Latest entries

Carrie Fisher and Debbie Reynolds: Can Stress Cause Stroke?

The year 2016 ended with hemorrhagic stroke in the mainstream news around the world. Most of you have already heard the story of Carrie Fisher and Debbie Reynolds at this point – a daughter’s unexpected death followed by the surprise of her mother’s passing within a day.

Patients frequently ask me if stress can cause stroke, and many younger adults report that at the time they sustained their strokes, they were under a great deal of either professional or personal (or both) stress. When I was training to become a physician, I asked this question, and was told that there was no definitive evidence linking stress to stroke. Over the years, though, I question this for a number of reasons.

First of all, studying stress is more challenging than studying diabetes or high cholesterol, where there are reliable lab values that can be tracked. Some studies follow levels of cortisol, a hormone released by the adrenal glands, but cortisol levels do not necessarily reflect the degree of stress that patients subjectively report experiencing. Also, an individual may report severe levels of stress on a questionnaire in response to what may seem to be a relatively benign situation, while another could claim to have “mild” stress during a period of great hardship. Patients can underreport their levels of stress too.

Okay, so if we can’t easily study stress, what does that mean in terms of whether it is associated with stroke risk? It is probably worth deciphering the downstream effects of stress that can be measured to answer this question.

I tell patients that stress can send blood pressure surging, and high blood pressure is a risk factor for stroke. With the release of cortisol during stressful periods, this can result in an increase in blood sugar levels (glucose), and if prolonged could theoretically lead to the development of insulin resistance and/or diabetes. Stress causes sleep disruption, and insomnia can place patients at risk for health complications. So does stress cause stroke? I would say that if an ongoing level of stress that continuously leads to stroke risk factors is present, then perhaps it can.

Back to Debbie Reynolds now. There is stress, and then there is distress. To the best of my knowledge, she was not living with chronic stress, but endured a sudden, unexpected, severe form of emotional distress with the news of her daughter’s unanticipated death. I was not surprised when her death certificate revealed her cause of death as “intracerebral hemorrhage” (bleeding within the brain). I have met patients who have collapsed into unconsciousness with these hemorrhages when receiving intensely upsetting news, such as the unexpected death of a loved one, or notification of eviction from their homes. I suspect there is a sudden increase in catecholamine levels (stress hormones released as part of our fight-or-flight responses), causing a spike in blood pressure, and the rupture of a small artery in the brain under such pressure. It is difficult to study hormonally what is occurring during a time of such intense emotional distress just prior to an intracerebral hemorrhage though.

 

Pondering “Telestroke” While Covering A Telestroke Service

This week is one of my on-call weeks for Duke University’s telestroke network. When I first came to Duke just over one year ago, I was very familiar with the telestroke concept and had attended a number of meetings discussing what went into developing a telestroke network, but with my transition to a new hospital system, I then had the opportunity to start treating patients virtually who might otherwise not have access to a neurologist when this access was the most time-sensitive – during an acute stroke.

The word “telestroke” may be a bit misleading at first, because the evaluation is actually performed via video stream rather than by telephone (although a phone call usually starts the process). A telestroke network is typically comprised of a central hub hospital (tertiary care center with specialists available), and what are known as its spoke hospitals. The neurologist performing telestroke consultations is frequently employed by the hub hospital (in my example, this would be Duke University Medical Center), and the spokes call for telestroke assistance from the neurologist when a patient is acutely experiencing signs and symptoms that may are concerning for stroke at that spoke hospital. There are also non-hospital companies that provide telestroke consultation services, and neurologists are hired by the company to cover the acute stroke needs of its customer hospitals, rather than the neurologist specifically being employed by a hub hospital.

This graphic is how I appear when "beamed in" on the robot. I can examine a stroke patient from many miles away, and can even "walk" around the room, or move into the hallway to find the emergency medicine provider to have a discussion about the plan.

This is how I appear when “beamed in” on a telestroke robot. I can examine a stroke patient from many miles away, and can even “walk” around the room, or move into the hallway to find the emergency medicine provider to have a discussion about the plan.

Typically, telestroke works something like this in my world. I receive a page from one of our hospital spoke sites, and it is expected that I call the hospital that is paging me in less than five minutes. I then speak by phone with (the majority of the time) a physician, physician assistant, or nurse practitioner in the emergency department at that hospital about a patient who is suspected of having a stroke. We discuss when the patient was last known to be without the stroke symptoms (“last known well time”), as this is an important factor in deciding whether the patient may be eligible for IV t-PA, the “clot-busting” medication that can be given within the first three to four and a half hours after stroke symptoms begin. We also discuss whether the patient is taking any medications, the blood pressure, and many other factors that may influence our decision to give or to withhold t-PA. I then am able to look at the patient’s head CT scan on my computer screen. It is necessary to perform the CT scan in order to rule out bleeding in the brain, since 15-20% of strokes are hemorrhagic. We don’t want to give a medicine like t-PA to someone who is bleeding because it could worsen the bleeding without benefitting the patient. Then, I get to “beam in” to the robot or computer in the patient’s room to start examining the patient from miles away.

Telestroke is a revolutionary concept. A game-changer. Rural areas may not have neurologists in the area to see patients at hospitals, or may not have the capacity to have them available 24 hours a day. This places a neurologist at the bedside, and in a situation where “time is brain,” we are able to not only treat more patients with t-PA, but can also partner with emergency medicine providers to give the drug as soon as possible. Clinical trials have shown us that with earlier administration of t-PA comes a greater likelihood of being independent three months after an ischemic stroke. The odds of returning to independence are greater when t-PA is given 90 minutes after a stroke starts than when given three hours after a stroke starts.

