Concussions and brain disease

[00:00:01]

RICK WEISS: Hi, everyone. I’m Rick Weiss, Director of SciLine. Thank you very much for being on the line with us today. I want to give you a quick introduction to SciLine so you know who’s hosting this meeting, and then we’ll get started with the briefing. I think as many of you know by now, SciLine is a philanthropically supported free service for reporters that’s all geared towards getting more scientific evidence and research based information into news stories. We do that through a variety of ways.

But primarily we do it through number one, our matching service, through which, if you are a reporter working on a story, you can get in touch with us. We have a huge database of scientists who are excellent in their fields and also very good communicators, and we get in touch with them. We get a good match for you, and we connect you to them in time for your story.

The second thing we are doing is producing fact sheets that are designed to be easy to use by reporters. They are posted on our website. They are produced in-house, but they are vetted by a half a dozen or so outside experts in each case so you can count on them. And it’s very easy to pull that information into stories that you’re working on.

And the third thing we do are these media briefings where we take topics where we think there’s some confusion or some ability to help reporters understand a complicated issue better, an issue that is going on in the news and we anticipate going on for a while, and pull together experts who can give you the specific research findings and the evidence in those areas so you can be as precise and as detailed as possible as you write stories on these topics.

[00:01:38]
I can’t think of a more timely topic for this early football season than the one we’re doing today, which is on concussions and the science behind them. We took a quick look back at what’s been going on on the football field just in the last five days, and I won’t read you the whole list. But I can tell you that the Dolphins tackle, Laremy Tunsil is out with a concussion as of Sunday. The Jets Buster Skrine is out of the game with possible concussion. The Saints Marshon Lattimore came out of the game with a concussion two days ago. Cooper Kupp and Brandin Cooks of the Rams were out with concussions on Sunday.

And the Baltimore Ravens cornerback, Tavon Young, was taken out of the game. And this sort of amazing thing I saw about a news story about that is that it says while the situation is dire. Well, it turned out, of course, they’re not talking about his health. They’re talking about who’s going to take his place on the field. This is a hole in journalism that really needs to be addressed by science and health reporters as well as sports reporters, and that’s what we hope we’ll be able to help you do today.

And by the way, it’s not just football, of course. It’s hockey. It’s other sports and it’s other situations. We noticed recently that Ryan Gosling ended up with a concussion because of some accident while he was filming First Man, the new movie that’s coming out about NASA’s mission to the moon so a timely and relevant topic.

Our three speakers today are going to give you a good variety of background on this. Dr. Ann McKee, first, from Boston University School of Medicine and the VA of Boston Healthcare will open. And their bios, by the way, are on the landing page so I’m not going to take the time to go through them now. Dr. Andrew Peterson will be second from the University of Iowa. And Dr. Angela Colantonio from the University of Toronto will be our third speaker. And then we’ve got plenty of time for Q&A after that.

I’m going to turn it over first to Dr. Ann McKee.

[00:03:36]

ANN MCKEE: What I’d like to do is just introduce CTE very briefly historically, talk about where we are with the research, and what our gaps are in knowledge and where we need to go. As you all know, CTE is not a new disease. It’s been around for centuries. It was first described in boxers in 1928 by Martland, who happened to be a pathologist. But despite his profession, he described the clinical features of something he called ‘punch drunk’. It was later known as dementia pugilistica because it was thought it primarily affected boxers, but by the middle of the last century, with the acknowledgment that it could be head injury of many sources, the term chronic traumatic encephalopathy or CTE was coined.

My first experience with CTE was in 2003, when I examined the brain of a boxer named Paul Tender. He’d been diagnosed during life with Alzheimer’s disease, but when I looked at his brain under the microscope, I saw a florid tauopathy, no beta amyloid, and what I saw was an extraordinary disease that I’d never seen before even though I’d been studying tau and tau based diseases for some 20 years. It was different than any disease I’d seen because of the pattern of the deposition. And I became quite fascinated with it.

Speed ahead five years and I examined the first football, first former NFL player, that was John Grimsley who was 45 when he died accidently. He’d spent nine years in the NFL. What I saw was the same unique tau based disease in his brain that I’d previously seen in the brains of boxers. So I thought immediately this is an important area of medicine. It was an area of medicine we didn’t know much about, that is the consequences, long-term consequences, of head trauma.

And we created a brain bank. It’s called the VA-BU-CLF Brain Bank. In the first year, with large recruitment and education efforts by my colleagues Bob Stern, Bob Cantu, and Chris Nowinski, we received about ten brains. And now, eleven years later, we have over 625 brains in the VA-BU-CLF Brain Bank, and we’re acquiring brains at approximately the rate of two per day.

[00:06:12]

We’ve selected brains from athletes of multiple sports, including American football but also rugby, soccer, boxing, mixed martial arts, professional wrestling, and also from military veterans, individuals exposed to domestic violence, poorly controlled epilepsy, and the like. We’ve received a very high number of brains from young athletes and also from athletes who’ve committed suicide. Approximately 100 brains of those 625 are from individuals aged 30 and under, and about half of those are suicides.

