On April 28, 2020, a letter published in the New England Journal of Medicine describing blood clots in large arteries supplying the brain (known as “large-vessel strokes”) in young patients testing positive for Covid-19 brought media attention to this particular facet of a disease physicians, healthcare providers, and researchers are endeavoring to understand. (Click here to read the brief NEJM letter.) The letter’s authors have been treating patients with Covid-19 in the Mount Sinai Health System in New York City. They note that, on average, every two weeks their hospitals typically encounter 0.73 patients with large-vessel strokes who are under the age of 50, but within a two week period, they encountered five, and all were Covid-19 positive. It’s a small sample size, but the trend is concerning.
As time passes and more information is published about what this disease looks like in its various presentations, it seems to start in many patients as a respiratory illness, but when patients become ill with it, it is because it has transitioned into a disease involving blood clots and/or severe inflammation within the arteries. Report after report has emerged of patients who are awake and talking with emergency medicine physicians and healthcare providers, who then quite suddenly go into cardiac arrest and die. Stories of patients losing limbs and fingers/toes due to blood clots are emerging. Lungs are full of blood clots (pulmonary emboli) in many patients. Stroke is yet another complication of blood that easily and readily clots when the brain is the organ on the receiving end of that impact.
And now children, who were initially thought to be safe from Covid-19, with “mild” or no symptoms initially, are being reported as developing inflammation within their arteries and going into heart failure, in what is similar to a syndrome known as Kawasaki disease.
(Click here for a good mainstream media article summarizing various effects of Covid-19 in layman’s language.)
As for my own patients – what I am personally hearing from people who have experienced strokes in the past who have been infected more recently with Covid-19 is that they seem to be losing the progress they made previously through rehabilitation and time. Old stroke symptoms from their prior brain injuries are rearing their ugly heads again, and deficits that they thought were in their rearview mirrors have now arisen again. This can happen after a stroke with any bodily infection, whether it is a urinary tract infection or pneumonia, and is called recrudescence.
As businesses begin the reopening process, we are still seeing tens of thousands of new cases emerging daily in the United States, and the death count in this nation now exceeds 78,000. Mind you, this is the death count. We’re not talking about patients who survive Covid-19 with long-term scarring in their lungs, or those who have suffered limb amputations or disability associated with strokes. We also still do not know what the long-term toll of this disease is. It was only about seven months ago that this virus began infecting human beings, and we really don’t know what the long-term effects will look like a year, five years, or ten years down the road.
I’m not trying to be unnecessarily alarmist or cause panic. I care about our economy. I deeply care about jobs, livelihoods, and businesses. But as a physician, I am being real.
I also know that people who need to get back to work will not be successful in the work place long-term if they are trying to recover from the aftermath of strokes, or if they have long-term breathing problems because of the lung damage they have sustained. I am looking at the Covid-19 pandemic as a long-term battle, and do not want all of the sacrifices that have been made to fight it to be in vain if/when it just keeps returning.
I mentioned in my previous blog post that Dr. Anthony Fauci announced to the press in March that models were projecting deaths of 100,000 to 240,000 people in the US, and reporters argued with him in disbelief. They didn’t like it. They didn’t accept it. He basically said he hoped for a better outcome, but the numbers were what they were. We are getting closer to this estimated range each day.
We can feel emotionally impassioned, bored, scared, or beyond ready to resume life as we knew it only a few months ago.
But unfortunately, viruses don’t play by our rules.
In 2012, I walked through a cemetery in Cashion, Oklahoma, eager to find the final resting places of my grandmother’s seven siblings and many other long since departed ancestors and relatives. My grandmother, Alta Jane Anderson, was still alive then, going strong in her assisted living facility in Houston, Texas at the age of 92, her mind as sharp as it had always been. She could talk March Madness brackets each year, still read a book every week or two, and never forgot the birthday of any of her children or their spouses, her seven grandchildren or their spouses, or of her 18 great-grandchildren.
When she suffered her ultimately fatal hemorrhagic stroke at 96 years old on my son’s third birthday, April 21, 2016, my aunt put her on the phone with me, and she said, clearly in pain and her speech heavily slurred, “Hi, Sweetie. Is Alexander having a good birthday?” How in the world did she have the mental clarity or compassion in that moment to ask me that, instead of being concerned for herself? To this day, she carries the distinction of being the person containing the most genuine goodness within her of anyone I have ever known.
