#263 ‒ Concussions and head trauma: symptoms, treatment, and recovery | Micky Collins, Ph.D.

24:40There is. And then we did another paper, a follow -up paper, we looked at dose response, and it's really powerful. So for every minute you try to play through your injury, you add on like seven or eight days of recovery. It's quite powerful. And so yeah, you don't want to play through this stuff. And a lot of kids and parents may not be aware that getting dizzy on the sideline is the most powerful predictor of outcome, or feelin' foggy, or feelin' tired, or blurred vision, double vision. I mean, I played sports my whole life as I'm sure you did, Peter. I wouldn't come out of play if I had those symptoms.

25:13I probably wouldn't report it at all. We need to do a really good job of educating parents on that. But at the same token, I want kids to play sport. I'm not fear mongering here. I truly believe this is an injury that's treatable and we can get kids back to the sports they love. But it just shows you the differences in outcomes when it's not managed properly initially early on. And we're getting now into all our research looking at how we treat this injury, which we're doing really well with. And we can get kids better faster by applying certain treatments and getting them back to place sooner.

25:44Well, I definitely want to hear about that. And I think that's where most people's ears all perk up. But let's go back again to these different types. I think you mentioned that there are sort of six different types. So basically based on presentation and based on subsequent testing that you might do, you would then elucidate these six different types? Is that how it works? Yeah, so we do an evaluation where we ask about symptoms. Obviously do a very good clinical interview. We have a physical exam that we do called the Volums. Stands for a vestibular ocular motor screening. We do impact testing.

26:16I'm familiar with the Neurocon of Test. It's a computer -based Neurocon of Test that has been FDA approved that allows us to quantify and look at the concussion in a more objective way, looking at their cognition. There's different neurocognitive correlates that we see with these different types of concussions, etc. But you put all this information together and yeah, and we're doing research now looking at these different phenotypes and different problems we see from concussion. But each of these different types of concussions are going to have different symptoms, are going to have different risk factors, different therapeutic techniques to treat it, and different outcomes and different return to play sort of situations.

26:53So do you want to, I mean, I'd love to hear them. Yeah, let's hear what they are. The six different types of concussions, cognitive, we actually call it conif fatigue. The second is vestibular, which is not the ear. It's more of the central pathways in the brain. The vestibular system is a very significant system in the brain that starts in the inner ear and then kind of goes the deep parts of the brain. We're talking about more centrally derived problems from the central part of the vestibular system or the brain part. The third type of concussion is ocular, which is your eyes, working together as a team.

27:25It's not your vision as much as ocular motor. The fourth type is migraine, which is what it sounds like, headache, with nausea, and or lighter noise sensitivity, and other symptoms as well. And then the fifth type is anxiety. The sixth subtype is neck. You can have some of these symptoms coming from the neck. Not very common, but you can. So those are the six different problems we will see from concussion. Now patients may have one of those problems, or they may have all six. They're not mutually exclusive. And the more you have, the more difficult it is to treat. But you are going to treat each of those problems in a distinct way and a targeted way.

28:01You know, if there's 30 different types of knee injuries, why do we think there's one type of concussion? We're starting to really be able to better identify kind of where the signal's coming from with this injury. And is there an age and or gender difference between these? Well, first of all, you may not be aware, but we've published a lot of data on this. The adolescent brain, we looked at high school kids versus college athletes, and then college athletes versus professional athletes, the high school kids take the longest to recover from concussion. The college athletes take the second longest and the professional athletes recover more quickly than the other two.

28:35There's a lot of sort of vulnerabilities of the adolescent brain to this injury. You got to be careful of love, but there is an age relationship that we've published extensively on. What do you think that's a result of? Do you think that the younger brain has a different hormonal milieu? Do you think that it? I do. Do you think that that's the biggest driver of that distinction? I don't know. And we're doing research on that now. We're actually doing a really cool women's study on concussion, looking at some hormonal influences. And we've found that menstruation can change after head injury. And that was the first question that was going to come to my mind is it would be so interesting to understand how a woman's menstrual cycle.

29:14and therefore, you know, not just menstrual cycle, but also like, where is she ovulating, where is she in the follicular and luteal phase? Because the estrogen progesterone swings in those phases are enormous. Of course it begs the question, are those hormones protective? We were just about ready to embark the first women's study on this injury. We're collaborating with McGee Hospital here at UPMC with our clinic and it's exciting work. We just got a grant to look at that. But we have published a paper already in JAMA, neurology, I believe, where we showed that the menstrual cycle does change relative to patients that don't have had injuries.

29:50So there's a lot to learn. That's a cool thing, again, we started doing this work when knowing cared about it. Now there's too much work to be done and everyone cares about it. It's fascinating. What do you attribute that to, by the way? How much of that do you think is an indirect or even a direct consequence of the attention that's been brought to brain injury through the light of CTE vis -a -vis the NFL. Yes, an interesting question. I mean, clearly the spotlight in this injury is iridescent. You know, and clearly the NFL is a very powerful enterprise and there's a lot of eyes on it, and there's a lot of discussion, open discussion on this topic, which is a good thing.

30:29In a lot of ways, it drives science and it drives awareness, but too much awareness without a solution is called hysteria. And we see that happen with this injury. When the reality is is that there's a lot of misinformation out there about concussion. And I think it actually hurts outcomes a lot of times. Clinicians that aren't aware of the recent advances in knowing how to treat this, clinicians that don't know how to do the right evaluation. And there's a lot of mismanagement and mistreatment of this injury that leads to very poor outcomes. Again, and you're going to hear it from me over and over again.