We are also able to identify patients who may be candidates for mechanical thrombectomy, a procedure in which a catheter can be inserted at the groin and threaded to the site of the clot in the brain, with physical removal of the clot. If a patient is believed to benefit from this procedure, we can work with the emergency department at the spoke hospital on transferring the patient as quickly as possible to a hospital where this procedure can be performed.

Sometimes I examine a patient expecting to see a stroke, and after a few minutes of evaluating the patient realize that the patient is in the midst of a seizure. Seizures can mimic strokes. So can migraines. So can a lot of things. It’s another way that bedside neurologist collaboration with emergency medicine providers can be beneficial.

Other times, a patient may be having a stroke, but is not a candidate for t-PA or for a mechanical thrombectomy. Perhaps the patient’s stroke began a day ago and changes consistent with stroke are already evident on the CT scan. Perhaps the patient had a history of a brain hemorrhage in the past and the risk with t-PA is considered too great. During those instances, at least a neurologist has evaluated the patient, and everyone can move on with managing the patient’s care without wondering if something more could have been done had a neurologist been at the hospital.

There are challenges that accompany telestroke evaluations for physicians. A physician must be licensed in each state in which he or she is providing telestroke consultation. In my case, our hospitals are only in two states. In other situations, though, I know physicians who have to keep 10 or 15 state licenses current, which have to be renewed every 1-2 years. Since medical licensing is performed at the state level, there is not a federal license a physician can acquire allowing him or her to practice in all 50 states. Physicians also have to apply for “hospital privileges” at each hospital in which they are performing telestroke consultations, and this can be very time-consuming to reapply every 1-2 years.

There is also the challenge of not being able to physically touch the patient. For example, testing for sensation differences between the right and left sides has to be performed by someone physically present. However, I have found great partnerships with nurses and other physicians who are at the patient’s bedside, and this fosters a spirit of teamwork.

Telestroke is only one application of “telemedicine,” or providing medical care via video conferencing at the bedside. Telepsychiatry places psychiatry providers with patients who need them, and telecritical care allow providers trained in critical care medicine to weigh in on critically ill patients in areas without these experts available. These are only a few of the many possible applications of telemedicine.

While the robots are pretty cool, hospitals who choose not to purchase them or who cannot afford to purchase them can purchase a computer on a cart that can be wheeled into the patient’s room, and the telestroke consultation still goes smoothly. Some companies, such as Vigilias, are working with hospitals to bring telemedicine to rural areas and keep costs at a minimum by using a full-size SmartPhone-based system. The technology continues to develop at an impressive speed, and many innovative people are working towards more efficient ways to provide medical care to more people.

Allison Pataki shares young caregiver’s viewpoint after husband’s stroke at 30

Today, Allison Pataki published a moving New York Times blog post about her husband’s stroke at age 30. Pregnant with their first child at the time of the event, she describes continuing to work productively, preparing for a newborn, and instantaneously becoming her husband’s caregiver following this unexpected circumstance that life threw their way. Click here to read her tale.

Clinical trial fails to show ticagrelor (Brilinta) superiority to aspirin in stroke prevention

The SOCRATES clinical trial has concluded with summary results having been released to the public. More detailed results will be presented at the European Stroke Organisation Conference in Barcelona, Spain next week.

Ticagrelor (Brilinta) carries a retail price in the United States of over $300/month. It was not found to be statistically more effective in preventing stroke in the SOCRATES study when compared with aspirin.

Ticagrelor (Brilinta) carries a retail price in the United States of over $300/month. It was not found to be statistically more effective in preventing stroke in the SOCRATES study when compared with aspirin. Source: GoodRx.com for price comparisons at retail pharmacies.

The trial randomized patients with transient ischemic attacks (TIA) considered to be high risk for stroke and patients with “mild” strokes to take either ticagrelor (Brilinta), a medication that impairs platelet function currently in use the prevention of heart attacks in patients with coronary artery disease or with coronary stents in place, or aspirin. Ticagrelor was taken at a dose of 90mg twice daily, and aspirin was taken at a dose of 100mg daily (plus placebo for the second dose – patients were blinded to which drug they were taking). Patients had to enter the trial within 24 hours of their TIA or stroke symptoms beginning. The endpoints were the amount of time until a recurrent stroke, a heart attack, or death. While the patients in the ticagrelor group are being reported as having fared slightly better than those in the aspirin group, the results were not statistically significant. This means that there is no significant benefit in the primary prevention of stroke after a TIA or in the secondary prevention of stroke following a mild stroke that ticagrelor carries over aspirin.

Aspirin for sale online in an assortment of packages from various producers. Image Source: GoodRx.com

Aspirin for sale online in an assortment of packages from various producers. Image Source: GoodRx.com

What does this mean? If you refer to the image to the left, you will see a big part of what it means

– about $300-plus per month in savings for some patients if they now opt for aspirin over a patented drug for which there is no generic equivalent.

