**Transcript of Cyberseminar**

**Timely Topics of Interest**

**TBI: Cognitive Rehabilitation; Assessment and Drug Therapy**

**Presenters:  Heather G. Belanger, Ph.D., ABPP-CN; Hal S. Wortzel, MD**

**April 15, 2013**

**TBI: Cognitive Rehabilitation; Assessment and Drug Therapy**

**April 15, 2013**

*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 http://www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact: ralph.depalma@va.gov*

Moderator:I want to thank everyone for joining us for today’s Timely Topic of Interest. Today’s session is a part of our TBI mini-series. Today’s session is Cognitive Rehabilitation Assessment and Drug Therapy. Ralph, can I turn things over to you?

Ralph DePalma:Yes it is a pleasure to introduce Heather Belanger who is a psychologist at the Tampa VA Poly-Trauma Center. She has done groundbreaking work in the diagnosis and classification and treatment of TBI. Accompanying her is Hal Wortzel who is a psychiatrist in Colorado at the University of Colorado and Director of the MIRECC there. He started life as an orthopedist and brings his sharps eye on the spotlight on diagnosis and treatment of TBI/PTSD. It is a pleasure to have them both on, we are looking forward to their talk. 

Heather Belanger:Okay I will assume you can hear me. hello my name is Heather Belanger. I am a clinical neuropsychologist at the Tampa VA and I am going to start the session today talking about cognitive rehab for mild TBI. 

First we are going to start with a poll question. I would like everyone to answer this question. My interest in mild TBI is as a – select one of these: as a clinician; a researcher; a clinician researcher; manager or policymaker or other. Please select one. 

Moderator:Responses are coming in we will give them just a few more seconds before I close it out there. there you go. 

Heather Belanger:Okay so it looks like most of us are clinicians. Thank you. Today’s talk these are my views and not those of the government. My objectives briefly are: to define mild TBI; discuss typical sequelae; summarize evidence-based for therapies and interventions both cognitive and symptom based. Then move beyond the evidence somewhat because as you are going to see it is quite limited at this time. 

A TBI is defined as a blow or jolt to the head or a penetrating head injury that disrupts the functioning of the brain. We typically discuss TBI in terms of its severity. I will be focusing on mild TBI today which includes people who following a blow to the head, experience a loss of consciousness of less than 30 minutes and/or a period of confusion called post-traumatic amnesia or PTA that lasts no longer than one day and who have normal neuro-imaging if it is done. This entity, mild TBI is also frequently called concussion and I may use either term, mild TBI or concussion during my talk. 

When we talk about mild TBI it is important to distinguish between symptoms and performance since those two do not always correspond. For example you may see someone many months post concussion who has normal performance on an objective memory test but nonetheless complains of memory difficulty. Please just keep in mind this distinction between cognitive performance and cognitive complaints. What we call post-concussive symptoms or PCS include self-reportive cognitive, emotional and/or somatic difficulties. 

This picture summarizes what we know about cognitive performance following a mild TBI. Immediately after the injury here, there is generally a decline in cognitive performance that typically clears by about seven days post injury in the sports literature, but no longer than three months post-injury in the civilian literature. Subsequent to that, beyond three months post-injury, people typically return to baseline. In contrast, individuals with moderate to severe TBI may in general be expected to continue to have difficulties. 

However, it is very important to note that context matters. These are the results of one of many meta-analytic studies of mild TBI. If we quantitatively combine all studies of mild TBI and put them on the same metrics, we see that patients seen less than three months post-injury tend to have cognitive impairments as you see here relative to controls. So .5 is considered a moderate effect size, so they have a moderate degree of difficulty we could say relative to controls. However, if we look at non-selected samples here, beyond three months post-injury here in the right most column meaning a sample john from all possible people with mild TBI we see that they are normal by three months post-injury. However if we look at clinical samples three months post here, this would be like a VA clinic, we see continued impairment. Finally we see that those in litigation actually tend to get worse over time rather than recover. 

Here is a useful figure from an article that Grant Iverson wrote which shows the cognitive effect sizes associated with different disorders. You can see that the long-term effect here of having a history of mild TBI is essentially zero. While the effective things like having a depressive disorder, ADHD, bipolar disorder etcetera, are much more significant in terms of cognitive performance. 

We have been talking about cognitive performance so far, what about symptoms. There are definitely a subset of people who continue to report PCS symptoms that they may attribute to their mild TBI. It is important to read studies that are longitudinal like some of those that I listed here to understand how symptoms are related or not related to mild TBI across time. In general when looking at longitudinal studies such as these, mild TBI is predictive of PCS in the first few days following injury but not in the post-acute to chronic phases. That is there is no difference in symptom reporting between those who have had a mild TBI and those who have other injuries like orthopedic injuries for example. Do people with concussion complain of symptoms in the chronic phase i.e. many months post injury, yes, most definitely and the numbers range from anywhere of five percent to 15% even as high as 20% in some samples. I think it is important to read these longitudinal studies to understand that as with cognitive performance symptoms are elevated acutely but not chronically relative to control. Cross-sectional studies that assess people only at one point in time, cannot really provide the same understanding of causality as a longitudinal study. 

Now some people may say okay yes but our military concussion is different somehow. In fact the VA has recently asked itself this question by having Queri review the existing literature on the effects of mild TBI in military and veteran populations specifically. I am showing you the cover page of that report here. Obviously we cannot go through all of it but here are the main findings of that review, I underlined the key points in pink. In a nutshell review of existing evidence suggests that mild TBI is not different from civilian mild TBI in terms of outcomes. However, it is noted that the co-morbidities in this population deserve attention and may moderate outcomes. 

