**Transcript of Cyberseminar**

**Mild TBI Diagnosis and Management Strategies**

**Differentiating the Long-Term Consequences of TBI and Psychological Trauma: When and Why Does it Matter?**

**Presenters:  Jennifer J. Vasterling, Ph.D.; Mieke Verfaellie, Ph.D.**

**May 27, 2014**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact Jennifer Vasterling at**jennifer.vasterling@va.gov**or Mieke Verfaellie at**mieke.verfaellie@va.gov*

*Moderator:* Here we are at the top of the hour so I would like to introduce our speakers. Speaking first, we have Mieke Verfaellie. She is a... I am sorry Dr. Verfaellie, she is a senior research career scientist at the VA Boston Healthcare System, and a professor of psychiatry at Boston University School of Medicine. Second, we have Dr. Jennifer Vasterling, who is the chief of psychology at VA Boston Healthcare System. She is also an affiliated investigator with the National Center for PTSD and a professor of psychiatry at the Boston University School of Medicine. So, at this time, I would like to turn it over. 

*Mieke Verfaellie:* Thank you, it is a pleasure to be with all of you as we speak today about the intersection of TBI and psychological trauma. I think we are all familiar with the term that TBI is the signature injury of the wars in Iraq and Afghanistan, but it’s also helpful to point out that that type of injury is not new. During deployment, exposure to blast munitions can result in injury, and that has been true for many wars, certainly not just the current wars in Iraq and Afghanistan. But the difference is that due to better body armor and better care on the battlefield, most soldiers are surviving this kind of injury and are coming back with traumatic brain injury. 

During World War I the term shell shocked was used to describe this same kind of injury and the term was vague enough that it would encompass physical injury and psychological trauma associated with the event. Now, we understand better that physical injury to the brain and psychological trauma are two distinct entities. But we certainly also are very aware currently of the intersection of these two injuries and the fact that they so commonly co occur; and that’s what we’re going to focus on in this presentation. 

I think it’s also worth keeping in mind that even in the military, and certainly among veterans, that the kind of TBI that we see is not limited to blast induced TBI, but that there are a number of different causes including motor vehicle accidents, gunshot wounds, and other kinds of injuries... even sports injuries. I would say that with the exception of sports injury, all kinds of TBI are also psychologically traumatic events, and so there is always a possibility of comorbid psychological and physical injury, which is what we will focus on. 

Just to lay out what we will try to accomplish in the next forty-five minutes, I will start by giving some of the epidemiology of these two disorders, and then talk in a little bit more detail about the clinical manifestations of mild TBI and of PTSD. Then, I will pass it on to Jennifer Vasterling who will talk about mechanisms leading to co morbid TBI and PTSD, and who will also discuss some of the clinical implications of these findings. 

First, a little bit about the scope of the problem that we are dealing with. This first slide here is one from the Department of Defense that gives us the sense for the incidents of TBI from 2003 to 2013. What we see is that when we look at the different kinds of injuries, by far the majority of injuries are mild traumatic brain injuries as opposed to all the other ones. What we also see is a steady increase in the diagnosis of mild TBIs from 2000 to 2011 Reflecting better diagnosis and more attention to the possibility of these diagnoses in service members. 

What we also see is the reduction in TBIs between 2011 and 2013. I should point out that this slide is not just deployment related TBI, it is also other TBI within the military. But this reduction here is very likely associated with a change in the deployment related TBI and you can see that on the next slide, these are the numbers of deployment related TBI again from a similar period, 2003 to 2013. What we see is with the drawdown from Afghanistan, we certainly have a reduction in deployment related TBIs. 

Now, the implication of that is that as we think about the impact of TBI in the veteran population, we need to be concerned, not just with blast TBI. As we see the emphasis will likely shift to other sources of TBI as we go forward from here on. 

Some of the earliest data on the incidents of TBI and the prevalence of psychiatric disorders came from the Rand study, which was a population based survey done in 2007 which found that the rate of screening for TBI... and I’m going to emphasize here that this was screening, these are not confirmed diagnoses... but TBI screening... That twenty percent of military personnel actually screen positive for TBI. They took PTSD and depression screening at fourteen percent, but importantly, if you look just now among those with TBI, you see that the incidents of PTSD and depression is significantly higher in line with the thirty percent range. 

This is population based data. Again, probably overestimates of numbers because it reflects screening. But if we think about the impact of this for care in the VA systems we get a very different picture, because of course, now we are talking about people who are seeking care in the system. 

This is data from a study by Kate Iverson and colleagues here, done out of VA Boston in which they looked at administrative records for all veterans who received a diagnosis of deployment related TBI between 2007 and 2009. There are a couple of things of interest here. This is deployment related TBI and not surprisingly, the main ideology is blast. But there are certainly others as well, including falls, vehicular injury, and other blunt traumas. Now, if we look among those with deployment related TBI, how frequently do we see psychiatric diagnosis as PTSD? We are seeing with a frequency of sixty-seven percent PTSD and depression at twenty-eight point nine percent. 

This study was one of the first to look at gender differences. There are a couple of interesting things here to note as well. Perhaps not surprisingly, blast is a more common etiology among men than women, probably reflecting different roles within the military. In terms of psychiatric diagnoses, if you look at simply percentages, they are not greatly different. PTSD diagnosis is a little more prevalent among men than women, but on the contrary, PTSD and depression is more prevalent among women than men. What we do need to keep in mind here, is that blast injury is more common in men, and given the possibility that blast injury may be uniquely associated with psychiatric diagnoses, it is important to take that into account. 

