Chapters Transcript Video Pediatric Concussion: What Science Tells Us About the Art of Management Stacy Suskaer, M.D. presents at the Johns Hopkins Department of PM&R’s Grand Rounds on December 19, 2017. So today, I'm gonna talk about um primarily concussion, a little bit about broader milder forms of traumatic brain injury and in particular, some of the issues I'm sort of grappling with moving between clinic and research settings. I have no relevant financial relationships. There you go. Um We're a little bit stuck. So the game plan today while we're waiting for this to load. Oh OK. Learning an objective is that by the end of the presentation, um I hope you'll be able to describe a little bit of evidence suggesting that there may be lingering changes in the brain even after a child appears to have clinically recovered from concussion. So initially, I'm going to start by describing some of the clinical scenarios that we have regarding concussion and open questions in terms of management. And then I'll talk a little bit about the research that we are doing now and then we're gonna come back at the end to sort of wrap up about how we incorporate some of what we're learning from research into clinical practice. And I have this yellow brick road here to signify that along the way, I'm going to talk about a little bit about my path and I think it's important to point out that things didn't go necessarily as I expected them to go and that, you know, there are certain sort of opportunistic changes along the way and that it's ok, perhaps not to know exactly what your destiny is going to be. So this is actually the clinical scenario that really drew me into pediatric brain injury. Um So I did a combined PS and PM R residency. I knew I was interested in Children with disabilities but had primarily been exposed to Children with more physical disabilities and not cognitive disabilities. And um we would get called to the IC U and we still do in our clinical practice to meet a child and family um where the child had just sustained a serious traumatic brain injury. And as we all encounter in our care, of course, the family really wants to know and the team wants to know what is this child or adult going to be like so that we can start planning and adjusting and making decisions. Um And of course, we don't have great answers to that today. And this is at a time when some of these emerging imaging techniques were coming out and I thought there must be a way to pair better imaging with answering this question. What I did not at all imagine was that someday I would spend a lot of my practice actually answering that same question. About teen athletes, typically developing kids who play sports. And with some of the emerging information that we'll talk about families really want to know what is my child's long term future going to be like, do I need to change their preferred activities to ensure a good outcome? And so we started our concussion clinic in 2010. And the reason it got started is actually the pediatric neurosurgeons called over and said, we're seeing a lot of these kids with concussion and we think that they would be better served in your clinic rather than our clinic. And um, so Jim Christensen said to me, well, I got this phone call. Would you like to start a concussion clinic? So I said, ok, years later, he told me, he thought I was gonna say no and that, you know, I needed to focus on my research. Um But here we are and um you know, again, as knowledge about concussion continues to develop and evolve, um instead of sort of just focusing on the here and now with these patients, we're really thinking about their long term future and the goal about maintaining um kids healthy throughout a long lifetime of physical health and emotional health and well being. And I have really come to see our role in part as a predictor of that long term outcome and that we need to do the best we can to figure out how we help ensure those outcomes. And um you know, particularly when we have a child who comes to see us and has experienced a concussion, how do we evaluate that child and how prognosticate about what their path down the road will look like? So it concussion is defined as a physiologic brain injury. And the definition includes that in most cases, there are no imaging findings. And as we go through this, I generally use concussion and mild TBI. I synonymously, although we talk about complicated mild TBI I as representing when there are imaging findings present. Uh but we're typically talking about what's believed to be a physiologic brain injury that's associated with some kind of trauma to the head or body that sends propulsive waves to the head, causing a concussion associated with onset of classic symptoms, which may or may not be short lasting when we talk about the epidemiology of concussion. Um what we have here is one of the CDC S slides. The these are all emergency department visits. So we know that these don't capture all mild traumatic brain injuries or concussions. But the solid line is um individuals seen in the emergency room and discharged. So typically mild TB is the middle line with the heavier dash is a individuals who are admitted to the hospital and then the line which is fortunately very close to the bottom is deaths related to traumatic brain injury. So we know of all TBIS, mild tbis are most common you can see that the frequency of emergency department visits is highest in the youngest Children, 0 to 4 year old. And overall certainly the highest number of visits for concussions happen in Children compared to adults. There was some recent uh study that looked at high school age Children and extrapolating from that population. They estimated that 50% of high school age students with concussion are never seen by a health care provider for that injury. So they're not seen by the trainer or their pediatrician or a sports medicine physician, they're not seen by anybody. So when we think about how we're going to have policies and procedures that really protect this large number of Children, it's really going to be quite a challenge, but certainly means that we need something that's going to be widely available in all settings. As we think about sort of Children who then go on to see their pediatrician or specialists. One of the, I think particular sort of highlights about the kids who come