One take home message of what I told you so far is, be mindful of the message you give patients regarding the cause of their symptoms and difficulties. The existing evidence really suggests that mild TBI is frequently not the driver in the chronic phase. Your message is important because there are many factors like the media that suggest to the patient that they likely have a permanent disability associated with concussion despite the large body of literature suggesting otherwise. Again though do some patients have impairments, the answer is most definitely yes, typically anywhere from five to 15%. 

Now we will spend a few minutes reviewing the literature as it pertains to doing cognitive rehab with patients who have a history of mild TBI and continuing difficulties. Briefly cognitive rehab or I will also call it CRT for short is defined as a systematic functionally oriented service of therapeutic cognitive activities based on an assessment and understanding of the persons brain behavioral deficits. 

CRT may be accomplished in a modular fashion such that a particular impairment like aphasia for example is the focus of the therapy. It might also be accomplished by a comprehensive or holistic program which is aimed at all aspects of cognitive functioning including social competence, emotional mastery, etcetera within the context of a therapeutic community. For those of you who are familiar with the VA’s poly-trauma system, both our acute and transitional programs operate in this more collective fashion. 

The answer to the medicine in 2011 produced a summary of the literature pertaining to cognitive rehab for TBI and you can see the cover page of that report here. 

This is a busy table that summarizes their findings. The plus signs in this table indicate some degree of evidence for efficacy. While they looked at the full spectrum of TBI in this report, I am going to draw your attention to the limited evidence they reviewed pertaining to mild TBI specifically so you can see I circled that in pink for you. What they found is evidence that there is some utility to using internal compensatory strategies for memory in individuals with mild TBI and ongoing memory problems. These are what those plus signs mean here. 

Internal memory strategies are things like using semantic association to remember things so categorizing and clustering information so you can better remember it; using semantic elaboration; using imagery that sort of thing. There is evidence that that works. Then in the far right hand column they also find evidence that there is some utility to multi-modal or holistic programs both in terms of improving symptoms and performance. I should note that there were only a total of three studies that led to the conclusions concerning CRT and mild TBI. There is definitely a grain of salt here. 

Let us look at one of the studies that contributed to these findings. One of the studies was by Tiersky et al which took 20 patients with mild to moderate TBI and persisting cognitive complaints at least one-year post injury. They assigned them a treatment group or a waitlist control group. The treatment group got 50 minutes of cognitive behavioral therapy three times a week for 11 weeks as well as 50 minutes of cognitive rehab with similar intensity. They found improvements on both a performance based measure specifically an attention task but quite a difficult attention task called the PASAT and on self-reported mood at one and three months post. 

Their CRT in this study focused on attention process training which is an intervention entailing repeated stimulation of attention processes and meta-cognitive training with the goal of strengthening underlying neural processes. It relies heavily on repetition and hierarchical progression. Their intervention also relied on memory compensatory skills and training like removal of distraction, focusing on one thing at time as well as using problem-solving strategies. Again the cognitive rehab was done in concert with CBT and emotional distress management. Again the treatment group did better in terms of both performance on an attention measure and in terms of mood. 

A question that remains though is would a less intensive intervention have similar effect? Maybe yes, maybe no, we do not know. There is actually currently a trial going on to try to address that question. 

Now turning to interventions focused specifically on post-concussive symptoms or PCS. We can think of different types of symptom based interventions. These may include symptom specific interventions like a medication or relaxation training for headaches for example, behavioral health interventions like sleep hygiene for example, cognitive behavioral psychotherapy and educational intervention. 

There is a good review of the mild TBI intervention literature by Comper et al that you should read if you are interested in this topic. It includes review of pharmco-therapy, cognitive rehab and psycho-educational intervention. I put the bottom line here for you to read of that review. Provision of symptom related information is effective in assisting individuals to recover from mild TBI symptoms. Studies evaluating education as an intervention were among the strongest studies methodologically. To sum it up there is clear evidence that provision of education improves outcomes when it is provided. 

Indeed many investigators have found that patient education about expected recovery early on is effective in reducing PCS symptoms down the road. These interventions include things like normalizing symptoms, providing positive expectancies, providing specific strategies for symptom reduction, etcetera. These tend to be brief interventions provided acutely. 

Wiley Mittenberg developed a ten-page manual that may be useful for folks working through more intractable symptoms since it incorporates cognitive behavioral principles in addition to providing education and reassurance. You can actually get this manual in his publication. Because it was developed for use with a more acute population though it probably would need to be adapted somewhat for our population. 

Indeed most if not all these educational studies have been conducted on patients seen rather acutely or days to weeks post-injury. It is unclear if this type of intervention is effective in those first seen in more chronic stages. 

We also have a high rate of psychiatric comorbidities in our military and VA settings. Again it is unclear to what extent this pertains to our patient. 

I think given all I told  you in the evidence-based to date limited though it may be, the question becomes what do we do with patients who have been diagnosed with a mild TBI and who are reporting difficulties. I think it makes sense to do a thorough assessment and determine if there are treatable Axis I disorders like PTSD for example for which we have evidence-based treatments. Axis I disorders can cause both cognitive complaints and objective performance decrements. Are there medical disorders requiring treatment, are there Axis IV difficulties like social support issues that can be addressed in therapy. Most importantly I think is to be mindful of what message you convey to the patients. Rather than cultivating a permanent disability mentality I think we need to foster self-efficacy and recovery. 

I think it is helpful to think about what you are treating so is it a perception or attribution? Is it substance abuse? Is it self-efficacy? It may be useful to examine the patient’s attributions in the degree to which they feel a sense of control. 

I also think it is important to validate someone’s injury in symptoms and understand their perception and figure out where to go from there. it is important to know that there is emerging evidence that evidence-based PTSD treatment is not only possible with mild TBI patients, it is effective. Preliminary data from our colleagues at the Cincinnati VA and my colleague here at the Tampa VA and other VA’s suggest that both cognitive processing and prolonged exposure therapy are doable and effective with mild TBI patients. 