Now, if you look at observationals that take into account the different incidents of blas injuries, then what we see is that the obs for PTSD really do not vary as a function of gender, but that the obs of PTSD and depression are significantly higher among women than among men. 

Does it matter what kind of TBI one has in terms of having co morbid psychiatric disorders? Here, some of the early data comes from a study by Hoge and colleagues, in which they looked at two units of Army and infantry personnel. What they found was in comparison to those who have no injuries and no TBI injuries, the likelihood of PTSD was significantly greater among those who have TBIs and it was even greater with those who have TBIs associated with loss of consciousness than in those with TBI without loss of consciousness. 

Bear in mind that these are overwhelmingly mild TBIs. That is the type of TBI that we see in deployment related cases, overwhelmingly. So this picture, where we see that mild TBIs may in fact be a risk factor for PTSD, really changes if we look at severe injury. 

I want to show you some data here from a study on civilians by Zatzick and colleagues. They looked at successive admissions to a level-one trauma center, and then looked at diagnoses for PTSD. Now, the non group here is the group without TBIs. They have other injury, but not a traumatic brain injury, and so the base rate of PTSD was twenty-four percent. If we compare TBI of various severities, what we see is that percentage is about the same in those with mild TBI, but it is significantly lower in those with more moderate or severe TBI, suggesting that this is a complex relationship. That more severe TBI can be a protective factor for PTSD, but mild TBI is not. At least in the military studies that we have seen, it turns out that mild TBI is a risk factor for PTSD. 

Let’s go from here and talk about the clinical manifestations associated with TBI and PTSD. The first thing to keep in mind is that it’s important to distinguish between TBI as an event that can lead to injury that leads to brain injury and post concussive symptoms. So when we speak about TBI, we are really referring to the pathophysiological injury. The fact that it was an external force that impacted on the brain, and that leads to changes in physiological brain function, and potentially also in structural brain function. That is not to say that all types of external impact on the brain causes TBI, and we certainly need to be aware of that in the context of blast injury. Many blast are not of sufficient severity that leads to traumatic brain injury. 

Having a TBI event, then we can talk about post concussion symptoms as the expression of symptoms that follows mild TBI. So, TBI refers to the acute event and can only be diagnosed with reference to the event. Post concussion symptoms are really the symptoms that we see in the aftermath of the event. 

What is the typical course of resolution of TBI? Typically, what we say... and let me first say post concussion symptoms are really quite a diverse group of symptoms. They include sensory changes such as difficulty adjusting to applied light, or dizziness, or nausea. It included cognitive symptoms such as distractibility or difficulty with memory, and it also includes emotional symptoms such as heightened anxiety or depression or irritability. So, typically these symptoms are at its worst within the first seventy-two hours after injury and they improve steadily subsequent to that. Typically, by three months post injury, we see full recovery. With that being said, there is a minority of individuals who continue to have significant symptoms even beyond three months period. And these are the individuals we have to be most concerned about. Those are the individuals that we often hear the diagnosis of post concussional disorder. But in DSM  post-concussional disorder is the disorder that you see when there are objective neuropsychological deficits, such as in memory or attention, or executive function; and then there are three or more post concussion symptoms of the kind that I described to you before. 

In addition, we only talk about post concussional disorder if the symptoms persist for at least three months and if they are associated with actual functional impairment, meaning impact on every day functioning. Post concussional disorder was a diagnostic entry in DSM-IV; it is no longer present in DSM-V. What we see in DSM 5 is a mild neurocognitive disorder due to TBI. This is one of a variety of forms of mild neurocognitive disorder, and these are characterized by a decline in cognitive performance and both expressed concern by the individual itself, or somebody close to the individual, and modest impairment in cognitive performance. 

In terms of mild cognitive disorder, the understanding is that these deficits do not interfere with independence in everyday activities; otherwise, it would be a more severe neurocognitive disorder. Due to TBI, it means there is evidence of TBI, and that these symptoms could then immediately after TBI, and persist past the acute post injury period. So it’s interesting to note the differences between DSM-IV and DSM-V. In DSM-V, there is clearly emphasis on the decline in cognitive performance, and it is acknowledged that emotional changes may happen as well, and these can be supportive of the diagnosis, but are not, in themselves, sufficient for diagnosis. Which probably reflects the understanding that a lot of post concussion symptoms are really non specific, and don’t necessarily indicate that they are a consequence to TBI. 

What about post concussion symptoms? The main point that I want to get across to you is that the presence of post concussion symptoms in itself is not sufficient to say that a TBI has occurred. For one, these symptoms are highly non-specific. Headache and concentration problems can occur for a lot of different reasons. And yes, TBI is one of them, but it’s certainly not the only one. 

Second, these kinds of subjective complaints occur even at high levels in a number of non-TBI populations. We see them in people with bodily injury of various kinds. Let’s say orthopedic injury. We see it also in normal populations, we see it in college students, and we see it in healthy adults. It is very important to our conversation today, post concussive symptoms highly overlap with symptoms of PTSD, and this is what is illustrated here in the following slides. 

There are some symptoms of TBI that are really specific to TBI, and these are symptoms like headache, or dizziness, or balance problems, sensitivity to light. There are some, which we will com back to, that are specific to PTSD like experiencing symptoms of shame and guilt. But the large proportion of post concussion symptoms can occur either to PTSD or to TBI, and these are symptoms such as depression and anxiety, insomnia, poor concentration, fatigue, hyper arousal, et cetera. 

