Jason Cheng, MD, discusses the demographics and classification of traumatic brain injuries. He also talks about long term clinical management and the difference with sports related brain injuries.
JASON CHANG: Hello, everyone. Thank you for joining me today in this review on traumatic brain injury. I'm going to be going over an update and a review of the current literature and the current treatment guidelines. My name is Jason Chang. I'm one of the neurosurgeons here at John Muir Walnut Creek. I've been here for the past year or so, after completing my residency at the University of California San Francisco. And I had a wonderful time here and look forward to sharing with you this latest update and review. Before we get started, I just want to go over conflicts and disclosures, for which I have none. And here's an overview of the talk for today. So first I'd like to go over and discuss the demographics of traumatic brain injury. Next I'll talk about the classification system that we use for traumatic brain injury, followed by the acute clinical management and the long-term clinical management. I'll also touch on some sports-related brain injury news, since it's been in the news for the last few years or so. And then lastly, I'll highlight some future developments in this field in ways that will hopefully be able to improve the care of our patients. So starting with the basics, there are approximately 1.7 million traumatic brain injuries every year, according to the CDC. This results in 1.4 million emergency room visits, 275,000 hospitalizations, and unfortunately, 52,000 deaths. Approximately 3/4 of these TBIs are mild, in the form of concussions, and unfortunately, many of these may not reach medical attention. The bottom line is the estimated cost to society is approximately $76.5 billion dollars, which is just a staggering number. When you look at the most common causes of TBI, according to the CDC, 35% of these are going to be false, typically at ground level. 17% are going to come from car accidents. Another 17% are going to come from collisions, and 10% are going to come from assaults. The mechanism of brain injury is quite simple. Our head is the skull. That's the protective layer for the brain. And the brain resides within the skull in a bath of cerebrospinal fluid. When your head hits an object, such as in this case depicted a wall, you will suffer a coup injury, which is the injury here on the front of the brain as a result of the direct impact against the wall. Similarly, you're also going to suffer a contracoup injury when the brain rebounds back and hits the posterior part of your skull, therefore bruising your occipital lobes, as illustrated here. This can similarly happen in a side-to-side fashion or in an oblique fashion, but the concepts are all the same. As a result of this type of injury, you can get a number of different presentations of traumatic brain injury. So here I've highlighted six examples that give you an idea of the severity of injury, as well as the heterogeneity of the types of injuries that we can see. In the upper left corner here is a classic image of a frontal contusion. So this is what you might find after that previous illustration depicting a frontal hit to a wall. Here in the middle, it's a bit more subtle, but this is diffuse axonal injury. So you can see here two tiny little punctate foci of increased signal. And this, believe it or not, represents the most severe type of brain injury, and it's signified by shearing of the axons. Moving over to our right here, you can see an example of a large epidural hematoma causing a lot of mass effect on the right side of the brain. Down here in the bottom left, we have a subdural hematoma, again, similarly exerting mass effect and mid-line shift, left or right. In the bottom center, we have a subarachnoid hemorrhage, where we typically see this in trauma. Also, we can see this classically in aneurysmal rupture. And then in the bottom right here, we have a great example of a depressed skull fracture. This could happen from a blunt object, such as a bat, a hammer, where we can see clear indentation of the skull in the brain that would require surgical fixation. In terms of the mechanisms of injury, we really have primary and secondary. Primarily we're talking about the physical, mechanical injury-- all of the mechanisms in the pictures that I just showed you. Secondarily, this is where a lot more long-term chronic processes come into play. For example, there's disruption of the blood-brain barrier. This can lead to inflammation. This can lead to excessive toxicity, mitochondrial dysfunction, and then ischemia, as well as cerebral edema. And similar to a stroke, many of these secondary injury mechanisms are as devastating or even more devastating than the primary injury itself. Now, as we turn to the classification system for traumatic brain injury, it's really quite simple. It's based on the Glasgow Coma Scale, which, as you know, goes a scale of 3 to 15. And based on the factors you see here in this table, the classification divides brain injury into mild, moderate, and severe. If you go across here on the mild column, you can see that these are patients a GCS of 13 to 15. So these are patients who are going to be awake. They're going to be alert. They're going to be confused. But typically, they can follow commands and have some relatively normal appearance, with perhaps some amnesia. So they might be forgetful of the event. And they may have had some loss of consciousness for anywhere between 0 and 30 minutes after the event. Now, when we switch to the moderate category, these are patients that are going to have a GCS of 9 to 12. So these patients are going to be more somnolent. They might still be arousable, but they're going to be pretty lethargic, may follow commands, but typically are going to