31:01If you bring me a patient with concussion, I pretty much tell you I can treat that and get that patient better and get them back to the sports they love. There are highly effective treatments with this injury. Is this the sort of thing where there's a relatively finite window in which you or the physician treating has to be able to access the patient and the further a patient is from that window absent the natural history resolution, the more difficult that gets? Okay. So I'll answer that with data. We just did a study again, published in, I think it was in JAMA neurology as well, where we looked at what factors best predict outcomes from concussion.

31:39My brain is a huge factor of predicting outcome, history of my brain, the certain symptoms that predict outcomes. But we looked at all those things. The one factor that best predicted outcome was how quickly they get into our clinic. If they were seen by us within seven days, that was the best predictor of someone who got better from the injury. because we can apply our treatments quickly. And if you do wait, it's harder to treat. But I still will argue, even if you're a year out, two years out, three years out from this injury, we can treat it effectively the grant majority of the time. It's not irreversible.

32:11You can get patients better, even if they've been living with it chronically. Peter, today, I mean, I saw patients all morning. I had 20 patients on my schedule before our podcast. I just saw a race car driver from Phoenix or someplace. place and they've been going through this for two years and miserable. We will get that patient better. They will be normal when we finish treating them. There's nothing I'm seeing that worries me about them. If you can without giving any information that would identify this individual, can you give a bit of a sense of this as a case study? So presumably two years ago this guy was involved in an accident.

32:47Yeah, was involved in an accident, had all the hallmark symptoms of a stibular problems. What type of accident, by the way, was this one where it was just a coup, contra coup injury where he whiplash. I mean, you know, we wear a Hans in a car, which limits our recoil now in our heads. I looked at the video on it and this isn't at the highest levels of racing. So I'm not sure. Sure. Yeah. And we do work a lot with those patients. But this is a small track event or something where the patient got somehow got hit in a way. Their car rotated it and went backwards into the wall. In this video, I actually saw the video the head and their head at the back of the head rests and there was no loss of consciousness, but the person immediately felt foggy, the slow -wavy dizzy, they had a headache, they felt fatigued, they had bilateral or blurred vision early on, but no loss of consciousness, no memory loss, no confusion.

33:38Obviously, the car was totaled so they didn't race, but they didn't also get medically evaluated after this. They kind of went about their lives and continued to have those symptoms and went back to racing two weeks later and got it in another accident and had the same problem occur, same mechanism even, and that's when everything obviously got worse and when they saw medical attention, but they've been living with that for two years. They've not improved. They came to me today they're having everyday headaches that can get up to an 8 out of 10, light sense of noise sensitive foggy. they don't like busy environments, they don't like exercising because they get really dizzy, they get headache, they get sick to their stomach, they've got a lot of car sickness, they have a lot of sympathetic nervous.

34:20This sounds debilitating. Oh, it's totally debilitating. This is destroys your life. It destroys your life and this is a person who is not racing anymore, they're not working because of it. Oh god. They have massive sympathetic nervous system arousal where they can't sleep at night, they're very foggy, very, very worked up and they very much are isolated. They don't want to be around other people because that triggers of a similar problems and so they become more reclusive. You know, they find themselves exercising minimally. They're socially very inactive. They're not preoccupied with their mind.

34:57So there's a lot, their thoughts are going so fast because the nervous system is racing. So they're in their head all day long. My grains, that's what I just saw this morning, Peter, and I do it all day long. This is an injury that causes so many problems in patients. So notwithstanding the fact that this poor guy has been needlessly suffering, you know, for a couple of years, tell me in broad strokes, what are you going to do to help this person? And what's a time course that you would give him for a reasonable expectation of recovery? Okay. So we saw the patients today and we have a very good evaluation we do.

35:30And the cool thing is we're very used to seeing out of town patients here. A lot of my patients run a town. So they have five appointments in one day. I'm the point guard of it, but we also have a vestibular therapist here. We have what's called exertion therapy here. We have a psychiatrist here. We have a behavioral optometrist that we can use. We have neck people we can use. So it's all under one roof. So people have appointments scheduled throughout the day. They come to see me. I did the evaluation. I kind of find out what was going on. But what we're able to identify in our evaluation today is the patient has a significant vestibular problem that has not been treated.

36:03And the vestibular system, when it's not working well, is going to cause a lot of dizziness. It's going to cause a lot of fogginess. It's going to cause environmental sensitivity. Bizziness environments will bother them. They don't want to exercise because movement bothers them. The vestibular system is responsible for interpreting motion. And when that system doesn't work, remember this injury decopensates that system that signal comes through aberantly and it will trigger all these really icky symptoms. It's like a bad car sickness that they feel. Now, the vestibular system, the same pathways in the brain that control that system, mediator, sympathetic nervous system.

36:37And so the patients will also have massive sympathetic nervous system arousal, fight or flight. So thoughts go fast or heart rate increases. They get a lot of cortisol, a lot of problems going on from the nervous system. And that's all triggered by the head injury. And so they're living in this fight or flight situation. And then when patients go into certain environments where they feel crappy, it not only triggers of a similar problem, but it triggers that fight or flight response and patients will then in a very Pavlovian way avoid those environments and then they don't want to work, they don't want to exercise and what do you think happens?

37:13It triggers migraine because patients that have a massive sympathetic nervous system arousal, they get headaches. People get migraines when they're stressed and people get migraines when they don't sleep consistently and people get migraines when they don't exercise consistently. That's why people get migraines. And so what started off is one problem with a vestibular problem becomes an anxiety problem or sympathetic nervous system problem and then it becomes a migraine problem. And then migraine actually feeds back through the vestibular pathways and the ocular pathways so you can also have a lot of problems from that secondarily to the migraine.

