Gait Ignition Using DBS Following SCI
Abstract
Deep brain stimulation (DBS) is an effective, relatively safe, reversible, and adjustable treatment modality for difficult-to-treat movement disorders. It has had little application in persons with spinal cord injury (SCI), even though a significant percentage of persons with new and chronic injuries are anatomically and motor incomplete and spared connections are retained between brain and spinal cord. Recent work in our laboratory has pointed to a potential target for controlling walking after partial SCI. This is the mesencephalic locomotor region or MLR, a major coordinating center in the brain for activation and control of spinal neurons generating walking. Based on our recent studies, DBS of the MLR (mlrDBS) enhances the signal transmitted along the pathways connecting the brain and spinal locomotor centers. mlrDBS produces immediate and highly significant improvements in gait, locomotor speed, and endurance in small animals (rodents) with mild and clinically relevant contusion (moderate and severe) mid-thoracic injuries. To achieve maximal clinical benefit from DBS and to minimize potential adverse effects due to stimulation, DBS electrodes need to be placed precisely into the target structure and the stimulation parameters must be optimized. This is especially important for its use after SCI since pathways responsible for generating walking are compromised and clinical benefit will depend upon utilizing the surviving pathways to the fullest extent possible. Unfortunately, there is great controversy concerning the location of the optimal site for mlrDBS in humans, indicating the importance of large animal testing to minimize the probability of negative or suboptimal clinical results, collateral damage to structures surrounding the MLR, as well as unwanted clinical side effects from stimulation. Furthermore, there is strong support in the SCI research community for demonstrating the efficacy of various therapies in large-animal models (in addition to rodent models), as well as independent replication of promising results before moving forward with human clinical trials. As part of our long-term goal of developing and optimizing treatments for SCI paralysis, the overall objective of this application is to determine the therapeutic potential of mlrDBS to improve walking following anatomically incomplete, acute, and chronic SCI in a large animal model (Yucatan minipig). We propose to provide conclusive data on the optimal stimulation sites and parameters for clinical use following SCI using Food and Drug Administration (FDA)-approved human DBS electrodes dimensionally compatible to the pig brain. A controlled study in a large animal model of SCI using FDA-approved human DBS electrodes will allow us to define DBS sites/parameters of stimulation and to delineate the benefits of mlrDBS in relation to the severity of injury (useful to optimize patient selection) in a preclinical setting, determine whether effective stimulation parameters are the same or differ with different grades of injury, and determine whether the effectiveness varies with time. DBS has the advantage that it can be calibrated on a case-by-case basis and that it allows the use of patterns of stimulation that better mimic normal neurotransmitter release patterns, thereby increasing the possibility of rehabilitation. This is important, since the effectiveness will depend upon the degree of sparing of pathways, which varies with each SCI. In addition, DBS can be adjusted to compensate for functional changes that evolve progressively from acute to subacute to chronic stages of injury. Many subjects with SCI recover some motor function and can ambulate under specialized conditions such as with body weight support. However, they do not achieve community ambulation and thus continue to use wheelchairs, placing them at continued risk for associated secondary complications such as pressure ulcers and loss of bone density. We hypothesize that per
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510584
Entities
People
- Brian Noga
Organizations
- United States Army
- University of Miami