This chart shows you some pre-imposed PTSD pilot data and depression symptoms following PE treatment in mild TBI patients. You can see the improvement there. 

Modifications when needed included things like memory enhancement strategies, for example using a PDA to plan exposure activities; increase structure or additional session time. 

It may be advantageous to address non-specific symptoms through the poly-trauma system of care when there is a concern about mental health stigma. The VA system is actually quite ahead of the curve I think in that care can be achieved at PM&R and primary care, post-deployment clinics, mental health, etcetera. We also have guidance provided through the clinical practice guidelines created collaboratively by DoD and VA. I provided the email address here for those of you who are not aware of these guidelines for you to access them. I encourage all of you who work with the TBI population to read these guidelines, they provide a nice framework for clinicians to work through treatment of PCS. There is even a pocket guide on this website for those of you like the Cliff Notes. 

There is discussion of symptom based treatment and triage. For those of you who like schematics this is a nice one developed by Heidi Terrio kind of like Maslows Hierarchy of needs. These start your thinking at the bottom of the pyramid in terms of providing education and considering behavioral psychiatric disorders. You move your way up the pyramid with the patient. The thinking here is that resolving issues lower in the pyramid will likely clear up the cognitive issues. If they do not then they are addressed. 

In a similar vain like the pyramid the Clinical Practice Guidelines suggest individuals who present with memory, attention and/or executive function problems, which did not respond to initial treatment, meaning that lower part of the pyramid, may be considered for referrals of cognitive rehab therapists with expertise in TBI rehab to use some of those compensatory strategies that I mentioned earlier in the talk. 

In summary, presently there is limited evidence for CRT in mild TBI. That does not mean it does not work there has actually been very few studies, but I presented to you the evidence that exists. Really the strongest evidence in terms of addressing PCS symptoms are educational interventions. However, those have only been thoroughly tested in more acute settings. 

I suggested to you that thinking in terms of the pyramid might be a useful way to conceptualize your treatment of patients who are having PCS difficulties and cognitive difficulties. Stress the importance of assessment followed by this sort of systematic approach. Then the importance of promoting a recovery mindset and being of course mindful of the message that you are conveying to patients. 

That is it, thank you for your attention. 

Moderator:Thank you Heather, I am going to turn things over to Hal at this point. 

Dr. Hal Wortzel:Okay, is my screen up yet? 

Moderator:Not quite yet, you need to click on that button to show my screen. 

Dr. Hal Wortzel:I did. 

Moderator:There we go, now we have it. 

Dr. Hal Wortzel:Okay. I will be revisiting a lot of the same topics we just heard about from Dr. Belanger. Some of those points really do bear repeating, emphasizing. Then I will hopefully culminate with some information regarding psychopharmacology specifically for the kinds of cognitive impairments we can see after a traumatic brain injury. Before we forge ahead we will do another poll question. TBI is? A devastating life altering injury. A common injury and inconsequential following recovery to the individual’s neuropsychiatric status. Or I am asking you a trick question. 

Moderator:We will give everyone a few seconds to respond to that and then we will  close it out and show the results on the screen here. 

Dr. Hal Wortzel:Okay we see a lot of people detecting the trick question but this is typical. We get people answering on both the sides here and this really emphasizes how important it is that we get this answer right because it is going to be various from veteran to veteran from patient to patient. Is my screen back up now?

Moderator:Nope, give me just a second. There we go, you are good to go. 

Dr. Hal Wortzel:Okay, thank you. The point here is that either of these things can be true in any given case in any given veteran. What we see all too often in our medical records are providers failing to distinguish between different severities of traumatic brain injury just referring to a history of TBI. Oftentimes what this results in is focusing on perhaps a mild TBI and overlooking other treatable neuropsychiatric conditions, conditions for which we have good evidence-based therapies. For instance depression or PTSD and focusing on a mild TBI. Conversely there are going to be other presentations involving moderate to severe injuries with neuronal injury accounting for significant degrees of cognitive impairment that needs to be identified. It is going to be a careful differential diagnosis process that we need to walk in answering that question for any given individual. That is because every individual and every brain is unique. A point that I like to emphasize a lot because this is true of our civilians but it is particularly true of our veterans is that the biomechanical forces that act on the brain result in a TBI rarely act in isolation. I mean that in a couple of ways. One is that the biomechanical forces are not just acting on brains, they are acting on inner ear, spinal cord, other things that can result in the sort of somatics. For instance damage to the middle ear resulting in dizziness as opposed to a TBI per se or cervical spine injury result in headache pain as opposed to a TBI per se. It is not just biomechanical forces, those biomechanical forces and again this is particularly true in combat, are typically going to co-occur with psychological trauma. That can result in things like PTSD and depression. All this is a rather elaborate way to say that the symptoms we can see after TBI are non-specific so we have to be careful to make sure we are identifying all of the potential conditions that need to be targeted for treatment. 

This is really crucial with our returning veterans. Rates of potential mild TBI are probably on the order of about 20% regardless of which of these studies we look at. Even with these most conservative estimates we are probably talking about hundreds of thousands of possible service related TBIs coming back into our clinics. If we do not get these questions right, if we assume that serious impairment is going to follow from a mild TBI or do not identify a moderate to severe injury, there are an awful lot of these injuries coming back emphasizing it is important to get this right. 

We have already seen from the prior presentation a general definition of TBI so I will not repeat that. But I will emphasize again the importance of trying to identify mild TBI and separating those out from the moderate and severe. There is quite a bit of literature out there that describes a natural history of mild TBI and the anticipated course of recovery. Asking in clinical interviews about loss of consciousness in trying to determine if it is less than 30 minutes if there is post-traumatic amnesia that is less than a day, again identifying at least some alteration and mental state at the time of injury whether it be feeling dazed, disoriented or confused or any focal neurological deficit. Again these are the numbers. If any one of these are in excess of the numbers recorded here we are going to break into the severe category of TBI. And that really does have important prognostic implications and is part of our formulation in terms of whether or not we need to be looking for another neuropsychiatric condition to explain symptoms two years after a brain injury. Or this is a moderate severe injury and ongoing cognitive deficits are likely to be attributable to neuronal injury from biomechanical forces. 