We have large gaps in the number of women’s brains we’ve collected. We need to know if there are gender differences in CTE, which we do suspect. But we don’t have evidence for it at this point. We also have a gap in understanding military related injury. We need to collect more military brains, especially from individuals exposed to blasts and improvised explosive devices because we know very little about the full consequences of those injuries. We also know that over 350,000 military veterans were affected with trauma from blasts or concussive impact in the last conflict in Iraq and Afghanistan.

During the 11 years that we’ve been studying CTE, we found CTE in 331 athletes and military veterans out of the 470 that so far have been examined. It is the largest brain bank devoted to trauma and CTE.

We’ve also established pathologic criteria to definitively diagnose CTE. We know that CTE is not Alzheimer’s disease. It’s not aging. It’s not any other disease. CTE is a unique degeneration triggered by exposure to head trauma. The trauma is usually repetitive and mild and although we initially focused on concussions, our work has repeatedly demonstrated that it is the little impacts that are not symptomatic, what we call subconcussions, the impacts that the players play through seemingly unaffected, those are the important factors in risk for CTE. We found that cumulative exposure to subconcussive impacts is significantly associated with higher risk for CTE and higher pathologic severity.

[00:08:42]

Last July, we reported CTE in 110 of 111 NFL players, or 99 percent, and 48 out of 53 college players, or 91 percent. And while that study has been criticized for selection bias, I should mention that there is always selection bias in brain bank studies. And while it exists, selection bias is not so high as to negate the importance of those very high numbers. What our study shows at the bare minimum is the people who play football for many years develop CTE much more often than those who do not play football. Or in other words, 110 former NFL players developed a devastating disease that is extraordinarily rare in individuals without a history of head trauma.

Our studies have also shown that inflammation is a critical part of CTE. It appears to be the earliest change in the brain. It develops in response to exposure to head impacts and becomes more severe as CTE develops and worsens. We’ve also identified a novel cytokine in CTE that may prove useful in diagnosing CTE in living individuals. We are in the midst of developing specialized PET scans that use tau ligands to detect tau protein buildup in living patients, and we’re looking at blood and spinal fluid markers to diagnose CTE. Importantly, we’ve also developed experimental models of CTE in order to develop and test possible new treatments.

So who is at risk for CTE? Well, we know that there are approximately 20 million current and former high school and college sport athletes; 20,000 current and former NFL players; and 360,000 military veterans exposed to mild TBIs, blasts, or concussive injuries. There’s a lot that needs to be done. We are using the knowledge gained from the precious resource of the brain bank to understand how, where, and why CTE develops in the brain, and we are using these advances in our understanding to develop ways to diagnose and treat the disease.

Right now we have no way to diagnose the disease in the living. If we could detect it in the living, not only would it give us a prevalence of the disease in the general population, but we would also have a way to monitor potential therapies. Right now, there are no treatments for CTE.

CTE is a preventable disease and a potentially treatable disease, but we have to care about it enough to take measures to stop it. How long will we allow people to suffer before we start making significant differences in the way we play sports and in advancing research that will enable better care for athletes and military service members? So thank you very much.

RICK WEISS: Thanks, Dr. McKee. That was fantastic. Dr. Peterson?

[00:011:39]

ANDREW PETERSON: Thanks. Hi. Yeah, I’m Andy Peterson. I’m a sports medicine doctor and pediatrician at the University of Iowa. I take care of athletes on the sidelines when you hear on TV about people being removed from the game for a concussion evaluation or the doctor looking at him for a concussion. Yeah, that’s what I’m doing on Saturdays with the Iowa Hawkeyes.

There’s a lot of people like me around the country who do the same type of work. So while I do concussion research and do some youth sport epidemiology work, I’m going to talk mainly now about what we do on the sidelines, what our concussion evaluation actually looks like. It looks like a lot of things.

The initial evaluation starts well before the injury. So preseason preparation is really important in these settings. We do a lot of work before the season to find out who our athletes are and what type of injuries they’ve had in the past. People with a lot of concussions in the past, we might consider doing some different things with them during the season. Or if people have underlying neurologic problems that might put them at risk for brain injury, we might treat them differently as well.

We also do a lot of testing at the beginning of the season for any of the tests that we might use to help recognize concussion later on. Concussion testing is a lot more useful if you have a baseline to compare it against. And that isn’t just for the computer based neurocognitive tests that a lot of people think of with baseline testing but also for balance tests, some of these symptom tests, their memory concentration, those types of things, we tend to test a little bit of that before the season as well so when we roll into recognition mode, we’re a little more prepared. We’ve got some more information about what that player is like at baseline.

Speaking of recognition, that’s really the next step. So when someone’s playing, whether it’s during a game or at practice or they just wander into the training room, it’s really important to recognize these injuries when they crop up. If you don’t have suspicion for it in the first place, you’re not going to make the diagnosis. And that recognition can come from a lot of different places.

Oftentimes, we actually see that mechanism out on the field. We’ll see people get hit hard or we’ll see people get up slowly after a big hit, and that’s an indication that we should further evaluate someone. There’s also a lot of other people that can make that type of determination. In the Big Ten, we’ve got spotters up in the booth who can identify people that should get further evaluation. Coaches sometimes ask us to take a look at someone. Other players commonly do this, will notice that a teammate isn’t acting well. And sometimes officials will remove people from the game for them to be evaluated.