Finally, there is one other thing that we have to keep in mind as we talk about post concussion symptoms. That is the fact that while these symptoms are often associated acutely with TBI and may in fact be acute affects of TBI, it seems that psychological factors may play an important role in their maintenance and Dr. Vasterling will come back to this last point in just a little while. 

So, what are the implications of all of this for care within the VA system? This is a busy slide, but I want to draw your attention to a few points here. This is a study from Scholten et al, again drawing administrative records within the VA system, and they looked at all veterans who had screened positive for TBI and then subsequently a comprehensive evaluation indicated that a portion had TBI, and another proportion did not have TBI. What we see here is common both concussional and behavioral symptoms, and these are indicated as subjects having mild to severe severity in the last thirty days. You see symptoms at the highest endorsement are those such as irritability, sleep disturbance, forgetfulness anxiety, et cetera; and then at the lower end we have things like loss of balance, nausea, and change in taste or smell. 

The important fact is that these symptoms are endorsed at very high rates. We have eighty percent range here by individuals that have TBI; but they are also endorsed with very high rates by individuals who did not have TBIs. You see the rate in the seventy percent range here. So even though the odds are greater to have these symptoms when one indeed has a TBI, nonetheless, these are very high percentages in both groups; and this is driven home even more clearly. 

If you look at the bottom here, moderate to severe symptoms that interfere with everyday living in the last thirty days... that is endorsed by seventy-four percent of individuals suffering from TBI and sixty-five percent of individuals not suffering from TBI; again, speaking to the non-specificity of symptoms. 

Let me move on now and talk a little bit about PTSD. Again, the first thing to realize is that when there is a traumatic event, there are a number of different responses possible, and PTSD is only one of these. Others that we commonly see are acute stress reactions, acute stress disorder, adjustment disorder, other anxiety disorders and depression, so we will focus here specifically on PTSD. 

In the context of DSM-V of PTSD is now diagnosed by five criteria... actually six criteria. First of all, there’s a traumatic event. There is a real or threatened death or serious injury, or sexual violence, which somebody has either experienced or witnessed directly or indirectly. If it is indirect, then that could be through a very frequent exposure to specific details of the event. 

Then here, there are these other kinds of symptoms that we see. First of all, they are intrusion symptoms. Patients may have intrusive memories, they have flashbacks, and they have nightmares. There is active avoidance of the trauma memory. It can be avoidance of the feelings or thoughts associated with the trauma, or avoidance of triggers of the trauma. 

Here, this is actually the interesting change between DSM-IV and DSM-V. In DSM-IV we used to have avoidance and emotional numbing as one criteria, and that now separated in two with C reflecting the active strategy for avoiding, and D a reflecting a passive strategy like alterations in mood and alterations in cognition. This includes things such as emotional numbing or social withdrawal, and also changes in cognition, primarily a lack of memory for the traumatic event. Finally, we have alterations in arousal, which may be things such as hypervigilance or detractability, or difficulty sleeping, various expressions of heightened arousal. Then again, as previously, to have a diagnosis of PTSD, changes have to be greater than one month and must have clinical impact. 

In contrast to TBI, which I think I have emphasized as a discreet event, PTSD is an ongoing diagnosis, and there are different trajectories possible for how PTSD evolves over time. I think this is a helpful slide from Bonanno and colleagues, and this is from the Millennium Cohort Study in which they have followed military personnel since 2000, for more than ten years. These individuals have been followed pre deployment, then again we are seeing on average three months later for a follow up, and then being seen three months later again for a second follow up. 

Now, if we look at the trajectory of PTSD over time, there are a few things to note. One is that an overwhelming majority of individuals have very low PTSD symptoms across the board. Eighty-three percent have low symptoms pre deployment, and it stays that way with subsequent follow-ups. So these are the individuals who are highly resilient and who fare well despite the traumatic circumstances that they may have found themselves in. 

Then there is a second group, the most frequent, but much less frequent with eight percent who start with relatively moderately severe symptoms pre deployment. Then, in fact, improve over time and their symptoms come down, gradually. There’s a third group who start off with no symptoms, but then have a steady increase over time and end up with high levels of PTSD symptoms even six years later. Then finally, there is a group with high and stable symptoms across time, but that is a relatively small number. Of course, there are a number of factors that will influence these trajectories; having to do with combat experience, with pre morbid personality characteristics, and many other things. But one potentially interesting factor is the question as to whether the presence of mild TBIs may influence that trajectory, and possibly produce so in this group here. And with that, I’ll turn it over to Dr. Vasterling, who will now talk about that possibility. 

*Jennifer Vasterling:*  Good afternoon everyone and thank you very much for being here. I see some familiar names, people who I know have been thinking very hard about this as a group over the last few years. 

What brings us here is talking about this co morbidity and this common occurrence and frequency of PTSD when there’s been a TBI and what I want to do now is turn to what we know about why... and even what we might be able to speculate about what happens with that. One of the points I want to make here with this slide is that if you consider this to be a blast event that leads to a TBI, and that’s also extremely stressful, this is occurring from a broader context of combat. In the combat itself, even aside from this event, it is going to place people at risk for PTSD. So, unlike the civilian literature, which is where for years most of what we knew about the co morbidity of PTSD and TBI came from that literature, that literature tends to focus on single events. So people were living their lives, had a horrific motor vehicle accident, and that one even led tot that TBI and PTSD. This is a much different situation. Even with a single deployment, we have this broader, six month, or maybe twelve months, or for some people, fourteen to eighteen month period where they have been exposed to stress upon stress upon stress. Not to mention people that have been deployed multiple times, so there is a context here. 

