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Editorials |
Department of Neuroscience, University of Florida, Brain Research Rehabilitation Center, Malcom Randall VA Hospital, Gainesville, Fla
Last summer I was fortunate enough to be invited to the III STEP Conference (Linking Movement Science and Intervention) in Salt Lake City, Utah. The meeting included an initial plenary session on the role of brain plasticity in rehabilitation. A handful of basic scientists— including Randy Nudo, PhD, Tim Schallert, PhD, Michael Merzenich, PhD, Larry Goldstein, MD, and me—were invited to give lectures on our research. The goal was to inform clinicians of our work examining plasticity during recovery from brain damage and explain how these studies might be relevant to clinical practice. The meeting began, at least for me, as an opportunity to educate clinicians on the process and merits of basic rehabilitation science. Within a few days, however, I realized that I was the one getting the education.
Historical context is needed in order to understand why having basic scientists and clinical scientists at the same meeting is at all interesting. There are few research areas with more disparate players than the study of rehabilitation after brain damage. Asking clinicians and basic scientists to discuss research is like asking Monet and da Vinci to paint together. Clinicians use very broad strokes with a single image in mind (get the patient better), whereas basic scientists use very fine strokes to detail many images within a single painting (determine the molecular, anatomical, and neurophysiological events that support recovery). We also speak completely different languages despite using the same words. Ask a basic scientist and a clinical scientist what "recovery" or "intensity" means, and you will get very different answers. Clinical scientists are primarily concerned with determining the critical behavioral signals that best drive functional recovery, whereas basic scientists are primarily concerned with determining the critical neurobiological signals that best drive functional recovery. We are housed in different buildings and are members of different university or hospital departments. We attend different scientific meetings and publish in different journals. Because of these differences in the tools we use, the questions we ask, and the company we keep, we are isolated from one another both institutionally and scientifically. On the rare occasions when we do interact, it’s a little like being on a first date. We’re not really sure what to make of one another. We discuss our work and nod politely but really have no idea what the other is talking about.
Despite these aforementioned barriers, I spent the week listening to lectures on clinical research and interacting with practitioners. I quickly realized how little I knew about the practice of rehabilitation and the process of clinical research. By the end of the week, my view on the process of rehabilitation research had changed, and I began to understand what our respective roles in the process should be. This editorial is a description of the main points I took home from the III STEP Conference and is an attempt to emphasize why such interactions are critical for the translation of basic science into clinical science and ultimately practice. It is possible that many of these points will be obvious to clinicians—which would be a testament to how little we basic scientists know about clinical research and the process of delivering rehabilitation services! Furthermore, it would reinforce the importance of meetings like III STEP for advancing the field of rehabilitation science.
1. The importance of patient history and comorbidity
In many of the III STEP presentations, the clinicians spent much of their time describing the patient’s personality, medical history, vocation, and psychological state. Those in the audience would nod in agreement as the speaker described how the patient was often depressed and difficult to motivate or had other medical conditions that impeded therapy. It became clear to me that these factors had as much to do with the patient’s progress as the therapy itself. They all directly influenced the patient’s willingness or even ability to participate both in the clinic and at home. This also explained why there was no standard recipe for rehabilitation for these patients. Each patient was unique with respect to impairments, psychological state, and physical condition. As a basic scientist using a rodent model of stroke, this was something I had never considered, let alone investigated.
2. The importance of the therapist-patient relationship
Given point #1, the case presentations also made it clear to me that the ability of the therapist to encourage, reward, and motivate the patient was a huge factor in determining how well the patient did. Establishing rapport was critical to fully engaging the patient in rehabilitation, and it struck me how much the physical therapists had to consider the patient’s emotional state. In addition, there was a wide range in the amount of hands-on assistance that any given therapist provided the patient. Some guided the movements continuously, whereas others provided no assistance at all. The optimal amount of guidance also was the subject of much debate among the therapists.
3. There is a need for standardization in clinical research
As I listened to the numerous presentations on functional outcome measures, I had difficulty comparing the efficacy of different interventions across the various experiments. This was primarily due to the fact that impairment and subsequent improvement in each study were measured in a number of different ways. Researchers used the Wolf Motor Test, Fugl-Meyer Assessment Scale, Jebsen-Taylor Hand Test, Ashworth Scale, Tinetti Performance-Oriented Mobility Assessment, Berg Balance Scale, Get "Up & Go" Test, visual analog scale, or the Barthel Index of Activities of Daily Living, just to name a few. When I asked about this wide spectrum of tests, I was surprised to learn that there is no standard battery of tests to assess impairment and functional outcomes. Without such standardization, it is difficult to directly compare and contrast the efficacy of the different therapies used across studies. This also makes it very difficult for a basic scientist to develop animal models that can be effectively translated into clinical experiments.
4. A critical mass of recovery is needed in order for improvement to endure
A number of presentations showed how several weeks of intense training (several hours a day) could produce significant motor improvements in some patients. More important, when these patients returned 6 months or as much as 1 year later, they were even better. The reason: They had restored enough use in the impaired limb that, when they went home, it was to their benefit to continue using the limb. In other words, they had reached a level of improvement that encouraged them to "self-rehabilitate" at home. If we can understand how to both progress patients to that level and recognize when they have reached it, many patients could show profound levels of enduring improvement. It also occurred to me that identifying surrogate neurophysiological markers, such as changes in cortical excitability, might help determine whether a patient has reached the required level of improvement. This is clearly an area that deserves more attention.