[00:13:43]

Once they get to the sideline or once we start that evaluation, it starts out relatively informally. You want to get an idea of what happened without going too deep into actual diagnostic testing right away because oftentimes these things can be explained by other problems. Sometimes they have a different injury that causes them to get up slowly, or sometimes they’ve got something else that has changed the way they’re playing. And you want to make sure that you’re not missing something else that’s obvious in the meantime.

But once you have some concern for a concussion, we tend to move into some diagnostic testing fairly soon. If it’s a game setting, we’ll move them from the sidelines. I take people back to the locker room. Some people use some of those isolation tent things on the sideline to be able to evaluate someone in a little bit more private or less distracted environment. And most of us will use some type of validated concussion test in that setting.

I use the SCAT5, which is something that’s part of the Berlin International Consensus Statement on Concussion in Sport. There’s some previous versions of that that were pretty similar. Some people will use other validated tests like Vestibular Ocular Motor Screen or the King-Devick Test, and there’s some complicated computerized versions of these types of tests as well that some people use as well. I don’t think that part matters quite as much. There’s no real gold standard diagnostic test for concussion at this point. You want to do something that gets you thinking about the types of deficits that someone might have when they’re acutely concussed.

So now let’s say that you had someone that you’re diagnosing with a concussion on the sidelines. The first step is just getting them out of there. If someone is injured, there’s only two things that really matter on the front side, that initial rest, making sure that they’re not doing anything extra, and then not putting them at risk for getting hit in the head again while they’re still concussed. These second impact types of events tend to be much worse concussions. When you get a concussion on top of a concussion, symptoms tend to be more severe, tend to last longer, and sometimes even lead to long-term disability and possibly death. These second impact events are important. So it’s important to remove your athlete from harm’s way while they’re still symptomatic.

After the first few days of the injuries, that rest period matters a little bit less. It’s still important to make sure that they don’t get hit in the head, but there’s some emerging evidence that we can start people moving a little bit more. And some people will do some early informal aerobic exercise. And other people will do a more formal exercise rehabilitation type of protocol. We use the Buffalo Treadmill Test at Iowa, but there’s a lot of different versions of that where we can get people moving after those first few days of initial rest.

And then as people are progressing out from their injury, as they’re recovering, we monitor them pretty closely. We tend to use the concussion symptom severity score every day, but also, we’ll do some measures of balance and sometimes we use some measures of cognitive function as well as they’re progressing through. These aren’t terribly fancy things. We’re not doing any big, fancy testing during that period.

[00:16:15]

Every now and then, people will have symptoms that last for more than a few days, and then we’ll typically move into some more rehabilitative modalities. If people have more vestibular symptoms, we’ll start doing some vestibular rehab. If they have more vision symptoms, we’ll do some more vision therapy. If they have more exercise intolerance and headache, we tend to do exercise rehabilitation. But there’s a lot of different rehabilitation modalities that we can use at that phase that are more targeted towards the symptoms that the individual player has.

Eventually, almost everyone fully recovers from their acute concussion. And at that stage, we’ll use some final testing to make sure that they’re really back to their baseline. We use a type of computer based neurocognitive testing called ImPACT at the University of Iowa. I’m not promoting or singling out that particular product. I think there’s a lot of good versions of that on the market. But we use it to improve our sensitivity to ongoing neurocognitive disfunction after someone has seemingly clinically recovered from their injury. So once they’re back to normal to us, we use that test as a last check to make sure that they’ve really recovered. There’s no real role for those types of testing to monitor someone’s recovery or to diagnose a concussion, but it is useful on the back side to make sure that someone is back to their baseline before we really put them back at risk again.

And then finally, once someone has passed that type of testing, we use graduated return to play to get them all the way back to the field. So there’s a stepwise progression from going from a symptom free injured player to getting back to play. We start to with some easy aerobic exercise that progresses to some hard aerobic exercise before seeing some skill specific work, some strength work, and then seeing some contact in practice before they see contact in the competition setting.

A couple other key notes about concussion diagnosis in general, a lot of you are still familiar with the old grading scales for concussion. There used to be a grade one, two, and three concussion, and after that there was a simple versus complex concussion designation. Those have really gone away. We don’t really use these grading scales anymore. A concussion is a concussion. We take each injury as they come rather than try to prospectively put some type of grading material on them.

So with that, I am done with my portion of the presentation here. Hopefully we’ll have a lot of good questions later.

RICK WEISS: Thank you, Dr. Peterson. And we’ll go now to Dr. Angela Colantonio from the University of Toronto.

[00:18:20]

ANGELA COLANTONIO: Hello. Thank you very much for the opportunity to be able to speak about the epidemiology of concussion and how it differs for males, females, and also vulnerable populations. There are important differences and rates across the lifespan by age and sex and by injury context.

According to a recent national study published in 2017 on mild traumatic brain injury based on emergency room visits, injuries are highest in the youngest age groups and where most of the injuries are due to falls. In adolescence and young adulthood, there is a spike in incidence among males where motor vehicle crashes are more common, and this is largely attributed or to presume risk-taking behavior at this stage in life. In older adults there is an increase in incidence again with the highest rates among older women for mild injury. And this is the fastest growing segment of our population.

