the body, do not go back to bed hoping to sleep it off. Seek medical attention.
Also, know your medical record. If you have kidney disease, vascular collagen defects such as Marfan syndrome, a history of smoking or a first relative with an aneurysm, you are at higher risk for stroke. By understanding the signs of stroke – and your own risk – you are in a stronger position to seek timely treatment.
Q: Does a stroke strike instantly or happen over time?
A: Most often, strokes occur in stages. During the first few hours, a stroke may be incomplete. If the blocked artery in the brain is not opened, the entire region of the brain relying upon that artery will continue to die. Using drugs or catheters placed through the leg and up the vast arterial highways to the brain, specialists can locate and eliminate a clot.
Roughly 85 percent of strokes occur from a blocked artery in the brain; the rest involve a bleed or hemorrhage within the brain itself. In a hemorrhagic stroke, seeking specialized care is even more critical. If the bleed is large, neurosurgeons may need to control pressure in the head or remove the clot with surgery while also identifying the source of the bleeding.
For example, cerebral aneurysms – a weakening of an artery of the brain – may burst and cause a hemorrhagic stroke. One-third of these patients will die before reaching the hospital. The other two-thirds will respond to aggressive treatment securing the aneurysm with catheter-based or surgical clipping treatments, combined with neurocritical care. A Comprehensive Stroke Center can provide the full range of necessary treatments for these critically ill patients.
While both forms of stroke can occur over time, immediate treatment has a dramatic impact on the patient’s ability to avoid disability and return to everyday activities. When in doubt, go to the emergency department.
Q: What newer technologies have emerged to treat a stroke?
A: In the last two years, huge strides have been made in the world of devices to treat stroke. At UC San Diego, there are two new FDA-approved devices that the neurosurgical team currently uses to rapidly remove clots, and in some cases, double the chances of saving a patient’s life.
Next-generation stents are also available to repair injuries or plaques in the arteries of the neck to restore blood flow to the brain. Solitaire FR (Covidien) and Trevo (Stryker) have both been proven to open blocked arteries in the brain with greater efficiency and fewer complications. Both of these devices dramatically improve the possibility of a functional outcome in stroke patients with a blockage of one of the major arteries in their brain.
Overall, the catheter-based treatment of stroke, aneurysms, and complex vascular lesions in the brain has taken once impossible problems and placed meaningful recovery within reach.
Malcolm Has a Mini Stroke: three questions for Alexander Khalessi, director of Neurovascular Surgery
Last week, former childhood star Frankie Muniz suffered a “mini stroke.” The news was remarkable for several reasons as Muniz, who was the titular star of Malcolm In the Middle, is just 27 years old and seems to live a healthy lifestyle. According to Muniz, he has “… never had a sip of alcohol in my life. I’ve never had any drugs, I’ve never even smoked a cigarette.”
According to the Centers for Disease Control, stroke is the leading cause of death in the United States, attributing to over 800,000 deaths a year. The causes for stroke range from existing conditions such as high blood pressure, to adverse behaviors such as smoking and excessive drinking. But what if you don’t have these risk factors?
Question: What is a mini stroke and how does it differ from other types of stroke?
Answer: “Mini strokes” usually refer to a Transient Ischemic Attack or TIA. These events involve a temporary lack of blood flow to part of the brain. Fortunately in these cases, blood flow to the brain is spontaneously restored without permanent damage. Symptoms vary based on the part of the brain involved and may include vision loss, weakness, numbness or speech difficulty. TIA’s carry an increased risk of future stroke and often signify plaque narrowing one of the four major arteries that provide blood flow to the brain. Sudden occurrence of these symptoms requires immediate medical attention.
Q: Frankie Muniz is 27 years old and, except for suffering a stroke, in good health. Does this mean that anyone can be at risk for stroke at any time?
A: Ischemic strokes are caused by a blockage of one of the major blood vessels supplying the brain, narrowing of the arteries of the brain itself, abnormal heart rhythms, or clotting disorders of the blood. Stroke risk increases with these known conditions or comorbidities including obesity, smoking, drug use, high blood pressure or diabetes. The incidence of stroke in young people has doubled in the last decade. In a young healthy person with Mr. Muniz’s presentation, a carotid dissection or traumatic tear in the wall of the carotid artery is likely the most common cause.