37:46Does that all make sense to you? It absolutely does and it's uncanny in how much it reminds me of an injury that someone very close to me had which was riding a bike down the side of the road 25 miles an hour, 40Ks, really at a good clip, and a runner jetted out between two cars. It was probably listening for cars, but didn't think about a bike, and there was a head -to -head collision. So cyclist head into runner's head, I knew the cyclist, not the runner. They both were devastated by this injury. The runner took the brunt of it at a complete fracture of the face, but the cyclist was for two years, couldn't be in a room with the TV on.

38:24any noise that the kids made would make this person very irritable, it's very similar to what you're describing. That's because it's similar, Peter, because that's the pathway these patients go down. And it's very predictable how they get on this. It's not only Pavlovian meaning their condition to go on this pathway, but it's all biological. It really triggers these things in a very robust way, and it's a very, very, very... These people describe it because I've now spoken with a couple of patients that have gone through this. they describe it in as stark terms as someone would the most severe mental illness, which is to say, I'm not myself anymore.

39:01So whoever I used to be, that person is gone. I am this new person that has nothing in common with the old one, and it's all in the wrong direction. What percentage of people of all comers in concussions? How many are this severe? The patients that come see me from out of town, almost all of them, because they haven't been treated. And now some come to me and they're actually feeling pretty well. They just want to know if they can go back to sports after having X -Motic concussions. And some of those patients aren't sick like that. But I have on my schedule every week, I have something like, I'll see upwards of 70 to 100 patients a week with this injury.

39:37I've got on my schedule slots for probably 12 to 16 out of town patients a week. Probably 80 % of those patients are sick as what we're describing here. So it's not fun for these patients to go through. What will be the next step for this gentleman that we're talking about? So we can treat all of that, but it's completely antithetical to how you think we treat it. So what's the one word, Peter, that comes to mind when you think about what should I do when I have a concussion? What's that word? Rest. You're exactly right and you're absolutely wrong in how we approach this injury. I'm O for two Mickey keys.

40:16No, I set you up there. But if you look Look at the literature over the years. It's like, oh, you have a brain injury. It's an energy problem. You need to rest that patient. That makes all of this worse when you take that tact. Because the way we treat a vestibular problem is by retraining it. It's not rest. The way we treat anxieties by increasing parasympathetic nervous system around them, which is exercise. It's regulated sleep. The way we treat a vestibular problem is by retraining it. So I want them in busy environments. I want them exercising. We got to get them on a good sleep schedule.

40:52We got to treat the vestibular problem with very targeted physical therapy. We have exercises that treat that. We actually have what's called exertion therapy here. If you come see me with a concussion, I don't care how sick you are. I am working you out and I'm doing it aggressively a lot of times. We take a very active, very targeted, very exposure -based model to treating this problem. But you need to see a specialist in how to do that because you can do it the wrong way and make patients worse. It's got to be very targeted in how you approach this with patients and every patient's different and it's breaking down in different ways.

41:30There's different types of vestibular problems. There's different types of ocular motor problems. There's different types of personality characteristics etc. that you have to account for when you're treating this injury. But at the end of the day, if you match the right treatment to the right problem, you can get better from this and that's what we do all day long here is treat those problems. What I find interesting is that, be it two years ago in the case of this gentleman, that injury took place. So you have the energy crisis takes place, the vasoconstriction takes place, the mismatch of supply and demand takes place.

42:03Is it likely the case that if you could biopsy his brain today, or let's give him more creative, you could put yourself onto a nanoparticle spaceship and enter his brain today, everything looks totally normal at the cellular level? Yes. Or do you think that it's still microscopically apparent? I don't know the answer that I wish I did. But my suspicion, based on everything I've learned about the pathophysiology, this is that we should see a normal brain structurally and anatomically, and even physiologically. That's just what happens when this injury happens as to what systems are affected. And then you can kind of go down these pathways if it's not treated appropriately, and that's what ends up happening.

42:44It seems that of those six phenotypes you described, this vestibular one is very problematic because it seems to amplify the other ones. But again, am I interpreting that correct? Yeah, you kind of are. We actually have done research on that. If you looked at the most common types of concussion we published a study on this as well, the most common problem we see after concussion is post -traumatic headache in migraine. That's the number one profile that we see. Oh, no, I'm sorry, I apologize, let me retract that. The number one profile that we see is anxiety and then migraine and then vestibular and then ocular and then fatigue, cognitive fatigue.

43:25So we actually have done work on that. So anxiety is ubiquitous across this injury and that is what is the most common clinical profile that we'll see is that nervous system issue. It's interesting though, because you also said if I recall that no symptom predicts a worse outcome more than dizziness, and that of course makes me think, well dizziness is so tied to vestibular. Yeah, right. And I agree with that. There is something about this vestibular problem that, by the way, would also amplify anxiety. You know how we do research and we look at the numbers and you publish that. My gut is the vestibular stuff carries the day with this injury, the great majority of the time.

44:04or at least it kicks it off, Peter. A lot of times I'll see patients. Right, it's a vicious cycle that spins out of control from that. Exactly. I would agree with that. I'm not gonna overgeneralize to every human being because there really is, it's a very different presentation of a lot of different people. Like I'll see people that come in here that have an ocular motor problem that no one's identified and have no vestibular issues, they have no migraine. They're completely normal, except they can't focus when they look at their math homework and they get headaches in the front of their head and they're tired.

44:32That's an ocular motor problem that we can fix pretty easily. And that's just a PT program? Yeah, we have to retrain the ocular system and we have exercises that can do that very effectively. And so we see those patients, but yeah, the vestibular stuff is ubiquitous. But there's patients I see where the vestibular problems clearly kicked us off, but that's not present anymore. It's all migraine and anxiety, but it came from that beginning, if that makes sense. And it sounds like your friend there that got that horrific bike accident. That sounds terrible, by the way. Like it sounds like he's gone down that profile.