It also raises the question about whether pharmaceutical companies will fund clinical trials that cost millions of dollars to run and carry to completion in order to obtain an additional indication for a drug’s use. It’s a gamble. If companies don’t fund trials to demonstrate efficacy, then insurers are less likely to cover drugs for patients, and patients are more likely to opt for a less expensive option, if available. If they fund trials and the drug being tested is not effective, or is not superior to a less expensive option that already widely exists, then not only is it millions down the drain, but negative press about the company and the drug. However, if the drug is shown to be more effective than the cheaper, more widely available option, then the return on investment could be huge.

Personally, I was shocked. Ticagrelor carries a reputation of being a potent antiplatelet medication, and many of us who treat patients with stroke or heart disease felt that this was a softball sort of trial. Of course the ticagrelor was going to win solidly – because it was being compared only to a substance that has been available over-the-counter for decades, a drug that went generic in the 1930s and whose history dates back over 2,000 years as a substance produced by the willow tree. Could it really be that something as simple and low cost as aspirin could rival an expensive, patented, relatively new prescription drug? According to SOCRATES, this may well be the case.

There were limitations to SOCRATES. It’s always difficult to incorporate every possible scenario into a clinical trial, especially in a disease like stroke where each one is different. This did not test whether the combination of aspirin and ticagrelor was more effective than aspirin alone. It also did not compare ticagrelor to other antiplatelet drugs that are generic, such as clopidogrel (Plavix). Medicine is still an art, because above all, it’s important to treat each individual patient with the information available while applying good judgment.

 

Transcranial direct-current stimulation (tDCS) at start of occupational therapy sessions yields more functional improvement after stroke, study demonstrates

A recent study published in the journal Science Translational Medicine earlier this month has demonstrated that an extra boost of electricity to the brain may result in improved upper limb use when combined with occupational therapy sessions following either ischemic or hemorrhagic stroke.

Transcranial direct-current stimulation (tDCS) has demonstrated in a small study to optimize the benefits of rehabilitative therapy for upper limb deficits after stroke. Graphic source: http://nwg.glia.mdc-berlin.de

Transcranial direct-current stimulation (tDCS); graphic source: http://nwg.glia.mdc-berlin.de

Twenty-four patients with upper limb impairment due to a stroke that had occurred at least six months previously were randomized to one of two groups. Patients in the treatment group received a small amount of direct electrical current, delivered via an electrode that was placed on the scalp over the motor cortex on the same side as the stroke. The second group of patients still had the electrodes in place, but no electrical current was being delivered. For the first 20 minutes of nine therapy sessions (one session per day, for nine consecutive days) the patients wore these electrodes. Following the 20 minute period, therapy continued as usual.

The idea was to determine if a small electrical stimulus could wake the brain up, so to speak. Neuronal plasticity is the term given to the concept that following a brain injury, surrounding cells can adapt to perform functions previously carried out by the cells that were damaged in order to restore function that may have otherwise been lost. While relatively small (24 patients participated in the study), there was a statistically significant improvement in upper limb movement in the patients receiving direct electrical current when compared to patients who did not receive electrical stimulation.

I always become intrigued (and excited) when options for stroke prevention or recovery that don’t involve more medications, surgical procedures, and/or significant risk to patients produce positive results, and this is such an example. This has the potential to be a sizeable step forward in producing better results with stroke rehabilitation, and larger studies are warranted. Perhaps what is most exciting is that the benefit was still seen three months later, despite patients not having not received electrical current stimulation during that time. This implies that the rehabilitation is effective and long lasting.

For more information about this study, click here.

 

#Redshoes4youngstroke: A Call to Action!

One of the central missions of The Stroke Blog since it went live in October 2014 has been to provide information to those who have survived a stroke or strokes that occurred at relatively young ages. The very first post, “Deconstructing the Mini-Stroke,” recognized that while there may be symptoms more-or-less universal to some stroke types regardless of a person’s age, that the young stroke population tends to struggle differently through what I call their stroke aftermath.

One problem in the young stroke population is that, while we have a drug (IV t-PA) that can help to minimize the long-term aftermath of ischemic stroke when administered within three to four-and-a-half hours of stroke onset, many young patients do not receive it. A number of my young patients have told me that when their symptoms began, they decided to take a nap or wait it out, either because stroke was not on their radar, or because even if it was, they believed stroke to be a disease of the elderly. Those who do take their symptoms seriously and seek emergent medical attention can be misdiagnosed, because healthcare providers may doubt that a stroke can occur at young ages. For hemorrhagic stroke, early medical attention can result in better outcomes for different reasons. Perhaps an aneurysm has ruptured requiring urgent surgical repair, or a hemorrhagic stroke patient requires emergent blood pressure control. When stroke symptoms develop, regardless of a person’s age, emergent medical attention should be sought. In the United States, this means calling 911 (not driving oneself to the hospital).

According to the Centers for Disease Control, in 2009, almost one-third of stroke hospital admissions in the U.S. were for patients under the age of 65. The Center for Health Statistics estimates that $15.5 billion was lost in productivity in the U.S. in 2008 as a result of stroke patients having to leave the workforce. When stroke strikes a young adult, it costs these individuals personally on many fronts, but it also takes its financial toll at a national level.

This is a public health problem. I want young people to know that when sudden paralysis develops in an arm or a leg, the right thing to do is to get to a hospital as quickly as possible in hopes that t-PA treatment may be a possibility. For severe strokes resulting in large artery occlusions, or “blockages,” we now have very compelling clinical trial data telling us that using a catheter to remove the blood clot is very beneficial in some patients, but only when the stroke is treated early. A delay of even a few hours may make the difference between being dependent on others for care, or returning to independence.