Q: After suffering a stroke, what can people do to limit their chance of reoccurrence?
A: After suffering a stroke, receiving a work-up at a center that diagnoses the cause of the stroke is critical to risk assessment and secondary prevention. Were an arterial blockage responsible, the patient’s stroke risk may remain high without open surgery (carotid endarterectomy) or treatment with catheters (carotid artery stenting). For strokes due to arrhythmias of the heart, blood thinning medications and heart rate control treatments may be required. Similarly, clotting disorders of the blood may require aggressive treatment. Stroke diagnosis represents only the first step in preventing a second event.
Image source: FanPop
Re-Defining Future Stroke Risk among Pre-Diabetics
Studies suggest greater danger, but risk appears to vary by definition
Millions of pre-diabetic Americans may be at increased risk of future stroke, say researchers at the University of California, San Diego School of Medicine in a new meta-analysis of epidemiological studies, but the precise degree of that threat is confounded by differing medical definitions and factors that remain unknown or unmeasured.
“The immediate implication of our findings is that people with pre-diabetes should be aware they are at increased risk of stroke, and that this condition is frequently associated with one or more major risk factors for cardiovascular disease,” said Bruce Ovbiagele, MD, a professor of neurosciences at UC San Diego School of Medicine and the study’s senior author. “Beyond that, there’s a great need to further refine our understanding of that risk and how it’s measured.”
Writing in the June 8 online edition of the British Medical Journal, Ovbiagele and an international team of colleagues reviewed 15 qualifying prospective cohort studies that looked at the association between pre-diabetes and stroke risk. The studies, published between 2004 and 2011, involved 760,925 participants.
Pre-diabetes occurs when blood glucose levels are consistently higher than normal, but not yet high enough to be diagnosed as diabetes. The condition is widespread in the United States: An estimated 35 percent of American adults – approximately 79 million people – are believed to be pre-diabetic, and thus at greater risk of developing full-blown type-2 diabetes, which afflicts roughly 26 million Americans. Diabetes is the seventh leading cause of death in the U.S., and a major risk factor for heart disease and stroke, the first and fourth leading causes of death.
People with pre-diabetes typically have the same risk factors for cardiovascular disease as people with type 2 diabetes – specifically, high blood pressure, high cholesterol levels and obesity – but the condition’s effect on future stroke risk has not been established.
Zebrafish model of atherosclerosis.
A study using genetically modified zebrafish to visualize early events involved in development of human atherosclerosis describes an efficient model – one that the researchers say offers many applications for testing the potential effectiveness of new antioxidant and dietary therapies.
The research, led by scientists from the University of California, San Diego School of Medicine, has been published online by the Journal of Clinical Investigation, and will appear in print in the December 1 issue of the journal.
Atherosclerosis is a process of lipid deposition and inflammation in the artery walls. Low-density lipoprotein (LDL) that carries “bad” cholesterol in blood is easily oxidized, and oxidized LDL promotes inflammatory responses by vascular cells. Inflamed atherosclerotic plaque can often rupture; this results in a blood clot, obstruction of blood flow to the heart or brain, and heart attack or stroke.
An international team of researchers led by Yury Miller, MD, PhD, of the UCSD Department of Medicine, working with colleagues in Australia, developed an approach to see – literally – the accumulation of oxidized LDL in genetically modified zebrafish fed a diet high in cholesterol. Because young zebrafish are transparent, the researchers were able to study vascular lipid accumulation, lipid oxidation, and uptake of oxidized LDL by macrophages – all in live animals.
An axial MRI of a brain depicts a cavernous malformation lesion (marked by the arrow) in the left temporal lobe.
New hope for brain bleeding disorder
Building upon on earlier work and in collaboration with researchers at the University of California, San Diego School of Medicine and Duke University, scientists at the University of Chicago Medical Center say they have developed a potential first-ever drug treatment to prevent lesions caused by cerebral cavernous malformation (CCM) – a disorder in which blood vessels in the brain swell and leak and can, in severe cases, result in stroke and death. The drug treatment is described in today’s issue of the journal Stroke.