45:09The vestibular stuff. Yeah, and here's what's amazing. After two, two and a half, three years maybe, he just kind of got better. That's good. Maybe part of it is that he did double down on exercise nutrition and sleep. That's it. He started getting the right information from someone. But that patient, Peter, if you sent him to me a month after this entry, I would have had him better. You to save them within how many months? How many months is he better? If I had seen him the first week after the injury, no, listen, I don't know the case. Was there a subject? Sure, sure, sure. But in general. But in general, we could have gotten him better in definitely weeks, not months.

45:47Wow. So this gentleman today that you saw, he's going to go back to Phoenix or wherever he's from. after he's had this amazing e -Val, what's his homework assignment, meaning what are the actual types of PT's and activities he's gonna do and when do you see him again? So I'll see him back in four weeks. They'll come back and see me. And he has been given a very detailed set of vestibular exercises to complete every morning and evening. He has been given an exercise program. We pretty much kicked him around the gym a little bit and got him moving. When this vestibular system breaks down, you have to move in certain ways to treat it and we're very good at doing that.

46:25We're in sports medicine so we know how to move people and we've given them very specific workout that will train that vestibular system. And while we're doing that, we're also increasing the parasympathetic nervous system by doing exercise. So it's killing two birds if that makes sense. And exercise also treats migraines. So that's three birds were killing by doing the exercise stuff. He'll do that work out program every day. How long will that be? How many minutes a day will he spend exercising? I'm going to have him walk in the morning for 45 minutes and he does that very rigorous work out in the afternoon And it takes about 45 minutes to an hour and he's to do that every day until I see him back Wow, can you give me an example of some of the exercises he'll do in the afternoon for this patient He had a horizontal vestibular ocular reflex problem So this is your vestibular ocular reflex and when he moves his head side to side he can't stay tracking Correct.

47:11He does this. And he also will stir him up with dizziness and fogginess and headaches. So we have him doing like a Russian twist where actually he's got a ball and he throws it against the wall. So we have him really kind of train that the similar system. We have him doing planks with head turns. We have him doing ladder shuffles, you know, that kind of stuff. And when you have it more of a vertical plane thing, we're doing a lot of burpees. You know, we're doing a lot of different things like that where it's more linear or vertical rather than horizontal movements. This system will break down in distinct ways.

47:44And given he's a race car driver, that vestibular ocular reflex when he's looking side to side like that affects his racing. That's his money maker. He's better at that than I am. That's why he's such a good racer. That injury affected the very system that makes him who he is. But we can retrain that by giving the reaction. So what this looks like, he goes home, does the vestibular exercise is morning, night, Does our workout program night? I want a regulated sleep schedule, gets up same time, goes to bed same time, no napping. I want him to do exposures to busy environments, grocery stores, restaurants, parties, whatever.

48:20I want him doing a lot of external activities. I don't want him internal. I don't want him thinking about his symptoms. I don't want him ruminating, because the nervous system is so fired up. Down time makes us all worse. So we're going to challenge him. There's three different types of exposures I want them to do every day in terms of busy environments and exercise and different Ocular things. It's a very detailed program that's all written down and they go home and do it and I don't want to talk to them for a month. And then he'll come back and see me sometimes we do telemedicine a month later, but this guy's coming back to see me because he's pretty sick.

48:54We have medications that can help sometimes with this depends on what the problem is, but there's meds. I'm not going to do that. I don't ever try to do meds initially. We want to see if we can treat this behaviorally and then we'll do meds. What are some of the meds that might be kicked in? I mean, are there meds that help with sleep, for example, like trasidone or? I don't like trasidone too much because the sleep is coming from the nervous system problem. So you're treating a secondary problem by putting them on trasidone. Sometimes it's an SSRI, sometimes it's a tricyclic, sometimes it's, you know, so there's different meds that we'll use for that.

49:25There's certain SSRIs that are a little more effective than others in treating the nervous system profile. I don't like SSRI. Which ones are? or surgery is a medication that can actually affect not only the vestibular system, but the nervous system as well. So we've had DCNOT comes with that. But sometimes you need a well buterin, sometimes you need an effectser, sometimes you need lexapro or asceteler parameter, or there's different meds that will help with these problems. And we have a psychiatrist here that's phenomenal. And he's not a good... And is this one of those things where it's just kind of empirical and you have a hunch as to what you're gonna do, but if in a month it's not better, you sort of abort regardless of what the data say.

50:01We follow these patients very carefully and I will see them every three to four weeks until they're normal, whether it be via telemedicine. And they need those follow -up appointments because they can get off the rails with this stuff. Some people aren't as compliant as they should be. Sometimes they hit walls with migraine or anxiety or different problems. But at the end of the day, Peter, and I'm not just blowing sunshine, we can get the great majority of these patients better. It just needs to be done in a very targeted, and diligent way, but I don't want this to come off as whatever, but there's not a patient, I don't believe I can treat.

50:36I mean, I really truly believe you come to me with concussion, I'm gonna get you better from this. I really do feel like - How many of the male patients come in with hypogonatism as a result of this? So something shuts off in their pituitary and all of a sudden, they're just not making testosterone anymore, for example. There's so many downstream things that can happen from a rampant sympathetic nervous system. It affects every bodily organ we have. You know, it affects the gut, it affects hormonal influences, it affects everything we function as is temperature regulation, migraine, there's so many different things that affects.

51:13There's a lot of downstream problems that we can see from this. I haven't looked at that topic. Would we find something? Perhaps? I just would wonder how the HPA axis functions after, especially in cases like this gentleman where there's such a chronic insult. I can't help but imagine if both centrally and peripherally there's some manifestation of this. And to your point, like you wouldn't want to just get into a game of whack -a -mole where you're just treating all of those things. You'd want to put all your effort, of course, into like what's the central problem here? How are we going to address the root cause?