As I walked through this sleepy rural graveyard, I called Granny on my cell phone, unsure of where to begin in my search for departed family members. Her voice lit up at the sound of mine, as it always did when any of her family called, and then she verbally navigated me to the correct area to pay my respects. Granny was born in 1919, and as I saw the grave stone of her older sister, Lottie, and the year of her death (1918, at age 20), the reality of my grandmother having never met her older sister enclosed around me. Lottie’s three month old infant son was buried next to her, having perished only four days before his mother.
I asked my grandmother what took both of their lives at such young ages. Her reply sounded like something out of a dusty history textbook, from a time in the very remote past: “It was the Spanish flu.”
(Interestingly, this pandemic received its nickname because the Spanish press was free to cover the impact of this flu, not because it originated in Spain.)
After finding other family grave sites, I wandered over to a shaded area beneath the canopy of a beautiful tree, and Granny and I proceeded to have a conversation about the great influenza pandemic of 1918. She recounted her mother’s stories of how her family could not have a proper funeral for Lottie and her son because of the fear around group gatherings, and the fear others had of catching this deadly flu. Burials were significantly delayed because of the high number of deaths within a short period of time, and local undertakers became overwhelmed.
As I sat in the cemetery on that gorgeous Oklahoma spring day, I distinctly remember having this thought: Thank goodness we live in the age of modern medicine and don’t have to live through the heartbreak of such a pandemic.
After all – the influenza pandemic of 1918 occurred during a time when only black and white photos were taken, almost a decade before the first “talking” movie premiered. We had advanced so far past that era.
As I write these words today on April 15, 2020, 33 days after schools shut down in Durham, North Carolina and group gatherings suspended, stemming from the same fears of more than a century ago, they seem naive. Even as a physician at that time, I was operating under the assumption that modern medicine could protect us from another pandemic. I knew that clinical trials and the development of vaccines take years to complete, but at that time, it seemed even to me that our technology, medicine, and people could spare us from another such pandemic of large magnitude.
And I still certainly hope that is the case. That historic pandemic took the lives of at least 50 million people worldwide, 675,000 of which were in the United States when its population was smaller than it is today.
Yet, despite our modern medicine, and brave, highly educated, and experienced doctors and healthcare providers on the front lines delivering care, the mortality rate as of the latest reported data in the United States from Covid-19 complications is at 4.2% (26,977 deaths and 617,628 cases – likely an underestimate of cases but an overestimate of the percentage of infections who die, given the lack of testing in people with mild or absent symptoms).
There is a fear that accompanies the Covid-19 pandemic such that most people have not witnessed anything like it in their lifetimes. I have, however, witnessed it in mine, on the faces of patients for whom I have cared who have suffered strokes at relatively young ages. I have seen numerous individuals who unexpectedly, while going through life in their primes, are stricken with a disease they thought only possible in older or unhealthier people. In particular, when a specific cause for the stroke cannot be identified, many of them initially live in daily fear, wondering if and when it will happen again.
Their fear stems from the unknown, and from the lack of control they have in their situations. Many of these healthy young people have asked me, “How is my cholesterol doing?” When I would inform them that their cholesterol had nothing to do with their strokes, often the question that would follow would be something to the effect of: “So what can I do not to have another one then?”
When Covid-19 existed primarily in China, much of the chatter in the western world among younger and healthier people involved words to reassure themselves that they would be safe, such as: “It’s really only older people and people with weak immune systems who die from this.” While older and immunocompromised patients are in the higher-risk categories for perishing from Covid-19, it didn’t stop the alarm many felt when stories began emerging of healthy young people who had succumbed to the disease. The 30 year old school teacher in New Jersey. The 39 year old disc jockey in Florida. The 17 year old in California. Eventually we learned that up to half of patients ending up in intensive care were under age 65. This did not fit our current ideas about flu, pneumonia, or any other passing viral contagious diseases to which we have become accustomed as a society. How, then, to ease the fear and gain a sense of control again?
What I have witnessed in stroke care since becoming a vascular neurologist in 2010 has been very similar. How do we explain it when a healthy 25 year old dies unexpectedly and quickly from a stroke when she had her whole life ahead of her? Is there a way of ever feeling in control again after witnessing such a thing?