be disoriented. And then we're going to have a period of amnesia anywhere between one day up to seven days after their injury. And they typically will have loss of consciousness ranging between 30 minutes to 24 hours after the time of injury. When you move to the severe category, these are patients who are nearly comatose, with GCS of 3 to 8. They're oftentimes going to be intubated in the field, they're going to clearly have a long period of amnesia, and their loss of consciousness oftentimes greatly exceeds 24 hours. So I'd like to go into each of these categories in a little bit more detail to give you more idea of what these patients look like and what their outcomes are going to be. When we look at the mild TBI category-- again, just as a reminder, GCS 13 to 16, amnestic for less than a day, loss of consciousness for less than 30 minutes. These are patients that are going to classically have a headache. They're going to present with confusion. They're going to have memory and concentration problems. They may have mild signs of nausea or vomiting on presentation and are going to have a lot of sensitivity to noise and light. All of these symptoms are classic for concussion or post-concussion-type syndromes. As a result, they're going to benefit from being in quieter, less noisy environments, dimmer environments. And really, we're going to be providing symptomatic control. And that's highlighted here. So if these patients present to the hospital, we will typically watch them for 24 hours. They'll receive support of fluids. We will medicate them for their headaches and for their pain. And again, we're going to reduce any kind of exacerbating factors such as excessive light, noise, or overstimulation so that they're going to be able to rest and recover as much as possible. If these patients present to the hospital, they will almost always get a head CT, just to rule out any kind of a focal intracranial hemorrhage. But the key treatment for these patients other than the supportive care is to avoid any type of repeat head trauma. This is important, because it's been shown that repeat head trauma results in worse outcomes if these events occur within one year's period of time. The symptoms that we described may last anywhere between weeks to months after the injury, and in rare cases can be permanent. However, most patients do make a full recovery after a few months, except for these following at-risk patients. So recurrent injuries that happen within one year, as you might see with professional athletes, or you might see with people who are particularly undertaking risky activities. These patients we know for a fact do worse in a number of ways that I'll touch upon Any patients that have other preexisting neurological injuries, so for example, prior strokes, prior brain surgery, are all patients who are going to be at risk if they have this mild TBI after. And also, unfortunately, patients who are older typically don't have the reserve and the ability to bounce back as quickly after even a mild head injury. As we move to moderate TBI, remember, now we're talking about Glasgow Coma Scales between 9 to 12, amnesia between one to seven days, and loss of consciousness between 30 minutes to 24 hours. These patients are going to be more obtended, and they're going to have altered mental status. They're going to be arousable, and oftentimes will follow commands, but not always. They're going to have more persistent or severe nausea and vomiting. They may have behavioral disturbances characterized by restlessness or agitation, and this can be particularly prevalent in patients who are also substance abusers or who may have a lot of alcohol on board. They may have speech difficulties in the form of dysarthrias or aphasias. And these can oftentimes compromise or complicate their care, simply because the communication barrier is made more difficult. These are patients that are going to uniformly become admitted to the ICU. They're going to all receive non-contrast head CT imaging to evaluate and assess for intracranial hemorrhages. And most of these patients are going to have some form of the findings that I showed you in the earlier CT examples. They will also typically require an evaluation by the trauma service in the form of a tertiary survey to assess for other occult injuries or long-bone fractures. Some of these patients on the lower GCS scale may require intubation and sedation for airway protection or due to their cognitive impairments. If these patients have mass lesions, such as an epidural or a subdural hematoma, we will consider them for surgical evacuation. And these are patients who are also at high risk for sodium dysregulations and cerebral salt-wasting. So following daily sodium levels is especially important in this population of patients. In terms of outcomes, many of these patients are going to have a prolonged hospitalization. We're typically talking about a week to even up to two weeks in order to go through their acute phase and to be able to have enough cognitive capacity to either participate in acute rehab or potentially go to a skilled nursing facility. These are patients who are going to be at risk for post-traumatic epilepsy as a long-term sequela of their injury, and they're at higher risk than the mild patients for permanent neurological deficits. Now, this is going to depend in large part upon where the injury occurred and the type of-- an area of the brain that was involved. So for example, if they had involvement of the parietal lobes where a motor strip resides, then they may have residual weakness on one or both sides. If this involves their left temporal lobe, they may have ongoing or permanent speech deficits. So the risks and the outcomes here are unfortunately going to be worse, given the increased severity of the injury. Now, moving on to our most