I challenge you to raise awareness about this problem. I challenge you to find a red pair of shoes in your closet, or purchase an inexpensive pair

Wearing my red shoes at the International Stroke Conference about 20 minutes before this blog post!

Wearing my red shoes at the International Stroke Conference about 20 minutes before this blog post! #redshoes4youngstroke

of red shoes, or if this is too much of a financial burden, to spray-paint an old pair of shoes red. Wear them proudly. The more they stand out, the better. If you are asked about them, use the opportunity to share with the questioner that a person is never too young to have a stroke. If you have a personal story to share, I challenge you to be bold enough to share it. If you are hesitant about sharing it, then communicate to others that stroke is not a disease only affecting the elderly.

Take a picture of your feet in these shoes, and post it to social media – to Facebook, Twitter, whatever. Include the hashtag #redshoes4youngstroke when you post it. Tag others in your posts whom you feel will care about this cause and participate. If you have the financial means to do so, consider making a donation to the American Stroke Association, National Stroke Association, Young Stroke, or another not-for-profit organization you feel has been supportive of the young stroke population. I will watch for interesting red shoe pictures with the #redshoes4youngstroke hashtag to come along, and will repost some of them with permission on The Stroke Blog.

Wearing my red shoes at the International Stroke Conference about 20 minutes before this blog post!

Moments before hitting “publish” for this post – hoping to bring more awareness around the plight of young stroke patients.

I’ll start. While purchasing a pair of boots for the winter online in January of this year, amazon.com recommended these shoes to me. I thought this was bizarre, as they looked nothing like the boots I had just purchased, but then it seemed almost fated. Somehow amazon.com knew me better than I knew myself, and realized that I would want these there’s-no-place-like-home shoes. Indeed I did, because I instantly decided to call them my “stroke awareness shoes.”

I wore them a few times earlier this month while caring for patients in the hospital to see how people would react, and I received multiple comments each day from patient family members, people in elevators, other parents when I picked my son up from basketball practice. I practiced giving my 20 second spiel about a person never being too young to have a stroke, and it resulted in a number of engaging conversations. Some people even said they would join me in wearing red shoes to raise stroke awareness!

I also want to thank the neurology residents at Duke University, who are not only fantastic physicians, but who have been my sounding board as I have contemplated this. They have been full of great ideas!

I am currently attending the American Heart Association/American Stroke Association’s International Stroke Conference, and am wearing my red shoes. I am encouraged at the response I have gotten over the course of the morning, and feel certain this can extend beyond those who care for stroke patients.

With greater awareness comes greater funding for research, greater compassion for the plight of a group of survivors, and greater understanding of an issue that exists in our society. Let’s wear our red shoes!

What does “blurry vision” really mean after stroke?

Visual symptoms are very common following both ischemic and hemorrhagic stroke. These complaints have a tendency to receive the label “blurred” or “blurry” by both patients and healthcare providers, but an important part of accurate diagnosis and increasing the chance of improving these symptoms for the patient involves understanding what the problem is. Not all “blurry” vision after a stroke is actually “blurry”! Over time, I have found that visual deficits following a substantial brain injury tend to fall into one of the following categories. While scores of neurological conditions can result in these visual syndromes, for our purposes we will keep the focus on stroke.

Diplopia, or double vision, occurs when more than one image of an object is being visualized by the patient. This occurs most commonly because the eyes are not aligning properly to fixate on a visual target, and as a result of failing to converge at a specific point, mixed visual information is presented to the brain. When a patient has experienced a stroke, most often I find that the injury was in the brainstem, as there are centers controlling eye movements in this location. Double vision can also occur if there is an injury to one of the cranial nerves controlling eye movement closer to the eye itself, even if the brainstem is not injured.

Visual aura often is described as “blurry vision” by patients, but is much more complex than this description would suggest. Stroke patients may experience temporary visual illusions, such as the visualization of distorted surroundings, blurring of a crescent-shaped area or a larger section in a person’s visual world, flashing lights, wavy lines, development of “tunnel vision,” or any other number of transient visual symptoms. Fortunately, visual aura is very benign and treatable in most cases. Patients may be concerned that episodes of visual aura are TIAs, or transient ischemic attacks, that may represent the start of another stroke. I have seen people who have been taking warfarin or other big-gun anticlotting therapy for years because of “TIAs,” but when we get down to it turns out to be visual aura.

This MRI was obtained from a young postpartum woman after she noticed that she was unable to see objects in the right half of her vision. MRI confirmed the presence of a left occipital and temporal lobe injury due to stroke.

This MRI was obtained from a young postpartum woman after she noticed that she was unable to see objects in the right half of her vision. MRI confirmed the presence of a left occipital and temporal lobe injury due to stroke.

  • Homonymous Hemianopia occurs when a visual field is distorted or absent, meaning that one half of someone’s visual world is impacted. Often patients will think they have lost vision in the right eye or in the left eye, when in reality upon testing, the eyes are fine, but the right half of the person’s visual world is absent. This typically occurs with an injury to the occipital lobe, the brain’s visual processing center. Put simply, the right occipital lobe processes visual information in the left field of vision, and the left occipital lobe processes the right field. A stroke impacting the right occipital lobe may result in loss of vision in the left visual field. The MRI brain (figure 1) was obtained from a young postpartum woman with a left occipital infarction with hemorrhagic conversion, which resulted in loss of vision in her right visual field.

