Magnets Wake Up Coma Patients -- In Depth Doctor's Interview
Dr. Theresa Pape, a clinical neuroscientist, at the U.S. Dept. of Veteran Affairs, discusses how transcranial magnetic stimulation (TMS) is being used to help patients with severe traumatic brain injuries (TBI) their cognitive abilities back.
Can you discuss the current study that you are working on to give patients with severe traumatic brain injuries their mental as well as physical functions back?
Dr. Theresa Pape: This particular study is looking at transcranial magnetic stimulation as a neuro-therapeutic for our veterans, warriors and civilians who have severe traumatic brain injuries. Those are the people that end up in a coma, a vegetative state or a minimally conscious state. We have no treatments for this population. We can save their lives, but most people who endure severe traumatic brain injuries will live, and we have no capacity to give them function. A lot of patients will regain consciousness (approximately two-thirds of people who have severe TBI will regain consciousness, however, a majority of them will go on to live with severe cognitive and physical impairments. We have no treatments to help restore function to that population. This particular study is a trial where we are looking at transcranial magnetic stimulation as a way to modulate neurological activity in hope of facilitating some neural repair and hopefully regain function over time.
Do you have any statistics of people who return from the war with severe TBI?
Dr. Theresa Pape: The Department of Defense’s number are as of fourth quarter 2010, there is a little over 25,000 warriors returning with severe traumatic brain injury, and that is about one percent of those traumatic brain injuries that are returning from the war.
Are these statistics in respect to every year?
Dr. Theresa Pape: They are for ‘in total’ thus far. So it is three hundred-something-thousand warriors that are returning with some kind of traumatic brain injury, and about one percent of those are severe. That is approximately 2,000 - 2,200 individuals or so. In the U.S. population this is about the same. About one percent of all of the traumatic brain injuries in respect to civilians is severe. Right now, the statistics in the general population are approximately 79 of every 100,000 individuals will endure traumatic brain injury, and roughly one percent of those will be severe. So it is similar in the sense that the proportions are the same.
Was Josh the first person involved in this study?
Dr. Theresa Pape: Yes.
How many individuals have you had since?
Dr. Theresa Pape: We have studies two people. It’s a very labor-intensive study as well as an expensive one to boot. Thus far, we have studied two and we plan to study around six in total for this portion of the study.
If I am not mistaken, the study commenced in 2008. How much longer are you planning for this research to continue?
Dr. Theresa Pape: I would say probably another three years. It really depends on myriad factors. They ultimately get admitted to the hospital. So Northwestern has a clinical research unit, and we will admit all of the patients to that research unit because they can get medical care there 24/7. Furthermore, if it is a veteran we will admit them to the Hines V.A. and as of this moment our next participant will be a veteran here at the Hines V.A., which we are currently working towards as of now.
Was the second subject a civilian?
Dr. Theresa Pape: Yes. The first two subjects were civilians and our third subject will be a veteran most likely. It just happened to work out that way.
What have your findings been thus far?
Dr. Theresa Pape: So far there have not been any adverse events that have been related to be provision of the TMS. The biggest concern we have is evoking a seizure and of course we don’t want to do that. Right now, just staying away from adverse events has been our utmost goal. So far so good. Both patients have yet to endure adverse events. As far as efficacy or recovery of function, both patients have made gains. With Josh for example, he progressed from not responding at all (I would ring a bell or call his name aloud, and his behavioral responses did not indicate that he was even aware of what I was calling out; if I touched his arm or stood in front of him for instance there was no response from him that I had done anything) to inconsistently following commands, occasionally vocalizing words, and began making considerable progress after the fifteenth TMS session.
So prior to your work with Josh, was he considered to be in a vegetative state?
Dr. Theresa Pape: Yes.
So Josh underwent a transformation from practically being in a vegetative state to being somewhat responsive?
Dr. Theresa Pape: Yes.
What is the condition called that Josh is currently in?
Dr. Theresa Pape: He is in something called a minimally conscious state.
What does that mean exactly?
Dr. Theresa Pape: A coma means that a person is completely unresponsive. They are not awake and they are not responsive. Someone in a vegetative state is awake but not aware. Someone in a minimally conscious state is awake and minimally aware. They may follow command, however, you cannot depend on them to follow it every time. It will be inconsistent. They are minimally aware of their external as well as internal environment.
