Optimising the post-operative management of Parkinson’s disease patients with deep brain stimulation

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has become a common procedure for the management of Parkinson’s disease (PD) symptoms. Based on the existing scientific evidence, it is well understood that high-frequency STN-DBS (e.g. 130 Hz) is effective at alleviating PD symptoms such as resting tremor and rigidity. However, it has been suggested that high-frequency STN-DBS stimulation may not be as effective for managing symptoms of postural instability and gait disability, symptoms strongly associated with falls in people with PD. In response to this, alternate STN-DBS parameters such as low-frequency STN-DBS has emerged as an area of clinical interest given its potential to better manage postural instability and gait disability for people with PD. This program of research addressed a series of questions concerning the post-operative management of postural instability and gait disability in people with PD following bilateral STN-DBS. Specifically, this dissertation includes four inter-related studies that sought to improve the understanding of how low frequency STN-DBS influences both clinical and objective measures of postural and gait stability in people with PD who have STN-DBS. The literature surrounding alternate STN-DBS parameters for the efficacy of managing PD motor symptoms were systematically reviewed in Study I. Only a small number of studies met the inclusion criteria. This meant meta-analyses were only possible for assessing the efficacy of low-frequency stimulation. The results of these analyses indicated that research in this area generally had poor methodological reporting quality, due to numerous sources of potential bias. The review suggested that research concerning the potential utility of alternate STN-DBS parameters had relied almost exclusively on outcomes derived from well established, yet largely subjective, clinical measures. It was recommended that the incorporation of objective measures may provide further insight into the strengths and weaknesses of alternate patterns of STN-DBS for managing people with PD. Given the findings of the systematic review and meta-analysis (Study I), Study II sought to determine whether novel, objective measures of gait rhythmicity provide unique insights into gait stability that is not otherwise captured by the clinical measures of symptom severity, postural stability, balance confidence and mobility. This cross-sectional study recruited postoperative those with PD following STN-DBS to evaluate gait stability using body-worn triaxial accelerometers. Specifically, the three-dimensional accelerations collected were used to calculate the harmonic ratios for the head and trunk segments. Analysis of the harmonic ratios, which provide insight into the step-to-step rhythmicity of an individual’s gait, indicated that the use of body-worn sensors can provide unique gait-related information that are not captured by clinical measures. To better understand the effect of low-frequency STN-DBS, Studies III and IV employed a double-blinded randomised cross-over design to investigate the possible benefits of low-frequency STN-DBS for managing symptoms of postural and gait stability. Sixteen postoperative people with PD completed standing and walking assessments while off medication and receiving high-and low-frequency STN-DBS therapy. In both studies, objective measures of postural stability were derived from either a force plate (Study III) or wearable sensors (Study IV) to provide insight into the efficacy of low-frequency stimulation. It was found that postural stability during the locomotion phase of gait initiation was improved with low-frequency STNDBS, while the postural phase of gait initiation was not different (Study III). During steady state walking, low-frequency STN-DBS improved medial-lateral and vertical trunk rhythmicity compared to high-frequency stimulation. The improvements with low-frequency were independent of electrode location and total electrical energy delivered. In contrast to these noted differences in objectively measured outcomes, there were no changes observed between the two stimulation conditions for the clinical measures of mobility, motor symptom severity, or gait retropulsion. Although the long-term effects of low-frequency STN-DBS were not examined in this study, the presented findings provided evidence to suggest that low-frequency STN-DBS may improve gait initiation and gait stability for people with PD who have STNDBS. Nevertheless, it should be noted that low-frequency STN-DBS therapy may not be suitable for all people with PD who have STN-DBS, as some experienced the re-emergence of limb tremor during low-frequency stimulation. This dissertation fills identified gaps in scientific literature and provides clinically relevant objective evidence for the potential utility of low-frequency stimulation to improve postural stability for people with PD who have STNDBS.