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Neural Interfaces Conference: Long Beach, California

The Parkinson Alliance attended the Neural Interfaces Conference this year, which was held in Long Beach, California on June 21, 2010. The Parkinson Alliance has been attending the Neural Interfaces Conference since 2005, and this is the first time the meeting has been held on the West coast. This particular conference kicked off the first official day with a Deep Brain Stimulation (DBS) consortium.  Suffice it to say, as it relates to Parkinson’s disease (PD), we have come a long way in understanding DBS and its impact on the “patient’s well-being,” but there continues to be much that we need to learn and investigate. The DBS community continues to be in the early stages of exploring this relatively new treatment for PD.  As was indicated at the conference, the DBS intervention in and of itself, although exciting and inspiring, is humbling in its own right. It has proved to be valuable in reducing some of the motor disturbances, but we need further understanding about the mechanisms that make DBS effective and how DBS impacts non-motor symptoms. 

In this context, this DBS consortium highlighted some of the ongoing needs for improving our understanding of DBS and the impact it has on those individuals who are recipients of this intervention.  Specifically, topics mentioned in this DBS consortium included: 1. identifying proper candidates for the therapy, 2. improving our understanding of the changes of mechanical, physical, and biochemical functions of patients who undergo DBS, 3. improving programming for patients (e.g., consider standardized approaches), 4. identifying the role of pre and post-operative imaging, 5. improving communication between institutions and research groups (working together is better than working individually), and 6. understanding the uniqueness of each patient  who is a candidate for DBS.

DBS for Parkinson’s disease: What is the Target?
Dr. Bill Marks, an Associate Professor of Neurology at the University of California San Francisco and Director of the Parkinson’s Disease Research, Education, & Clinical Center at the San Francisco Veterans Affairs Medical Center, presented the results of study attempting to differentiate the pros and cons of the two most common targets for the PD patient (the subthalamic nucleus (STN) and the globus pallidus interna (GPi)).  The study is known as the VA/NINDS Cooperative Study. This study is a well designed research endeavor incorporating a large group of individuals with PD, with enrollment for the study occurring from May 2002 through October 2006.  The participants in the study were evaluated at several time points, and data continues to be collected to assess the effectiveness of DBS overtime.

The bottom line is that both the STN and the GPi are effective for treating motor symptoms and have favorable outcomes for many of the patients who are good candidates for the for DBS therapy.

Dr. Marks provided the following concluding statements:

1. Research has confirmed that DBS is useful in smoothing out motor fluctuations, and DBS has been found to be better than the best medical therapy (medications alone) on some of the outcome measures, such as quality of life and UPDRS III motor scores in the “off” state.  There was no difference between DBS and the best medical therapy on the UPDRS motor “on” state and measures of cognition (thinking skills) and emotional well-being.

2. There was not a significant difference in motor improvements between the subthalamic nucleus (STN) DBS and the globus pallidus interna (GPi) DBS at baseline, 6 months, and 24 months.  In other words, one target was not superior to another target; both targets appear to be effective in treating motor symptoms for PD.

3. The benefits of DBS (e.g., whether it was minimal improvement or major improvement) that was seen at the 6 month mark was steady and found again at the 24 month mark. 

4. The study only used one measure to assess motor improvement (UPDRS III motor score), and data was collected at a single point in time on several occasions (rather than looking at motor functioning more fluidly – e.g., multiple times a day).  Thus, this is one piece of good data, but it is only a snap shot and does not provide the “whole story.”

5. Motor diaries (where patients documented their perspective of their PD symptoms) revealed that patients with DBS of the STN and GPi had less “off” time after DBS, and “on” time without dyskinesia improved for both STN and GPi DBS.

6. There needs to be more detailed analyses for specific motor features.

7. Although emotional well-being remained in the minimally depressed range between the GPi and STN groups, mood was slightly improved for the GPi group over the STN group.

8. There were a greater number of falls with STN over the GPi target with otherwise no significant event differences between groups.