We also have people that have not been injured or exposed to blast concussions once, but maybe multiple times. So, it’s a more complicated situation of exposures and therefore potentially, a more complicated situation in terms of recovery from either the TBI or the psychological trauma involved in this. What I am going to talk about next is how TBI might impede recovery from the psychological trauma, and/or PTSD and vice versa. 

First, let’s ask ourselves the question, does TBI increase risk of PTSD? It seems like it because we have all of this evidence of a high rate of co occurrence. But what our colleague, Richard Bryan in Australia has done, is look at this longitudinally, which is more of a gold standard in terms of being able to make some determination of causal direction. This is civilians, this is not military growth, but these are the people that I was talking about a moment ago that may have had this single event that led to PTSD and TBI. So he followed over a thousand people with various types of traumatic injury, not all brain involved but physical injury associated with whatever trauma they had at the hospital, and assessed them very early on for psychiatric symptoms to document whether there was a TBI. Twelve months later, what he found was that those patients with traumatic brain injury, as opposed to other physical injuries, were about two times more likely to develop a new anxiety disorder of various sorts, including PTSD. But interestingly, what he also found was any functional impairment that was documented, tended to be more closely related to their psychiatric status, than to the TBI. So more closely related to the psychiatric status a year later; and that timeline, as I’ll demonstrate later, may be really important in terms of what’s causing what, when. 

So, if TBI, especially at the mild level, think back to Mieke’s slide about when it gets severe enough, it may actually be protective, but at this mild level, how is it that TBI increases risk of PTSD following an event that was both psychologically traumatic and caused a physical brain injury? One of the reasons that this might happen is just the disease burden. There is a lot going on with people; and an interesting study by Bell and colleagues, where they were looking at intervention, they did a two group RCT; again with civilians with a mild TBI. They did phone counseling and that phone counseling, during the first three months of the... post the mild TBI included education and reassurance and reactivation, versus those under emergency care that people receive after a TBI. What they found was that the intervention reduced those post concussive symptoms, and functional impairment. 

What that suggests, is if you can quickly reduce the burden caused by the TBI in what we know of as one of our best methods now, which is a psycho educational approach, the symptoms tend to dissipate and there is actually something we can do about that disease burden, which is good news. 

There may also be a neural overlap, at least in the acute stages of the physiological impact of the brain injury. In some of the neural areas that are implicated in both PTSD and TBI, maybe really important to the symptom manifestation of PTSD later on, because some of these networks are actually implicated in a fear response. Those are some of the same networks that are compromised in TBI. What might be particularly relevant here are some of these frontal areas that have inhibitory functions. That is really thought of in PTSD conceptualizations as very central from a psychobiological perspective, and how symptoms may manifest themselves. 

What about neuro-cognitive mechanisms? There are two different situations to consider. There is that small group of people that may have chronic cognitive impairment at a mild level. And what about this small group of people that may be experiencing on a longer term basis, changes in cognitive control in particular? That is not going to help the situation with PTSD. One of the things that can go awry with PTSD is significant emotional dysregulation. Related to what I said from a neural-anatomical perspective about inhibitory control within brain structures, the direct behavioral, or cognitive analogy, is the cognitive control. Can people inhibit dysregulated emotions? Can they control how and when they think about traumatic memories? Can they control their effective responses? 

The other situation has to do more with the acute cognitive manifestations of traumatic brain injury. Because for many people, there are only acute changes in cognitive functions that resolve. But when you think about it for an event that’s both psychologically traumatic and results in brain injury, what happens to someone’s memory of that psychologically traumatic event if they are experiencing an altered state of consciousness? That gets back again to that grasp that Meike demonstrated. Intuitively, we say well, gee, it would be really good to not remember a psychologically traumatic event. Well, that is probably true if your lack of memory is complete. But where you can get into some trouble, is if your memory for something psychologically traumatic is partial. In that particular instance, it is probably much better to have a very organized memory, and a very detailed encoding of the event so that when you recall it, you have more of a volitional control over it. That is particularly important for the emotions and the assets that are associated with a traumatic event. 

We do not know this for sure, and a number of people are looking at this, but it is a critical time when somebody is experiencing the event, to integrate their emotions, their affective response to form a cohesive trauma narrative; in other words, a cohesive story, a cohesive memory of what has happened to them. If consciousness is altered, if cognitive skills are compromised at that time, there may be a real degradation to this process that can lead to what we see sometimes happening to PTSD, even in the absence of traumatic brain injury, and that is unpredictable emotional or affective responses to reminders of the trauma. This is speculative, but people are really beginning to look at this in more detail to understand it better. 

Does emotional distress impede recovery from TBI? Most of the evidence that we have to address this question is from cross-sectional work so we are not as confident about the direction of causality. A number of studies with a few examples here have indicated that when adjusted for PTSD symptoms, the relationship between TBI and most, but not all post concussive symptoms seem to disappear. There is not much longitudinal work on this, especially for mild TBI as opposed to moderate or severe TBI. We do have one longitudinal study, that a colleague, Jenny Ponsford in Australia, conducted... again on civilians... where she looked at people admitted to trauma care, some with a traumatic brain injury, and some without brain injury involved trauma. She looked at a number of predictors, some having to do with TBI, whether or not people had a TBI, and then TBI attributes like posttraumatic amnesia duration. She looked at neuro cognitive performance, not just self-report, but how they performed on performance based tests, pre entry psychiatric history, and then symptoms... anxiety symptoms and then PTSD symptoms. 