This again has to do with the anticipated course of recovery. I am not going to belabor this point but just again it is important that we appreciate that most people with isolated mild TBI do get better and get better pretty quickly. Dr. Belanger already referenced her own study. One year before that a similar meta-analysis was conducted by the World Health Organization with very similar results. Unfortuatnley these two studies, these are not the kind of studies that are making the headlines and telling all of us the good news about mild TBI and that most people recover. It is important that we as clinicians know that so we can appropriately educate and communicate that to our patients. 

Moderate to severe TBI though is a horse of a different color and we see a lot more in the way of persisting deficits after these kinds of injuries with 35% to 60% of victims of moderate to severe TBI going on to develop persistent neuro-behavioral or physical symptoms. Not surprisingly the more severe the initial injury the greater the likelihood that we are going to see incomplete recovery whether that be neurological symptoms, emotional symptoms, behavioral symptoms or cognitive symptoms. Of course getting back to work, parenting, whatever it is an individual wants to be doing with their lives the ability to do is inversely proportional to the severity of this persistent symptoms. 

We already have seen similar charts depicting the course of recovery after TBI. I want to just emphasize a couple of points. One is that this is generally an upward slope regardless of whether we are talking about a mild injury, a moderate injury or severe injury, the course is one of recovery with eventual plateauing, as opposed to someone doing well and then falling off the cliff and going downhill. That is not what we tend to see with TBI. The other point that I think is worth emphasizing is that while severe and moderate TBI does potentially pretend to worsen more than mild TBI people can recover from these injuries as well. So we see a broader spectrum of outcome with these moderate severe injuries. Again keeping in mind that people can recover and that identifying a moderate or severe TBI does not obviate the need, you need to also look for other neuropsychiatric conditions that might be interfering with cognitive abilities or optimal functional recovery. 

This is superimposed here, the neurotransmitter storm that we see with traumatic brain injury that also resolves in a way that is analogous what we see clinically. 

Of course when we talk about the cognitive impairments that can follow we see problems with potentially arousal, processing speed, attention, working memory, memory, functional communications and executive function. 

In terms of the behavioral problems or emotional problems that follow we are not going to discuss all of these because of time constraints, but I really do want to emphasize a couple which we will talk about again in just a moment being depression and anxiety because these very frequently follow traumatic brain injury. Oftentimes can interfere with functional recovery and oftentimes can masquerade with cognitive impairment. 

When we talk about TBI and neuropsychiatric comorbidity there really is a careful assessment that needs to occur prior to engaging psychopharmacology. That comprehensive assessment is going to a mandate attention to a few different things. Number one, we have to think about the brain that was injured, meaning pre-injury factors. What kind of individual went into that brain injury event? Was there depression beforehand? Was there a tendency towards risk taking behaviors or impulsivity beforehand. Needless to say if those were problems before brain injury there is a good chance there will be problems after brain injury and it might not be the consequence of brain injury at all. We also want to consider the brain injury itself meaning TBI severity. As we have been talking about separating out the mild TBI versus moderate severe TBI because that is going to be an important, again clue when we identify mild TBI a clue that if we are not seeing that anticipated course of recovery we probably really need to be looking for some other neuropsychiatric diagnosis or comorbidity. Also pay attention to other physical injuries that poly-traumas of course is very common among our returning veterans. 

Finally, we have to pay attention to the receiving environment or the environment into which that injured brain is received. Any of these things can independently yield cognitive behavioral or emotional symptoms. That is not to say we cannot ever identify or determine that cognitive symptoms are the direct result of the TBI, but before we do so, we have a careful process to engage. That is because there is a broad differential diagnosis for posttraumatic neuropsychiatric impairments. Again that can involve cognitive problems, emotional problems and behavioral problems. Of course, these domains are somewhat indistinct and can overlap with emotional impairment looking a lot like cognitive impairments sometimes or even yielding cognitive symptoms and complaints. 

As we engage a differential diagnosis we want to keep in mind the potentially emotional behavioral physical problems as well as things like substance abuse disorders, medical conditions. Really important are prescription as well as other medications so those narcotic pain medications we see so frequently are benzodiazepines. All of these things need to be assessed in a thorough manner and really are a prerequisite to treatment for cognitive impairment subsequent to a TBI. Another way to say all this is to say that we really want to avoid logical fallacies of the post hoc ergo propter hoc variety from the Latin meaning essentially after TBI, therefore because of TBI. Again we see this just all too often where complaints following a brain injury are presumed to be due to brain injury. That is unfortunate when it results in lost opportunities to target other treatable neuropsychiatric conditions. Similarly conditions can co-occur so we should not assume that it is occurring with TBI therefore due to TBI. Again this is all about not missing opportunities to target treatable conditions and not miss opportunities to really optimize our veterans functioning. 

In terms of some principles of TBI psychopharmacology generally not just for cognitive symptoms but for any of the neuropsychiatric symptoms we can see after injury there are a few principles worth discussing. First define target symptoms clearly. If you are going to deploy a medication, be able to say what you are using that medication for as every once in a while I will do a consult and someone is on a med and what is it for, you get a general well, he was not doing well. We really want to have a better sense of specifically what we think that medication might get at whether it be depression or anxiety or some sort of pain condition, be able to have a very clear sense of what it is we are targeting with a medication. If we are going to engage a therapeutic trial, do it for real. Meaning use an adequate dose for an adequate duration of time before we declare treatment or medication a failure. We of course want to monitor side effects and side effects are a legitimate reason to abandon the treatment trial prior to adequate dose or duration. We want to think about the duration of maintenance treatment meaning that sometimes folks are on meds after a brain injury and it never gets revisited if those meds still need to be continued. At least periodically asking that question. Thinking about ease of use, some medications require dosing many times a day, others do not. Taking that into consideration, obviously paying attention to drug/drug interactions and being prepared to augment partial responses when necessary. 