to rehab is that they tend to often be some of the most complicated kids in terms of being slow to recover, having comorbidities and needing a lot of resources. And so overall sort of concussion ranges from this really major public health issue to some Children, a small number of Children who need a lot of care. And when we talk about concussion, I think to me, I take this very seriously as high stakes medical decision making again. I never thought when I started residency or started practice that it would be the kids with the mildest injuries who perhaps we were making the most critical decisions about. But in many ways, I think it is the first decision which often happens before the child comes to see us is when do you remove a child from their activity and related to that? When can a child return to activity? And we know that there are risks both with holding, with sending a child back too soon when they may be at risk for this sort of second hit phenomenon, or at least prolonging their time to recovery. But we also know that if we hold a child out too long from sports, unnecessarily that they become withdrawn. If they don't get back to school, they become very anxious about their school work, they lose their identity and it's not really a safe thing to hold the child out longer physically. They also become deconditioned, which isn't healthy or helpful in terms of their ongoing sports career. Another issue is how we conceptualize persisting symptoms. And so in many ways, I think we tend to think about especially a single concussion or mild traumatic brain injury as an event that should not cause lasting concerns. And thus, we want to look for other reasons why the child may still be presenting with symptoms. Although I'm going to challenge that notion of it today and then finally, again, this anticipatory guidance about future risks. What do I tell this family when they want to know what's the risk of sending their child back to lacrosse or basketball or football? So we talked about how concussion is a physiologic brain injury. So that said none of what we do in evaluating these Children directly measures brain physiology. So the gold standard in evaluation is we look for the presence of symptoms with and without cognitive and physical exertion in pediatrics. We're asking the parents as well as the kids to rate on how they think the child is doing. We're doing a neurological evaluation including often looking at balance and um in our testing in our clinic, every child receives neuropsychological testing and we compare that to either um what we have documented or what we can sort of guess about the child's baseline based on their academic history. Um But again, all of these are sort of behaviors which we can't say exactly what is leading to that behavior. Um And so when we declare a child recovered using this gold standard, again, I think what's being called into question is what does recovered really mean. So these are data which have looked at the rate of lower extremity, muscular skeletal injury when um primarily college athletes return to play after a concussion. Um The two studies at the top, um and Dan Herman is also a rehab physician specifically look at compared to peer athletes who did not have a concussion over a 90 day period, how many athletes who just came back from a concussion versus uninjured sustained again, a lower extremity injury in those 90 days that kept them out of at least one practice. And so in the Brooks study, what we see is 15 of 72 athletes from concussion or I'm sorry, 15 of 87 had a much skeletal injury and only 17 of 100 and 82. So a much higher rate of the lower number of individuals with concussion. And then uh the Herman study is a survival graph. So what we're looking at, I want to call to attention here that the Y axis starts at 50%. So we're looking at 50 to 100%. And then over a period of days, how many people have not sustained a lower extremity muscular skeletal injury? So the dash line here is concussion. The solid line is control athletes. And what you can see is that the the concussed athletes are dropping off much quicker. So that by about 90 days, post injury, 50% of them have now sustained a muscular skeletal injury compared to maybe 80% of the control group. So suggesting that there's some kind of vulnerability when individuals come back from concussion that translates into other injuries. And so the question would be, well, are these athletes who had a concussion just somehow at baseline at higher risk for being injured and that's why they had a concussion to start with. So the study on the bottom looked at comparing to an athlete's own history prior to concussion compared to after. So here we have the group that had a concussion and here we had a control group again, looked retrospectively and then prospectively in terms of musculoskeletal injuries and the horizontal lines are 90 days, 180 days in one year. What we see is that the rate of lower extremity injury doubled in the concussion group after their concussion compared to before, whereas there was no change in the control group. So I use this again to sort of provide one level of evidence that there seems to be something different once you come back from a concussion about your risk for any injury. So moving on from muscular skeletal injury, kids who have had prior concussions are at a much higher risk of having another concussion. So the top table here looks at the rate of concussion in high school athletes based on whether they've had 01 or two or more concussions in the past 24 months. And what we see is that the rate is 2 to 5 times higher in the athletes who have already had one concussion. Um So not only are they at risk for musculoskeletal injury, they're at risk for another concussion? Ok. Well, then, so what, why do we care if these kids have another concussion and these are uh data here in the bullet points looking at for a child who's had a prior concussion at the next concussion, they're more likely to have loss of consciousness. So the next concussion is more likely to look worse. Um, compared to kids who have never had a concussion, they're more likely to have gate abnormalities after a second concussion. So perhaps some sort of additive factor. Um and between concussions, kids with more concussions are more likely to have report more symptoms at baseline. So that's