What happens is the pattern of predictors changed over time. So, if we look to start here at what post concussive symptoms look like one week past the event, the injury itself, TBI makes a difference. As does whether somebody had a pre injury psychiatric history, and whether they were experiencing anxiety symptoms. Well, we could not... they did not look at PTSD symptoms at one week because they were looking at PTSD from more of a diagnostic standpoint and were waiting for that one month of symptoms to transpire. So, psychiatric history played a part, as did acute anxiety symptoms. 

The picture changes though, when we go to three months later. TBI no longer makes any difference. What makes a difference is this whole host of psychiatric variables. Again, whether somebody entered the injury with a psychiatric history, what their anxiety was like, not just concurrently, but way back when they had the injury, and then their current anxiety and PTSD symptoms. 

Looking at this from a slightly different perspective and at a slightly different longitudinal timeframe, we looked at military personnel, Army soldiers, before and after they deployed to Iraq. We gave them neurocognitive assessments both at baseline and then at post deployment. We look at people as a function of whether they had TBI during the deployment, or whether they did not have TBI during the deployment. I know this is small, but what this indicates is when the TBI is adjusted for PTSD symptoms at post deployment, the only thing that the TBI was related to was a degradation in functional impairment related to physical symptoms. On the other hand, if you look at PTSD symptoms at post deployment, and you adjusted that for the presence or absence of a TBI that was related to all sorts of pre to post deployment changes on cognitive performance measures. 

So, why am I presenting this? In part to show you different predictors of how things change over time longitudinally. But also, because sometimes there’s a temptation to think, well if only we can capture this with a performance based cognitive test, that’s going to really reassure us that this is related specifically to a TBI, and it doesn’t. Because PTSD can be as, or more, strongly related to how somebody performs on a cognitive test than TBI at its mildest levels. We actually repeated those analyses looking at depression symptoms rather than PTSD symptoms. We found a very, very similar pattern. Do keep in mind that this was early in the war where people had only had one deployment, in terms of their PTSD symptoms. There was not quite the issue that it turned into be with IEDs at that point in the war; so most of the people with TBI had had only one exposure to TBI during their deployment, very mild, indeed. 

Now, in continuing to think about what’s going on with TBI and how it relates to cognitive deficits, Jasmeet Penny Hayes at VA Boston, along with Mieke Verfaellie and others, looked in the cohort of OIS/OES veterans. Whether people had been exposed to blasts, whether they met criteria for a historical, mild TBI event deployment related, what their cognitive performance was like, and then looked at... used infusion tensor imaging to look at white matter integrity. They came up with some interesting findings. 

So, TBI was in fact related to white matter abnormalities, although PTSD was not. If you look just at TBI in relation to cognitive deficits, there is... I did it with my colleagues in my deployment longitudinal study; they did not find an association, or direct association with TBI and cognitive abnormalities. But they did when they looked at white matter as a mediator. So, to the degree that the TBI was associated with white matter changes, those white matter abnormalities were, in fact, associated with cognitive deficits. 

Then finally, PTSD, like I, and others, have found was associated with cognitive deficits, but not by a white matter abnormality. Why am I giving you all these rich details? It is because sometimes when we see a clinical manifestation of a symptom, even if it is on something that’s performance based and objective, there are many different ways that people have of getting that very same clinical manifestation. And although by my work, by Mieke’s work, by Jenny Ponceford’s work, there are really strong associations between psychiatric symptoms in both self reported post concussive symptoms and cognitive deficits. TBI actually does appear to do something in terms of neural changes in some people. 

Now, how does emotional distress impede recovery from TBI in terms of these clinical manifestations that we are talking about? Again, it does not seem to really affect any resolution of white matter, but how does the emotional distress impede the clinical manifestations, the recovery, as shown by the clinical manifestations from TBI. 

One thing to think about is the concept of resilience which can be defined as adaptive coping, positive emotions, how well people can reappraise things, how they can reframe it, accept it, social competence, purpose in life... all those good things that we know are healthy for people to do. So, in this particular definition of resilience, it does not necessarily mean just a lack of symptoms, it is really how somebody handles and manages those symptoms. We do know that psychiatric status has a lot to do with resilience. It is very difficult for people to be coping with a psychological stressor to have that extra burden of anxiety symptoms, lack of sleep, increased arousal, and be as resilient as they possibly could. 

The other potential mechanism is somatic preoccupation. It is not talked about a lot, but we do know that anxiety disorders tend to be related and associated with a tendency to over attend to somatic symptoms and to possibly appraise them with a certain degree of cognitive distortion. That is not to say that people are malingering, it is not to say that people are exaggerating, it’s not to say that this is the whole concept of a conversion disorder. What it is to say is a very real thing that if you have high levels of anxiety, it is hard not to be tuned in to things that might indicate threat, and physical symptoms do indicate threat? Pain is there for a real reason, it has to tell you that something is wrong. So if you have high anxiety, you are sometimes prone to being more attentive to those things. So, the difficulty with PTSD and other anxiety reactions to psychological trauma, is that they increase attention to these somatic symptoms and then that attention to the somatic symptoms can really make people more anxious, and it gets into a bit of a vicious cycle. The symptoms, post concussive symptoms, a good many of them are somatic. So, you can see where early on, these symptoms that might very well be transient, can get perpetuated in that particular way. 

