Summary - Deep Brain Stimulation Consortium Meeting

2003 Event Series Calendar

2003 Deep Brain Stimulation Consortium Meeting
September 29-30, 2003
Wyndham Hotel, Washington DC
Sponsored by the National Institute of Neurological Disorders and Stroke
in partnership with the
Parkinson's Alliance, Parkinson's Disease Foundation and California Neuroscience Institute
[participants]

The National Institutes of Health (NIH) Deep Brain Stimulation Consortium is a core group of researchers funded under a series of National Institute of Neurological Disorders and Stroke/National Institute on Aging/National Institute of Mental Health sponsored Requests for Application (RFAs) to explore Deep Brain Stimulation (DBS) and its therapeutic applications from different disciplinary perspectives. The RFA specified that an annual workshop/meeting of grantees should be organized to develop collaborations among members of the consortium and promote an enhanced sense of community among DBS researchers and practitioners.

The second of these meetings, which took place in Washington, DC on September 29-30, 2003, expanded beyond the core group of awardees to any and all interested members of the DBS community. It brought together an international gathering of physicians, basic scientists, patient advocates, industry representatives, and governmental officials in order to identify opportunities for collaboration among groups within the full extent of the DBS research community. The long term objective of the group is to develop better and more broadly applicable therapies through a better and broader understanding of mechanisms of action as validated by rigorous clinical trials. The theme of the meeting was our evolving understanding of mechanisms of action through experiment and experience and how this in turn leads to expanding indications for the use of DBS.

In welcoming remarks, Dr. William J. Heetderks, Associate Director for Science Programs, National Institute of Biomedical Imaging and Bioengineering welcomed the participants and highlighted the NIBIB interest in new technologies for brain imaging and implantable devices that may contribute to advancement of DBS. He stressed the potential for NIBIB to partner with NINDS and the other institutes to advance DBS techniques.

Dr. Paul Sheehy, a Program Director at NINDS, reiterated the welcome and stressed that the objective of the meeting was to promote multidisciplinary collaborative approaches to the study of DBS. He noted that the afternoon's poster session offered a great opportunity to develop new projects.

Carol Walton, Executive Director of the Parkinson Alliance, described that organization's partnership with New York University's Re-Wired for Life Foundation, which sponsors a survey to record the total experiences of people before, during, and after DBS surgery. This patient registry hopes to help answer questions about the long-term use of DBS. The results of the survey were presented during the workshop's poster session.

Robin Elliott, Director of the Parkinson's Disease Foundation, described the Foundation's efforts to promote awareness of needs and opportunities in Parkinson's Disease research among the patient, medical, research and private sector communities. He particularly noted the growing collaborations among these groups, describing them as legs of a stool, where each is essential for all the others to properly function.

Kimberly K. Seidman, Director of the California Neuroscience Institute, described the Institute's activities in promoting awareness of potential therapies for patients and the critical need for participation in clinical trials. In the initial scientific session, representatives from sixteen of the eighteen DBS Consortium member institutions currently funded by the NIH presented brief snapshots of their progress to date. The material covered a wide range of topics, including new device and guidance technologies, mechanisms underlying the effects of DBS in different brain areas, DBS effects on non-motor symptoms of Parkinson's, beneficial and adverse effects associated with DBS, and ethical concerns about the protection of patients undergoing surgical interventions and implantation of devices that alter the brain. In the next session, the speakers focused on how experimentation and clinical experience are changing the way we think about the normal and abnormal functional of the brain circuits that are affected by Parkinson's Disease.

Dr. Jim Surmeier addressed the twin questions "Why do stimulation and lesions in different brain regions affected by Parkinson's offer similar clinical benefit?" and "How does DBS work at a cellular level?" He presented data that support recent findings that the cells of the basal ganglia have unique electrophysiological properties that cause them to act as autonomous pacemakers at very high frequencies driving the striato-pallidal and cortico-striatal circuits without fatigue. While each has an intrinsic firing rate, the actual frequency is determined by input from other parts of the nervous system.