what's in the chart here. These were data gathered at pre preseason testing. So no child was currently experiencing concussion. They were doing impact as part of getting ready for their season and impact tally symptoms as well. And what we see here is the rate of endorsement of physical cognitive, emotional and sleep symptoms based on no prior concussions, one prior concussion or two or more with a significant increase in baseline level of concussions based on prior concussions, baseline level of symptoms based on prior concussions. Um So all of that is to say that concussion seems to cause problems. It doesn't necessarily seem to be what we once thought that a single concussion kind of you're scot free and no lasting sle of that. Um This I pulled from a systematic review of the literature looking at the growing literature regarding chronic traumatic encephalopathy and other potential long term consequences of repetitive injury to the head and I'm not going to say a lot about this. Um, except to say that certainly there seems to be a subset of individuals that with the right exposure appear to have adverse outcomes. We know it's not every ex NFL player and I think that's really important, but also confuses the situation in terms of who's at risk and who's not at risk. Ok. So I use all of that to say that I think we need to do a better job of evaluating kids with concussion. And perhaps someday before their first concussion, I think sports are very important. It's part of my job to send kids back to sports. I think it's really important that we maintain an opportunity for kids to have the physical exercise and the social experience of playing sports. But on the other hand, somehow we need to go from encouraging that at a population level to better identifying who can continue to participate in certain sports long term and not have adverse outcomes related to that. Ok. So we're gonna transition now, um to talking about some of the research that we have done and I initially started down this line of research back to that patient from the IC U intending to look at kids with moderate to severe injury before I sort of got into the world of concussion. Um and sort of made a fortuitous, I wouldn't call it mistake but decision when we defined our inclusion criteria for moderate to severe TBI I. Um so we did this study to look at kids prospectively two months and 12 months after injury and we use these inclusion criteria. Um, so hospital G CS of um less than or equal to 12. So defining mild to moderate loss of consciousness greater than 15 minutes. Um And so I'll just point out especially for the residents, the typical um accepted definition of concussion is loss of consciousness greater than um the borderline between concussion and more severe injury is 30 minutes of loss of consciousness and 24 hours of post traumatic amnesia. So, basically, what I did here is I used a messy definition in research. Um And then we included kids with in intercranial injury and clinical imaging. Um And so, while I intended initially to study a more severe group, we wound up with a number of Children who we would now say meet common criteria for mild traumatic brain injury uh in this study, which wound up being a good thing. So, um as Dr sick alluded to one of the modalities I have used is uh resting state F MRI. So F MRI refers to functional MRI. And so the idea is you're looking at how regions of the brain activate or deactivate, which is a nice physiologic measure when we're talking about a physiologic brain injury as opposed to an atomic injury for resting state, as opposed to a task where you're asking the patient to do something in the scanner and looking at associations of brain activations with that particular task for a resting state, we just tell them go in the scanner, we ask them to keep their eyes open and look at a cross hair. So we have kind of that standard eyes and they're just to be still, we don't give them any other instructions except try not to fall asleep. Um So one of the important advantages to this compared to doing a task is that kids move less compared to a task when you ask them to do a task, even if they're just moving a hand or their eyes or moving something, and that sort of generates more motion. If we have too much motion, we can't use the data. Um In addition, we're not limited to studying associations with a specific task. The caveat to that is I can't tell you specifically how the brain activations we see relate to task performance, but we have the ability to look at different associations. Um And then another important piece for TB I is that blood flow may be altered in TB I. And so if we're just looking at absolute activation in a group with TBI, compared to a control group, we may have some confounds based on the timing of increases in blood flow. When we look at resting state, what we're really looking at for correlations within each individual brain, what areas activate together or deactivate together or one activates when the other deactivates. And so the child's own cerebral blood flow rate, sort of takes care of that. And we don't have to worry about between group differences from that perspective. So if any of us went into the scanner and we're just resting, we would see that regions of our brain activate and deactivate together in a predictable pattern. And so these are resting state networks, but you will also recognize them as networks which underlie common behavioral functions. So we have regions of the occipital lobe that activate together and that we know are associated in visual function. We have the sensory motor networks, we have language networks that involve the parts of the brain that we know are important for those things. I'm going to talk a little bit more about two specific brain networks called the default mode network or the DMN and the dorsal attention network or the DAN. The default mode network is also called the task negative network. And the idea is that the DMN is active when we're not doing any outward task. So we might be just thinking um sort of daydreaming processing our day sort of inward self, self referential thought um as opposed to the dorsal attention network, which is a task positive network, which is activated when we're attending to some outward task. And so these networks are anti correlated. So the idea is if any of us were in the