Visual Hallucinations occur when a patient detects objects or movement that is not actually present. This can occur for a variety of reasons, involving either the brain or the eye. Charles Bonnet Syndrome is the name given to visual loss followed by the brain “filling in” missing visual information in the form of hallucinations. I have seen cases where the hallucinations are pleasant (a cuddly appearing kitten), and cases where they are disturbing (large insects). If visual hallucinations are present after a stroke, I always think it is worth performing an electroencephalogram (EEG) during the hallucination to better exclude seizure activity in the area of injury.

Oscillopsia is present when a patient perceives that objects at rest are “swaying” back and forth when movement is not actually present. This can occur with brainstem or cerebellar stroke, but I have seen it in other locations as well. Patients without stroke may experience this visual phenomenon with benign paroxysmal position vertigo (“inner ear” vertigo, as a lot of patients describe it) or with migraine as well.

Cortical Blindness typically involves injury to both occipital lobes. Patients lack vision, even though the eyes may be healthy. This can be devastating for patients, as these are typically patients who have always relied on vision who abruptly become blind without warning since stroke is usually of sudden onset. I attended an event in 2013 (Dining in the Dark) in which a nice dinner was served to us as we wore blindfolds. Have you ever considered how heavily you might depend on your vision to get through simple tasks, such as a meal? It gave me tremendous appreciation for what patients with cortical blindness after stroke must experience – to have vision one day, and for it to be gone the next is difficult to imagine. To make things even more challenging, some patients with cortical blindness develop Anton Syndrome, which involves blindness without the recognition that blindness exists. Now can you imagine everything around you seeming real, but none of what you are visualizing is actually there?

Finally, there is vision that is truly blurry. Regardless of the stroke’s location, patients often complain that their glasses prescription does not seem correct any longer. They may obtain a new prescription after the stroke, only to find that it is no longer accurate six weeks later. A neuroophthalmologist (this is a neurologist or an ophthalmologist who specializes in visual problems after a brain injury) can be helpful here, but it takes patience from both patient and physician as symptoms tend to fluctuate.

Want to participate in a clinical trial? Try clinicaltrials.gov!

There is still a vast amount that remains unknown in the world of stroke treatment, particularly when it comes to managing what comes after the initial hospitalization and rehabilitation process. Fatigue, pain, insomnia, anxiety, depression, spasticity, walking deficits, headaches, dizziness, visual symptoms – sometimes our typical approaches to managing these symptoms do not seem to be as effective after a brain injury. For example, patients with thalamic pain syndrome after an injury to a part of the brain known as the thalamus often struggle with uncomfortable pain, tingling, burning, and/or a sensation of “tightness” around an arm or a leg, and they may quickly exhaust all of the available options. Medications that are generally effective for many painful conditions frequently fail to provide relief for this patient population. Once healthcare providers and patients are both out of ideas, the question about available clinical trials arises.

Clinicaltrials.gov contains information on more than 206,000 clinical studies.

Clinicaltrials.gov contains information on more than 206,000 clinical studies.

Clinicaltrials.gov is a fantastic resource available for physicians, investigators, and patients, but the problem is – many patients are unaware of its existence. It is a registry of most clinical trials involving human subjects in the U.S., and also includes information about thousands of trials taking place in other nations. Currently, the site contains information about more than 206,000 studies!  If one is seeking study information on Fabry disease, a relatively rare genetic disorder that can result in stroke at a young age, as of this post’s publication date 102 results were identified from searching on the term “Fabry.” Nations outside of the U.S. have also created their own registries. In Europe, for instance, the EU Clinical Trials Register serves the same purpose. Similar registries are available in South Korea, Japan, and Australia, to name a few others.

If you feel you are out of therapeutic options, regardless of what medical situation you may face, I encourage you to try an easy search through an online clinical trials registry. This information is free of charge, and can empower patients as they navigate through complex conditions and symptoms. Type the name of your diagnosis in the search bar, regardless of how rare it is, and allow yourself to explore. Not only might it be beneficial for you as a patient to consider a clinical trial if there are no known answers, but the more willingness there is on the part of patients, physicians, and investigators to participate in research, the sooner the answers that have evaded us will come.

Reflecting on Cerebral Venous Sinus Thrombosis, and the U.S. Presidential Election

Just after New Year’s Day in 2013, I was asked by a local news station about a story in the mainstream media involving a “blood clot in the brain.” At-the-time Secretary of State Hillary Clinton had fallen and hit her head, and this was followed soon afterwards by a diagnosis of a blood clot “in the vein between the brain and…skull,” according to this news article. I recognized over the following week while the story played out in the news that, while Clinton’s clot was not the same thing as one might think of an ischemic stroke, there was little understanding outside of the medical community of how her neurological issue differed from the large majority of blood clots in the brain. I even received several questions about it from patients, the most common one being – did Hillary Clinton have a stroke? And my answer was – not exactly.