Now more specifically we are talking about the treatment of posttraumatic cognitive impairments, again paying attention to that differential diagnosis spanning emotional, physical, substance abuse, medication problems, sleep. It is generally the case that when we are talking about psychopharmacology for cognitive impairment specifically we want to optimize these other issues, depression, substance abuse, medications that might be interfering with cognitive abilities. We want to clean up those issues before we start deploying new medications to target cognition specifically. I also want to emphasize to do that the medications we use to treat cognitive impairment at this point augment other forms of treatment. Meaning that our first line treatments are really non-pharmacologic for cognition at this point. Education being a huge one particularly for those mild TBI cases. Helping patients with more severe injuries, set realistic goals and expectations, helping them identify and achieve environmental and lifestyle modifications and of course getting them to cognitive rehabilitation that may be helpful. 

I eluded to this before, depression is so frequent after TBI and can look like so many things including cognitive impairment that it is important that we are thinking about and ruling this out when we see these presentations. Up to 77% of individuals may experience depression after a brain injury with a very broad range reported in the literature. As we see here cognitive complaints and impairments can feature prominently in depressive illness including problems with sustained attention and memory. All this to say we really want to make sure we are identifying not missing depressive illness and optimizing that condition before deploying medications to treat these cognitive symptoms. If they are occurring because of or in the context of severe depression it is unlikely that medications deployed specifically for memory are going to have much effect in that context. 

Similarly anxiety disorders are very common after TBI. SSRIs are first line treatments for those. If we are concerned about an individual with a brain injury and cognition in particular it really is best to avoid benzodiazepines. But we see this come up very frequently and of course, these benzodiazepines can be the cause of cognitive problems, not infrequently. In fact the chart that Dr. Belanger showed with spec sizes I think has benzodiazepines listed on it and you will note that it is effect size for cognitive impairment is substantially higher than that of a mild TBI. 

Sleep disturbances are also very common and again we want to avoid medications that will make the situation worse. So things like benzodiazepines and diphenhydramine which has significant anticholenergic effects can make the problem worse. Again optimizing sleep and fatigue prior to targeting cognition specifically. 

Now a little bit on the medications that we use. Two targeted cognitive impairment when we think we ruled out these other issues, optimized neuropsychiatric comorbidities and offending medications and now it is time to go after cognition. When we think that we have neuronal injury resulting in these problems due to neurotransmitter deficiencies. Typically there are two mean strategies for cognitive psychopharmacology catecholaminergic augmentation meaning norepinephrine and dopamine or cholinergic augmentation. 

With catecholaminergic augmentation we are typically targeting the symptoms of arousal, speed of processing and sustained attention. There is some emerging evidence it is usually from McAllister identifying some differential effects of dopamine in norepinephrine on  posttraumatic working memory impairments. These, some of which may be the consequence of some genetic polymorphisms, but never the less this is one of the main strategies for treating posttraumatic cognitive difficulties particularly when it has to do with we are seeing problems with attention, speed of processing. 

There are a few different strategies even within the catecholaminergic augmentation strategies. We can talk about dopamine augmentation, focused dopamine augmentation, mixed dopaminergic noradrenergic and indirect dopamine augmentation strategies. I think probably most frequently and with some of the best evidence-based are psycho-stimulants – Ritalin, Adderral those sorts of things which can be very helpful for problems with attention and speed of processing are generally very well tolerated. Also potentially beneficial in that they can address some common comorbidities. Ritalin might be helpful also with some depression or fatigue that after TBI may be experiencing and generally would start with this class of medication. Realizing that there are other strategies to get dopamine indirectly, things such as amantadine or mematine as well as direct dopaminergic strategies for things like bromocriptine, carbidopa or levodopa. 

Here we just use some of these a diagram or cartoon illustrating just a little bit or neuro-anatomy of these dopamine and norepinephrine systems. Really just making the point though that there are mid-brain or brain stem nuclei that have very broad projections that go up to our frontal lobes and really help optimize our attention abilities or speed of processing. These projections are susceptible to brain injury forces. This is why we sometimes need to augment them for these individuals. 

In terms of cholinergic augmentation this strategy is probably better selected as opposed to speed of processing or attention being the prominent complaints, we have problems with memory whether it be memory coding retrieval or both. Theoretically, arousal would also be a good target symptom for cholinergic augmentation but at this point really we are talking about augmenting memory problems and doing so with cholinergic augmentation strategies. 

There are a number of agents out there, prominently we are using things like donepezil or Aricept or rivastigmine which is now available in patch form. And generally well tolerating good ways to augment acetylcholine in the brain and really help these folks who have a memory component to their cognitive presentations. Again another cartoon illustration the widespread cholinergic nuclei and projections to parts of the brain that are just essential for memory function, executive function and things of that nature. 

To really sum up, we want to think about catecholinergic augmentation when the presentation has more salient features surrounding speed of processing attention. Then cholinergic augmentation when there is more salient component surrounding memory problems in those cases when we get at the memory with cholinergic augmentation we may also see some benefit in terms of attention and executive function as well. Again it is worth keeping in mind we can combine these strategies. Some folks will benefit from a combination of catecholaminergic and cholinergic augmentation getting at these different neurotransmitter systems. We should think about augmentation strategies for patients who are inadequately responsive to either approach alone. 