severe category of TBI, these are patients with the GCS between 3 and 8. They're going to have amnesia for more than seven days, and they're going to have loss of consciousness for more than 24 hours. These patients are going to uniformly present in an obtunded, comatose, or even moribund fashion. They are almost certainly going to be inhibited and sedated on scene prior to arrival in our emergency department, and there is going to be a significant and fixed neurological deficit upon presentation. These are patients you might think of in high-speed motor vehicle collisions, motor vehicle versus pedestrians, bicycle accidents-- anything that has enough high-speed force to cause multisystem injury. Oftentimes these are considered life-threatening conditions, and they're going to require emergent evaluation. They will all uniformly obtain an emergent non-contrast head CT scan while they're in the emergency department. And in nearly 100% of these cases, there's going to be a significant or multiple significant abnormalities on that scan. A GCS of less than 8 is a frequent indication for intracranial pressure monitoring. So these patients are at very high risk of cerebral swelling and cerebral edema that can cause increased intracranial pressures that can result in downward herniation in a brain in a skull that's fixed. They're going to require multiple medical therapies, with osmotic therapy for these elevated pressures, along with the intracranial pressure monitoring. They're going uniformly be admitted to the ICU, and they're going to have prolonged hospitalizations, oftentimes in the two-, three-, or even four-week range. As I mentioned, multi-specialty care is essential in the care of these patients, and that means having trauma, neuro-critical care, orthopedics, or any other specialty that would be involved taking care of these patients on a continuous basis. Unfortunately, due to the prolonged hospitalizations, these patients oftentimes require a trach and a peg for their long-term airway and nutritional management. Now, I mentioned intracranial pressure monitoring, so I wanted to just go into this in just a little bit more detail. So this is our ability to monitor the pressures within the skull and to be able to treat those and address any elevated pressures in real time. There are a number of different monitoring modalities that are available. And you can see highlighted here really simply-- this is the brain. Above the brain, we have the subarachnoid space. Above that, we have the dura. And above that, we have the skull. So as you can imagine, we can insert monitoring devices into pretty much each of those spaces. Now, I will say that epidural monitoring devices are really growing out of favor, and those are not used very often. Intraparenchymal is one that can oftentimes be used. As you can see here, it's a catheter that simply sits in the brain parenchyma and measures the local pressures in that particular area. If we want to become even more invasive, we can do an intraventricular monitor, which has the ability to enter into the spinal fluid space, the lateral ventricle. And not only does it monitor pressures, but it also enables us to drain spinal fluid as a means of being able to control and treat that pressure. Lastly, there are some subarachnoid drains that again, are also typically not used very frequently. Now, in terms of surgery for these types of conditions, much of it is similar to what we've been doing for several decades now, which involves accessing the cranial vault to remove any of those lesions I showed you on the previous CT. So if, for example, the patient had a very large subdural, we would consider doing what's called the craniectomy. We would remove this amount of bone. So as you can see on these 3D reconstructions as well as the CT scan here, this is essentially the entire hemisphere. So it would be right or left, obviously, given which side was affected. And depending on whether or not there's significant brain swelling or edema at the time of the surgery, we will elect to either remove the bone and leave it off, such as in this case of this patient here, and allow that swelling to reach its peak, subside. And only when the patient had reached a new baseline and the swelling was reduced-- and we can see that in this example here, where there was a nicely sunken brain on this side-- would we then consider putting the bone flap back. This might happen for six or even three months after the surgery, the initial surgery, depending on the patient's clinical condition. In the meantime, we would have them wear a helmet, and they would need to obviously be cognizant of the fact that they're missing their bone on that side. In cases where the swelling is not severe, and we feel like we're able to put the bone back right away, then of course, we'll simply replace this defect at the end of the surgery, and we'll plate it with titanium screws and plates. And that patient will then be able to continue without having to have their bone off. Now, in terms of outcomes after severe TBI, it's not surprising that these patients are going to have the worst outcomes. So you can see some of the references here on the bottom. I've summarized some of their results for you. First of all, it's been shown very clearly that if patients end up at a non-neurosurgical trauma center immediately after their injury, they have a more than two-fold odds of death if they're treated at that center. So that really emphasizes the importance of getting these patients to a trauma center with neurosurgery as early and as soon as possible so they can be triaged and treated appropriately. In patients who present with a GCS between 3 and 5, the mortality is 95% in the initial 30-day period. In patients who present with a GCS of 3 and in addition, have bilateral fixed and dilated pupils, these