Ischemic strokes, as we think of them, involve an obstruction in an artery that is preventing oxygen-rich blood from reaching its target destination within the brain. Arteries can be blocked by blood clots, plaque accumulation within the wall of the vessel, a torn lining in the wall of the artery (dissection), or even overgrowth of cells within the blood vessel wall (hyperplasia). Veins, on the other hand, drain blood away from the brain and back to the heart once the oxygen has been extracted from it. Veins of significant size in the brain are called venous sinuses, as they are structured more like collecting pools for the drainage of blood that is no longer rich in oxygen. A clot that occurs in one of these venous sinuses are known as a cerebral venous sinus thrombosis (CVST). It is much less common to develop an obstruction blocking blood flow in one of the brain’s veins than it is within an artery. According to the scientific statement published by the American Heart Association/American Stroke Association in 2011, only 0.5 to 1 percent of strokes result from a blood clot in a cerebral vein.

People might be familiar with the concept of a venous clot, such as in a leg if one sits in a car or on an airplane for a prolonged period of time. However, venous clots can occur anywhere in the body, including in the brain.

Various factors may lead to increased risk of clotting in one of the venous sinuses or in a cerebral vein. It is important to understand that in all of us, our blood is in a constant state of flux. Just as the American government is set up with checks and balances such that the branches can more-or-less keep each other in check, our blood has millions of molecules pushing it towards clotting, and millions breaking down clots. We need to clot so we do not hemorrhage. Yet, our blood needs to be able to flow to our organs, and if it can’t because of extensive clotting then heart attacks, strokes, and other catastrophes develop.

There are certain genetic mutations that can cause blood to clot more readily, such as the factor V Leiden mutation or the prothrombin mutation. There are people who lack certain proteins that assist with breaking down clots, and in the absence of these proteins clots are more likely to develop. Deficiencies of protein C and protein S are two of the more common examples of this. Autoimmune disorders can increase the risk for clotting in general, such as can be seen with lupus and antiphospholipid antibody syndrome. The use of certain types of birth control pills can cause elevated risk of CVST, as can pregnancy, because elevated estrogen levels have been associated with thrombosis. Cancers and systemic infections/sepsis can cause massive hemorrhaging or diffuse clotting. Significant concussions or skull fractures can also result in CVST.

The most common initial symptoms of CVST are headache, visual changes, and/or seizure. A headache that continues to escalate for days to weeks, especially in a patient taking birth control pills, who is pregnant, or who has a history of abnormal clotting should undergo MRI of the brain. Standard MRIs are sensitive enough to detect most CVST, but if there is any question an MR-venogram or a CT-venogram of the head should be performed. If CVST is identified, the treatment is an anticlotting medication. Warfarin is the most common medication used for this, although rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa) have been used more recently as off-label agents. In pregnant patients, enoxaparin (Lovenox) is typically used because it is thought to be safe (pregnancy Category B). Warfarin is known to cause birth defects (pregnancy Category X), and the effects of the other oral agents on fetal development is unknown at this time. Warfarin can be used safely in breastfeeding mothers once the baby is delivered.

Venous sinuses within the brain drain blood and send it back to the heart. Image source: http://www.dartmouth.edu/~humananatomy/

Venous sinuses within the brain drain blood and send it back to the heart. Image source: http://www.dartmouth.edu/~humananatomy/

In my experience, patients with CVST do very well clinically once started on an anticlotting therapy, especially if the clot is identified early. Secretary Clinton’s treating physician claimed in this news article that she had a clot in the transverse sinus. The nice thing about transverse sinuses is that there are two of them, and when one is blocked due to the presence of clot, blood is usually still able to drain from the brain. Her physician also noted that she had a deep venous thrombosis (DVT) in the 1990s, suggesting she might be at risk for clots. If people are at particular risk for clot formation, being dehydrated does not help (Clinton was reported to have influenza during that time), as the blood becomes more concentrated. While he described the condition as “potentially life-threatening,” in the dozens of transverse sinus thromboses I have treated, none of these patients have died, and the recovery is very favorable. Even patients with very large superior sagittal sinus thromboses do very well typically if recognized early and started on therapy.

When making a determination about whether a patient has had a stroke if an artery is blocked, we require that some degree of damage has occurred in the brain before calling it a stroke. If there is no damage and the patient has no lingering symptoms in this scenario, then the diagnosis of a TIA, or transient ischemic attack, is made. In the case of CVST, if diagnosed and treated early and lacking any evidence of damage to the brain, it probably should not be labeled as a stroke either. While it may be convenient to throw all CVST cases in the “stroke” bucket, many of these patients will not sustain permanent brain injury, and will go on to lead productive lives without lingering evidence that such an event ever occurred. So did Secretary Clinton have a stroke? I stand by my answer of – not exactly.

Would I expect something like this in Secretary Clinton’s medical history to prevent her from carrying out the duties of the presidency if she is elected in November? No more than migraines would have stood in Michele Bachmann’s way in 2012, or than atrial fibrillation would have prevented Bill Bradley from performing presidential tasks. By the time adults reach their 50s or 60s, it is almost an inevitability that a health condition of some sort will be present. If we want candidates for president in near-perfect health, we could change our laws and elect a very young person as our commander-in-chief, but then we lose the presence of life experience.

Disability Income In The United States After Stroke Made Simple

Some of the topics I spend the most time discussing with patients and their families who are facing the aftermath of stroke have nothing to do with actual medicine. Medical school, residency, and fellowship provide the opportunity for physicians to learn that drug A treats condition B, and that we use drug C because Clinical Trials X and Y suggested it is beneficial. When physicians enter the world of clinical practice, while our patients depend on us to guide them in making decisions that impact their health, they also want to answers that physicians are not formally trained to answer. Personally, the non-medical topic I find myself discussing the most frequently with stroke patients is the process of applying for disability income in the United States.