Now there are also important differences in subgroups of injuries such as sports related concussion. It’s been found that for some sports with similar rules, the rates of concussion are high among females. One large study based on national collegiate athletes, females were found to have a one point four higher overall concussion rate than males in sex comparable sports such as soccer, basketball, baseball, and softball.

Further, the rates of reported concussion and mild traumatic brain injuries has increased dramatically over the last six to ten years with the greatest increases among teenage girls in particular. For instance, one large study based on emergency room and physician visits show that six point three percent increase in rates for children and adolescent females versus a three point increase among boys.

[00:20:07]

In vulnerable populations, such as persons who are incarcerated or homeless, most of which are milder injuries, the injuries tend to be higher rates among males, and also to more likely have a fall as the major cause of injury. In one study we published, we reported that 58 percent of homeless men and 42 percent of homeless women reported lifetime prevalence of traumatic brain injury mostly occurring prior to their first incidence of homelessness. Among incarcerated individuals, estimates range from nine to 100 percent of sampled.

In workplace injuries, we see the most severe and fatal injuries disproportionately effect men, whereas when we include milder injuries, the rates of injury are more equitable. In one of our samples, it was 42 percent women when all levels of severity are included.

Now a largely overlooked area in concussion is in the context of intimate partner violence, which disproportionately effects women. It’s estimated that one in four women in North America are being effected by intimate partner violence, and of those, a majority of the hits are to the head, face, and neck. While there are no national estimates, to my knowledge, on the topic, commonly cited rates of injury are between 30 and 74 percent, but even higher. And this is a staggering number. And the injuries tend to be repetitive. Furthermore, they’re more likely not to be reported.

Overall, I want to say it’s really difficult to get accurate numbers of persons who sustain concussions as not all individuals may realize they had a concussion. You don’t have to lose consciousness to be diagnosed with a concussion. Also persons who may be effected may not seek care and it’s underdiagnosed and maybe missed in emergency rooms and other context.

So in terms of recent insights of sex and gender based difference and how people experience concussion, the literature is mixed. However, it overall supports that females on average take longer to recover and are more likely to have symptoms that persist for more than a month. A lot of this literature is based on sports related concussion. And some recent review of the literature have identified that girls and women experience a greater number and more severe symptoms.

[00:22:21]

Also injuries by sex may have different comorbidities. In the work we’ve done, for instance, we found that females with a concussion related emergency room visit between the ages of five and 49 have a higher rate of comorbid neck injury.

So you might say, what is this attributed to? This is very much an important area of future inquiry. So you look at factors related to biological sex, so biological and physiological characteristics, but they’re also social cultural. So for instance, girls and women have generally less neck strength, neck girth, head mass resulting in lower levels of head and neck stiffness that may make them more susceptible to rotational forces after a blow to the head. There may be hormonal differences that are different among women. So there’s some evidence that where you are in the menstrual cycle may effect your outcome. Girls and women have found to report concussion like symptoms in the absence of concussion, and they have been found to report higher total symptom scores both prior to and after the injury. Any preexisting mental health conditions, which are more common in women, are risk factors for poorer outcomes after a concussion.

In terms of social cultural factors, it’s been proposed that women and girls are more likely to be honest in reporting symptoms, although that’s controversial. And it’s also deemed that women are more likely to seek care in general. Other factors that should be considered is whether girls get differential coaching that may put them more at risk or whether athletic equipment should be different. Also it’s been proposed that some of our instruments may better capture symptoms like depression among girls and women versus men.

So why is it important to look at sex and gender based differences for injury management and prevention? It’s really important to understand sex and gender based differences as well as similarities as this is considered good science in order to inform more tailored management and prevention. There’s a dearth of attention to sex and gender reporting to date. For instance, a systematic review of over 200 studies on prognosis after mild traumatic brain injury published in 2016, reported only seven percent of studies had sex stratified data. This information is needed to form guidelines.

[00:24:46]

Data that is predominantly based on a male sample, for instance, may not be entirely generalizable to women. In our focus groups with women with brain injury, women report feeling dismissed when reporting symptoms which may be expressed differently than male counterparts. Also there are sex specific considerations, for instance, menstrual cycle disruptions being documented after a brain injury, including concussions, which is related to maybe hormonal fluctuations. In work we published, also we found that in more severe injuries there are different care preferences for young men and women, and that might be true for concussion as well.

To my knowledge, there’s been no intervention studies that have given explicit consideration to sex and gender. And our lab is currently funded by the Canadian Institutes for Health Research to see if educational materials that integrate sex and gender result in better outcomes.

And finally, importance to consider is that a lot of trailblazing work in concussions based on sports with a younger, fit population, how well this information translates to other contexts such as older adults, intimate partner violence contact, workplaces still remains to be investigated.

[00:26:07]

RICK WEISS: Great. Thank you. Thank you very much, Dr. Colantonio. We’re now going to open it up for Q&A. Once again, for reporters, if you have a question, you can type it into the Q&A box, which should be, I think, in the bottom right-hand corner of your screen.