patients have a 100% mortality at one year. So clearly, a very devastating and grave prognosis. Regardless, all patients with severe TBI are going to for the most part require permanent, long-term care, oftentimes in a skilled nursing facility, due to their high level of needs. When we're talking about the long-term consequences of TBI-- and this primarily refers to all TBI-- you can see that incidences of generalized anxiety disorder are on average about 53%. Post-traumatic stress disorder occurs in about 20% of patients. Post-traumatic epilepsy occurs about 1%. And even though there isn't sufficient data to draw a conclusive link between neurodegenerative conditions such as Alzheimer's disease, Parkinson's, and TBI, we're starting to see early evidence in both animal models as well as in case series of humans what appears to be a link. And the studies to prove that are ongoing. Chronic traumatic encephalopathy-- this is a condition found primarily in football players, boxers. And this is a condition that's been well-documented, but I'll touch on it in just a moment, that comes as a result of repetitive injuries over a short period of time. Permanent neurological deficits, of course, are always concerns for traumatic brain injury. Now, what's being done currently in clinical trials, and specifically neural protection? So this is-- because of the major public health problem that it is and the amount of health care dollars that are going to treat TBI, there have been a number of studies looking at many different mechanisms of trying to give the brain neuroprotection in the early hours after injury, and we'll go through these one by one. So first, there were a group of people that thought that calcium-mediated damage could lead to a lot of the secondary effects of injury after TBI. So there were multiple trials, five in total, looking at nimodipine, which is a calcium-channel blocker, to see if early administration of nimodipine had any significant effect. Unfortunately, all of those trials were for the most part negative. Next, I mentioned glutamate toxicity as one of the mechanisms of secondary injury. So there have been various compounds that have been tried, again, five trials, without any significant effect on reducing glutamate excitotoxicity on long-term outcomes after traumatic brain injury. Next, there is free radical damage and lipid peroxidation. Again, various compounds-- three trials have been completed, all of which again showed no significant effect. Lastly, steroids are always a good option, because steroids seem to work for everything. So there have been four trials that have been tried with varied dosing mechanisms, and again, all of them similarly show no mass effect or no significant effect on outcomes. If you want to look at these studies in more detail, this Lancet Neurology 2008 article provides a wonderful summary of each of these trials, the specific compounds that were used, and a little bit more about the data and why it came out to be negative. Next I'd like to talk about some sports-related injuries. So this is probably something that your patients are coming in and asking you about. It's certainly been in the news in the last five years or so as it pertains to football, soccer, and to some extent, boxing. This was made even further prevalent by the recent movie with Will Smith with Concussion, which talked about the story of Dr. Bennet Omalu, who was a neuropathologist in Boston at the time who was doing studies on football players that had had a history of behavioral disturbance, aggression, and violence who then ultimately took their own lives. And this was probably no more touching than with Junior Seau, who committed suicide, as you'll remember, a few years ago, and in some other books and publications that have really focused and targeted the NFL as being the organization that has not had the welfare of its players in mind, and rather, their own pocketbooks have been kind of the driving force to try to keep the real data on head injury under wraps. Now, nobody knows for sure what the NFL knew and when they knew it. However, it's becoming clear that the injuries that football players are suffering, with repeated concussions and repeated injuries, is something that is likely not good for the brain and causing some of these behavioral problems. Similarly, boxers-- Muhammad Ali here who had Parkinson's disease. There has been some question as to whether or not that type of head injury could similarly cause a phenomenon such as chronic traumatic encephalopathy. So what's the evidence behind this? Well, there have not been major clinical studies that have been completed. So most of this data comes from case reports or small case series of patients, but I think the findings are relatively compelling. So here in the upper left, we have a basic histological slice of a normal brain, here on the left, with an abnormal brain on the right that was diagnosed to have chronic traumatic encephalopathy. And this is actually the brain from a former NFL player. So it doesn't take a trained neuropathologist to tell that there are a number of significant and gross abnormalities between the left and the right. You can see larger ventricles here. You can see shrunken cortical white and gray matter. And overall, the size of the brain is certainly smaller than the normal age-matched control on the right. Now, when you move over here, you can look at the functional MRI studies done of a control on the left and an NFL player and another NFL player. And the control gives you an idea of what the normal image should look like. When you move over to a player in the NFL, you can see that specifically, this region here is called the thalamus, and this region here is called the amygdala. They're both lighting up very intensely, and you can see that demonstrated even more so on the