Dr. Surmeier's presentation ended with the proposition that the symptoms of PD result not simply from disruption of a circuit but rather from the loss of a "carrier signal." Thus, the action of DBS may not be to inhibit one or another structure but rather to change the pattern of neuronal firing.

Dr. Roy Bakay addressed questions resulting from clinical experiences with DBS such as why unilateral stimulation is so effective, particularly with respect to both motor symptoms and overall quality of life. He noted that while one surgical site is currently more favored, this practice has yet to be validated by a controlled clinical trial. He also reviewed data on the effect of DBS on dyskinesias, an important side effect of pharmacotherapy for PD. In summary, he noted that it is still early days in DBS therapy of neurological disease; much remains to be learned and systematically confirmed. The final scientific session comprised a broad overview of clinical research in DBS.

Dr. Barbara Vickrey addressed the study of outcomes. This is a much more subtle question for chronic diseases than it is for acute ones (i.e., mortality is not appropriate.) The trend in chronic disease is to use patient self-reportage of health-related quality of life (how they function or feel.) Dr. Vickrey noted that such measures have been collected in PD research, but not often in randomized clinical trials. The challenge is to develop measures that are reliable, valid, feasible, responsive to treatment and interpretable. There are concerns with self-reported quality of life outcomes in clinical trials (double blinding is difficult and patients' cognitive status may change with time or treatment) but they do represent the ultimate goal of our research: the health of the patient.

Dr. Mark Dichter addressed the experience and potential for DBS in other neurological disorders. He first reviewed the critical role of thalamic relay nuclei, other modalities of stimulation (transcranial magnetic stimulation, cranial nerve stimulation) and the current hypotheses as to whether the mechanism of action is via activation or inhibition. Dr. Dichter noted that it may vary by region and frequency of stimulation. At present, we don't have an adequate appreciation of the suitability of DBS for other neurological disorders either current being currently treated with DBS (dystonia, pain, epilepsy) or with the potential to be treated with DBS (headache, persistent vegetative state, depression and neuropsychiatric disorders such as obsessive-compulsive disorder or schizophrenia). One of the fascinating aspects of DBS research is that most of the knowledge we currently possess comes from direct experience in patients, which is in stark contrast to other therapies that are based on animal models.

Dr. Ken Follett gave an overview of a 5 year, 12 site clinical trial that tests DBS versus best medical management and compares GPi to STN with the endpoint of time "on" without troubling dyskinesias. Trial sponsorship is an innovative public/private partnership comprised of NINDS, the Department of Veteran's Affairs and the Medtronic Corporation. He noted that while recruitment is approximately 33% complete, it has been slower than expected. This lead to a discussion with the audience about the importance of controlled clinical trials and the invaluable contributions of voluntary and advocacy organizations in raising the awareness of patients and physicians with respect to participation in clinical trials.

Dr. Keith Wheatley described a UK-based clinical trial studying surgery versus best medical management with quality of life as the endpoint. This trial is notable both for its size (400 to 600 patients) and its duration (at least 10 years). He expanded upon the need for rigorous clinical trials by noting that, of the 450 reports describing more than 10,000 surgeries for PD, only 9 were randomized.

Dr. Jens Volkmann described the Germany-based Competence Network consisting of 20 regional and 5 coordinating centers. One of many studies conducted by the network uses Quality of Life to assess DBS in the subthalamic nucleus. The network has also recently initiated a study of DBS for dystonia.

Dr. Celia Witten gave an introduction to FDA with specific emphasis on components that oversee DBS. She described relevant policies and procedures.

Dr. Paul Stypulkowski reviewed potential future indications for DBS, with particular focus on pilot studies in epilepsy.

Paul Sheehy ended the meeting by reiterating the participants' common goals: "We need to make DBS work better and determine for whom it works best."