Through this therapy though, you were able to move him up a level and in due course allow him to regain some of his cognitive abilities.
Dr. Theresa Pape: His prognosis for recovery was very poor in general. We can’t determine cause and effect until we perform a randomized clinical trial, however, he has made improvements from being in a vegetative state to the minimally conscious state. In general, his mother tells me that he is easier to care for and that he is occasionally interacting with his environment. You can’t count on him to do that, but he does do this occasionally. The mom was pleased with the progress made as well. We did try to give him an extra ten sessions because ethically we did feel like he made substantial progress within the last fifteen session. We gave him the additional ten sessions, however, that did not give him any further gains.
Would you ever consider going back and giving Josh further therapy sessions?
Dr. Theresa Pape: I think at some point we will once we progress in the research stages.
At this point, what stage would you say that you are in?
Dr. Theresa Pape: We are in the safety study stage. When we are ready we will go into an efficacy trial depending on the data as well as various other factors.
Is it considered a clinical trial?
Dr. Theresa Pape: Yes. It is labeled as a safety clinical trial. It is not a randomized clinical trial although I have some control groups that I will be comparing the results to specifically for efficacy purposes. The next step will be to go into a randomized clinical trial. We would then basically compare TMS alone to something. What will that compare to? That is still something I am in the process of conceptualizing. I have some ideas. I would like to open it up to individuals with new injuries as well as older ones for the reason that we simply don’t have anything for either of them. This really depends on what I see. Our next subject will be someone who is many years out and still in a vegetative state (perhaps five to six years after the injury occurred). We would like to see the effects of what these treatments can do for someone who has an older injury – they have an older brain, there is more scarring and ultimately less chance for repair. Once we see whether we are having the same effect in someone with an older injury, we can then open the clinical trial to people with older injuries down the road.
As it stands now, people with older injuries have no options for treatment?
Dr. Theresa Pape: There is hope in the sense that they lived and survived, but what can we give them for function. Right now there is nothing out there that can be administered to these patients to help in facilitating their functions. That is what this study is about. Can we help them recover function?
Some doctors who look at this study might say that it is just spontaneous recovery, right?
Dr. Theresa Pape: Yes. These are the answers that you will have once you get to the randomized clinical trial. What I am doing right now for the safety trial is establishing their prognosis at baseline. We are doing some basic tests. These particular tests will show that if they don’t have any response, than typically the evidence shows that this was a very poor prognosis. Also, we can compute the probability for recovery using some neuro-recovery data. Each of my patients so far have had a 22 percent or 40 percent chance of recovery of any function or consciousness for that matter. With the data combined, we can tell that they have had a very poor prognosis. We cannot say with certainty that TMS caused their recovery. We do know that they had a poor prognosis, and until we have undergone a randomized trial we cannot justly say that it was a cause and effect.
How do you feel about this?
Dr. Theresa Pape: I feel that it merits further investigation. It holds promise at this point and it certainly warrants further investigation.
What was your reaction when you saw the vast improvements in these patient’s symptoms?
Dr. Theresa Pape: My co-P.I. Josh who is also a neurosurgeon just kind of looked at each other like, “Whoa!” Our mouths kind of hung open and we both thought, “Whoa!” Then we said, “Let’s see if we can repeat this.” My partner’s name happens to be Josh, and my first patient’s name is Josh as well so I will try my best to clarify who I am referring to. So, after Dr. Josh finished his study participation, we both knew that we needed to see if we could repeat this with a different patient. When the second individual repeated, we were kind of just like, “Holy cow!” our mouths hung open and we both had the wow factor. There has been maybe three or four instances in my career where I have had the wow factor. After both patients showed signs of improvement I knew we were onto something. So it certainly merits further investigation.
Is this study married to voice recording study that you are currently working on as well?
Dr. Theresa Pape: Potentially. When I go forward to a clinical trial with the TMS, there is a possibility that it might go TMS plus familiar voice. So when I compare TMS alone, I am going to potentially piggyback TMS with something. By piggyback, I mean in the traditional sense that with this population we need a big wow (that might be the TMS), but we need something to carry the TMS forward and I don’t know what it is going to be at this moment. It might be TMS plus the familiar voice intervention. On the other hand, it could possibly be TMS plus a medication. I am looking into all of the possibilities that are available to me right now.