The first time a patient asked me why she was turned down for social security, I had no idea. She clearly was physically disabled from her stroke. I had completed the appropriate paperwork sent to my office. I could see she was visibly upset at being denied this needed income, and I felt guilty, as if it was my fault in some way, despite having meticulously completed the forms. What happened?

Fast forward to 2015, and I think I have gained more insight into why this scenario occurs. My disclaimer here is that I am not an attorney, employed by the federal government, or a certified account, so what I am sharing is what I have gained watching hundreds of stroke patients navigate the process. Patients frequently do not understand how the system works, and many healthcare providers don’t either. To be perfectly frank, I am naïve to all of the inner-workings of “the system,” but I can boil it down to a few key points that I hope will provide clarity to anyone out there living with neurological deficits after stroke and seeking answers.

Stroke patients in the United States essentially have two options available for long term disability income:

  • If a long term disability insurance policy was purchased prior to the stroke from a company such as The Hartford, MetLife, or Liberty Mutual (these are only a handful of carriers out of the many available), then an application can be filed. The patient’s healthcare provider, usually a physician, will be asked to complete paperwork, and copies of relevant medical records will be requested.
    • Typically there is a waiting period, which is variable. If a patient has short term disability insurance, income from the short term disability policy can be used for part or all of the waiting period until the long term disability income is available. If there is no short term disability policy in place and no sick leave available, there is usually a lengthy unpaid period as the patient waits.
    • If a patient improves over the course of the waiting period, even if a long term disability policy is present, the patient may not be eligible to receive income if the level of disability cannot be verified in the medical records or from the paperwork completed by the healthcare provider.
  • Then, there is social security. This has to be one of the most misunderstood systems in the U.S. Patients have so many different ideas of what social security is, how it works, how one receives benefits, and so on. The National Stroke Association does a fantastic job of breaking down social security on its website. Click here if you would like to read more.
    • In the example I mentioned above, the reason the patient was denied social security income was not because she was not physically disabled, but because her stroke was less than one year old. Her stroke was too recent. The condition has to be expected to last “at least 12 months.” My advice to stroke patients who have been denied social security income if they applied less than one year after the stroke is to reapply.
    • If a patient is already receiving social security income because of his or her age (let’s say – a 70 year old patient who has been receiving social security income for five years), then the patient is already receiving the money! People do not receive double the amount of money for becoming disabled over the age at which they become eligible to receive social security income.
    • If an adult has never worked, or worked but somehow never paid into the program, or if a person worked but did not contribute enough to the program while working, then a person is probably not eligible to receive social security income. If there are questions about your personal situation, I recommend contacting an attorney with expertise in this area. It’s important for patients to understand that social security is an annuity, meaning that people pay in to the program as an insurance policy. In return, money is paid out, either when a person becomes disabled or when a person reaches retirement age.

Clinical trial shows no difference in stroke prevention between antiplatelet agents and anticoagulation in carotid or vertebral artery dissection

Due to the number of readers of The Stroke Blog who have identified themselves as having experienced carotid or vertebral artery dissections with or without stroke, I believe a clinical trial from the United Kingdom is very much worth sharing here.

The Cervical Artery Dissection in Stroke Study (CADISS – Markus HS, et al) set out to answer a question that has existed for many decades in the world of stroke management. When a dissection (a tear in the innermost tissue layer of an artery) of a carotid artery or vertebral artery (arteries in the neck that bring blood to the brain), how is a stroke best prevented going forward? In patients who have already had a stroke at the time the dissection is diagnosed, the goal is certainly to prevent further strokes from occurring. If a patient has not already sustained a stroke, then sparing that person a permanent brain injury is the top priority. It has not been entirely clear how to achieve these goals though. Should a patient be treated with antiplatelet agents (medications impairing platelet function), such as aspirin, clopidogrel (Plavix), another antiplatelet agent, or some combination of these? Or should a patient be treated with anticoagulation, a drug that actively prevents clotting, such as warfarin (Coumadin) or heparin?

I have heard many arguments on all sides. Some neurologists say that antiplatelet therapy is just as effective as warfarin but carries a lower risk of hemorrhage. Others say that antiplatelet therapy is not aggressive enough and anticoagulation with warfarin or heparin (or both) should be used. Some say to start on antiplatelet therapy or anticoagulation and if symptoms get worse to switch to whatever therapy was not initially used. Others argue for placing a stent in the dissected artery. Until recently, there was no clinical trial actually comparing antiplatelet therapy to anticoagulation in patients with carotid artery or vertebral artery dissection, and the medicine selected for treatment was based entirely on anecdotes and the bias of the treating physician.

In the CADISS trial, patients presenting to one of the participating medical centers in the United Kingdom who were diagnosed with carotid or vertebral artery dissection (with or without stroke) believed to have occurred within the seven days prior to presentation were randomized. Half of the patients were started on antiplatelet therapy, and half were placed on anticoagulation. The duration of treatment was three months. The endpoint was to determine how many strokes or deaths occurred in each group. Whether or not the patient had already had a stroke before enrolling in the trial, the endpoint was to see, once antiplatelet therapy or anticoagulation was started, how many patients went on to have strokes despite that therapy.

The CADISS trial, published in Lancet Neurology in April 2015, did not find a statistically significant difference in stroke prevention in patients presenting with acute carotid or vertebral artery dissections when treated with either antiplatelet therapy or anticoagulation.

