After Concussion, What Blood Can Reveal About the Brain

JOHN DANKOSKY: This is Science Friday. I’m John Dankosky. Anyone watching last Sunday’s NFL game between the Miami Dolphins and the Pittsburgh Steelers might have seen it– a huge hit on Dolphin Matt Moore’s chin took him to the ground he was unable to stand up for a few minutes.

Yet afterward, he was checked for a concussion by medics, and then he was sent back to play almost immediately. Moore said this week he doesn’t have any concussion symptoms. But is there an ironclad, objective way to be sure a player is ready to dive back into the game, whether the same day or a week later? And what about the growing body of research that’s linking small hits, so small they don’t register as causing concussions, to degenerative CTE?

Going to be talking about concussions, sports, and brain health with two researchers in the field. If you want to join us, our phone number is 844-724-8255. That’s 844-SCI-TALK.

Dr. Jessica Gill is a clinical research scholar at the NIH’s National Institute for Nursing Research and chief of its brain injury unit. She’s in Washington, DC. Dr. Gill, welcome to Science Friday.

JESSICA GILL: Great, it’s so great to be here. Thanks so much.

JOHN DANKOSKY: And Dr. Robert Stern is professor of neurology and director of clinical research at Boston University’s Chronic Traumatic Encephalopathy Center in Boston, Massachusetts. Dr. Stern, welcome to the show.

ROBERT STERN: Thanks very much, John.

JOHN DANKOSKY: We’re going to start with you, Dr. Gill. Tell us about your research and what a blood test can tell us about how bad a concussion is.

JESSICA GILL: Sure. So one of our recent studies, which was a collaborative study with Dr. Jeff Bazarian at University of Rochester showed that elevations of tau in the blood of athletes within six hours of a concussion were predictive of a prolonged return to play, such that these elevations could distinguish those athletes that had a concussion and needed to be out of play for more than 10 days from those athletes that had a concussion and could go back to play within 10 days, which is what we would consider a healthy or a normal return to play.

And so in this study, specifically what we looked at was tau, and we looked at it in the blood. And from what we know from other studies is that tau is a really sensitive indicator of brain injury. From more severe patients, we can see that elevations of tau relate to the severity of the neuronal injury following this. And they also give us an idea about how these individuals will recover. So the higher the tau is, the less prognosis that they’ll recover within a normal period of time.

But the problem we’ve had in this area of science is that we’re not able to measure tau in the peripheral plod in a sensitive and reliable nature because it’s in such low concentration. So really, when we’re looking at tau, we’re trying to measure grains of sand in an Olympic-size swimming pool. And so only recently have we had the ability to look at tau in a more sensitive way.

And so we’ve linked with Quanterix, which is a biotech company outside of Boston, and they have developed the ability to look at tau using an ultrasensitive assay that allows us to reliably quantify the amount of tau and look at these more subtle changes following these more mild type of concussions. So really allowing us to do this type of work.

JOHN DANKOSKY: I would like to back up a bit and just maybe have you explain what tau is and where exactly it comes from.

JESSICA GILL: Sure. So tau is a protein. And what happens when a neuron is damaged by injury is tau is released from that neuron. It then goes into the cerebral spinal fluid, and then it goes into the blood eventually. And so that’s really where we’re trying to measure it, because that’s where we can clinically make relevant decisions about return to play.

JOHN DANKOSKY: So when it comes to concussions, how much variation is there? I mean, we were talking about Matt Moore getting hit and there’s no concussion. Some people have terrible concussions with one kind of hit. Tell us about that.

JESSICA GILL: Sure. So there’s a huge variation in response to a concussion. So one athlete can have the same injury as another athlete but have a completely different recovery trajectory. But what we know from a lot of studies is that most athletes will recover within seven days to up to 30 days following a concussion. But there is a subset of athletes will go on to have chronic type symptoms that doctor Stern can talk more about.

And so what we’re really trying to do with these tests is to identify that subset of athletes that will go on to have these chronic symptoms so that we can monitor them over time, and then provide preventative interventions that mitigate those risk factors.

JOHN DANKOSKY: So Dr. Stern, we’re finding chronically elevated levels of tau protein in former football players, people who’ve played the game since they were children. Is this linked to having multiple concussions over their careers, or something else?

ROBERT STERN: Yeah, it’s a great question. I think it’s something else. One of the things that I study is this neurodegenerative disease, chronic traumatic encephalopathy. And what we know about that disease is that the necessary variable for getting it is a history of repetitive hits to the head.