Have you implemented any of the familiar voice techniques with Josh?
Dr. Theresa Pape: I used it in the fMRI protocol. For example, when we do functioning imaging with this population, we want to see if there are areas of his brain that are reacting in response to somebody calling his name out loud – someone he knows versus someone he doesn’t know. We want to see whether his brain is even responding at all, and sometimes it is easiest to do this in the auditory modality for this population, thus we did use familiar/nonfamiliar voices in our imaging tests, but we did not use it as an intervention.
How does it work as an intervention?
Dr. Theresa Pape: The familiar voice study is where the patients basically listen to loved ones telling stories that they can recall from their childhood, or at least one year prior to their injuries. Their loved ones are describing an event that they all participated in, and most importantly this someone that is telling the account is someone that is known to the patient. So they will listen to these stories forty minutes a day for six weeks and they will listen in ten-minute increments. So essentially four times a day for ten minutes they will have headphones on and listen to these stories. It is a very passive therapy where the patient doesn’t have to do anything other than listen. All they have to do is tolerate the headphones. Some patients will listen to the real stories where as others will be listening to silence. What we will do then is after six weeks, we will cross them over and then they will get the real treatment or the alternate one, so ethically everyone gets the opportunity to get the real treatment. The theory behind that intervention is that we are taking advantage of the fact that we all have encoded certain events and experiences in our brain (episodic memory). We are trying to take advantage of the fact that we have these sort of episodes or events encoded and hardwired into our brains in long-term memory. For example, my husband, I recognized his tactic language structure so I know how he presents himself. I also recognize the pitch and tone of his voice. Those are also in my memory. We are trying to take advantage of the fact that these are hardwired into our memories, and we are hoping that it facilitates either faster recovery of consciousness or some kind of neurobehavioral gain. If not consciousness than some other form of improvement. So we will see.
Is that study ongoing?
Dr. Theresa Pape: Yes. That study is still going on. It is a double blind randomized clinical trial. Way back when I was doing a pilot study, I didn’t have to do a safety study for that trial in particular, however, I did need to do some efficacy work on that and demonstrate that it does merit some promise for a full investigation. So now we are at the double blind randomized clinical trial stage with that. We will enroll thirty to forty-five people. It is not like these studies with hundreds of people that you typically see, with this population we need to find a way to study smaller sample sizes. The Department of Veteran Affairs funds that study as well.
How does knowing that you are impacting people’s lives make you feel?
Dr. Theresa Pape: There are two or three moments in every scientist’s life where you get the wow. To know that I am having an impact on society . . . well, that is why I do this. This is a very unrecognized population, and nobody really knows where they even go after their injury. A lot of them are in nursing homes, and often time families lose touch with them. In other cases, the family will make arrangements to care for them 24/7. If we can save their life . . . then we have to give them a life. That’s my opinion, and that is what motivates me to do what I do. It’s amazing to see these patients sit up and say, “Hey Jennifer.” Before that, they were sitting in a vegetative state for eight or nine months. That is pretty cool.
Can you discuss some of the things that Josh is now able to do?
Dr. Theresa Pape: He is able to vocalize. One time he told us to “Get out,” – not the most polite of words. Another time he said “Help me.” Another time he said, “Mom.” His speech was really slurred but yet it was understandable. He would say mostly single words whenever he talked, and typically it was in regards to needing something: “Mom,” “Help me,” “Pain.” He then was able to follow rudimentary one-step commands such as ‘lift your head,’ or ‘move your arm.’ If they were trying to help him get dressed, they would ask him to move his arm and he would do so. A lot of the one-step commands that were given to Josh related predominantly to a lot of needs as well as how to help him live as comfortably as he can.
Were some of these same results apparent when working with the second subject?
Dr. Theresa Pape: The difference between his verbalizations and Josh’s is that the second individual would actually initiate the conversation. He would say, “Hey Jennifer,” often times out of the blue. Other times, he would ask where somebody is. He was exceptionally aware of his environment more so than that of Josh. The other things that he would do is follow one-step commands. For example, if they were helping him out of bed they would say, “Okay, now move your leg,” and he would move his leg. He could never have lifted up his leg before study participations.
Are you going to be able to release his information soon?
Dr. Theresa Pape: I haven’t decided exactly what I am going to do. I might wait for the next subject to finish up, after which I will publish a set of case reports.