51:46Yeah, thank you for that. because yeah, if you treat the root cause, those secondary downstream problems don't occur. And that's why seeing these patients early can really lead to better outcomes and we don't see those problems happen in the first place. I want to ask you about a couple of other things that I get asked about a lot for which I have no answer. One of them is the use of hyperbaric oxygen. Have you guys studied this? Yeah, and I'm not a believer in it, and it's not something that's going to reverse the problems we see with this injury. And quite honestly, I don't want patients doing superfluous treatments that aren't well -founded empirically because it leads them into this sort of anxiety, sort of model where they're just feeding into the problems.

52:27And we see that a lot with this injury. And I don't blame them because no one's getting them better. So they're trying all kinds of different things. But no, I will not have patients to have a better treatment with this injury because it just leads to more searching and seeking that's not targeted. And we see patients that want to do hyperbarics. But there's no data that has compelled me to tell you that hyperbarics would have any effect positively or negatively on how it comes from the syndrome. Yeah. And the one thing I always discuss with my patients, they're usually asking me in a different context, which is, hey, does hyperbaric chamber improve longevity?

53:03And they always point to this very poorly done study in Israel that supposedly showed that telomere has got longer in a hyperbaric chamber, although I have to break it to them that telomere elongation has nothing to do with longevity. But the point I always make to them is the one of opportunity cost. So, you know, we're here in Austin, there's a hyperbaric chamber in town. So if you want to go and do hyperbaric work, you got to go drive 30 minutes to get there. You're going to spend an hour in the chamber at two atmospheres and then you're going to drive back. So you just put two hours a day into this for four or five days a week.

53:37And so the question is, even if you're completely cost agnostic, are you truly time agnostic? What could you have done with that time vis -a -vis improving your health? And in the case of longevity, I mean, if you spent half that time exercising, you're going to get 10x the value. And I suspect in the case of your patients, the same is true, right? If they, you're asking for 90 minutes the two hours of their time in total to do the brisk walk and this vigorous exercise. Well, that's more time than they would put into a chamber. And of course, the data, it sounds like that the chamber isn't efficacious.

54:09Is that true? You know, another question I get asked is if you could get into a hyperbaric chamber the day of the injury, would that move the needle? Has that been studied? No, because it's hard to study that. But to my knowledge, no, there's no compelling data. And any way she'd performed the Schuss hyperbaric treatments to be effective at treating this problem. And I think you just stated things very well, Peter. I agree entirely with how you just sort of conceptualize that. To add to it, what do you do when you're in hyperbaric chamber, where you think about crap a lot? You're ruminate. Yeah, and we don't want rumination with this.

54:44It doesn't go well. Another treatment option that I've had an interest in is the use of synthetic ketones, specifically acetoacetate or beta hydroxybutyrate, being in the system if one could do that prior to an injury. So, again, this assumes only in certain cases you would do it. It wouldn't help you against the car accident because you don't know when you're going to have a car accident. But if football players were drinking synthetic ketones in their system such that they had one to two millimole of BHB coursing through their system at the time of an injury, there's There's at least a very strong theoretical argument and there's some animal data to suggest that could ameliorate some of these symptoms because of course you immediately have a solution to that energy, that short -term energy crisis in that you don't have to rely on glucose.

55:31You get 70 % of that injury from ketone. Have you looked at any of those data? No, we're not doing animal model work here nor are we doing that sort of research to my knowledge that has not been done. I think theoretically it's interesting. This injury is such a hot focus on it. I'd be interested to look at that specifically in literature, but I'm not aware of any research, but it makes sense. To study that rigorously, you'd want to have a pool of presumably athletes where the frequency of concussion is high enough that you could basically study. Is it safe to say like, I don't know, high school or collegiate football players would have the highest incidence of concussion?

56:11Yeah, football leads away, But women's soccer is very high as well women's basketball is high But yeah football is the most actually the sport that carries the highest risk of concussion in terms of lifetime Incidents, what do you think that sport is? I mean, I would have to guess boxing 90 % of equestrians have concussions over the course of their a question I love that I'm now over three just we got to keep this quiz Tell me why are they falling or is it the bouncing? No, it's not the bouncing It's the falling and the horses have a very large beast. You know, you fall from a high degree, but given that the goal of boxing is to render your opponent can cussed, I would expect that probably is even higher than equestrian sports, but the research has been really good there because a lot of patients don't report the problems that occur.

56:59Obviously, boxing is a very common sport where this happens. This is a very common injury. I don't know if you realize Peter, but 1 .8 to 3 .6 million concussions per year alone in sports and recreation in this country per year. It's crazy. It's very common. What is the natural history of this if untreated? Let's start with what percentage of patients that sustain a concussion and let's just take all comers so we're not going to differentiate how they got their concussion, whether it's in a car or on a horse or whatever. What percentage will end up like the gentleman you saw today where this thing ain't getting better until he sees a specialist?

57:41Is that like 5 % of people, 25 % of people? I wish I knew. No one's done that kind of work. We don't know the denominator basically. We don't. If you walk today in my shoes, you think it was very common. You have a huge selection bias, obviously a feel like a lot of kids will be fine after concussion, meaning that they probably work out of it and they're fine. I don't know about you but I've had moments in my life where I remember playing sports and getting hit and feeling foggy and dizzy, you know, and I didn't have any problems from that that I'm aware of. So this happens, I think fairly commonly, and kids are fine, but certain risk factors, certain personality types, certain biomechanics, it's a confluence of factors that that end up with these patients ending up down this pathway where they can really get in trouble with it.