A few additional medical considerations. Patients with TBI are very susceptible to side effects from a number of medications among those anti-psychotic medications. If augmenting dopamine is sometimes the road to improving attention and speed of processing, potent dopamine blockade may actually make those sorts of problems worse. Being thoughtful in our choice of anti-psychotics and potentially trying to avoid those that are going to potently block dopamine systems and interfere with attention or speed of processing aspects of cognition. Seizure disorders are not infrequent following traumatic brain injury. Some of the antiepileptic drugs used for these individuals can complicate cognition, in particular things like phenytoin and carbamazepine sometimes it is worth the call to the neurologist to see if something like depakote which is more cognitively neutral might be a viable alternative for controlling seizures. At the same time have less implications for cognitive impairment. I have already touched on this, I want to emphasize really paying attention to benzodiazepines and other  Medicaid patients interfere with cognition whether it be benzos narcotic pain medications, anticholinergic medications. It is really essential that we clean up the pharmacology before we start deploying new agents so we are not working against ourselves in terms of neurotransmitter systems. That was a lot to cover in a brief period of time. We will pause for questions I guess here. 

### I do want to let everyone know about a new suicide risk management consultation program that we have available at the VISN 19 MIRECC now. The number is here and you can go to our website for more information about that program. I guess I can turn things back over. 

Moderator:Great thank you so much Hal. For our audience this is a great opportunity to submit questions to us. Take this opportunity we have a few minutes here to go through questions. We did get one here – if slides and audio will be made available for this lecture. Yes slides are available right now. We include a direct link in the reminder that was sent out to you this morning. Please go back into that email, scroll down a little bit and you will find that link in there. 

We are also recording today’s session and we will be sending the link to that recording out to you sometime within the next day or two, as soon as we get that posted. You will have access to all of that as soon as it is available. 

For those of you who do not know where to submit questions, please use the Q&A screen on the dashboard that came up on the right hand side of your screen. If that collapsed against the side of your monitor just click on that launch area to open that back up and please type your questions in there. we do have a few pending questions. I am just going to start from the top and work our way through. It could be for either Hal or Heather, I am not sure if you guys could just listen and we will see where the questions fall here. 

The first question – Heather I think this came in while you were talking. What does normalization of symptoms mean?

Heather Belanger:Okay I do not specifically remember how I used that phrase but I guess there are a couple of answers to that question. If we are talking in the research sense which is probably how I used it, normalization of symptoms would mean that in a research sense the mild TBI group is reporting symptoms at the same level and intensity as a control group, people who have not had a mild TBI but perhaps have had some type of other injury. That is the research sense. I think in the clinical sense it means someone for example has headaches perhaps but to what extent is that impacting their functioning in an adverse way. I think clinically it may have a slightly different meaning. 

Then I think the next question is also probably for me because I  mentioned Axis I disorders. I do not know a lot about DSM 5 I know it is not out yet and I have ordered it. what I was referring to there is the DSM for those who do not know is Diagnostic Manual to assist psychiatrists and psychologists with labeling behavior I supposed or diagnosing patients. It is organized according to axes. Axis I are clinical disorders so for example depression, PTSD, substance abuse disorder that kind of thing. I think on the slide I was suggesting that providers do an assessment and think in terms of those axes to organize their thinking. We have good treatments available for Axis I disorders in many cases so I think that was the point of the slide. There are other axes as well so medical or physical diseases and disorders on Axis III, Axis IV are things impacting the patient functioning like the environment to the extent to which they had social support for example. That is what I was referring to there. 

Moderator:Great, thank you. 

Dr. Hal Wortzel:I was going to add it looks like there was a question specifically about the DSM 5 which is the new version that is coming out in terms of the axes. The axes are going to be changed significantly for DS 5. My understanding is that Axis 1, II and III are actually going to be collapses to a single axes. Things will look a bit differently and ti is not clear from the previous that I have had or what is out there how TBI is going fall in terms of these axes. Presumably since they have collapsed this the reital all these things are going to start to fall on a single axis. 

Moderator:Great, thank you. the next question that we have here – does TMS have a role in the treatment of TBI?

Dr. Hal Wortzel:TMS folks who are familiar is transmagnetic stimulation. I think that is probably an area of active investigation. Theoretically if you have a focal lesion that you can reach with the magnet you can potentially stimulate or augment functioning in areas that are deficient. It is a nice idea but I think that we are lacking in a sufficient evidence based, just recommended as a treatment for traumatic brain injury in cognitive impairment at this point in time. 

Moderator:Great, thank you. the next question here – how do you distinguish between memory deficits due to antinational problems versus primary memory pathways deficits?

Heather Belanger:I guess there are a couple of ways you can think about that. certainly if someone were to have let us a full neuropsychological evaluation if they are having difficulties on attention measures per se that could be contributing to any memory deficits that are seen. There are sort of patterns that neuropsychologists look at to try to tease that kind of thing apart both in terms of looking at specific tests of attention but also performance within memory measure. Then I guess in terms of thinking about treatment Dr. Wortzel can speak to this as well, but I guess my question would be what difference does it make to some extent? It would depend on your therapeutic approach and if you are using some cognitive rehab, strategy and/or medication, I do not know Dr. Wortzel if you would like to add anything. 

Dr. Hal Wortzel:I think what you said makes sense to me. when I think about cognition I sort of think or parametal scheme with arousal and attention being at the base. If a person is not sufficiently awake and attentive the ability to assess higher cognitive domains like memory is going to be complicated. If you need to be sufficiently attending to in code or retrieve information subsequently. Prominent attention on parent will interfere with your ability to optimally assess memory. and in that setting you are going to do your best to treat the attentional impairment and given the limited number of strategies we have for treating these things, there is going to be overlap and hopefully you will get at both of them if they are there if that makes sense. 

Moderator:Okay, great, thank you. the next question we have here – are there studies that look at the effect of moderate to severe TBI on specific pre-existing mood or personality disorders such as intermittent explosive disorder or borderline personality disorder. 