scanner, um when our default mode network is active. Our DAN tends to be deactivated because we're not using them at the same time. And the same goes for the opposite. If your dorsal attention network is activated, your DMN tends to be deactivated. Um In the picture here, the um default mode network is in blue and the dorsal attention network is in orange. So before we started this work, most of the work looking at network connectivity after traumatic brain injury had focused on connectivity within networks. Um So how connected are nodes of the DMN or the DAN to each other? Um And I thought there were some interesting results. So I have typically thought of exon injury, DA I and TB I as sort of a disconnection syndrome, right? We know they're sharing, it seems like regions should be physically disconnected from each other. Um This paper is one of many that have shown some regions or networks in which individuals with TB I were actually had more connections among their nodes compared to individuals without TB I um which I'm not really sure what that means. And so what I was interested in was looking at, well, how are networks sort of connected with each other? Maybe networks are more connected to within itself because you're disconnected from other networks. So that's the approach we chose to take. And we looked at the whole brain connectivity of the default mode network and the dorsal attention network and went in there really with no a priority hypotheses about what regions would be activated. The study overall looked at processing speed and inhibitory control as important outcomes after TBI I. And so we had related behavioral measures. So we first looked at these kids two months post injury, we had a small group of 14 kids who despite our wide inclusion criteria really wound up with mostly mild to moderate TV. As kids who were appropriate to bring in for a research visit. At that point, post injury, they were between one and three months, post injury. Only four of these Children had clinical imaging findings. Initially, an epidural hematoma, a subur hematoma and two Children with contusions and seven of these Children, you know, as we sort of think about them now met criteria for concussion and not only that but were clinically recovered by the time they came in for their visit. So you might have even thought why would we even be studying them? But it sort of met our inclusion and exclusion criteria and recruitment was tough. So we brought them in. Um and then we had imaging but not behavioral data from age and sex ma controls. So these are some of the details about how we do our uh imaging acquisition and analysis. Um It's a 5.5 minute scan that the child is in the scanner over at the Kirby Center at Kennedy Krieger. We use um seeds based on the literature to define each of the networks. And the most, one of the most important piece is that we did a very strict um uh correction for multiple comparisons. I have a couple of slides here just to sort of prove to you that these kids don't have grossly abnormal brains. So we can't make any conclusions based on just looking at these gross images. Um Except I can show you that, in fact, the kids with TBI, I generally look like the kids with control. So in the middle, this is the DMN, the default mode network, we have sort of a picture from the literature of the DMN. On the top, we have our TBI I cohort and on the bottom of the control cohort and they all kind of look the same, we're not missing like a chunk of activation somewhere. The same is true for the dorsal attention network. So these are our findings from that sort of whole brain analysis of what's different between kids with TD I and controls with the default mode network and dorsal attention network. And um completely sour surprises to me, all of the regions that came out were motor related. Um And so we had uh differences with connectivity of the right dorsal premotor cortex, the bilateral primary sensory motor cortex and the left. And we both also had regions where the group of TD I was more connected and the group of TB I was less connected. And I'm gonna break down a couple of examples to show you because it's not really clear what it means to be more or less connected. It depends on what the control group looks like. Um So this was very interesting, but I don't really believe anything unless we feel like it actually, we can tie it to something else and feel like this is meaningful. Um So we then went to our behavioral data and said, do these data relate to any performance on any of the tests that we did? Again, the behavioral testing was all done outside of the scanner. Um So the measures that we had, which are sort of pretty standard motor measures included pegboard test, looking at speed, the deca trails looks at connecting dots and seeing how fast you can do that. And we had a go no go task and had just a measure of reaction time for go responses. And there was no relationship between any of these connectivity findings and those tasks. Um And so we also had the pan and I'm going to talk a little bit more about the pan. So the pan stands for the physical and neurological examination of subtle signs. This is a task that was developed by Martha Dunk who's a developmental cognitive neurologist. Now retiring from practice. And um the reason I was even exposed to this is because my research mentors were Martha Dunk and Stuart MAOs who study a DH D and autism and look at subtle motor findings in that group. And they used to talk about this all the time in lab meeting and broke down some of the tasks and the residents will know I bring some of these over to the clinic and look at things like finger tapping and sequencing. And I'll point out what makes the pan a little bit more different. But I had started looking at some of these things in my TV I clinic and found kids had these subtle signs. So we threw it into the research protocol. Um And at first pass, what stood out to me is that we know in typically developing kids scores on the pan, s kids get better as they get older. It's very common for young kids to have overflow movements, but those should go away. And in our TV group, there was no relationship between age and the subtle motor findings suggesting that the TV itself may play more of a role. So these are the tasks that are involved in the pan. They're broken down into walking