58:35So, and I don't think it's that all that infrequent. It does happen. Mickey, do we know anything about the effect of concussion on subsequent risk of brain disease? So one of the things we talk about a lot on this podcast, of course, is dementia, both Alzheimer's dementia and, of course, all other types of dementia, everything from Lewy body to small vessel, et cetera. Do we have any insight into a relationship between those two people who are identical in every way in terms of predisposition and whatnot and other factors. One person sustains multiple concussions in their life. The other does not.

59:15Do we know if that has any bearing on risk? There's been some pretty good research done on that. A lot of work done out of mass general in Boston, Grand Iverson's written really well on this topic. And the studies that have come out from him and his group, and I respect that group, we can see some relative increases in anxiety in some of those patients. But overall, the studies have been pretty good about showing us we're not seeing any proclivity towards dementia with these patients or proclivity towards Louis body or proclivity towards other neurodegenerative illnesses. Now, it depends on what research you're looking at, is you know, the research world is highly variable.

59:59And, you know, you look at other camps that would support that people that have repetitive head injuries will end up with chronic traumatic and cephalopathy. And, but you talk about selection bias. I mean, they're studying patients who are donating their brains because they have problems. And so, we have a study going on right now here at PMC. I think it's one of the best controlled studies done in the area where we have a number of form of NFL players, very large sample size coming to us and we're doing a three -day evaluation. We're doing a full neuropsych battery. We're doing really fancy imaging with them.

1:00:38We're doing lumbar punctures. We're looking at CSF. We're looking at different biomarkers. we're looking at sleep study, we're doing a full deep dive on their neurological health. I mean, like the deepest dive you could do. And then importantly, we're matching them to controls that haven't had the exposures. And we're doing a very well controlled study looking at the prevalence of neurodegenerative issues in patients that have had repetitive head injury versus patients that have not. And we're year two and a half into that study right now. And we're just about to dive into our first statistical analysis, looking at all this information.

1:01:17So this is one of the better controlled studies out there right now, and there are other groups doing similar work. So we're going to have very good scientific answers on this question and then relatively near future. In the next several years, you'll see studies come out from these different groups. And that's why we do research. You don't want to get your research in the New York Times. That's for sure. You want to do well controlled empirical work, which we're doing. And I think we're going to have a very good understanding of this issue and more clarity to it and then relatively near future.

1:01:51Is it and I know that CTE is not your area of expertise, but is it your intuition that CTE is the result of untreated concussions that accumulate repeated injuries, speaking of the New York Times as my source of information. My vague recollection of this was the idea that CTE was not so much the result of major concussions, but basically constant accumulated sub -concussive injuries. But again, I could be totally misremembering that. No, I think you're remembering it right now, whether that's scientifically accurate and not it's a different story. And I don't know the answer to that. And that's why we're doing the research.

1:02:31But the science hasn't evolved to have a definitive statement on these issues, in my opinion. And what I know anecdotally is I see patients who are absolutely convinced they have CTE that get better with our treatments and don't have problems after we treat them. And there's nothing worse than patients that think they have some debilitating life -threatening disease where there's no possibility for help. It doesn't go well in those patients. When in fact, a lot of the problems that we see, there are treatments. And a lot of patients aren't aware of that. And it's very sad to see that happen. And we see that a lot.

1:03:09That's kind of an amazing thought. I never really imagined that. But it's certainly possible that there are gonna be a lot of people who either played sports professionally or at a very high level who could easily think that they're in the stages of CTE. And maybe they're not. Maybe this is a concussion that hasn't been appropriately treated. I'll even take that a step further. We see patients that are suicidal from this. And it's very scary where this will take you because remember we're talking about patients that have biologically derived sympathetic nervous system arousal and high anxiety and they feel horrible.

1:03:46They're not working, they're not exercising, they're not regularly with a sleep, they're not social, they're ruminating all day long. I mean the suicide risk in that population is very, very high. And so you wonder where this leads to and some of the suicide alley that we see in patients, like what percentage of those patients didn't have those problems, but they believe they did. And that's a function of, again, when I talked about earlier about how when you have an increased awareness with no solution, it can really lead to a lot of hysteria. And unfortunately, we can see that. and it's very devastatingly sad to see that in some of our patients.

1:04:28And I think we need responsible science to lead us to better answers to we really understand this. And I understand the need to talk about this stuff in the media. And you said it earlier, we see so many patients because of that awareness. And that's a good thing. I mean, it's really leading to a lot of people getting help that wouldn't have received help. But on the flip side, it can be very dangerous as well. There's going to be a lot of people listening to this Mickey who are parents. Their athletic heyday might be behind them. They're not taking the high risk activities. Their risk of concussion will talk about later because that's going to be the car accident to fall.

1:05:03Literally, I know somebody the other day that was bending down to pick something up under a table. And when they came up, they had that enormous posterior whack at the head sustained a concussion there. And thinking about their kids who are playing sports, whether it's soccer, football, you name it. What is the best advice you offer to those parents? So they're saying, I think little Billy or little Suzy has a concussion just based on the symptoms. We just took them off the field right away. Do we need to come out and see you in Pittsburgh? How many other centers of excellence are there in the country where we could go and get this level of bespoke treatment?

1:05:40That's a hard question to answer Peter, but it's a great question. And yes, there are centers around the country that do a really good job with this injury. And you want to start at places that have experience and they call themselves concussion clinics or specialty clinics I think they're much more equipped to do the work than a general pediatrician I mean you might want to start with your pediatrician if you have specialist clinics in your area You want to start there because they're familiar with the literature and the tools and in by and large You're very well equipped to manage these injuries Approximately how many of these are there does every major medical center have one now?