Recently, I observed Dr. Anthony Fauci, the now-familiar face of the National Institute of Allergic and Infectious Diseases, speaking at a press conference, explaining that models were projecting a “best case scenario” of 100,000 to 240,000 deaths in the United States from Covid-19 if social distancing continued. Members of the press immediately launched critically into him. What they seemed to be saying was…we don’t accept that. That’s not right. He kept looking back at them, reiterating that the numbers were suggesting this, that he hoped for a better outcome with continued social distancing, but this is what the numbers suggested at that time, and that he was merely the messenger of this news. They argued with him. They didn’t like it.
As I watched, I thought – so many people in this country have not faced death. They have not seen the fear on a patient’s face as he or she wonders if today is his or her final day. This is the first time in the lives of millions of people when they have truly had to confront the question of how much time they have remaining, and they, understandably, find this distressing.
I have written before on The Stroke Blog about how I try to live my life to the fullest each day, not knowing if each day will be my last, because I have seen so many young people who think they have decades in front of them, only to find themselves struck unexpectedly with disability or death. It led me to a telemedicine career in 2018 so that I could savor my days with my children while they are still young, so they can remember their mother if that last day does arrive earlier than expected. It has led me to reflect on why stroke-related deaths in “young” celebrities impact us emotionally. Two years ago, stroke survivor Brett Patterson shared his story of searching for answers as to why he had a brain hemorrhage in his 20’s. He would be the first to tell you that he lives each day now with gratitude and perspective since that time, understanding that each day counts.
Silver linings exist in each human tragedy, as difficult as they may be to find. In the case of the Covid-19 story, perhaps a silver lining is bringing perspective to millions about the fragility of life such that we can learn to appreciate our days here, and understand what young stroke survivors have already known about the importance of making each day count. It’s the understanding that we can and should follow the recommendations of public health officials to prevent the spread of the virus and save as many lives as possible, but to find joy in the everyday-ness of life. Knowing that the ordinary is extraordinary. Having a conversation with a neighbor. Dining in a restaurant. Taking kids to school. Birthday parties. Working. Life.
Tomorrow is not guaranteed to any of us, global pandemic or not.
Have you ever had the experience of going five, ten, maybe even 20 years and not given a single thought to something, only to find that when it pops up on your radar again, it repetitively re-enters your world in an almost surreal way?
I am having that experience right now with a television show that was incredibly popular when I was in middle school and high school called Beverly Hills, 90210. I arrived in Honolulu, Hawaii a month ago for the International Stroke Conference, and as I was checking in at the hotel, I noticed a blues and jazz club entrance in the hotel lobby – The Blue Note. I did not have anything on the agenda for the evening. My father had just turned 70 in December, and surfing the waves on Hawaii’s North Shore had always been on his to-do list. His flight was due to arrive very late into the night. After checking in, I walked to the kiosk to buy a ticket to The Blue Note, and learned that Vanessa Williams was the singer performing that night!
Excuse me for a moment, but AAAAAAAHHHHHHH!!!!!!!!!!!!
Those who know me best understand that I am quite possibly bordering on obsessive when it comes to music of the ’80s and early ’90s, and nostalgia for that time period, no matter how ridiculous some aspects of those years may have been, runs deep within me. Don’t get me wrong – I savor the present and have a “Carpe Diem!” mindset, and don’t dwell in the past, per se. But I was only a kid then, and man I loved music and TV growing up! I have attended a lot of concerts of ’80s and early ’90s artists and bands, but had not had the opportunity to hear Vanessa Williams perform, even though I very much wanted to do so.
Vanessa did not disappoint. I had the privilege of reliving my childhood through her songs from a serendipitous front table at the base of the stage in the intimate venue of about 120 fans (apparently people had been watching The Super Bowl earlier in the evening?!). Save the Best for Last, Colors of the Wind, The Sweetest Days… but it was Love Is that hit me emotionally for some reason. With the opening notes, my mind immediately leapt back to the Beverly Hills, 90210 soundtrack, the pictures of Luke Perry that some girls had in their lockers, and how much I enjoyed hearing that song on the radio during 1993, a pivotal year as I transitioned from middle school to high school.