And just to get things started, I wanted to get back to Dr. McKee because I think reporters might want to know when you talk about having one of the largest brain banks or the largest brain bank for this kind of study, what are we really talking about here? Are we talking about rooms full of entire brains? Are you talking about brain samples from hundreds of participants? What does a brain bank really look like?

[00:26:56]

ANN MCKEE: Okay. Well, when we bring the brain in, preferably it’s what we call fresh. It’s not been fixed. And we immediately bisect the brain, photograph it, and we snap freeze it. So we’ll preserve one half of the brain snap frozen in minus 80 freezers. And we have about 12 to 14 of those at this point. And then the other half of the brain will be fixed. It’ll be put in a formalin or formaldehyde derivative that mildly fixes the brain, and that will be used for diagnostic and neuropathological studies.

So if you were to walk in the brain bank, you would see a morgue table where we do the dissections, a photography setup, and then you’d see walls and walls and walls of freezers with frozen brains in them as well as containers in what we call a refrigerator or a refrigerated room full of brain. So half brains in each section.

[00:28:07]

RICK WEISS: Interesting. Okay. We have a question for Dr. Peterson wondering if so much of the diagnosis, to the extent there is a diagnosis, depends on patients reporting of symptoms, how accurate is that and how much are you dependent upon that as opposed to objective observations of some kind by a physician like yourself?

[00:28:33]

ANDREW PETERSON: Yeah, so patients lie on these things all the time. People under report or over report their symptoms all the time, and that’s something we always struggle with. There’s no great data on sideline evaluation, how often people lie about their symptoms.

I’ve got a few opinions about this. So a bit of a trend recently is to have independent medical examiners do these types of evaluations on the sideline and try to move it away from something that the team or the athletic department or whoever controls or has power over. In my personal opinion, nothing really replaces knowing the kid. I’m lucky here at the University of Iowa. I’m in the training room every day. I get to know all of our players. And I like to think that when I see them and they’re off their game, I recognize it. Now I use tests. I use validated tests and that’s part of it. But I still think that there’s no real substitution for just knowing the kid and being able to identify when they’re not themselves.

[00:29:29]

RICK WEISS: Great. Another question, this is from CeCe Morton, a freelance reporter. I think maybe Dr. McKee, I’ll ask you first. Others should feel free to chime in on any of these. But it has to do with your mention of the tau protein for those who aren’t familiar with that, the T-A-U, protein which she notes has been implicated in Alzheimer’s disease as well in plaques and tangles, I believe. What is the relationship between tau proteins presence in CTE versus its implication or its possible role in Alzheimer’s?

[00:30:05]

ANN MCKEE: Sure. So tau protein is a normal protein in the brain. It’s part of our nerve cells. It helps maintain the internal structure of the cell as well as helps pinch nutrients down the cell. But after trauma, with that traumatic stress to the nerve cell, the tau becomes abnormally phosphorylate. And as it becomes abnormally phosphorylate, it falls off the internal skeleton and clumps up in the cell as a toxic aggregate.

Now tau protein, abnormal tau protein, is a feature of many neurodegenerative diseases. It is a feature of Alzheimer’s, like you mentioned. It is a feature of progressive supranuclear palsy, corticobasal degeneration, primary age related telepathy. I won’t go into all of them, but just the presence of tau protein itself is not specific for a specific disorder, rather it’s the pattern and the region involved and the type of nerve cells or other cells that is involved.

In CTE, there’s a very distinct pattern. It tends to collect around blood vessels. So it’s a perivascular tauopathy where the tau in the nerve cells surround small arterials. That’s not seen in any other disease. For example, you wouldn’t see that in Alzheimer’s disease. Alzheimer’s, the tau protein tends to be diffuse, widely distributed throughout the brain, whereas in CTE it’s very focal.

It generally is most profound at what we call the depths of the cell site or the crevices of the brain. And the reason or that is, we think, related to the biophysics of traumatic injury. There’s the greatest distribution of the stress in the crevices of the brain and also around the blood vessels. So it’s a unique disorder that is easily distinguishable from those other disorders by looking at brain tissue.

[00:32:24]

RICK WEISS: Great. A question here for Dr. Colantonio to talk a little bit more about sex differences. Two things come up from questions here. One is – are some of the differences you mentioned perhaps due to different kinds of injuries? In some cases, maybe for males we’re talking more head impacts versus for females is it more neck injuries or other kinds of injuries that account for some of this difference? And a second question related to sex differences, is there any evidence that women do better in some cases than males, either in terms of prevention, because of more careful practices, or in terms of their recovery?

[00:33:08]

ANGELA COLANTONIO: That’s a good question. I would like to say this are of inquiry is in development because historically there has been not a lot of attention or systematic of integration of sex and gender in our research. There are some studies. Like I said, the studies are mixed in terms of who does better, girls, women, men. So there are definitely some studies that are…there’s inconsistent results. So that is the case. I don’t know if that answers your question.

[00:33:48]

RICK WEISS: Is there a difference between head injuries versus neck injuries…?

[00:33:52]

ANGELA COLANTONIO: Oh, the types of injuries. Well, what could be happening, too, is that there are comorbid injuries that disproportionately effect women. And what’s interesting is that some of these symptoms are overlapping, whether it’s some symptoms from a neck injury or for a concussion. So I think that makes it very challenging in terms of trying to disentangle. So that is an important area to investigate and also to consider, for instance. Another issue, too, is in an intimate partner violence context, you also have strangulation that’s associated with the intimate partner context, which also can effect outcomes as well.