1:06:13Isn't that crazy? We were the first program literally in the world doing clinical work or studying this injury. And now I would say that every major geographic area has a center like this now, which is really exciting. It's crazy, isn't it? Blows my mind. Let's talk about that. It's only 20 years later. So yes, this does exist in most places. If you're in rural Idaho or something, you may not have access to it. But you know, now that telemedicine is a medium that's widely used. I mean, you have that option available a lot of times, et cetera. So the access is better than it ever has been with that.

1:06:48Just off the top of your head, kind of top five programs in the country that you would say would be great places for people to start if they're willing to travel and there's availability. Obviously your program, what would be the other five that you could have? I have an incredible one. I respect for is a Nova in Washington, DC, one of my former fellows is there. We've had 33 fellows trained under us, under me, and they're at various sites around the country. I think most of them do a really, really good job. I would say off the top, my head, I think Boston Children's does a pretty good job overall.

1:07:19I know this clinic's down in Houston, Texas that do a good job. This clinic's in Phoenix that do a really good job. This clinic's in California that do a good job. I mean, one of my fellows is in North Dakota right now doing great work. They're out there. You could even go to our website and kind of find out who we train and where those patients are. There's access to places, but there's really good programs out there. I have great respect for and we're actually collaborating with a lot of these programs and doing research as well So which is a good thing and would your advice Mickey to that parent be?

1:07:47So let's just say the child experiences a concussion on Monday afternoon. Is your advice to them? You know what? Why don't you just kind of keep the kid doing his thing her thing and if in two weeks It's not better go see the specialty clinic or is your advice no go to the clinic right away on Tuesday I agree with that. But again, based upon our research, the earlier we see someone, the quicker they get better. And you do want to start these treatments pretty quickly. And I would say if you can be seen within seven days of an... You know, the first thing you have to do, Peter, is make sure there's not an intracranial bleed, right?

1:08:20I mean, you think... Yeah, you have to do the medical thing. You have to make sure the red flags aren't there, etc., and rule that out. But once that's ruled out, I do think seeking specialty care within a week of injury is going to lead to a much quicker outcome, which is what we're looking for. So basically, it's never too early and it's never too late to seek help for this. I agree with that. Yes. Does all of that apply as we now move from the kid to the parent? So if it's me and I'm out there playing with my kids and they somehow talk me into climbing a tree, which they often do, but I fall, whack my nog in.

1:08:54Same thing. Let's say I go to the ER, we get the CT scan, I don't have a bleed, there's nothing going on. Let's say I feel totally fine. I'm like, I got a bump on my head, but I feel fine. And I medically cleared, should I go and get evaluated, or only if I have a symptom. Yeah, if you feel fine, I wouldn't necessarily feel that's necessary, no. But again, the symptoms can be subtle, you know, what we talked about. That's my point is like without someone in the ER who's gonna do the real ocular motor test or whatever, I can speak to the symptoms, but I can't speak to the signs on my own, correct?

1:09:26Yeah, and it's even hard to speak to the symptoms. Dizziness, fogginess, fatigue, light -sensitive, noise -sensitivity, headache, obviously, difficulties falling or staying asleep, nausea, car sickness, difficulty in busy environments, cognitive issues, you know, all those things can... But as long, if you're not having any of those problems and no, live your life, man, it's okay, you know? But it can be subtle, that's for sure. But it's not going to bite you, Peter. You know what I mean? It's not like I don't want to, if your symptoms are pretty nasty and they're not getting better, yeah, you better see someone, you want to get in, the sooner you get in, the better it's going to be.

1:10:02It's a symptoms are very subtle and improving. I'm not that worried about it, honestly. You just don't want another head injury while that's going on. And so that may be a reason if you're a weekend warrior, you got to pick up basketball game you want to play in and next weekend, you probably want to get it checked out to make sure everything's normal. If you're not a weekend warrior, you're not going to hit your head again and it's getting better, I'm not necessarily so sure you need to see some work. Do you know anything about the role of the APOE4 genotype in terms of susceptibility to concussion or any traumatic brain injury?

1:10:34So, APOLIP protein has been looked at with this injury and there is no compelling data to suggest that would put you at greater risk. It's not augmentive concussion plus APOE4 allele leads to x, y or z. So no, I wouldn't say there's any hard data suggesting that to be a big risk factor. Although it's an interesting one to look at. And I don't think the research is definitive, nor is it comprehensive and looking at that, but no, nothing to date has been. I raised that issue in the JAMA paper we published in 1999. It's the same place I went when I wrote that paper. It's like people need to explore that relationship.

1:11:13Nothing has been found to be definitive there, no. And I guess the last thing I want to just chat about is a little bit more of an understanding of what you said about the older folks. So we talk a lot about this on our podcast, right, which is once you hit about the age of 65, your mortality from falling becomes really high. It's actually surprising when you look at the population -adjusted mortality associated with falls, accidental falls. And we talk about it mostly through the lens of, hey, here's all caused mortality that in the first year post of fall that results in a fracture of the hip or femur.

1:11:48One of the things that's happening in the aging person, of course, is their brain is shrinking a little bit and their skull is not. So presumably that's making them more susceptible. They're going to have more movement of the brain within the head. Is that why we're seeing a greater susceptibility in an aging population? In addition to the fact that they're obviously more susceptible to a fall. I don't know. It's a great theory. But yeah, we obviously we see atrophy in that population, et cetera. And the other thing is there's a lot of unprotected falls in that population. There's a a sinkable events in that population and there's a lot less motor control when you do fall.