After the show, despite being extremely exhausted at this point since it was about midnight in Hawaii and I had flown from North Carolina that day, I was up for hours more, reflecting on middle school days. The joy of newfound independence and responsibility that came with having a locker. The rejection from someone I thought was a friend. Being 5’7″ tall in seventh grade but dancing my heart out at school dances even if I was taller than all of the guys. Learning from some of the most wonderful teachers imaginable. Laughing until I cried. Crying until there were no more tears.
That’s middle school. Or at least, that was middle school before social media and the internet.
I then stayed up even longer, reading online about Shannen Doherty’s battle with breast cancer, and Luke Perry’s acting career since his days as Dylan McKay on 90210. My dad then arrived just before dawn, and we had coffee together while watching the sunrise. What a great start to the trip!
About a week later, on the long journey back to North Carolina, I heard two people in the Seattle airport discussing the television show, Melrose Place. (For those of you who are unaware, it was a spin-off of 90210). Again, strangely, after not giving 90210 a single thought for at least 25 years, there it was in the forefront of my consciousness. Weird? Or just a coincidence?
Unfortunately, I see young people who are disabled or killed by strokes with relative frequency as a vascular neurologist, and focus much of my effort around advocating for young stroke survivors (thus, this blog). It is sobering when I no longer feel surprised when a young person arrives in an emergency department with a stroke. The media is treating stroke in young people as “rare,” but it is not.
And yet, for some reason, despite being fully aware that stroke can strike the young and the old, I was surprised when I heard this tragic news about Luke Perry.
Perhaps it’s because 90210 had already been floating around in my mind since hearing Vanessa Williams perform Love Is.
Perhaps it is because I thought of my middle school-aged self during Luke’s reign on 90210, and I was so young, naïve, and innocent then. I had never seen death. I may not have even known what a stroke was then.
Or perhaps I felt stunned because Luke wasn’t really 52 in my mind. His presence on our television screens was one of youth, and that youth persists in my visual memory of him. He stayed young, even as time moved on off of the set.
Luke’s death is different than many celebrity deaths, because it touches on a vulnerability. Someone still in his prime years, young, and in a way, forever young in our minds, had a stroke. If it happened to him, it could happen to anyone.
But then again…he was 52. Is that young? Yes, I think it is, but it’s not 20 (although young stroke survivors know that one is never too young to have a stroke, but hopefully you will take my point here). Luke Perry was 52. And he died from a “massive stroke.”
And then another thought occurs…I was only in middle school when he was on billboards, in commercials, and on television; I was most definitely on the younger end of the 90210 generation, but despite being on that younger side, a few months ago I turned 40! How is that possible? 90210 (in its original form) was only on TV a few years ago. Was 52 young to me when I was 20? It certainly seems to be young now that I’m 40.
Wait. About the original 90210 being on TV only a few years ago. Make that…28 years ago that it premiered. Where did that time go? There has been much to show for it, but still…wow.
Luke’s death forces members of a generation to face the reality that we may feel young and act young, but we are getting older. Yet, it also demonstrates in the harshest of ways that people who are young can lose their lives very quickly to stroke. I have often written on The Stroke Blog that tomorrow is not guaranteed to anyone. I stand by that assertion.
I sincerely hope a day will come when we can rid the world of this awful disease.
I have spent the past week debating whether to post publicly about an email I received from The State (South Carolina’s most widely distributed daily newspaper). Ultimately, I concluded that it was important to do so. Stroke patients need a voice, and while The Stroke Blog was started to empower the younger stroke population through sharing information pertaining to their circumstances, empowerment leads to advocacy.
The email response I received from one of the editors, frankly, shocked me: “THanks [sic] but we’ll have to pass. We don’t generally run columns on all these made-up months, weeks and days…”
I had difficulty understanding what prompted this. Stroke has created a public health crisis, has disabled millions of Americans, and remains the fifth leading cause of death in the U.S, killing over 130,000 people annually in our country. In addition to these alarming numbers, according to the National Stroke Association, as many as 80% of strokes can be prevented. Plus, we have effective treatments within the first few hours of when a stroke starts! Therefore, stroke seemed like the perfect condition upon which to build more awareness. It’s devastating, but we have the power to change that on a large scale, both through preventative efforts and by rapidly treating strokes when they occur.