CCM occurs when brain capillaries become enlarged, irregular in shape and inelastic, with abnormally thin walls that are prone to leakage. The disorder occurs in approximately one in 200 people, or about 0.5 percent of the population worldwide.
One form of CCM is heritable. Mutations in three identified genes account for 70 to 80 percent of all cases of familial CCM. The cause or causes of the remaining sporadic cases are not known, but may be due to unidentified genes.
Roughly one-quarter of persons with CCM never experience any related medical problems. But more often, they report headaches, seizures, paralysis, hearing or vision deficiencies and bleeding in the brain (cerebral hemorrhaging). Severe brain hemorrhages can result in stroke or death.
Until now, there was no method to prevent CCM lesion growth, and treatment after diagnosis was generally limited to treating symptoms, monitoring patients and waiting to see if the abnormal blood vessels grew large enough to require brain surgery to remove them.
The University of Chicago researchers, with colleagues at UC San Diego and Duke, tested a drug called fasudil, currently used in Japan to treat a condition called cerebral vasospasm after aneurysm rupture, on mice genetically modified to model CCM. After four months of treatment, the mice given fasudil displayed fewer and less severe lesions and fewer signs of hemorrhage and inflammation than did mice given a placebo treatment.
“This animal model and humans have lesions that are aggressive and symptomatic: They leak blood, they show inflammatory properties and endothelial cells multiply or proliferate,” said Issam Awad, MD, professor of surgery at the University of Chicago Medical Center and senior author of the study. “None of these features were present in the fasudil-treated mice. It was like the lesion was chilled and shrunk.”
The Chicago results are based on earlier collaborative research by Mark H. Ginsberg, MD, professor of medicine, and Rebecca A. Stockton, PhD, assistant adjunct professor of medicine at UC San Diego who produced the initial cell signaling studies that gave rise to the use of fasudil in the mouse model.
More specifically, they showed that knocking down a specific gene called CCM1 resulted in elevated activity of a signaling protein known as ROCK, which can cause blood vessels in the brain to become leaky. They proposed using fasudil as a therapeutic block to lesion formation.
Ginsberg’s and Stockton’s work, in collaboration with Awad’s research group, revealed that lesion samples from human patients with CCM have abnormally high ROCK activity. The model mouse brain lesions also had similarly high ROCK activity, providing an experimental target for fasudil, which inhibits ROCK very effectively and thus prevents lesion formation.
Said Stockton, a co-first author of the Stroke paper: “These fasudil studies show for the first time an effective way to prevent CCM lesion genesis in an animal model. We hope to move this to human trials with our collaborators, and provide some real benefit to the many patients suffering from CCM a prevalent disease, for which no specific drug therapy exists.”
People with prehypertension have a 55 percent higher risk of experiencing a future stroke than people without prehypertension, report researchers at the University of California, San Diego School of Medicine in a new meta-analysis of scientific literature published in the September 28 online issue of the journal Neurology.
Prehypertension is clinical category created by experts in 2003 to describe patients whose blood pressure was elevated, but still considered within normal range. Hypertension or abnormally high blood pressure is a major risk factor for cardiovascular disease and strokes, but much less is known about the health threat posed of prehypertension, which is defined by a systolic pressure reading between 120 and 139 mmHg (the top number) and a diastolic reading between 80 and 89 mm Hg (the bottom number)
“The experts reasoned that, generally speaking, the higher the blood pressure, the greater the risk of death and disease, possibly starting from within the normal blood range,” said Bruce Ovbiagele, MD, professor of neurosciences at UC San Diego School of Medicine and senior author of the study.
However, Ovbiagele said, conclusive evidence was lacking, “so we decided to compile all the published studies in the scientific literature to date, and using statistical techniques find out if there is indeed a higher risk of future stroke in people with prehypertension, the extent of that risk, and whether particular characteristics were associated with higher stroke risk.”