tasks. So not only heel, walking and toe walking, but walking on the sides of your feet and then walking tandem, forward and backward. And for each set of tasks, we're looking at some sort of global performance measure. So either can you do that gate without having to come out of it or taking a side step but also some measure of subtle motor performance like overflow. There are standing tasks and then there are six repetitive motor tasks. Uh three are um patterned and three are sort of repetitive and they include a measurement of both the upper and lower extremities and the right and the left side. Um So just a little more information, this is um on here uh modeling one of the stances. So standing with eyes closed hands out for 20 seconds and looking for any subtle motor signs in that position. This is an example of setting the patient up to do one of the repetitive motor tasks. And so um I'm gonna use this uh video clip to show you some of the movements we're looking for. So first of all, speed is being measured in this finger sequencing task. How long does it take to do 20 taps? Um But in addition, we're looking for overflow movements and dysrhythmias or sort of disruptions from a normal smooth sequence. This child is wearing um what, what uh the child is wearing is electro goniometer. This is actually to quantitatively measure the amount of overflow. Um So that's not typically done as part of this task but can be done to look carefully at that. So as I start the video, we are gonna start by looking at the hand that is down on the pillow here. So the child is being given instructions about to sequence and we're gonna see some overflow movements, we're going to look for a very large overflow movement and then I'm gonna move your attention to the hand that's doing the sequencing and we'll see some dysrhythmias there. So let's so there was just the double and so there are a couple of double hits there. So this is sort of the level of um additional motor findings that we're looking at and then we can break this down into scores based off of the gates and standing tasks and the total time tasks as well as looking at overflow across all tasks. So taking a step aside from the imaging for a little bit longer, um this is the first of multiple um works that I'm going to talk about that. Jacqueline Stevens is the first author on. So Jacqueline finished her postdoc fellowship this summer and is now an assistant professor uh out at Colorado State, so very proud of her and you're going to see a lot of her work. So initially what we did is just look at pan performance in this group of kids at two months, post injury, at 12 months, post injury, relative to a control group. And so what I have is the total score for the TB group. Again, two months, post injury, 12 months post injury compared to controls. So two months post injury, the TBI group performed significantly worse than controls, whereas they did not, they did not have any performance deficits on the group peg board and the DECA trails task that we typically use in our neuropsychological evaluation of these kids. So the piano was more sensitive. And then when we look at the 12 month performance, the kids with TBI, I improved significantly over that amount of time and their total scores were no longer different, different from controls, although they continued to have different scores in terms of gates and stations subtask. OK. So now looking at the pan combined with our imaging data, well, we break down one of those associations. Um And so this is the relationship between the default mode network and the right dorsal premotor cortex. And what we have here is a region where the kids with TB I had more connectivity between the default mode network and this premotor region. Um Now the catch here is that the control group was actually anti correlated. So if you think about with that default mode network, which is sort of in inner referential not outward task directed, there may not be a reason for the DMN and sort of motor networks to be connected. So it may make sense that they tend to be anti correlated, which is what we found in the control group. And what we found in the TB I group is that they were more connected because they were actually less anti correlated. So it was like there was loss of that, of those two being functionally disconnected. Um So then we looked at the relationship between connectivity values. So again, higher connectivity here in the TD group is more atypical with the pans total overflow score in this case and higher scores on the pans are worse. So here we see more abnormal connectivity is associated with worse performance, which is exactly the kind of finding that we thought we would have so worse is worse. So then looking at the dorsal attention network, this is looking at the connectivity between the dorsal attention network and the left primary sensory motor cortex. So again, the TBI group had more connectivity. But here it's that in the control group, they're not really related at all. They're sort of the connectivity level tends to be around zero that they just there was no reason to sort of co activate or separate out the attention network and the motor network as opposed to the group of TB I, which actually showed more co more connectivity between attention and motor network. So then when we looked at this compared to the PN total overflow, what we found is that the kids with more abnormal connectivity here performed better. So these are kids who looked more normal on the subtle motor exam, but it's not because their imaging was the same, their connectivity was the same as controls. It was perhaps because they were using a compensatory technique. So this is the kind of kid that we would see them in clinic and say behaviorally your exam looks really clean, you must be recovered but you know, the question is, are they really recovered or is the brain doing something different to obtain that good performance? So just to sort of summarize, we kind of had two separate groups here, we had the group that had high subtle motor dysfunction, which had one set of increased connectivity pattern and the group that looked more normal, that had lower levels of subtle motor dysfunction. Um and maybe we're compensating. And then my next question is if, if the brain is compensating after one mild injury, is that a vulnerability for