After deliberating, I replied to this particular editor, and explained that Stroke Awareness Month was being recognized by the mainstream media and hospitals across the country. This person’s quick response was that all months/days devoted to causes should be viewed the same way, whether they were about heart attacks, diabetes, “or chocolate or bicycling or … anything.”
At that point, I called a friend who has worked with hundreds of stroke patients professionally, and asked her what I was missing. I understood that there were numerous “_____ Awareness Month” recognitions, but it made perfect sense to me that the importance of calling 911, the recognition that prompt medical attention can save a person from lifelong disability, the understanding that stroke is not just a disease of the elderly, that education about the importance of smoking cessation was critical, that the knowledge that patients with high blood pressure should comply with taking their medications would all be important points for coverage in the media. And raising awareness around issues that can lessen the incidence of a disease that kills so many people annually still seemed like a good thing to me. As much as I love chocolate (and I do – seriously), lumping awareness around stroke and awareness around chocolate into the same statement rubbed me the wrong way.
In talking with my friend, she reminded me that Stroke Awareness Month was, indeed, “made up” – by President George H.W. Bush in 1989 when he signed a proclamation declaring every May as “Stroke Awareness Month.” I then began reading articles, editorials, and reflections about Stroke Awareness Month, and contemplated how important this time is to so many people affected by stroke. One of my favorites was a piece by Kirk Douglas from 2014 on The Huffington Post (click to read it).
I truly believe that everyone has the right to his or her opinions, and the right to express these opinions with language. The State can make its own choices about the importance or lack of importance of Stroke Awareness Month, and I can make mine. I believe we do need more awareness around stroke, because I want to be treating more patients with t-PA and mechanical thrombectomy, but I can’t if they don’t call 911 or get to an emergency department quickly after a stroke starts. If they lie down on the couch to take a nap, there is a good likelihood that it will be too late to treat them once they show up at a hospital. That decision – whether to call 911 or lie down – often alters the course of a person’s life, determines whether that person will ever return to work again, will be able to care for himself or require assistance from others for decades to come.
What ultimately shifts people in the 911 direction over the lying down direction?
Bill Paxton was one of those versatile actors who had always just been around for us. When his unexpected death at 61 was recently announced, I heard reactions such as: “Oh, I loved him in True Lies” and “He was in Apollo 13, right?” My immediate thoughts turned to Titanic (yes, I’m a girl – I saw it in the theater three times), and to the quirky explorer played by Paxton, attempting to recover the remains of the sunken vessel while understanding the stories of those who had perished. He has existed in my memory as a youthful individual, perhaps because he is frozen in time in that role for me. Film does that. It prevents us from believing that aging occurs, and yet it still does behind the scenes.
Bill Paxton, exploring the Titanic in the 1997 film
According to mainstream media sources, Paxton had rheumatic heart disease, and underwent surgical replacement of one of his heart valves on February 14, 2017. First lesson in this story: the reason for treating strep infections of the throat (strep pharyngitis) with antibiotics is not necessarily only to prevent the infection from worsening, but more so to eradicate the infection so that a more serious problem involving the immune system does not develop later. Following strep infections, the immune system can mount an inflammatory response, which can then result in an immune attack on the valves of the heart. The inflammatory state is known as rheumatic fever, and the valve injury is known as rheumatic heartdisease. Eventually, many patients end up having surgery to replace defective heart valves years after their initial encounter with rheumatic heart disease.
Following his heart surgery, Paxton had a stroke. In one study published in December 2016, after data from 21,821 patients having undergone mitral valve surgery was analyzed, it was found that 3.89% of them experienced strokes soon after the procedure. The risk seems to be slightly lower in those undergoing aortic valve replacement. The truth is, however, that general anesthesia alone carries a risk of stroke, even when the heart is not the target for surgery. Blood pressure decreases under anesthesia, which can result in difficulties getting blood flow through tight areas where plaque build up may be present. Short-lived irregular heart rhythms that can generate blood clots, such as atrial fibrillation, are not uncommon during or following surgery. Procedures involving catheters (wires inserted into blood vessels) can cause stroke if plaque is “knocked loose” by the wire, or if clot forms at the tip of the wire.
Paxton’s death brings further awareness that, while we attempt to keep procedural risks as low as possible, surgery does carry the risk of stroke. The desire is for the potential benefit of surgery to outweigh the risks involved, or else the surgery should not take place. Risk assessment is a game of odds, and hoping that patients will land on the more favorable side of the equation.