[00:34:46]

RICK WEISS: Dr. Peterson, a question from Adam Zielonka at The Washington Times. What unique challenges does the sport of hockey present for diagnosing head trauma for players wishing to avoid head trauma? And do you have any personal thoughts you’d like to share about the NHL’s position in their retired players’ litigation against them?

[00:35:08]

ANDREW PETERSON: I don’t have any particular comments about the litigation in the NHL. Hockey’s challenging for a lot of reasons. The main reason is the ice. You have someone who’s hurt, and it’s hard to go out on the ice and to deal with those things. Second of all, your evaluation area is oftentimes really tight. You’re oftentimes doing it around the bench in very cramped areas with a very rowdy group of folks hanging all around you. I don’t have hockey here at Iowa, but when I’ve covered hockey at other places in the past, it’s always been a challenge to get a good evaluation just because of the setting.

Other than that, it’s really the same type of thing. people get injured in different ways than they tend to get injured in sports like football, but once you have the injury, the evaluation is essentially the same. You’ve got to find a controlled environment where you walk through things in a stepwise manner and be thoughtful about what you’re doing.

[00:35:56]

RICK WEISS: We have another question here for Dr. McKee wondering if the brain bank includes healthy brains as control comparators.

[00:36:04]

ANN MCKEE: It’s absolutely critical to get healthy brains as controls. I’m just going to mute this. I’m getting a double sound. So the question is about healthy controls. It’s absolutely essential to get healthy controls in our brain bank. We need them at every age group, 20 year olds, 30 year olds, 40 year olds, 50 year olds. Control brains are actually the most difficult brains to acquire. People don’t think of it after death, and of course we need the brain quickly after death. But it’s essential that you get controls, and we do have a wide variety of controls from the Framingham Heart Study as well as veterans as well as athletes who’ve donated their brain. But it’s always something that we need more of.

[00:36:44]

RICK WEISS: Thank you. A question here from Sheila Eldred in Minneapolis directed to Dr. Peterson. She says she’s curious about best practices in sports that aren’t as easy to monitor and deal with immediately from the sidelines, things like mountain biking for example. And I guess we’re talking here about best practices for prevention and maybe for what to do immediately after a possible concussive injury.

[00:37:12]

ANDREW PETERSON: Yeah, that’s a great question. A lot of what we think about when we think about sport related concussion assumes that’s there some type of medical provider around. In my opinion, most of the time that should be an athletic trainer. And most of the time doctors don’t need to be involved in that process. But we really assume most of the time there’s medical providers around.

For a sport like mountain biking, when you’re racing, there’s usually some type of medical team there and so that helps. But if you get hurt out in the woods all by yourself, boy, that’s a much tougher situation. And it’s a lot like other injuries. The first step is to make sure that things are stable and then get people out of harm’s way. It’s good to have these things looked at relatively soon. Most people who are lucid, who don’t have a declining level of consciousness, who don’t have major neurologic deficits as they’re coming out of the woods in a situation like that, don’t necessarily need to be seen right away. But it’s good to have them seen reasonably soon so that initial first steps can be discussed through and people can start thinking about what that initial management would look like.

A concussion in a sport like mountain biking doesn’t really get treated much differently than a concussion in other sports unless the energy is higher. If someone falls off a cliff or something like that, obviously you’ve got other injures you need to worry about. But it’s still the same issues. You’ve got initial early rest making sure that you’re not doing extra things, allowing your brain to recover a little bit on the front side. And then once you get out past a few days, starting to gradually return to exercise but not risk, and then making sure you’re not getting hit in the head again while you’re still sick. There’s not a whole lot else to do about it.

Mountain bike helmets, so bicycle helmets, probably do a slightly better job of preventing concussion than other types of helmets. But most helmets are really meant to diffuse impact rather than absorb impact. But bicycle helmets are single use items. They’re really meant to quash, and that quash does absorb some of the energy. So theoretically, at least, a little less energy is imparted to the brain crash on a mountain bike helmet or a bicycle helmet compared to a football helmet, for example.

[00:39:07]

RICK WEISS: And a question from Jennifer Joy Madden. This might also be a Dr. Peterson question. Again, anyone should chime in on these. But how can we best detect subconcussion in high school athletes, and what are some of the best prevention practices? I think prevention might be much along the lines of what you were just talking about with mountain biking. But yeah, if it’s a subconcussion, how do you know?

[00:39:31]

ANDREW PETERSON: Yeah, I don’t think you do most of the time. There’s only really one way to prevent these types of concussive blows in football, and that’s to limit hitting. The less people hit, the less opportunities there are to get either concussive blows or subconcussive blows.

There’s nothing to think that anything that we do from an equipment standpoint is going to make much of a difference. Rule changes can make a difference, and we’ve seen that decreased concussion risk in a few settings, mainly in kickoff, both in the NFL and now in the Ivy League with some data coming out of the last couple weeks. So there’s rule changes and limiting hitting, and that’s about the only tools you have at this point. We don’t have anything really better to protect brains from these subconcussive blows.