after the next injury or as we start to age, um that sort of as you have a second hit, whatever it comes from, are you more susceptible to showing problems? Um And this is a graph that just shows um those that the kids really did sort of fall into one group or the other, that there was a negative correlation between these two patterns of connectivity. So the TBI group here is in blue. So if you are high on one pattern of connectivity, you are low on the other pattern of connectivity, the green is control. So you can see how spatially distinct they are from the group with TBI on this plot and there's no relationship between these connectivity patterns and controls. Um And so then sort of a separate issue for another day before I move on, but is if we have sort of better changes in connectivity versus worse I think this also opens up the question of is there a means to intervene for the kids who maybe have worse connectivity and function to bring them over to the better function group? And I think the fact that this is our findings are in the motor network makes it sort of perhaps a nice area where we know what kinds of interventions we might use. You say something about the timing of this correlation service because we go sure the finance was done two months after and the imaging element is around two months. But these ideas of compensation should be more important as you go to the 12 months for the director. So, so all the data except for that behavioral data, thank you for pointing that out. This is all the two month data, but I'll remind you that seven of these kids were clinically recovered before they even came in for this visit. And so those kids, you know, not everybody was sort of abnormal at that visit. So those kids who fell in the more normal range at that point, um sort of have better scores and their imaging again still seems to be different than controls. Um We did look at the common markers of severity of TD to see if that was related to connectivity and loss of consciousness, duration of post traumatic amnesia and presence of acute imaging findings did not relate to these connectivity patterns. Suggesting that these measures of severity of injury don't necessarily help us at least in the small group to predict sort of where a child is headed. Um So I think we hit on these. Um, so the next step we did do was go to the 12 month data. Um and in the interest of time, I'm going to move through these kind of quickly. But basically, we had 11 of the original kids, including six of those with concussion who were recovered before we even saw them. At two months, post injury, we changed our analysis to a region of interest analysis to make it more statistically robust. Um And so we have an area between group differences here between the default mode network and left V 40 which is an area involved in integration of sensory information and inhibitory control. But looked at that across a region of interest rather than just in those foxholes in terms of connectivity. And what we found is again, there was a relationship between connectivity and performance. This is on the contralateral and conflicting motor tasks for the contralateral task. What happens is the examiner is sitting across from the examinee and lifts one hand and I'm sorry, they tap one of the patients hands and the patient needs to lift the hand and for the conflicting motor task, the person, the examiner gives one motion and the child has to give the opposite motion what is given. So basically they can either lift a finger or lift a fist and whatever the examiner does, you have to do the opposite, you sort of have to inhibit that automatic response to what just happened. And um again, more abnormal imaging was associated with more abnormal function here, though, these test scores are all in a very tight range suggesting that there was no child who was really significantly impaired in terms of inhibitory control. Um And so what we have here is sort of imaging findings that go along with perhaps very subtle differences in performance. We did not have control data on the behavioral task, which is certainly a limitation of interpreting this. Um But what I take home from this is that alterations and functional activity with relevance for behavior are still identified one year after injury and a group of kids who by this point are all back to their normal school program. Again, many have been back to sports for more than 10 months. No child is coming in for like routine complaints related to TBI. And one of the things that I sort of really take home from this is we do have a number of kids who the residents have seen in concussion clinic or elsewhere who seem like they should be totally recovered and continue to report that they feel like it's more difficult to concentrate and they test fine on our standardized tests. But it does make me wonder if it still may be subtle changes relative to their baseline that don't score as impaired but may be related to changes in brain physiology. Here, we did not clearly define a compensatory strategy that was going on to underlie better behavior. Ok. So now of course, the question is we started with concussion, we're going to end with concussion. How does this relate to peer concussion? Um So this was our study designed for the R 21 study where we looked at a group of kids with concussion, specifically sports related concussion. Um, within two weeks, post injury again about a month after that. And then if they weren't clinically recovered at that point, we brought them back for one more visit. And then here we had a control group that we tested twice. So we had uh better behavioral data. These are data from the pans after concussion. So what we have here in the white bars are the controls. These kids were all athletes since our concussion group was all athletes. These are age and sex max. And we see that between the first visit, the 1st and 2nd times of testing, there's little difference in the scores of controls, which is nice shows us that there's pretty good test retest consistency here. When we look at the group in the blue bars, we see that initially within those first two weeks after concussion, they score significantly worse than the controls and that over time they improve. But even so at this point, when we have called them clinically recovered, they continue to perform worse than