Browsing by Author "Cole, Michael"

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    Alternate subthalamic nucleus deep brain stimulation parameters to manage motor symptoms of Parkinson’s disease: Systematic review and meta-analysis
    (John Wiley & Sons, 2018-09) Conway, Zachary; Silburn, Peter; Thevathasan, Wesley; O'Maley, Karen; Naughton, Geraldine; Cole, Michael
    ABSTRACT Background The use of alternate frequencies, amplitudes and pulse widths to manage motor symptoms in Parkinson's disease (PD) patients with subthalamic nucleus deep brain stimulation (STN-DBS) is of clinical interest, but currently lacks systematic evidence. Objective/Hypothesis Systematically review whether alternate STN-DBS settings influence the therapy's efficacy for managing PD motor symptoms. Methods Systematic searches identified studies that; involved bilateral STN-DBS PD patients; manipulated ≥1 STN-DBS parameter (e.g. amplitude); assessed ≥1 motor symptom (e.g. tremor); and contrasted the experimental and chronic stimulation settings. A Mantel-Haenszel random-effects meta-analysis compared the UPDRS-III sub-scores at low (60-Hz) and high frequencies (≥130 Hz). Inter-study heterogeneity was assessed with the Cohen's χ2 and I2 index, while the standard GRADE evidence assessment examined strength of evidence. Results The meta-analysis indicated a very low quality for the pooled evidence due to risks of bias, significant heterogeneity and imprecision. Separate analyses involving studies that attempted to maintain the total electrical energy derived by increasing amplitude at 60-Hz frequencies suggested that low-frequency STN-DBS reduced UPDRS-III sub-scores by 5.8 points (95% CI=1.5-10.2; Z=2.6; P=0.009) compared to frequencies ≥130 Hz. This alternate stimulation strategy may be beneficial for those with severe axial symptoms post STN-DBS, however, benefits may only be short-term. Conclusion(s) The meta-analysis reported a very low quality of evidence for the efficacy of low-frequency STN-DBS for managing PD motor symptoms. Furthermore, it highlighted that lower amplitudes lead to the re-emergence of motor symptoms and further research is needed to understand the potential benefits of alternate STN-DBS parameters for PD patients. This article is protected by copyright. All rights reserved.
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    Balance control systems in Parkinson’s disease and the impact of pedunculopontine area stimulation
    (Brain, 2018-08) Perera, Thushara; Tan, Joy; Cole, Michael; Yohanandan, Shivanthan; Silberstein, Paul; Cook, Raymond; Peppard, Richard; Aziz, Tipu; Coyne, Terry; Brown, Peter; Silburn, Peter; Thevathasan, Wesley
    Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.