When are you expecting to have that done?
Dr. Theresa Pape: I would say towards the end of the calendar year – then there’s peer review and that typically takes awhile. So I will submit several case reports at the end of the calendar year, and around springtime perhaps is when the case reports will emerge from the scientific journals. So, at this point in time I have not released any of his data, and want to see how it correlates with that of an individual who has had severe trauma for an extensive period of time, after which I will publish imaging data. I haven’t published any imaging data on anyone thus far.
How does traumatic brain injuries compare in regards to the physiology of the disease to that of Parkinson’s disease?
Dr. Theresa Pape: The traumatic brain injury population would in due course be the population that is picked last for neurological populations when it comes to examining for treatments for the reason that it is so much more complicated, and we know so little about the actually physiology of brain injury compared to what we know about strokes and the spinal cord. We know a lot more about Parkinson’s disease as well as other diseases that we don’t know about traumatic brain injury.
How does that compare to what you knew ten years ago?
Dr. Theresa Pape: We know a lot more than we knew ten years ago, but we still don’t know much about the population in particular.
Can you briefly discuss what the treatment entails exactly?
Dr. Theresa Pape: These are the TMS generators. When I provide the TMS treatment, what I will do is turn the generators on, and each of the generators will put out a pulse. Think of it like an MRI. An MRI will put out roughly 1.5 tesla in strength. So each one of these generators will put out about one tesla in strength. It puts out an electrical current, and once it goes through the coil (it circles around the coil), and in doing that a magnetic field is created. When the magnetic field goes through the coil – the greatest strength is here at the intersection of the circles – it will transcend through my scalp and down into the burning tissue just beneath the coil. Essentially, what we are doing is creating a magnetic field in the brain, which then if the nerve cell or neuron is excitable, then we will create a potential neuron in that current. We hope then that the neuron will talk to one neuron, and that neuron will ultimately talk to another neuron, which will then talk to another neuron each time we do TMS. The theory is that when we do TMS for the first time, we want to activate one nerve cell – by activate I mean evoke an actual potential so that it then reaches out to another neuron in hopes of connecting with yet another neuron. The reason that we do it at the right prefrontal dorsal lateral cortex (right front area of the brain here) is because it is largely connected to the attention network. We don’t know whether attention is related to consciousness or awareness but surely (regardless of if we understand it or not) they are related in some way of form. The attention network is driven largely from somewhere up here. Additionally, there are numerous rich connections between the prefrontal area and the brain stem. The prefrontal area contains a lot of neurons that keep us aroused, aware and alert. If we can get these neurons up here to activate, and eventually descend down to the brain stem, and then ascend back up to the cortex, we should be able to facilitate the repair of the brain. That is the theory. Since there are a lot of rich connections [prior to injury]with axons from the prefrontal to the brain stem that descends down as well as ascend back up, we are trying to tap into those aforementioned connection. They may be there. They may not be there. We may be rerouting the connections. We don’t know exactly how that is happening. We do know that we are seeing changes in neuroactivation in response to TMS. Our imaging data shows that in addition to our evoked potential data which is published. That is basically the theory. We are trying to get nerve cells to activate, at which point it will then proceed to communicate with another and so on.
What is the most fascinating aspect of this research?
Dr. Theresa Pape: I would have to say the families. The families are phenomenal. They have gone through so much, yet they still continue to participate. Foremost, the family support. One year after injury, often time families will visit at the acute age where you will then see the families gradually die out. These particular families that I am working with stay with the patient. That is very cool to me. The other neat thing is when I see the patients wake up.
Is there anything else that you would like to add in regards to the ongoing research to help give these people back their quality of life? We’ve already given them their lives . . . but is that enough?
Dr. Theresa Pape: No. The reason that I agreed to do the interview is that often time the news is filled with incessant stories of how people make miraculous recoveries from an injury. The medical technology allowed them to survive and live, but then society forgets about them and forgets that we also need to give them functions. We can’t just let them live. We also need to give them a life is we are going to save them. Most importantly, we need to give them a better quality of life than what they have now. If we are going to invest in the technology to help these people survive, then we also need to invest in the research to give them function.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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If you would like more information, please contact:
Cheryl Odle, Project Manager for Dr. Theresa Pape
U.S. Department of Veteran Affairs
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