controls on the subtle motor tasks. And again, you'll see it's not necessarily the entire group that's performing worse than controls. But there seems to be perhaps a subset, um who may represent some of the more vulnerable, um, quote recovered patients when we look at PS compared to impact at the first visit. So impact is the computerized testing, which is widely used for evaluation of concussion pan s actually performed better in discriminating controls from kids with concussion than did impact when you combine as much data as you have, that works better than using one individual test, which is not surprising. This is a larger group. Again, looking after clinical recovery where we see the group with concussion performs worse than the controls. This holds up after accounting for differences in socioeconomic status race in addition to age and sex and after the point of clinical recovery, we do not see changes in impact, which of course makes sense with how impact has sort of been designed and used. So it appears that the pans may be more sensitive to ongoing vulnerabilities. Um This is a reminder of what we talked about with the imaging that more connectivity between the default mode network and the dorsal premotor cortex was associated with worse uh pans performance in the group with mild to moderate TD I. Again, we've now taken this to a region of interest approach. Um looking at imaging findings over a larger area of the brain rather than a small amount of auel. When we do this, we see that the Children with concussion do tend to still have higher um connectivity scores than uh controls. This doesn't quite reach statistical significance. So I was actually quite happy given the small groups and the large regions of interest that we still see that suggestion. And then when we look at the connectivity compared to PNS scores all in kids with pure concussion, we see that again, there's a relationship with this more abnormal, more connected or loss loss of anti correlation of the DMN to the premotor cortex associated with worse pan S scores. It's not 100% right. So this person here clearly has a different pattern going on that we need to understand. Now, um when we look at this, the question also becomes. So what? Right. So what if you have this more abnormal connectivity and um this higher score and this study was not designed to follow kids past the point of clinical recovery? However, anecdotally, we had this one participant who came back to concussion clinic because she had another concussion. So getting at that who's at risk for additional injuries. Interestingly, it was one of the kids with the highest most abnormal connectivity and highest pianist scores. And so that needs to be more studied. I again, bring up the question of the chicken versus the egg was this child at higher risk from the beginning, we don't have a pre injury ps, which is something that a larger study would be well designed to do. But again, we do have the work I showed you earlier that suggests that compared to themselves, kids with concussion have a higher rate of injury after concussion compared to prepare before. Um I want to point out here that we are not the only ones reporting subtle lasting motor deficits after clinical recovery from concussion. So they've been shown um basically in gate lab settings with instrumented balance um assessments. And I also just want to pause and say, I don't mean to say that um subtle motor findings may exist in absence of other findings. Like I mentioned before, Children tend to report ongoing cognitive symptoms that we don't detect with our standard testing. But I do wonder if perhaps there could be similar processes for attention and memory. Um So in summary, I would say these are preliminary data that combined with data from other places that uh suggest that there appear to be persisting vulnerabilities after apparent clinical recovery from concussion. And we sort of need to low a lot more. So this is the basis of the R one which is essentially going to replicate. The goal is to replicate these findings in a larger group with robust control data and looking at multiple periods of time. So starting at clinical recovery and looking three and 12 months later, we are also asking task related F MRI. So in addition to looking at the resting state connectivity, we'll be able to more directly look at activation patterns underlying a finger tapping task, which is part of what's in the pan. We have also submitted a grant to be able to better refine the pan for use in this population. It's primarily been used in younger developmental disability populations. And so we have proposed to look at a large number of high school athletes to ideally be able to trim down the battery, right? It takes 15 to 20 to 30 minutes to administer and it's very difficult to teach because of all these subtle motor findings you have to try to keep track of. And so we're hoping to pair it down to maybe something that could be done in five minutes and would be much easier to teach so it could be disseminated for additional use. So in the meantime, coming back to clinical practice, how do we sort of reconcile needing to give families advice every day and and having a suggestion that there may be more than meets the eye but no good hard solid evidence to work off of yet. So this is our approach for the Children with typical recovery who seem to recover well and fully and want to get back to their sports. Certainly, we think due diligence is needed for careful evaluation of injury and recovery. I think every child merits really careful July decision making about what sports they participate in and why. And the classic example I always give of this is the child we saw who plays football to stay in shape for lacrosse and felt that he had a college career in lacrosse. And we sort of talked about was football, the decision that was going to help him actually succeed most and stay in lacrosse longest or not helping families understand available data. And we have a lot more time in clinic than a pediatrician does to sort of help families think through and understand that. And then individualized return to play plans based on families' wishes. And we're finding some families kind of want to add in some additional time. There's no evidence to suggest how that changes long term outcome. But I think if a family is more comfortable