The CADISS trial, published in Lancet Neurology in April 2015, did not find a statistically significant difference in stroke prevention in patients presenting with acute carotid or vertebral artery dissections when treated with either antiplatelet therapy or anticoagulation.

Two hundred fifty patients were enrolled (118 carotid artery dissections and 132 vertebral artery dissections). Interestingly, 52 of these patients were not found to have carotid or vertebral artery dissections when their radiology studies were carefully reviewed as part of the study, despite initially receiving that diagnosis. Of the 198 patients remaining, there was no significant difference in strokes between the two groups. There was one episode of symptomatic bleeding in the anticoagulation group (subarachnoid hemorrhage, or bleeding in the brain that occurs when an artery in the brain ruptures). There were no deaths in either group. Of the 198 patients with radiological evidence of dissection confirmed, there were only four total strokes following initiation of the designated medical therapy in both groups combined.

The CADISS trial began as a feasibility study – a trial to see if it was even feasible to enroll enough patients with a condition not diagnosed with frequency in the emergency department. This phase of the study was statistically sound and convincing enough not to proceed with a larger trial.

A trial comparing stenting to medication alone has not been performed, and given the low number of strokes in patients on medical therapy in the CADISS trial, it is unlikely that a dissection stenting trial will be performed any time in the near future.

For more details about arteries bringing blood to the brain and about carotid and vertebral artery dissection, please refer to a prior post on The Stroke Blog by clicking here.

The take-away points from CADISS are as follows:

  1. The overwhelming majority of patients with carotid and vertebral artery dissection, if started on either antiplatelet therapy or anticoagulation soon after the dissection has occurred, will not go on to have a stroke while on therapy during the aftermath following the vascular injury.
  2. There is no significant difference in stroke prevention in patients with carotid and vertebral artery dissection between those using antiplatelet medications and those using anticoagulation.

The trial does not address the myriad symptoms many dissection patients notice lingering after the injury – migraines, neck pain, and anxiety, to name a few. One trial cannot address every possible issue associated with a medical condition. However, physicians who care for young stroke patients with this particular vascular injury should be celebrating the fact that we finally have evidence-based guidance for preventing stroke in these patients.

Mechanical thrombectomy makes a comeback in treating acute ischemic stroke

Intravenous (IV) t-PA, a “clot-busting” drug approved by the FDA for the treatment of acute ischemic stroke within three hours of the start of symptoms, has been recognized as the standard of care since the pivotal NINDS clinical trial that demonstrated reduced level of disability 90 days after ischemic stroke in eligible patients who received it. However, the subject of acute treatment with the use of thrombectomy has remained controversial until recently. Thanks to recent clinical trial results, the American Heart Association/American Stroke Association guidelines have now been updated recommending the use of this procedure in eligible patients meeting appropriate criteria.

Depending on the geographical region and practices, approximately one to 25% of acute ischemic stroke patients will receive IV t-PA, with the national average being around six to ten percent. Questions that have continued to plague physicians delivering care to this patient population include:

  • What, if anything, can be offered to patients who are not eligible for IV t-PA, but who still present to the hospital within hours of stroke onset?
  • What should be done for patients who have received IV t-PA, but who are failing to improve clinically, and there is a known blood clot that remains in a major artery of the brain?

A mechanical thrombectomy is a procedure performed with a catheter (a specialized type of wire) with the intention of physically removing the clot if it is not dissolving on its own or with the assistance of IV t-PA. A mechanical thrombectomy can be performed either with or without the administration of a dose of t-PA directly from the catheter within the artery at the site of the clot.

MERCI clot retriever (ref: Medscape)

MERCI clot retriever (ref: Medscape)

An early catheter for this procedure was the Merci Clot Retriever. Its tip is shaped like a corkscrew, with the goal being to spear a clot and extract it from the artery, restoring blood flow. This was followed by a suction device, made by Penumbra, which aimed essentially to vacuum the clot from the artery. Despite the excitement around

Penumbra vacuum suction catheter - from Penumbra site

Penumbra vacuum suction catheter – from Penumbra site

offering patients these procedures in the acute stroke setting, the outcomes trials were discouraging, largely failing to show improved functional outcomes for patients  than they could achieve with IV t-PA.

Graphic of a stent retrieval device for clot removal

Graphic of a stent retrieval device for clot removal

This has changed in the past year though. Five papers have been published within this timeframe showing improved functional outcomes with mechanical thrombectomy with early therapy intervention. The newer retrieval devices involve the use of wire stents to extract the clot, and the result has been less time required to open the artery to restore flow to the brain. A key difference between these more recent trials and the failure to demonstrate improved outcomes in previous mechanical thrombectomy trials is likely due to the more rapid restoration of flow. The mantra of “time is brain” still holds true. The recent trials have shown what is possible when a team of healthcare professionals collaborate effectively to start the procedure as soon as possible. While thrombectomy may have been available for years, waiting on a key person to become present when the others are ready to start creates delays.

The updated guidelines from the American Heart Association/American Stroke Association emphasize the importance of continuing to treat patients with IV t-PA who are candidates for the drug. After all, IV t-PA can be administered quickly, its benefit has been proven, and it should not be withheld in eligible candidates. However, mechanical thrombectomy with stent retrieval devices provides another tool in the battle against acute ischemic stroke.