player labeled NFL3 over here in the third column. Now, we know that the amygdala is your fear center. So this is what drives a lot of your fear, your emotional-based decision-making. This can certainly be responsible for violent outbreaks or violent outbursts. And your thalamus has many, many functions, but it also similarly acts as a relay center connecting sensory input from the rest of your body into the upper, higher-level cognitive functions. And it can also play a significant role in cognition, wakefulness, consciousness-- things along those natures. So given the symptomatic phenotype we see in these players, which is oftentimes emotional lability, aggression, violence, and anger, these correlations with MRI findings are very consistent. When we look at a histopathological section down here, you can again see normal age-matched brain here on the left. And on the right, you can see that there is a significant increase in these dark little spots here. Well, these are neurofibulary tangles, which are collections of tau protein. And this is something you might remember from medical school as being a pathological feature of Alzheimer's disease and other neurodegenerative conditions, such as Pick's disease, frontotemporal dementia. And you can see there's just simply a lot more staining here at the microscopic level in the NFL player compared to the control. So as a result of all of this bad press, what's currently being done in the NFL, and similarly, in football in general, to try to protect the players and to provide them with a safer environment? Well, first of all, there have been the implementation of field physicians. So there are now neurosurgeons on the sidelines of each team during all games. These are physicians that are not employed by the teams for which they're on the sidelines for. And they theoretically should have no financial bias in terms of their judgments. They're the ones that are responsible for removing players from play and also for being able to determine whether or not they're fit and able to return to play. And there's now been a very strict set of return-to-play guidelines that have been put in force in the NFL, so players must meet these criteria stage-by-stage before they're allowed to return to play. And they essentially consist of not having symptoms at baseline at rest, followed by being able to participate in light and then increasingly strenuous workouts in the gym. This is then followed by light no-contact field practice, followed by full-contact helmeted field practice. And only after they've met all of those criteria are they then allowed to return to play in a game. Similarly, there's a lot of research in trying to understand what are the forces and what are the factors that are causing this type of head injury. So a number of companies have put out products that have G-force sensors and accelerometers in football helmets, as well as in mouth guards, to try to measure some of these forces that occur at the time of impact on the field. And then there's a long-term study of retired NFL players that's currently underway to understand their health problems, as well to do regular and standardized neuropsychological testing to understand how their development of any of these conditions might occur many years after their playing careers have ended. Now, one of the last things I want to touch on is this link to neurodegeneration. So clinical evidence, as I mentioned, is still being collected. So there is not a definitive study that says that repetitive head injury leads to Alzheimer's disease or Parkinson's disease. However, from the pathology I showed you, we know that tau and amyloid-beta are key features in neurodegeneration. We've known that for decades. And the fact that we're seeing it in human samples of chronic traumatic encephalopathy clearly suggests that there might be a link. This was actually an area of interest to me during residency. And here is the paper that I published at the time, looking at mouse models of traumatic brain injury. And in this particular study, I developed a new model of mild repetitive brain injury in a mouse and then looked at different histopathological outcomes. But specifically, we looked at behavioral outcomes that looked at spatial learning and memory deficits in mice that had reduced levels of tau and in mice that had normal levels of tau. And as you can see from the title-- I won't go into here, but you can see from the title, tau reduction diminished their spatial learning and memory deficits after injury compared to mice that had normal levels of tau. So even though this is an animal model, I think that it gives further evidence that the human studies are even more important and that similar strategies at treating Alzheimer's disease could potentially be effective against traumatic brain injury. So in conclusion, I hope that I've given you a nice overview of traumatic brain injury. I hope I've shown you that this is a major public health problem that really deserves a lot of our attention and a lot of our health care dollars. This causes huge burdens on society and particularly on caregivers taking care of these patients. TBI is a very heterogeneous entity, so patients that come in with mild injury are very different and require very different levels of care than those with severe injury. Because of this heterogeneity, this is a difficult population and problem to study. It requires significant numbers of patients, and that means significant dollars. Because of that, there have been no successful randomized trials to date, and this has major implications for athletics, particularly children's and college-level athletics, where the patients' brains are still, perhaps, in the formative stages. So thank you again for attending, and I hope that this has been enlightening and informative for you. Thank you.