taking an extra two months off, um that's fine with me. And then for the patients with atypical recovery who seem to have persistent prolonged symptoms, we continue to sort of treat them comprehensively. I think validating them. And this is definitely a line. I hate the term postconcussive syndrome because I feel like something that seems very hard to climb out of what you have. And we tend to refer more to headaches, maybe which were triggered initially by concussion. Um But so while trying to support and promote and encourage patients that they'll get better and move on, also still making sure that they have a home in the concussion care world or TBI care world, if that's what seems most useful for them. And also in this group, careful thought about pros and cons of continued participation and preferred activities. So there's certainly some food for thought. And I think care may continue to evolve over time in terms of how we treat and how we clear and how we discuss long term risks with families. Um And I'll end there and acknowledge my collaborators and those who have provided support including the department, um which has been very supportive of me when I initially came as a T 32 fellow and has since stayed as we talked about sort of my road and going to other places. I think I'll also point out that I have not, I took my time getting here. I did a lot of training mechanisms and um again, just because things don't sort of work out the first time or immediately, it doesn't mean that there won't be success down the road. So thank you. Any questions. Um A lot of symptomatic treatment can be done, like because you are just getting something we hear a little better after you are compensating the problem. Do you think some of those uh uh application is looking for activity changes, some of those applications are used for management? So, um just to make sure I'm understanding. So the question is, are medications we're using to treat symptoms, potentially changing brain physiology, all these medications that you are. Um, sure. I mean, I think it, that could certainly be studied. Um, you know, I think a lot of times when we sort of use those medications clinically, we are hoping, for example, um, a lot of times kids seem like they might be low serotonin and we're giving medications that are good for pain and good for mood and think, you know, I think hoping that we're going to help restore something that's been atypical in the brain. And so then I guess, could ask is that, can we then identify recognizable connectivity patterns, which we are changing time they have this? Yeah, I think it's a great question. You know, there's a lot of heterogeneity as there is in TB I to start with and kids with concussion and I would love to at least have a starting point of feeling like we could tease out, you know, exactly what's, you know, contributing to the baseline because that may then change what we expect to get out of treatment. But, um, you know, I certainly, I think under identifying good methods of treatment and understanding how they work is an important goal. Yes, the understanding of the distinction between terms of bigger 10 score equally important to. Yeah, absolutely. Um So thank you for bringing that up. So in pediatrics, there's a big push that first return to learn actually needs to happen before we're even worrying about return to play. Um And then along with that, we use a lot of sort of activity based rehabilitation, I would say in our clinic, in terms of all the good literature that's coming out that supports that rest is not likely ideal treatment. And in fact, I think it makes sense to all of us as rehab professionals that getting kids moving often helps them feel better. And even if we don't feel that they're ready to get hit on the head again, they at least can be back to doing some active things. So certainly in our treatment approach, that's a very important issue. And we're always starting with sort of the return to learn and return to other physical activity before we're actually talking about return to play. Um And certainly these issues are important for that. I think um to some extent, we're not so much, a lot of the sort of initial return to activity is symptomatically based. And so we haven't been thinking about that from, for example, looking at some of these imaging parameters. Um But I think the whether or not we're ultimately sending a kid back to play, certainly the child's overall function and their cognitive function and their risk of perhaps motor vulnerabilities and falling down the stairs or something like that remain important outcomes. Did that address your question? OK. Yes. Um We talk about that. Um Help fight, what's your sense of what is related to this happening. Um You know, in the short term, I typically tell those families that it is maybe a cognitive efficiency, um sort of thing. Our testing is done in a structured one on one assessment as opposed to being in school where it's noisy and there are other pieces. Um A lot of these Children tend to get headaches when they do work and we sort of tell the family, it's not that your brain is getting worse, but your, you know, your brain is still not working as efficiently perhaps, and you have brain strain. Um So, so that's how I conceptualize it initially, I think longer term. That's where I start to wonder, do some of these data, maybe give us insight into that, that for some of these kids that perhaps there are some subtle changes in perhaps efficiency, maybe this idea of anti correlated networks are no longer anti correlated and there's like fuzz or noise, you know, is, is that part of what the child is experiencing? And, you know, fortunately, in many cases, the child can continue to succeed in what they do though. They may feel like they're working hard, harder, it's not coming as easy to them. Um And I do think that, you know, those are pieces we probably need to attend to in terms of thinking about what's this individual child's risk of getting another concussion that even if they pass our tests and we think they're doing Well, if they really feel like they're a little bit different and working harder, I think there's a risk that if they get injured again, that they're going to build on that and see that history continue. Thank you. Created by
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