I am finally able to share the results of the largest study to date evaluating treatment of young adults in the first hours after the onset of ischemic stroke! First, though, I would like to provide some background for you.
When I left practice in the community hospital setting in order to start at Duke University in June 2015, it was in part to have the resources to study stroke management in younger adults. I had questions. Lots of question.
Are young adults receiving IV t-PA (the “clot-busting” drug for early ischemic stroke) with the same frequency as their older counterparts, or are they less likely to receive it because they are misdiagnosed?
Stroke patients who are presented with the option of receiving IV t-PA early after a stroke are often told there is a 6% risk of bleeding from the drug, but is this accurate for younger adults? Or is the bleeding risk lower in younger, healthier individuals having strokes?
Are there delays in treating younger adults because of a reluctance to treat, or delays in recognition that strokes are occurring?
In September 2015, I submitted a research proposal to the American Heart Association/American Stroke Association as part of an application for the “Young Investigator Award,” which would allow access to the largest stroke database in the United States, as well as funding for statistical analysis. I learned in January 2016 that the AHA/ASA agreed that these were questions worth answering, because the proposal was selected for the award. Over the course of the spring and summer of 2016 my colleagues and I worked on this project and getting the abstract ready for submission to the International Stroke Conference, and yesterday, the results were finally presented!
Poster summarizing some of the results from the study described in the blog post. Details will be published in a forthcoming journal article.
Overall, data on the strokes sustained by over 30,000 patients between the ages of 18 and 40 was analyzed, and compared with stroke data on 1.2 million strokes in patients over age 40. 12.5% of the younger patients received IV t-PA, versus 8.8% of patients over 40. Of patients who arrived at the hospital within 3.5 hours (more likely to be eligible for IV t-PA because they made it to the hospital within the time window to receive the drug), 68.7% of younger patients received t-PA, versus 63.3% of patients over 40.
The part of the study that excited me the most was the low rate of bleeding complications in the younger adult stroke patients – only 1.7% had symptomatic bleeding in the brain within 36 hours of t-PA, versus 4.5% of those over 40. Regarding severe bleeding elsewhere in the body, only 0.3% of younger patients experienced this problem, compared with 1.0% of those 40 and older. The reason this excites me is because we as neurologists finally know what the real bleeding complication rate is in the young adult population from t-PA, and instead of giving these young adults numbers that were generated from the more typical, older stroke population, we can say with good data to back us: “Your risk of bleeding from this drug is only 2%, and the likelihood of benefit far outweighs the potential risk.” Young people in the midst of a stroke deserve accurate data to consider when making the decision about whether to accept t-PA as a treatment.
We found significant delays both in getting the head CT scan done after arrival and in starting t-PA in the younger stroke patients. Adults over 40 who receive t-PA are more likely to receive it less than 60 minutes after arrival to the hospital, and are more likely to have their head CT scan done less than 25 minutes after arrival.
There is a lot of work to do in treating all stroke patients more rapidly, and we have to find ways to treat more patients overall when they present to the hospital in the midst of stroke. This is a step forward in understanding how younger adults with stroke are treated, and in comprehending the real complication rate, as opposed to giving them information that applies to the older population.
(Reference: Dodds JA, Xiao Y, Sheng S, Fonarow GC, Matsouaka R, Bhatti DL, Peterson E, Schwamm LH, Smith EE. Intravenous Recombinant Tissue-Type Plasminogen Activator Use in Young Adults with Acute Ischemic Stroke. AHA/ASA International Stroke Conference, Houston, TX – 23 February 2017.)
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.
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.
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. 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
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.
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.
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.
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 sinusthrombosis (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/
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.
The traditional teaching about the role of the cerebellum has typically been that it coordinates movements and “fine tunes” them. It provides balance when walking, and stability of a hand when reaching for a glass of water. When the cerebellum sustains an injury or is malfunctioning, then the result may be gait disturbance, falls, dizziness, or tremor.
The cerebellum is featured in red in this image. Image credit: http://www.brainhealthandpuzzles.com
The ideas above are what I learned in high school biology, in anatomy, and in physiology. Even throughout my neurology residency training, I largely thought of the cerebellum as a structure that provided balance and fine tuned movement.