1:12:18The biomechanics are going to be more violent in that population. And also cerebral spinal fluid is not as robust in that population. So you don't have as much protection of the brain moving inside the skull either. So there's a lot of reasons for it. But oh my goodness, is that an understudied area and boy is it a huge problem that we see day and day out in our clinic? I have a definite passion of working with older people that have this injury and we're doing some of the first research looking at concussion and geriatric population and it's a very rewarding population to work with because you can treat it.

1:12:50It's so exciting to see someone. I just saw a 90 -year -old this morning, Peter, that fell and they want to get better so bad they have so much energy and how long ago did this person fall? About eight weeks and they're not well. Tell me about the fall. If I remember Right. They had a sink up a episode where they hadn't hydrated well, maybe a little stress going on their life Disregulated blood flow, you know, dysonomic stuff They get up from going to the bathroom collapse hit their head on the linoleum floor fall forward off the toilet Correct face first basically facial fracture small subduro bad concussion fortunately no intracranial intervention the blood from the subdural we absorbed, but they're left with this pretty bad concussion.

1:13:38Very, very dizzy in bed, very, very dizzy in life. Don't like busy environments, feel fatigue all the time. Bad headaches they've never had before. A lot of anxiety that they're not even aware of. And of course, they're living alone at the time. And now, family members are around. They have to get support from them. And they get enabled. And they get really protective. they think they're gonna fall again so they don't move as quickly and of course the vestibular problem doesn't get treated because they're not moving, they're not doing anything, they're not exercising, they're not going to busy environments and so the anxiety levels are up, they have benign positional vertigo that no one ever noticed, that's why they're getting really dizzy and bad, we can fix that.

1:14:21What we get them in the right physical therapy, the right vestibular therapy, the right approach, we get family members on board and tell them how to approach things and and get them more active and challenge them more and make sure the parents aren't protecting them as much as they, you know, overprotecting them and explaining how you treat this problem. And oh my God, they do really well. It's amazing. It's very, very rewarding to treat a patient like that and we'll get that person better and they'll be, they'll look great here in the few weeks hopefully. This person will be doing how much exercise as a part of their rehabilitation program.

1:14:53Walking for now, you know, they're not a fall risk. we looked at them see our vestibular therapist and on a fall risk which is good. So we gave them some balance exercise to work on. We'll give them some vestibular exercise to work on. Tell them to go to grocery stores. Don't hold onto the buggy, you know, walking up and down the aisles, challenging themselves, going out to busy restaurants, going back to church, you know, explaining to family members how to approach all that stuff. It's really cool to see this stuff wash off the patient. When in fact they are helpless. They don't think they're ever going to get better, they think their life's over like literally.

1:15:25And they think it's beginning of the end, you know? Yeah, beginning of the end for sure. Tell me your research is mostly funded through NIH? Oh, we got funding from a lot of different places, but we do have NIH funding. We have funding from the NFL. We've got funding from Centers for Disease Control. There's a really cool foundation here in Pittsburgh called the Chuck Noel Foundation for the former coach Chuck Noel. I talked a little bit about baseline testing. Chuck Noel was the Steelers with The first team to ever do baseline testing in Chuck Nol was a huge proponent of treating head injury the right way.

1:15:57And Joe Maroon had a lot to do with that. But anyways, the Chuck Nol foundation gives out grants for researching head injury. And we've received a lot of funding from that. And many other grant sources. It's pretty cool. It's a pretty hot topic. And so there's a lot of money's available to study this, which is exciting. As soon as you mentioned this, but I assume you have neurologists in your group now as well. We have a few, but neurologists do a phenomenal job with this injury, okay? but you're not trained about concussion in medical school. That's not in the curriculum. Just because your neurologist doesn't mean you know concussion.

1:16:29Just because you're a neurosurgeon doesn't mean you know concussion. This is new science, new information, and that's why it's really important to see a specialist. Just don't assume that you go to one of these people that are going to know this injury, because most of the time they don't. How many fellowship programs are there in the US now for training concussion specialist? So, I mean, what I'm hearing from you is you have a neurologist that would have to then specialize in concussion. You have a psychiatrist, you have vestibular therapist or ocular therapist. I mean, everybody basically has to be under a concussion training umbrella.

1:17:01How many places are there besides UPMC? I would say conservatively 15 to 20 fellowship, you know, maybe 10 to 15 fellowship programs. That's off the top of my head. That would do training specific to this topic. So it's not that many, but they do exist. Well, Mickey, this has been really interesting. I know you've got a busy day in clinic, so we were lucky to get time with you today, but I want you to get back to those patients. I cannot believe the volume of patients you see. That is staggering. It probably also speaks to how amazing your team is, and it's sort of like you've got that almost the executive physical situation where people can come in for two days and they can see every doctor in the medical center.

1:17:42It sounds like it's that fine -tuned. I came away from this discussion actually, far more optimistic. I don't think I had nearly an appreciation for how positive the prognosis was even in those patients with long -standing concussion with the right therapy. I thought it was the exception and not the rule that one could get better if you were two years out and still suffering. No, Peter, it's been great. I've really enjoyed it actually. You do a phenomenal job with what you do and you have an interesting job. you get to hear a lot of different people talk about a lot of different things and I think you conceptualize this very well and I really appreciate your time.

1:18:20It was a lot of fun. Thanks Mickey. Do you want to ask me one more question just to see if I can go 0 for 5? Do you have any other trivia for me? We'll just leave it at 0 for 4. Oh, sip with the 0 for here. Yeah. I set you up on all those dope, Peter. I did. No, that's good. I kissed me humble. All right, thanks Mickey. Take care. Thank you. Thank you for listening to this week's episode of The Drive. If you're interested in diving deeper into any topics we discuss, we've created a membership program that allows us to bring you more in -depth exclusive content without relying on paid ads. It's our goal to ensure members get back much more than the price of the subscription.

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