Now, that includes those symptomatic concussions that Dr. Gill has been studying, but also what we refer to as sub-concussive trauma, meaning the many, many more frequent hits that football players and others get that don’t result in the symptoms of concussion but still might do something to the functioning of the brain cells. And so what we’ve looked at is the relationship between the total number of estimated hits former players received over a lifetime. Not the number of symptomatic concussions, but the overall number of hits, including those sub-concussive hits. And we looked at the same type of blood test that Dr. Gill’s group looked at, this plasma tau developed by the Quanterix company.

And we found that there was a very strong direct relationship between the total number of hits these former players got earlier in life and now the total amount of tau in their blood, suggesting that maybe we’re seeing the leftover stuff that Dr. Gill’s finding. Or maybe we’re now seeing something new as an objective way of being able to detect this brain disease later in life.

JOHN DANKOSKY: So this is really interesting, Dr. Stern, because we’re talking on one hand about these elevated levels being present after a serious hit to the head that results in a concussion, and then wondering when to send a player back into play after that level has lowered. But what you’re talking about is, over the course of time, this building up in someone from a series of very small hits. In some ways, they almost seem like two different things. But for someone who’s been playing football for their entire lives, you seem to be suggesting that these very small hits are what’s building up.

ROBERT STERN: I’m not even sure if it’s what’s building up as much as perhaps evidence of a progressive brain disease that also results in the release of this tau. So there’s two different things. One is the acute injury that releases this bad form of a protein. And then there’s the disease that occurs in some people that progresses over time and results in the destruction of brain tissue. And again, we might be seeing that tau that can be measured this same way.

But what we’re looking at is really not those acute, big hits that result in the symptoms but rather those multiple, repetitive hits that some– even youth players, 8 to 12-year-olds might get a couple hundred per year or more, per season. And they don’t rest in between at all because there’s no symptoms. And so they keep on getting hit after hit after hit, and the natural ability of the brain to clear out the bad stuff is unable to work well. And that might result in the development of the beginnings of this brain disease later on in life.

JOHN DANKOSKY: And I want to get back to that in a moment. But I want to turn to Dr. Gill and ask, so if tau protein is also linked to CTE, what about the athletes you studied? Should they be worried that if they had this big spike in tau, even if it was a short-lived spike from a major concussion?

JESSICA GILL: So that’s exactly where we’re going with the next directions for our research. So how do these acute changes in tau after a concussion, especially this individual variation where we have some athletes having a lot of tau coming into the bloodstream, and how are those individuals then at greater risk to have these more chronic or long-lasting symptoms? And so we don’t just look at CTE. We look at symptoms across the spectrum.

So we look at things like post-concussive syndrome symptoms, including headache, to behavioral symptoms, to things like light sensitivity. And so we know that these have a big impact on quality of life, even if they don’t progress on to CTE psychopathology. But we want to understand and target those athletes that really have this higher risk for those symptoms, and try to understand the nature of that risk, and how can we monitor those patients and those athletes to provide greater monitoring, and then prevent those risks over time.

JOHN DANKOSKY: I want to go to a phone call here. Hugh is calling from Silver Spring in Maryland. Let’s go to Hugh. Hi there, Hugh. You’re on Science Friday.

HUGH: Hi, thanks for taking the call. My question is– and this is interesting as a former football, lacrosse player, all the hits I took to the head, jokes aside. Is there an analysis, blood test, or attention being paid towards that testing for duration of effects in, say, traumatic brain injury in combat veterans?

JESSICA GILL: So actually, we’ve looked at tau in combat veterans. Also, we’ve found that elevated tau in individuals who had a deployment-related brain injury in Iraq or Afghanistan had higher tau when they came back from that deployment, even years after that, and it was linked to chronic symptoms of neurological and behavioral change. And so we do see that this elevation of tau is related to both blast exposure as well as this blunt force brain injury that they often sustained during deployment.

So we have seen that tau seems to shape the recovery from that type of brain injury also.

JOHN DANKOSKY: And that might lead to some of what you’re looking at, Robert Stern.

ROBERT STERN: For sure. One of the big things that Dr. Gill’s work has done is it’s leading to the ability to measure in an objective way when the brain is hurt by one of those impacts. Right now, the definition of a concussion involves the clinical examination. Person has to have symptoms, they have to complain, they have to have problems in an examination. But so many people don’t want to complain for lots of reasons. The macho thing, or the lack of being able to stay on a team.

And so there’s been this tremendous need to be able to measure what is a concussion objectively. And Dr. Gill’s work is moving us tremendously in that direction. For me, since I’m also interested in what happens when people keep on getting hit over and over again, whether it’s in the military or in contact sports, if we don’t have the ability to measure changes in the brain because there’s no symptoms, so we don’t stop them to play and then take some type of test, we want to be able to figure out what’s too much in terms of those repetitive hits. What is putting someone over the edge in terms of changes to their brain?