What are the clinical implications of all of this? Getting to a central question, we see all this symptom overlap and we see how PTSD, TBI, post concussive symptoms, and psychological trauma/exposure are all very closely linked. One question that we can ask ourselves is does the etiology really matter, and if so, when does it matter? 

One of the answers to that has to do with PTSD treatment. There are some symptoms that are specific to PTSD as Mieke pointed out. Re experiencing symptoms like nightmares and intrusive thoughts are very good examples. The wonderful things that we have available to us now are evidence-based interventions for PTSD... prolonged exposure therapy, cognitive processing therapy, other varieties of cognitive behavioral interventions... So what we don’t want to do is say, gee, there’s so much symptom overlap, let’s throw in the towel and not differentiate at all, when we know that these treatments for PTSD that are very trauma focused and specific to PTSD, can really do people  a lot of good. So that’s one of the places where it actually does matter to try to get at the etiology. 

It’s also important when there’s a documented TBI event, and it’s especially important soon after the event to be cognizant that there has been an injury. What we know is that education around the symptom course and the recovery from TBI appears to be one of the most effective interventions we have for mild TBI. a lot of the literature comes from psycho education delivered in the very acute phases. There is evidence that it is not ever too late for psycho education, but we do know that it is particularly effective early on. So if there’s been a TBI event, regardless of whether there are PTSD or anxiety or depression symptoms, it will prove helpful to make sure that there’s a lot of good patient and family education around what to expect in terms of the recovery from TBI. 

When are the etiology of symptoms less important? Probably when we are looking at some of these cognitive deficits that have multiple pathways to them, and some of the other non-specific symptoms that can be addressed through various cognitive rehabilitation and psycho educational interventions. There are several examples of these out there... CogSMART, Beth Twamley’s intervention and Cognitive Strategy Training. Both of those interventions have been described in J.R.D., the references are up there, and seem to be very effective. They are not necessarily... the cognitive deficits do not need to be specific to any particular etiology for them to be effective. 

In summary, we know that PTSD occurs frequently in veterans with history of TBI, and I suspect that the majority of you on this call could have told me that and have been thinking that for some time now. There is considerable symptom overlap between post concussive symptoms and PTSD symptoms. It is very likely that bi-directional relationships occur and that recovery from TBI is impeded by PTSD and other stress related disorders. Likewise, that history of a TBI may affect the manifestation of PTSD symptoms following a psychological trauma. In determining the etiology of symptoms, it is helpful in some circumstances, but not in others. I hope that people are reassured by that, because I know in clinical context, it can be frustrating to tease the two apart. And sometimes we can do some good by simply treating what it is we can treat. 

With that, I think I will be quiet and see if there are questions. 

*Moderator:* Great, thank you so much to the both of you. I know that a lot of our attendees joined us after the top of the hour, so to submit your questions and comments, please use the Q and A box that’s located in the upper right hand corner of your screen. You can simply type it into the lower box and press the speech button, and that will get it submitted to us and we will get to those. We do not currently have any pending questions, so we will wait to see if any of those come in. in the meantime, if either of you would like to make any concluding comments or thoughts you are welcome to, or we can just sit tight for a minute. 

*Jennifer Vasterling:* I don’t really have anything in particular to add, do you Mieke? 

*Mieke Verfaellie:* No, not this moment; let’s see what input people have. 

*Moderator:* Great, we do have a comment that just came in. the problem in reaching any conclusions about the effects of mild TBI in military personnel and veterans, is that the definition of mild TBI used by the DOD and the VA is so broad, and often based on self-report long after the event. But the individual... I am sorry; did one of you guys touch the Q and A box? 

*Jennifer Vasterling:*  We did not. 

*Moderator:* Huh, interesting... my computer seems to have frozen... give me just a minute... okay, there we go... sorry. So anyway, the definition by the DOD and VA are very broad and self-reported long after the event, but the individuals in the mild TBI group are extremely diverse in their nature and extent of their injury. In other words, they are not really a well-defined group of people. Thank you very much for that comment. If you ladies would like to comment back, you’re welcome to. And we do have some pending questions. 

*Mieke Verfaellie:* ... and I think that regardless of the source of mild TBI... mild TBI is always a very heterogenous injury. Now, on top of that, we are dealing with the problem within the military context that very often, the diagnosis isn’t made at the time of the injury and in the VA system we are seeing patients months, often years, after the injury. Which brings up the additional problems, as the person mentioned, that we are really dealing with retrospective reports. And we know that these are... suspect that there are some biases that come into that memory. By definition, is reconstructed, so no one can be exactly accurate in describing what happened, sometimes years ago. So I think that’s a very real challenge that we’re dealing with. Added to that, in terms of these intersections between mild TBI and PTSD, we are also dealing with the fact that the confusional state is very difficult. It is very difficult to know whether that confusional state, which is one of the definitial aspects of mild TBI, whether that actually reflects physical injury to the brain, or just the chaos and the situational aspect of the situation, or in the psychological response to trauma. So again, this even makes the definition more difficult. 

*Jennifer Vasterling:* Yeah, I couldn’t agree more with both Mieka and with the comment from the audience member. And to add to what Mieke said, keep in mind, if the psychological stress reaction is severe enough at the time, you do wind up with a fight or flight type response; and you’re having physiological changes that could certainly involve neurochemical and neurohormonal systems, and you could have an alteration in consciousness in time. It’s not even purely psychological, it’s psychobiological and it’s really tough for people later on to say well, gee... you know with... was it just really upset... was I so stressed at the time, it’s chaotic, it’s dangerous, people are concentrating on surviving. It is a tough one, especially with the inclusion of altered consciousness in the absence of an outright loss of consciousness, what to make of that particular criterion for TBI in that context. 