[00:40:09]

RICK WEISS: A question here that I think Dr. McKee or Dr. Colantonio could handle. What will it take to develop a diagnostic test for CTE? This from Alexis Wnuk at BrainFacts.org. What will CTE tests look like, and what does it take to get there?

[00:40:32]

ANN MCKEE: Well, I’ll start first. This is Dr. McKee. It’s going to take a massive research effort. It’s not going to be simple. It most likely will require several tests used in combination. There may be genetic risk tests. We’re starting to do studies on genetic susceptibilities and resistances to the development of CTE. So it may be that you look for a genetic profile. Then we’re looking at markers in the blood and spinal fluid. So you may combine that information with levels of tau protein or inflammatory markers in the spinal fluid or in the blood.

And then, of course, there’s a lot of optimism about being able to scan the brain using imagine and being able to detect the tau protein. I think we have made huge advances in that regard. But it’s not ready for primetime. It’s not unusual for it to take five to ten years to really develop the specificity of tests. You want to be sure that it’s detecting accurately the disease before you go out and use it in the field. It’s just going to require more money, more people working on it, and I think greater incentives to really make a difference.

[00:41:55]

RICK WEISS: Dr. Colantonio, do you have anything to add to that?

ANGELA COLANTONIO: I have nothing to add to that other than to ensure that there is sex specific data in these analysis.

[00:42:12]

RICK WEISS: We have a follow up question here for Dr. McKee from Breeden McKenzie to follow up on the healthy control question. Are there any published studies from your lab that include healthy controls, and if not, do you see any issues defining CTE as a cause and effect relationship?

[00:42:26]

ANN MCKEE: Well, yes, we have used healthy controls in all our studies. We didn’t use it in the JAMA study because that was a clinical pathological series. They didn’t want controls. But we’ve examined all our controls for CTE. We look very comprehensively. It’s not something we have disregarded. So we’ve published in some hundred controls that we don’t see the evidence of CTE. Other groups have looked, like the Mayo Clinic Jacksonville group reported in 200 control brains they didn’t see the neuropathologic changes of CTE. And it was also reported back in the 1990s by Geddes, et al., when they first reported some of the early changes in CTE.

[00:43:18]

RICK WEISS: And a question for anyone on the panel. We’ve talked a little bit about diagnostic tests and the possible development of them. But if we don’t really know what is the best treatment or what is the best thing to do with a diagnosis like this, what is the clinical value of a diagnostic test if there’s not a clear treatment protocol?

[00:43:43]

ANDREW PETERSON: As the designated clinician here, maybe I’ll chime in. This is a stepwise process. Pretty much any disease process requires good, firm diagnostic criteria before you can come up with treatment modalities. And so if you don’t know who you’re treating, if you don’t have a good sense of the patients, boy, it’s hard to create drugs. It’s hard to create randomized control trials. It’s hard to do good science for treatment. So the first step in developing a treatment for this problem would be coming up with a gold standard diagnosis that helps us know which patients we should be studying these types of treatments on. This is just good science.

[00:44:21]

ANN MCKEE: Yes. I would just like to emphasize that we don’t…aren’t able to treat the CTE anything but symptomatically at this point because we don’t have a way to diagnose it in life. Even if we had, and we probably have many drugs that may be helpful or therapies, but we don’t have any way to measure any of their success. So there’s no way to monitor whether or not they’re effective. So at this point, really the next step is diagnosis during life.

[00:44:55]

RICK WEISS: Got it. Let’s see. We have another follow up question here for Dr. Peterson regarding the helmet question. In your opinion, are the helmets that are specially marketed for concussion prevention worth it? Do they really work? Are they better than your standard helmet?

ANDREW PETERSON: Can I just say no?

RICK WEISS: Okay.

[00:45:17]

ANDREW PETERSON: I’ll elaborate on that a little bit. But the short answer is no. There’s no real reason to think that most helmets the way helmets are constructed today are going to do anything to prevent concussion. And I don’t want to make it sound like I’m against helmets. Helmets do a great job of preventing skull fracture and brain bleeds and other very bad problems. In a way, we have the luxury of worrying about concussion instead of the types of brain injuries that people got playing football back in the 1910s, ‘20s, ‘30s. But [helmets] do a great job of taking these direct linear forces that people are exposed to and diffusing them. But the energy is not absorbed. The energy still gets imparted into the brain and you still get these shear or tearing types of forces through the brain. And those are not mitigated by the helmet. They do do a good job of preventing those direct linear forces from reaching the brain, and that’s why they prevent a lot of the traumatic brain death that used to happen in football.

[00:46:03]

RICK WEISS: That’s really interesting. A question here for…and we just have a couple of minutes left but we’ll try to squeeze in a few more questions. Dr. Colantonio, are there social factors that might account for the gender differences we see in concussion prevalence between men and women? Are there any data, for example, about the likelihood to report symptoms in women versus men? You might’ve made passing reference to this, but I’m not sure if you quite hit that.