And so using the types of tests that Dr. Gill is developing for concussion might allow us to kind of lower that threshold and be able to detect brain injury objectively without the person having the symptoms of a concussion.

JOHN DANKOSKY: I want to go to Alex, who’s calling from California. Hi, Alex, go ahead.

ALEX: Hi, I’m a sports medicine physician out here in California, relatively novice in my career, and I have a question and a comment. My first question is when you’re doing this research into CTE– I think of CTE and dementia pugilistica, which is a much older diagnosis, as almost the same thing. And is there any sort of difference when you’re thinking about this from the clinical and a research point of view? That’s my first question.

And second of all, my comment is I see these kids in clinic every day who are absolutely terrified of being active and doing anything where they might possibly hit their head because they’re scared, and rightfully so. I mean, there’s so much we don’t know about concussions, and I really feel like a lot of the media attention is sometimes scaring your kids away from being physically active, which is potentially having more of a detrimental effect long term on their health than a couple concussions here and there.

So my question and my comment. I’ll take my thoughts off the air. Thanks very much.

JOHN DANKOSKY: Alex, thank you so much for the question. Before I get to your answer, Dr. Stern, I just want to say that I’m John Dankosky, and this is Science Friday from PRI, Public Radio International. Go ahead, Dr. Stern.

ROBERT STERN: Those are both fantastic questions. The question about dementia pugilistica, or punchdrunk, brings up a very important thing. We’ve known about this brain disease and the long-term consequences of repetitive head impacts since the early 1900s when it was looked at in boxers, and looked at the long-term consequences of getting your head hit over and over again in boxers. And that was originally referred to as punchdrunk, than dementia pugilistica. And then, in the 1940s and ’50s, it was starting to be referred to as chronic traumatic encephalopathy, or CTE, with a more general term.

But it wasn’t until the early 2000s that people started paying attention to it when our beloved American football players started to die, and their brains were examined, and they were found to have the same thing as the boxers had. So to answer that first question, dementia pugilistica is really the same thing as CTE. We’re just talking about it a lot more now.

And that leads to the second question, which is what’s happening with all the hype surrounding CTE. Is it leading to too much fear? Is it leading to kids being afraid that they have one concussion and they’re going to become completely impaired the rest of their lives? There’s a couple of ways to answer it.

One is people should realize we’re still in the very early stages of our research of CTE, and that people don’t have to be concerned that a concussion– even a big hit, if it’s on its own, or even a couple or three– is going to have long-term consequences. And the caller was so astute in saying that we need to keep our kids active. We need to keep them involved in wonderful sports and athletics for overall health.

But we have to ask the question. Is it appropriate– for kids, especially, whose brains are developing– to expose them to repetitive hits to the head that may be altering the successful trajectory of their brain development. And that’s one of the things that we’re really trying to focus on, is what’s going on when kids get their heads hit over and over and over again. Not necessarily the big hits and the symptomatic concussions.

JOHN DANKOSKY: Dr. Gill, before we run out of time, I want to ask, though, what are we learning about concussions, how to treat them, how to prevent them in the first place?

JESSICA GILL: So we’re really looking for new treatments for concussions. Right now, when a patient comes into the clinic– and I can also respond to the other callers. I’m a parent, too. I’m a concerned parent who has two kids playing competitive sports who are at risk for concussion.

So if I bring them into the clinic, I want to be able to understand the nature of their brain injury, and how quickly they can go back to play, and how they can have those successful trajectories that Dr. Stern is talking about. And right now, we’re really not at that place. We don’t have any treatments to mitigate the risk of concussions on brain function. And so we’re really understanding the mechanisms, and so that’s why we’re focusing on these blood biomarkers to understand, really, the individual variability in response to a concussion, and how can we identify those patients at risk, and then do individualized treatments to really modify those risk factors.

So that’s the focus of research moving forward. And it’s really an exciting time to be in this area of research because there’s so much collaboration and so much excitement going forward to look at this very critical and complex issue, to address it through multi modalities, and many scientists coming together to address this issue.

JOHN DANKOSKY: Dr. Jessica Gill is a clinical research scholar at the NIH’s National Institute for Nursing Research and chief of its brain injury unit in Washington, DC. Dr. Gill, thanks so much.

JESSICA GILL: Thank you so much for having me.

JOHN DANKOSKY: And Dr. Robert Stern, professor of neurology and director of clinical research at Boston University’s CTE Center in Boston, Massachusetts. Thank you Dr. Stern.

ROBERT STERN: Thank you very much, John.

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