*Moderator:* Thank you both. We have prompted the audience and now have numerous questions pending, so thank you. We have some feedback... wonderful workshop... thank you. I will be forwarding them along to colleagues as soon as I get the slides. When those are available, you can refer to your reminder e-mail. And the next question, is there a reversible effect of white matter in people with TBI? 

*Mieke Verfaellie:* That’s a very good question; and there is limited evidence that the changes that we see in TBI of the white matter changes, that in fact, these do decrease over time, at least as we can measure them. So, there seems to be changes occurring over time. Whether that’s fully reversible, I think we really don’t... again, as Jennifer has emphasized the importance of longitudinal studies, we really don’t have longitudinal studies at this point to know that for sure. 

*Moderator:* Thank you for that reply. We are going to move to continue with the Q and A. I just want to real quickly put up our feedback form. This is for our audience members. Please do take just a moment to fill this out while we continue with the Q and A; it is your responses that help guide what subjects we have presented for us. Is PTSD associated with any white matter changes? So, you may have already touched on this. If so, how do you distinguish these from TBI related white matter changes? 

*Mieke Verfaellie:* That is a very good question. There is actually limited evidence for white matter changes associated with PTSD. there are a couple of early studies that found changes possibly in the cingulate, but more recent work has really not... at least in our own work as well... has not shown white matter changes in PTSD. 

*Moderator:* Thank you for that reply. The next question, if you were to respond to a consult where clinicians were asking you to differentiate between TBI and PTSD, what would your response be?

*Jennifer Vasterling:* How do you know that we get so many consults like that? You must be here. That is a frequent question, and again, we do our best to kind of tease that particular question apart to answer what we can of it. So, first, we try to establish whether there has been a TBI event and that’s the very most basic question that we answer. Second, we try to establish whether it was psychologically traumatic, or whether there has been some other psychological trauma. Then we start getting into symptoms. Like symptoms that are self-reported as well as cognitive performance, and we look at symptoms that can be more or less specific to TBI versus PTSD, so we look at those things like light sensitivity that Mieke mentioned, that are not so likely to be associated with PTSD. It is on that slide, we took that from another paper, but there is actually a fair amount of stress related pain of various sorts associated with PTSD. 

And we look at PTSD specific symptoms. The cognitive performance is tough, as so well demonstrated by Mieke’s study and Penny Hayes’ study. We look at the course of symptoms, so that is when it is interesting and sometimes helpful. We do have that small percent of people who maintain post concussive symptoms after TBI, even in the absence of PTSD, so you have to acknowledge that, but we do not necessarily expect to see in TBI, but you can see more frequently in PTSD is increasing symptoms. So, looking at course for that type of differential is very helpful and we don’t necessarily expect to see the type of fluctuations in cyclical patterns that you can see in PTSD as symptoms waxing and waning. 

Beyond that, we address that to the degree that we can, and when we cannot differentiate, which is very often, we say so. What we instead try to do is focus on what we can treat. Has the patient been... has anyone talked to the patient about what to expect from the TBI and what mild TBI is about? Does the patient have PTSD symptoms that would be amenable to treatment? Are they having cognitive symptoms that would be perhaps helped by some sort of cognitive rehab strategy? So, we’re comfortable in saying when we can’t differentiate the etiology. 

*Moderator:* Thank you; we appreciate the replies. It looks like questions are still coming in; we have about nine pending. The next one, do you think it hurts to provide the behavioral and cognitive treatments at any rate since they seem to help both groups? 

*Jennifer Vasterling:* No, and the evidence suggests that it does not hurt. There have been studies of cognitive behavioral treatments on TBI patients outside of PTSD and those treatments have been geared around making sure that appraisals are adaptive of the symptoms that people are having, both physical and psychological symptoms that people might be having. Those studies suggest that it is beneficial in terms of post concussive symptoms as well as any emotional symptoms. Richard Bryant really looked at his longitudinal study in the presentation... He did a study of people with acute stress reactions following mild TBI... did a cognitive behavioral treatment aimed at reducing those acute stress reactions, and randomized clinical trial formats, and found that people were much less likely to go on and develop full blown PTSD if they had that early CBT trial. Some of the groups Kate Shaw and others have started looking at as they are doing PTSD treatments, whether or not people have TBI and they are certainly not contraindications. What we do not know is whether things might proceed more slowly if there is enough cognitive impairment or not, but there is nothing to suggest that people should not get those good evidence based therapies. 

*Moderator:* Great, thank you. The next question we have: in the more recent studies related to the white matter abnormalities with MTBI you referenced, what has the prevalence of these white matter abnormalities been in the groups studied? 

*Mieke Verfaellie:* That’s a good question and I can’t give you a direct answer to that because typically, these studies... the technology is not far enough along that we can say this is on an individual subject based on... This is what we consider abnormal or normal. There are various approaches that are used; one is to just look at the fusion of water molecules in the brain. and there are various measures of that... fractional entrocepathy is a common one, but very often, studies look at average measures across a group of patients and a group of controls, and so we really don’t yet have the level of precision to know what’s normal or abnormal. 

Another approach, because the injuries are commonly very variable, is to not look at specific places in the brain, but say anywhere in the brain, are there voxels, are there areas where there are sufficient number of voxels that are abnormal, and so it doesn’t matter where in the brain they are. Again, that is primarily been done at a group level comparing patients in the TBI group to those who have not suffered TBI. But we’re really not far enough along to be able to use that as individualized measures; and that’s what the next task ahead of us is. 