9. With regard to medication reduction, more individuals in the STN group experienced medication reduction than those in the GPi group. Thus, the need or desire for medication reduction may influence choice of target.

Pedunculopontine Nucleus Deep Brain Stimulation:
Dr. Clement Hamani, an Assistant Professor of Neurosurgery at the University of Toronto, facilitated a lecture regarding the outcomes of some of the research regarding the pedunculopontine nucleus (PPN) for DBS.  The PPN is a “brainstem locomotive center” that also processes sensory and behavioral information.  Through its connections with the basal ganglia (brain structures that include the STN and GPi, among others that impact motor skills) and the spinal cord, the PPN is thought to play a role in some of the motor symptoms of PD.  This site for DBS is of importance as it may help to treat gait and posture that is often unmanageable in the later stages of PD.

Dr. Hamani stated that a few open label studies published to date have shown improvements in freezing, the frequency of falls, and to a lesser extent gait and posture.  There are, however, varying outcomes to several of the studies that have looked at PPN as a target for improving some symptoms of PD.  Some of the differences in outcome have been attributed to the slight variability in target location, the regions of the brain that are changed by the stimulation,  and some of the clinical features of patients included in the trials.  Although there are some controversial perspectives of PPN DBS in its role for motor symptoms of PD, there appears to be evidence that PPN stimulation improves sleep and cognition.

Further studies are needed to determine the effectiveness and benefit of stimulating this brain structure.

Computational Models of Deep Brain Stimulation:
Cameron McIntyre, Ph.D. is a world renowned biomechanical engineer who is a faculty member at the Cleveland Clinic Foundation where he is appointed as an Associate Staff in the Department of Biomechanical Engineering, and he holds an adjunct professorship at Case Western Reserve University.  He facilitated a talk about using computational models (computer models) and sophisticated software to help improve the effectiveness of DBS.   He said with humor, “The first decade of DBS was the clinicians time, but the second decade is for the bioengineers [to make it even better]”, implying that the engineers have an opportunity to help the clinicians improve the effectiveness of the promising DBS intervention.

More specifically, Dr. McIntyre discussed cutting edge software tools capable of predicting theoretically optimal stimulation parameter settings on a patient-specific basis.  He stated that this software program could help identify how the voltage (electric energy) is distributed , the volume of tissue activated by DBS, the optimal settings, and a clearer picture of the effectiveness of DBS.

Following some preliminary results from studies assessing the usefulness of computational models to assist with DBS, the following conclusions were made:

1. Computer models are an effective way to assist the clinicians in optimizing the effectiveness of DBS.

2. Computer models will help establish finer control over the DBS as well as better methods of understanding and identifying our targets and the related neurophysiology.

3. Patient specific DBS computer models are useful tools for the selection of DBS parameter settings. Automated algorithms (step-by-step problem-solving procedures) help to minimize the clinical guess work.

4. Computer modeling helps to reduce the time necessary to effectively implement DBS in clinical settings.

5. There is a potential to improve clinical outcomes for patients even further.

6. By narrowing/reducing the area that is stimulated (due to better targeting), the result will likely be greater controlled benefit and reduced unwanted side effects.

7. Reduced power was evident, with the implication that battery life will likely be extended.

Closed loop control in Parkinson’s Disease:
Jerrold Vitek, M.D., Ph.D., the Chair of Neurology at the University of Minnesota, provided some comments about closed loop control for DBS in patients with PD.  Closed loop control in deep brain stimulation is an engineering design where feedback signals [from the body to the device] will be interpreted by the DBS device and will then modify stimulation parameters, stimulation locations, and other factors that can have an effect on the overall system performance.