Dr. Hal Wortzel:I am not familiar with studies looking at moderate to severe TBI and those disorders specifically. Certainly moderate and severe TBI particularly those involving frontal lobe injuries are well known to potentially increase impulsivity, effective instability and a lot of the difficulties with things like borderline personality disorder or intermittent explosive disorder already struggle with. You can make a bad situation worse for sure. 

Moderator:Okay, great, thank you. the next question – do you know how evidence for physical exercise compares to CBT in pharmacotherapy for cognitive symptoms especially aerobic and/or aerobic plus weight training with heart rate monitoring. 

Heather Belanger:I will start, I am sure you will have something to add Hal. There is not that I am aware of a literature specifically in a mild TBI population that I know of any way looking at exercise comparing it to CBT. There certainly is literature that exists showing that aerobic activity improves cognitive performance. I think that is an interesting question. I do not know of literature that is specific to TBI at this point, do you Hal?

Dr. Hal Wortzel:I am not real familiar with the TBI specific literature, but I think to your point exercise is a good thing and if it helps people’s mood or sleep or helps improve fatigue and their overall level of wellness then we would expect that their cognition would also probably look better so exercise is good. 

Moderator:Okay, great, thank you. the next question – are there any outcome findings to date form the view VA neurocognitive programs that exist for MTBI?

Heather Belanger: I am not sure what you are asking exactly so I will just talk. There are people currently doing trials within the VA and DoD looking at various cognitive therapies if you will. There are pilot data out certainly, I have some of those, with regard to reducing post concussive symptoms and using some of the pyschoeducational therapies that I mentioned in my talk. There is also a trial going on called SCORE which is based in San Antonio. One of the questions I proposed in my talk after the Tiersky, I described the Tiersky study where they did a pretty intensive CBT post-cognitive rehab therapy with mild TBI patients in found efficacy. I pose the question do we need that level of intensity. Actually the SCORE trial is attempting to answer that question by having a hierarchical degree of intensity and trying to answer that question. That trial is ongoing and I know there are other trials ongoing as well. Unfortunately these things take quite a bit of time to complete. 

Moderator:Okay, great, thank you. the next question – which type of professional is appropriate to deliver CRT involving compensatory strategies? Neuropsychologists, speech pathologists? Do you deliver CRT?

Heather Belanger:I think the answer to that question is yes. I think as with any endeavor one would not want to practice beyond ones purview. I think if you are trained in these techniques and have some confidence in your abilities to do so, a practical answer is it varies by VA. In some VA’s neuropsychologists do cognitive rehab and other VA’s it is the speech therapist. In other VA’s it is both I guess the collective is yes. 

Moderator:Okay thank you. we are at the top of the hour, Heather and Hal I am not sure if either of you are able to stay late to answer any questions. We do still have seven pending questions out here. If you do not have time to stay that is fine, we can figure out something to do with these questions, but I did want to respect your schedules to see if it was something you were able to do. 

Dr. Hal Wortzel:I can stay on. 

Heather Belanger:I can too. 

Moderator:Okay, sounds good, we will just push through. For our audience I know that many of you cannot stay late. We are recording this and we will get the link to the archive out to you as soon as it is available so we will capture the questions and responses out there if you are not able to stay. The next question we have here – what tool would be best utilized for team approach in the healing process of a TBI veteran? For example rancho scale?

Heather Belanger:Could you repeat that I am not sure I understand the question. 

Moderator:I can repeat it. what tool would be best utilized for team approach in the healing process of a TBI veteran? For example rancho scale.

Heather Belanger:In our acute TBI rehab program we use the rancho scale to communicate a patient’s level of function. I think it is more useful with a moderate to severe TBI population because of the grossness of the level of that particular scale. I do not think it would be useful with a mild TBI population because everybody is at the ceiling. Mild TBI patients tend to be high functioning and on that particular scale, the rancho scale they all would be the top two tiers so to speak. I think typically when we are talking about mild TBI we again talk about their degree of symptom intensity and the extent to which they are being bothered by their symptoms. Also can talk about cognitive  performance. I hope that answered your question. 

Moderator:If it does not the questioner can send in a clarification there. the next here looks like it is direct to Heather. With all the potential confounders such as environmental stimulation and so on and with no really clinically useful definition of MTBI, what is your position on performing cog rehab research studies in the mild population. Might it not be sufficient to take what we learn from specific domains in moderate/severe and simply use them in the complex mild patients. 

Heather Belanger:Yes I think that makes a lot of sense. You are right, if a technique works in any population in any patient group then it is likely to work in another population that has that same impairment. I think a larger question is to what intensity, of a system of care, I would think we would want to be efficient. If we want to be efficient we do not want to overly treating someone. Nor of course do we want to be under-treating someone. I think the research is useful because it can help us answer those questions as a system of care. I showed you an example of a study and I am wondering okay well is that level of intensity needed? I do not know. 

Moderator:Okay, thank you. the next question here – how do you explain patients with mild TBI who after two to three years still complain of an impaired attention, poor focus and concentration. 

Dr. Hal Wortzel:That is a difficult question and it very much depends on the individual. In my experience most of the time I am encountering an individual in the post-acute recovery period from a mild TBI who is still complaining of these things. There are other things that can be identified whether it be chronic pain, depression, anxiety, medication affects, something that PTSD that better accounts for those cognitive impairments then the affect of an isolated mild TBI. That is not to say, might there be outliers meaning folks who it takes them longer than the expected few months to recover. Or at the end of recovery have some relatively subtle deficits I think every brain is different and that may happen. The more dramatic presentation is that two years out from an isolated mild TBI and a person is presenting with profound functional impairments and they cannot work or do basic activities because of cognitive impairment, it really at that point should become apparent that we need to identify better explanations for that presentation. That is starting to get beyond the outlier’s status, that this does not make a lot of sense in the context of a single isolated mild TBI. 