[00:46:30]

ANGELA COLANTONIO: Yeah, that’s been attributed, that women are more likely to report these injuries or it’s said it’s more socially acceptable for women to report these injuries versus boys. I think there’s been some studies documenting under reporting for boys, in particular. So that is often brought up. I know some studies with respect to athletes, that this tends to less be the case. It depends also on how you rate in terms of certain gender instruments, like for instance, your conformity to male gender norms. There was a study showing that girls and women that more likely identify with male gender norms are more likely to just play through injury. So it’s almost not what biological sex you are but rather to what extent you identify with certain gender norms.

[00:47:37]

RICK WEISS: Great. A question about…maybe for Dr. McKee. Is there any such thing as early onset CTE? Is CTE just something that you don’t see until people are older after a sum of numerous injuries? Or for example, is there even a risk among children of this syndrome?

[00:48:00]

ANN MCKEE: Well, we definitely see what you would call early onset CTE. We’ve described and reported a number of teenagers and more often 20 to 30 year olds with the earliest signs of this disease. Tyler Hilinski was diagnosed at a different center, not mine. But he was 21 when he died. And we’ve reported on many other instances like Owen Thomas, who was 21 when he died; Michael Keck, 25 when he died; Zachary Langston, 25. So we see very early CTE in young people. That’s what’s especially disturbing. If we could detect it in life, we, I think, have a good chance of reversing some of those changes, but we can’t detect it. So at this point, our hands are tied. The earliest we’ve ever seen it is in a 17 year old. He was not symptomatic. He died of second impact syndrome, and we just saw the earliest beginnings.

But our research is focusing on these early changes because that’s what we need to address. How does this goes from being a low level injury into something that could develop into a progressive neurodegeneration? That’s a big question for science.

[00:49:24]

RICK WEISS: Got it. So I think we have time for one more question. To do that, I’m going to try to combine two questions that have come in here into one. And it has to do with long-term prognosis for concussions. It seems that some people recover more quickly than others. So part of this question is what do we know about the differences between people who recover quickly and who take longer to recover? But also are there any biomarkers on the horizon that would help stratify patients this way so we can figure out who needs to be treated more aggressively or for a longer period of time? Dr. Peterson, why don’t I start with you and see if anyone else wants to chime in on that.

[00:50:05]

ANDREW PETERSON: Yeah. So it’s definitely true. There’s a lot of heterogeneity in how people recover from concussion. It’s difficult to predict who’s going to take longer to recover at the beginning. Most of the time when we’re looking at this, we’re looking more retrospectively and trying to piece it together.

There is some evidence that people who have had multiple lifetime concussions take a little bit longer to recover. People who have a history of prolonged recovery after concussion take longer to recover. And there’s some evidence that the initial symptoms might give us a clue. People with more vestibular disfunction and visual oculomotor symptoms seem to take a little bit longer to recover than people that don’t have those things at the beginning.

There’s controversy about how much genetic factors contribute here. Now clearly there’s a lot of heterogeneity in the normal population, but we may or may not have some genetic testing or genetic markers that can help us predict who’s going to take longer to recover.

The other part of this is once you get further out away from the injury itself, it becomes less and less likely that it’s the concussion itself that’s driving someone’s symptoms. So once someone has been sick for a while, once they get out a couple of months from their injury, boy, I start thinking a little bit harder about other things that might be bothering us here, whiplash type injuries; vestibular problems; underlying mood problems, depression, anxiety, PTSD, those types of things start to drive symptoms a little bit more. So I’ll start doing some other diagnostic testing and try rehabilitation for other things once we get a couple months out from the injury because it becomes less and less likely that it’s actually the brain that’s driving symptoms once you get a few months out.

[00:51:36]

RICK WEISS: Got it. Any last remarks from Dr. McKee?

[00:51:42]

ANN MCKEE: Just again that for a long time we focused on concussion and concussion is a very important injury, as Dr. Peterson has mentioned. But we really need to address the subconcussive injury in sport. We need to monitor it in active players, and we need to learn better ways to detect it. We may see some of the earliest changes after subconcussive injury that in some individuals may trigger a long-term slow, progressive deterioration.

There are ways to detect subconcussion. Right now they’re all used in research, but they’ve been primarily changes on MRIs looking at light matter changes. They’ve been looking at neuro psych tests and seeing some. And I’ve seen recent research on eye movements and reading tests. So I think we really need to address subconcussive injury in sport. And the sports that have a lot of subconcussive injury are football and boxing. So anything we can do in those sports to reduce the amount of impacts that each individual player experiences will be helpful in preventing CTE.

[00:52:59]

RICK WEISS: Thank you. And anything final from you, Dr. Colantonio?

[00:53:05]

ANGELA COLANTONIO: Thank you very much for the opportunity to speak today, and I think it’s great as journalists to start asking scientists if they have considered sex and gender in their research study.

[00:53:18]

RICK WEISS: Well, great. I want to thank all of you for participating and for the reporters who are on the line. A reminder here that within the next couple of days, this entire one hour video and a timestamped transcript will be posted on the SciLine website for you to refer to. We encourage you to follow SciLine on social media, thank you, at @RealSciLine, and get in touch with us at SciLine.org when you have needs as reporters to get in touch with experts or scientific expertise. That marks the end of this media briefing. Thanks again for everyone who participated and we’ll see you next time.