Researchers at The Ohio State University’s Wexner Medical Center have demonstrated the safety and effectiveness of using deep-brain stimulation (DBS) to improve the quality of life and functioning of people with severe disability from traumatic brain injury (TBI). Dr. Ali Rezai, lead author of the study, spoke with Medical Design & Outsourcing to discuss the patient population, the results of his research, and his plans for moving forward.
Medical Design & Outsourcing: Who is affected by traumatic brain injury?
Dr. Ali Rezai: Traumatic brain injury affects a large population. Basically, every 15 seconds, somebody in the U.S. suffers from brain injury from an accident, a fall, or other cause. The vast majority of these injuries are concussion or slightly worse. But a significant number have severe traumatic brain injury. About 80,000 U.S. patients each year become disabled because of traumatic brain injury, so it’s a lot of patients. And, tragically, usually they are younger patients. They have to live the rest of their lives unable to work or care for themselves. They are significantly impaired and dependent on their families and loved ones.
TBI severity and effect depends on what part of the brain is damaged. The frontal lobe gets damaged more frequently because it is the biggest part of the brain and because of where it sits in the skull cavity. This can cause impairments in attention and alertness. Communication skills can suffer, as well as executive functions including cognition, memory, planning, decision-making, judgment and behavior. These significant cognitive and behavioral impairments can result in long-term harm. Patients experience ongoing anxieties, fears, impulsivity, addiction, etc.
The brain itself recovers within one to two years following injury, but it does not necessarily heal in the same way, so these patients may never regain abilities. There really is no medication for TBI, and the medical community largely abandons these patients once the physical healing process is complete. We can treat the anxiety or depression, but that is only treating the symptoms. And there is still a large portion of patients left with severe disability, for whom there is no treatment. They are awake and alert, but they have major problems managing stress control and temper, holding a job, managing money, decision-making, finding work or participating in community. It’s not trivial, these behavioral and cognitive manifestations. Externally these patients can look fine, but internally, their brain is significantly impaired. The rest of their lives are damaged.
MDO: How can your research help these people?
Rezai: We wanted to see if using DBS could help these patients. We studied those who have had two years since their injuries, so the chance of natural spontaneous recovery is minimized.
DBS is FDA-approved for tremor and dystonia, Parkinson’s disease and obsessive-compulsive disorder. We were involved in the obsessive-compulsive disorder studies about 17 years ago at Cleveland Clinic. Those studies helped us identify the nucleus accumbens as an area we believe is involved with behavioral self-regulation. We want to explore this target in the brain to improve behavioral self-regulation and function in these very disabled patients. This target has a safety track record that goes back to the year 2000, in terms of implanting deep-brain system electrodes. It is a few millimeters away from the standard location we go to for Parkinson’s, for example. The equipment is the same. The technology is the same.
MDO: Tell me about the study and its results.
Rezai: This was not a random controlled trial, so I have to be careful – that is the next step. But here is what we did:
We found four patients within our brain injury database that met the criteria of significant dysfunction due to severe traumatic brain injury. They ranged in ages from 30 to 46 years, and all of them had been “recovered” for several years. The most recent injury occurred 6 years ago, and one patient was injured 21 years ago. They each required continuous care. The disabilities in these patients included severe anxiety, low frustration tolerance and depression, with episodes requiring hospitalization. There were problems with impulsivity, irritability, anger control and poor judgment, as well. One patient was very disinhibited and made inappropriate sexual comments, so the family had to keep him under very close guard.
We used the Mayo-Portland adaptability inventory (MAPI) to measure outcomes for FDA. MAPI is an accepted scale to determine abilities and is used in rehab communities. In addition, we looked at functional improvement methods such as eating, grooming, bathing, dressing, bladder management, bed-to-chair transfer, as well as comprehensive expression in social interactions, such as problem solving, memory, and following tasks. This was a very detailed study involving a lot of team members over a 3-year period.
What we found was that three of the four patients show significant improvement in disability scales, resulting in statistically significant improvement. All four also have composite functional improvements in cognitive and motor skills. This was not a random controlled trial, so I have to be careful – that is the next step. Some of the more interesting observations we saw were decreased fatigue and an improved ability to cope and respond to environment. We saw a reduction in anxiety, [increased] participation in the community, and being able to interact with friends and family. The patients were able to do volunteer work, jobs, and engage in new learning. We believe it was effective in improving overall behavior and cognitive function.
As I mentioned before, one of the patients for example had a very severe irritability and impulsivity that made inappropriate comments. He was able to now go out and interact with families and outside, whereas before they could not take him outside. When we asked him why it was different now, he said, “I still get the urge to say those things, but I know it’s not right, so I control it.” Which is what we all do.
In these four patients, we pleasantly observed that they had progressive and significant improvements in their outcomes in standardized scales all function over time. We think that this part of the brain may be a target for dealing with behavioral control. The same target has a link to obsessive-compulsive disorder, and is also being studied for addiction, alcoholism and obesity. These are investigational studies, but we think that this part of the brain may play an important role in behavior, cognitive function and self-regulation.
MDO: How does the technology work?
Rezai: We used open-label DBS devices, like those typically used for Parkinson’s Disease. It sends that signal. We are working on detection of signals; obviously the future of these technologies is closed-loop, or sensing and feedback. Our study was just straight stimulation.
Programming the devices and making surgical adjustment is very complicated for this procedure. It is different for Parkinson’s patients, because as you are adjusting, you can physically see a tremor stop. Movement or tremor is far easier to measure than behavior and anxiety. Here, you don’t know where you stand. You adjust, and see some changes. Then you wait to hear feedback from the patient and family, and adjust further. We need a better mechanism and better technology to adjust these changes for the target.
MDO: You mentioned that a lot of people were involved in this study. What roles did they play?
Rezai: These patients were followed for four years with a psychologist, trauma rehabilitation doctors, nursing staff, and social workers. As you can imagine, these patients are not routinely coming to the hospital. They’re at home, being managed by social workers, nurses, or aides, as well as family. It required a very large team to observe and care for these brain injury patients routinely, chronically. And remember, these patients have had brain trauma for years. There are tens of thousands of data points on each patient. It was a very exhaustive study that we conducted. We had funding from donors who want to help patients with traumatic brain injury, as well as the Ohio State University Medical Center. But because of the scope of the study, funding was an issue. That’s why we’re looking for funding and grants for the next steps.
MDO: What are those?
Rezai: Our team, and again this is a team of specialists, this is a team of neurosurgeons, neurologists and psychologists. It’s a very large team. Now, through this study and other studies, we’ve shown that there is safety in this target. We’ve shown safety in an open-label fashion, we’ve shown prospective improvement. The next step is for us to pursue a randomized, controlled, deep-brain stimulation to remove any placebo effect. That’s what we’re working on right now: A randomized, sham-controlled trial to determine whether this is definitively helping these patients, where some have the DBS turned on and some don’t.
I think it’s important not to forget these individuals. These patients are forgotten in many ways, because there is no cure for them. These people are profoundly disabled and they are very young. They have a huge future and life ahead of them that is taken away. We need to explore ways to help these individuals. We are optimistic about DBS but it needs to be explored more.