Moderator:Great, thank you. the next here  - given so many veterans report multiple concussions, some with ten plus at what point do you start being more conservative in usually telling a person that chronic symptoms are likely not related to concussion as you would with a person presenting with only a few remote concussion. 

Heather Belanger:That is a great question. The truth is we do not know the answer. I can point you to some studies that suggest that two or three concussions have the same outcome as one. I can also show you other studies that contradict that. there is definitely some level at which people there is some sort of threshold effect at some point. We do not know where that is for any one individual. We do not even know in group studies where that is. I tell people the truth as I know it I guess. I say this is what we know about single concussion,  a lot of the stuff I presented in my talk. We know less about multiple consciousness, we really do not, we just do not have those studies. 

Moderator:Okay thank you. the next question we have here – how do you make sure that someone with symptoms of both MTBI and PTSD is not regarded as only have PTSD and no MTBI?

Heather Belanger:I would need discount anyone’s injury. I hope the spirit of my talk and Dr. Wortzel's as well was not misinterpreted. I think it is important to know the literature on mild TBI and what the long-term outcomes are. That is not to suggest that injury should be dismissed, that would not be the approach. I think  our collective point is that if somebody has PTSD for example we have evidence-based treatments to treat that disorder. I think it is important to get people that treatment. What tends to happen in some cases is people tend to overly focus perhaps on mild TBI because in some ways it seems our system of care is probably overly focused on TBI. There becomes this I am permanently disabled mentality that is counterproductive for the patient. It is not to dismiss that they have a concussion it is to let us help this person get better. I think that is the spirit of both of our talks. 

Dr. Hal Wortzel:I would add it is not just our system of care. I think we are more broadly facing a mass media environment culture where everybody may be a little bit too sensitized to mild TBI. I think to the point that was just made what I see all too frequently is not just the mild TBI getting overlooked, but mild TBI becoming the point of focus such that the PTSD or the substance abuser, the depression gets overlooked and people get bogged down in a sense of permanent disability while evidence based treatments are not being deployed. 

Moderator:The last question I have here – what recommendation would you make for use of pharmacological agents and exercise for patients with cognitive attention deficits when poor cognitive attention should slow his rehabilitation efforts?

Dr. Hal Wortzel;It depends on a little bit where you are talking about in the rehabilitation effort. A lot of folks early on if they are having problems with fatigue and maybe a little bit of depression and low energy and cognitive deficits and that is interfering with physical as well as cognitive rehabilitation efforts the psycho-stimulants like Ritalin can be quite beneficial and get at a number of things including energy, mood and cognition and can be very safely deployed in those settings and are oftentimes a good first line choice. 

Moderator:Great, thank you. the next question I have here – once a veteran leaves the poly-trauma area, CLC units are receiving TBI veterans exhibiting numerous symptoms of anxiety, agitation, explosive behavior, etcetera, rancho level five or six level. Would a CLC unit be an appropriate area for healing?

Heather Belanger:I do not know that I can answer that. Dr. Wortzel?

Dr. Hal Wortzel:I am not sure I know that one myself. 

Moderator:that is okay we cannot expect you to know everything. I will move on to the next question I have here – what recommendations or resources do you suggest for spouses who are key in the home rehabilitation process and who wish to participate in the cognitive rehabilitation of the patient once they transition to home?

Heather Belanger:That is a great question. Hopefully if they have had acute rehab I know within the VA the focus is on the family being part of the rehab team. Here in Tampa we typically meet with a family frequently through acute rehab and if they are sent home they are sent home with instructions and help for the family to continue with the rehab. In terms of resources there are several websites unfortunately I am not an expert on all of the resources that are out there, but I do know they are there. The DVBIC, the Defense and Veteran’s Brain Injury Center is one really good website that you could Google and there are family resources on that page. There are other pages as well, they are not coming to me at the moment, but there are online resources for families as well. 

Dr. Hal Wortzel:More generally for TBI veteran or not, most states have, in Colorado there is the Brain Injury Association, BIAC Brain Injury, I cannot remember what the acronym stands for, but that can direct you to local resources, brain injury support groups. Then I would add also education for spouses or families as well. The same sort of understanding or misunderstanding that can perpetuate symptoms among the veterans can also be a problem for spouses or families, so offering that same education. 

Moderator:Great thank you. we received a response from one of our attendees on the CLC question, Mya O’Neil sent in the response  - the CLC might be an appropriate venue for healing if the treatments are evidence-based treatments for specific symptoms or comorbidities. For example depression, PTSD, headaches, sleep difficulties, pain management perhaps rather than attempting to treat a global MTBI diagnosis. Mya thank you for sending that in. we have one last question here and then we can wrap things up. The question is – has the VA utilized hyperbaric chambers in the TBI healing process?

Dr. DePalma:I can respond to that because, this is Dr. DePalma, I reviewed it. no the VA has not done that but in conjunction with the DoD, Dr. Cifu has published a study with 45 people in each arm that showed no difference between hyperbaric and sham hyperbaric therapy. The caveat being that both groups who are treated together improve significantly over a two-month period. Probably that is one of the best negative studies. 

Moderator:Thank you very much for sharing that. That does wrap up our questions for today. I want to take this opportunity to thank our presenters for putting the time into prepare and present for today’s presentation. We very much appreciate the time that you put into this. for our audience thank you very much for joining us and especially those of you who have stayed for this extended session, we really do appreciate you sticking around with us. The next session in this TBI/PTS mini-series is scheduled for this Thursday, April 18th at 2:00 PM eastern and that session is PTSD Complimentary Health Approaches. You should have all received registration information in your email if not you can register on the HSR&D cyber seminar catalog. 

As you leave today’s session you will be prompted with a feedback survey. We would appreciate if you would take a few moments to fill that out. We really do read through all of your feedback and take that into consideration for our current and upcoming sessions. I want to thank everyone for joining us for today’s timely topics of interest cyber seminar and we hope to see you at a future session. Thank you. 

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