Dr. Vitek stated that there is promise for closed loop control in a variety of diseases that utilize DBS or some form of stimulation in the brain.  As it relates to PD, however, he indicated that it is premature to underscore a promise for sound effectiveness of closed loop control.  Moreover, he indicated that many questions remain before the concept of a closed loop control could actually be implemented.  Specifically, he stated that “We have not looked at PD patients closely enough.  We have not looked at many of the non-motor symptoms closely enough.  Are we changing things down stream by bombarding the brain with stimulation (creating either a negative/adverse effect, a neuroprotective effect, or even an absence of an effect)?  What is the signal that we are trying to understand?  What do you want to change the signal to?  Does the control signal depend on the target site?  Can we change the signal to what we want with DBS?  Is the signal different for different symptoms within a disorder?  Do we know what the physiological marker is for tremor?  For rigidity?  For bradykinesia?  What is the pathophysiological basis for bradykinesia?” He provided many important questions for the audience to consider as we think about the possibility for a closed loop control for DBS.

He concluded by stating the following:

1. Before we consider the closed loop control for patients with PD, we need to identify the signal.

2. Clinicians and researchers need to know what we want to change the signal to.

3. Clinicians and researchers need to change the signal predictably and consistently over time.

4. Clinicians and researchers do not yet know what we want to change, how we will change it or what we need to change it to.

5. The obstacles are significant, but they can be overcome.  Clinicians and researchers need to ask the right questions.

6. A closed loop control will likely be helpful for specific populations (such as patients with seizures). For right now, PD is a complex medical condition with variations in presentation. We will need to continue our research to see if it will be effective for patients with PD.

Balance Confidence in Patients with Parkinson’s disease with and without Deep Brain Stimulation: The Patient’s Perspective

There were several poster sessions and related presentations at the Neural Interfaces Conference.  The Parkinson Alliance had the opportunity to present our most recent research project assessing balance confidence in patients with PD with and without DBS.  Below you will find the authors of our paper, their affiliations, and the abstract.

Jeffrey Wertheimer1,2, Julie Fitzgerald Smith1, Carol Walton1, Valentina Trepatschko1, Dow-ann Yeh1,3, Fay Horak4, Margaret Tuchman1.

1. The Parkinson Alliance, 2. Cedars-Sinai Medical Center, 3. Fuller Theological Seminary, 4. Oregon Health & Science University

Abstract:
The inability to move around due to gait and balance problems is one of the most important causes of decreased quality of life, morbidity, and mortality in patients with Parkinson’s disease (PD).  There have been reports that Deep Brain Stimulation (DBS) can improve gait and balance, while other studies have found either no improvement on or worsening of gait and balance following DBS.  The objective of this research was two-fold: 1. to assess balance confidence in PD patients with and without DBS, and 2. to investigate the relationship between balance confidence and non-motor symptoms commonly associated with PD. 

Two hundred and ninety-three patients with PD participated in this study, including 130 individuals who have undergone STN DBS (DBS group) and 163 participants who have not undergone DBS (Non-DBS group).  Survey-based methodology was used.  The participants completed the Activities-Specific Balance Confidence Scale (ABC Scale), the Geriatric Depression Scale-Short Form (GDS-SF), and a questionnaire designed to inquire about other variables that could impact the patient’s perception of balance confidence.

Over half of the participants that underwent DBS believe that they have experienced improvement with balance, walking straight ahead, and the ability to change directions.  When looking at specific age groups, however, (
Balance confidence was adversely impacted by symptoms of depression and sleep disturbance for both the DBS group and Non-DBS group.  Perceived cognitive impairment, particularly as it related to attentional functions, was predictive of one’s level of balance confidence for the DBS group, but not the Non-DBS group.

Findings of the present study highlight predominant similarities in balance confidence between the DBS and Non-DBS groups. The relationship between non-motor symptoms and balance confidence is addressed, and the practical implications are discussed.

Should you want to review the paper in greater length, please click here.


CONCLUDING REMARKS FROM THE CONFERENCE AS A WHOLE:

The meeting highlighted the many advancements we have made in neural prosthetics like DBS, but it also underscored the importance for the need to come together in our research and clinical community to better understand DBS from instrumentation design (DBS technology), to candidacy selection, to follow-up care and all the processes in between.

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