It has interested me during my time in clinical practice to witness the fallout from cerebellar stroke, particularly in the younger stroke population, because it is often far beyond balance and movement. Yes, the symptoms mentioned above are often present in some form when the cerebellar stroke occurs, perhaps along with a headache and/or nausea. However, the patients who struggle with recovery for months or years following a cerebellar stroke often complain of symptoms that do not fit with the traditional concepts of what the cerebellum is supposed to be doing.
Some of the complaints I have heard from numerous cerebellar stroke patients are as follows:
– Many struggle with the same cognitive symptoms that patients with strokes injuring the frontal or parietal lobes experience, such as difficulty with focus and multitasking, and because of this, they complain of difficulty with short term memory retention.
– Other cognitive symptoms may exist as well, such as feeling overstimulated, or having difficulty following a conversation in a group of people.
– Difficulty with language fluency (aphasia) has afflicted cerebellar stroke patients in my own experience, and their frustration after being denied disability benefits is palpable.
– Some cerebellar stroke patients express that they are unable to dream any longer, or that when they close their eyes to picture a scene – being at the beach on a breezy day, or running through a field of grass and flowers – they are unable to mentally visualize such a thing.
– Sometimes their significant others claim these patients have demonstrated changes in their moods or personalities, and that their relationships seem different since their strokes.
MR images of Jonathan Keleher’s brain (A and B). The black diamond-shaped void in images A and B reveals Mr. Keleher’s missing cerebellum. The images on the right demonstrate the presence of a cerebellum in the space in a normally developed brain. Photo credit: Massachusetts General Hospital, courtesy of Jeremy Schmahmann for use on NPR.org
Last month, as I was driving home from work one evening, I heard this segment on National Public Radio’s All Things Considered, and I thought – yes! I have to share this on The Stroke Blog with readers! This piece summarizes the complexities of the cerebellum so well for the public, and I hope those of you who read this will take a few minutes to listen to the segment if cerebellar injury is of interest.
The piece features Jonathan Keleher, a 33 year old man who was born without a cerebellum. In the segment, it is explained that Mr. Keleher struggles with emotional complexity, language, and other cognitive tasks beyond imbalance and impaired motor skills. However, because he received intensive physical and speech therapy at a young age while lacking a diagnosis, he was able to demonstrate the wonder of neuronal plasticity – the ability to utilize other parts of the brain to accomplish tasks normally dependent on the cerebellum. He walks independently, and he works in an office environment. He lives independently.
We like to believe that each function is neatly packaged within a certain compartment of the brain. Patients often ask: “If my stroke was here [pointing to a specific part of the brain], then what problems should I expect to have?” While some structures in the brain correlate more or less with certain functions, it really is not that simple, as evidenced by the complexity of the cerebellum, and by what a young man who lacks one has been able to accomplish in its absence. The brain is a large community of cells, an interdependent network that makes us who we are, and which enables us to survive from one second to the next.
Update on November 14, 2017:
When I published the above blog post on cerebellar stroke in 2015, I never dreamed that it would become the most frequently visited page on The Stroke Blog day after day. The comments readers have posted in response to it, and the emails I have received from patients and their loved ones, have underscored the need for more resources about cerebellar stroke. I have heard you, and am working currently to create such a resource beyond a blog post. Stay tuned.
I have also received many emails from patients who have been diagnosed as having vertebral artery dissections believed to have caused their cerebellar strokes. Until recently, there was no largely comprehensive resource for patients struggling through the aftermath of vertebral dissection, but a few months ago, my speech language pathologist colleague, Amanda Anderson, and I published a book for vertebral and carotid artery dissection survivors (click here for more information) and their families in hopes that it would provide badly-needed answers to lingering questions. If you are a vertebral artery dissection survivor, I sincerely hope you find the book useful, and that it at least somewhat helps to validate your “new normal.”
Cerebellar stroke can be more difficult to accurately diagnose because the symptoms frequently don’t scream “Stroke!” the way that weakness on one side of the body or a facial droop may. I have seen cerebellar stroke patients in the acute setting diagnosed with migraine, benign forms of vertigo, intoxication, and substance abuse. When diagnosed early, situations leading to cerebellar stroke can be successfully treated with better outcomes for patients. Awareness of cerebellar stroke in both the community and amongst medical providers is critical for earlier diagnosis and more optimal management.
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