5. Therapeutic needs are incompatible with Medicare and other health care policies
My excitement at the prospect of point #4 was quickly quashed when I was told that most therapists see individual patients for only 1 hour per day due to the limitations in health care benefits. Medicare simply does not cover the high cost of one-to-one therapy for several hours a day. I imagined my pharmacist telling me, "We have this great drug to cure your flu, but your health care only allows for 1/10th of the required dose. See you next week." I cannot pretend to suggest how this needs to be reconciled. Gathering evidence to prove point #4 might help justify changes in the system to allow patients the opportunity for such treatment.
6. Our animal models are inadequate
It is easy for me to criticize clinical research as I sit in my highly controlled laboratory surrounded by genetically identical animals with discrete lesions to the same brain area. After listening to the III STEP presentations, watching patient videos, and talking with therapists, I realized the inadequacy of our animal models.
Basic science studies of rehabilitation typically involve producing discrete brain damage in a rodent or monkey, placing the animal into a training apparatus, "asking" it to perform a task, and carefully monitoring every detail of its behavior. The first problem is that our rehabilitation is very "hands off" by comparison to what happens in the clinic. To be fair, the ability of the experimenter to motivate the animal and reduce stress levels during training is an important factor. However, we do not systematically examine the "experimenter-animal" relationship and have no good way of replicating the clinical environment. Second, our animals are very similar to each other, often coming from the same litter or breeding colony and being housed in identical cages. There is very little variation in the medical history or psychological state of our animals. This is a good thing, as it allows us to more clearly identify the efficacy of our manipulations. But variation is something that we can study in the laboratory by manipulating the experience of the animal prior to inducing damage and applying treatment. A few laboratories are now attempting to do this, but this is not something that can be easily addressed in our experiments.
Third, I was struck by the severity of impairment of many patients entering rehabilitation. Therapists spend much of their time initially trying to get the patient to sit in a chair and initiate any movement. Although the sorts of brain trauma we induce in our animal models produce movement impairments, in most cases the animals maintain their capacity to produce movement. If they didn’t, they wouldn’t attempt our motor rehabilitation regimes. We therefore spend a lot of time and effort using fine kinematic analysis to define the often subtle impairments and concomitant improvements. Again, in our defense, if our manipulations fail to improve the condition of animals with mild impairments, they are unlikely to help animals with severe impairments. But we are in need of models where animals have more profound, chronic movement impairments to challenge putative therapies.
7. The role of basic scientists is to provide guiding principles and not specific answers
This was the most important point I took away from the meeting. As a basic scientist studying rehabilitation after stroke, I am often asked very specific questions about how rehabilitation should be done in the clinic. Frankly, it is flattering to have physical therapists tell you that they read your paper and want to know how they should use the results to change what they do in the clinic. The truth, however, is that we have very little to tell you, at least right now, and we should be careful not to overstep our bounds. There is a long history of interventions that were successful in the laboratory but failed in clinical trials.
As I realized at the III STEP Conference, basic science can provide fundamental principles that can be used to guide clinical research and ultimately practice. For example, the debate about "how much handson assistance a therapist should provide" can be truly answered only in clinical experiments. Our basic science experiments can point out the importance of factors such as timing, intensity, reward, and the nature of training. We also can use our understanding of basic neuroscience to identify novel manipulations to optimize recovery. For instance, we know that recovery appears to be supported by changes in neural connectivity within residual brain areas. Knowing this, we can test the efficacy of novel pharmacological or electrical stimulation interventions known to promote changes in neural connectivity. But the specifics of how human motor rehabilitation should be conducted will be clearly defined only in clinical experiments. It is the job of basic scientists to identify the fundamental neural principles of brain adaptation in response to damage and rehabilitation in order to guide the development of novel therapies. It is the job of the clinical scientists to test in the clinic the utility of what we observe at the bench.
8. Moving forward: interaction, translation, and dissemination
My final impression from the meeting concerns what has to happen in order for the field to move forward. More interaction is needed between clinical and basic scientists. Basic scientists need to be more aware of what physical therapy in the clinic actually involves so that we can develop better animal models. Clinical scientists need to standardize their tests so that basic science findings can be systematically tested in the clinic. This will improve the translation of basic science into clinical research. Increasing interactions could be achieved through novel funding opportunities and changes in institutional organization whereby clinicians and basic scientists are encouraged to work together.
Finally, the results of these interactions need to reach the practitioners. The information gathered in the clinical laboratories needs to be infused into the education programs that are producing new therapists in order to influence daily practice. It also is important to point out that practitioners are really field researchers. They are conducting research every day by observing the responses of different patient populations to different interventions. There should be a mechanism to share this information with clinical scientists so as to allow for continued optimization of treatment.
Conclusion
Although there are no easy solutions to the issues raised about collaborations between basic and clinical scientists, the III STEP Conference was a great start. At a minimum, it served to identify what has to be done. It was a rare opportunity for basic scientists, clinical scientists, and practitioners to sit in the same room and discuss rehabilitation science. This is the sort of interaction that is critical in order for the field to move forward. The translation of basic science into clinical science is a critical process toward the development of more effective rehabilitation interventions. To return to my "first date" analogy, and to quote my colleague Pamela Duncan, PT, PhD, FAPTA, "It’s time to quit holding hands and jump into the back seat."
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