*Moderator:* Thank you for that reply... the next question, would it be possible to provide a bibliography of references cited in this presentation? 

*Jennifer Vasterling:* Sure, sure. 

*Moderator:* If you want to send that to me at your leisure, I can post it with the archives and handouts of this. Next question, other than CTT, PE and education, are there any other treatments that are helpful for cognitive, emotional and reintegration? 

*Mieke Verfaellie:* This covers a broad basis. 

*Jennifer Vasterling:* Yeah, it’s broader... It sounds like that’s broader than just a PTSD question, and even in PTSD there’s a broader range of cognitive behavioral treatments, and some psychological treatments that people use, so the answer is yes, but it’s broad enough that I would hesitate to start naming specific interventions, because it’s likely that I would leave something out. 

*Moderator:* Not a problem, if this is not the forum for it, it is not. It was shown that telephone counseling improved outcomes for TBI. What was it about the counseling that leads to improvement compared to the non-counseled patients? 

*Mieke Verfaellie:* Not having done this particular study, but some of the theory behind why psychoeducation works for mild TBI is that there are... it evokes positive expectations about recovery, optimism... all of those things that are helpful in terms of being resilient. It is going to decrease anxiety because keeping in mind, all of you have thought a lot about mild TBI, but some of the patients coming in, it is just really scary to have a brain injury, and what does that mean in the long term? Could this be devastating to their lives? And sometimes the reassurance is really helpful in taking the edge off of the anxiety, which is going to complicate the recovery in and of itself. So, I think that type of mechanism of expectancies and reassurance are probably really, really important components of that type of phone... which is really psychoeducational orientation. 

*Moderator:* Thank you, can you comment on the high prevalence of findings of sub-optimal performance in neurocognitive testing in patients with MTBI, both in the VA and outside the VA; and any implications for treatment? 

*Jennifer Vasterling:* Are we meaning suboptimal effort? 

*Moderator:* Not sure, it says sub optimal performance in neurocognitive testing. If that person is still on, feel free to write into the survey section for further elaboration. 

*Jennifer Vasterling:* I will give it a minute to see if they write in, if not we will interpret it as... 

*Moderator:* No problem, we can move on to the next one and we will come back to it. In terms of treatment, would the focus be on psychological in the absence of physiological symptoms? 

*Jennifer Vasterling:* If I understand the question, no not necessarily. I think it is hard to separate the two, even if you are just talking about PTSD; there is a physiological component. The somatic symptoms are very real regardless of whether they have a more strongly emotional basis versus a brain injury basis. They are nonetheless real and present and there are colleagues here at _____ [01:12:17] and John Otis [PH] for example, has an integrated pain in PTSD treatment protocol that is proven to be helpful to people and he is dealing with both very real somatic symptoms as well as the emotional component to his target. 

*Moderator:* Thank you; we just have a few more pending questions. I have noticed that people are writing in and asking for more topics on TBI research. I just want to bring to your attention that we do have an entire series dedicated to TBI, so please check back in our catalogue as we have regular sessions on a variety of topics related to TBI. the next question, can you comment on the high prevalence of findings... we just did that one... given the available data in veterans, do you have ideas about the next needed research steps to determine the effects of time since injury, or the course of mild TBI recovery, particularly for those with symptoms beyond three months. 

*Jennifer Vasterling:* I do think longitudinal studies would be helpful. 

*Mieke Verfaellie:* I think that is a very important question, and there is the possibility that in some people with even mild TBI, and especially with repetitive TBI, that we could see a worsening course over time. There is work now on CTE on chronic traumatic encephalopathy suggesting that in fact, over time one might see degenerative changes. That may be in a very small proportion of individuals, but nonetheless, it raises the importance of following people over time so that we have a better understanding of what happens longitudinally. 

*Moderator:* Thank you; you mentioned that psychoeducation is most effective immediately following the event. Do you know whether that currently is being provided and thereafter in MTBI? 

*Jennifer Vasterling:* I am sure it varies per setting, but I do think my understanding from talking to other clinicians in the field is that people are trying to do that. 

Computer: Your conference is scheduled to end if five minutes. 

*Mieke Verfaellie:* I think that is very much the case. I think the challenge in the VA system is it is so often we see veterans so long after they incurred the injury, and I think Jennifer already raised the question, certainly psychoeducation is never bad, but can it still be effective when it is provided so much later. We do not know that very well yet. 

*Moderator:* I am going to get our call extended just a minute, so if my line goes mute... 

*Jennifer Vasterling:* I’m actually going to... I will be leaving the questions in about five minutes to Mieke, because I do have another obligation.

*Moderator:* Okay, no problem, we actually... if you have time for that... sorry, did I leave you Jennifer? 

*Jennifer Vasterling:* Yes, yes... we were... 

*Moderator:* Sorry about that, I was trying to get the call extended. That actually wraps up all of the Q and A, so I just really want to thank you ladies for taking the time to present to us and also for staying after the top of the hour. We did have a lot of questions come in. Also, thank you very much to our attendees for joining us. We really appreciate it and we do have another TBI seminar tomorrow at noon Eastern, so feel free to join us for that. That does conclude today’s HSRND cyber seminar, so thank you again. 

*Jennifer Vasterling:* Terrific questions from the audience. 

*Mieke Verfaellie:* Thank you everybody. 

*Moderator:* Have a good day. 

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