Browsing by Author "Silburn, Peter"

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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.
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    Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology
    (Karger AG, Basel, 2016-10) Hamani, Clement; Aziz, Tipu; Bloem, Bastiaan; Brown, Peter; Chabardes, Stephen; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne; Lozano, Andres; Mazzone, Paolo; Okun, Michael; Hutchison, William; Silburn, Peter; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Moro, Elena; Krauss, Joachim
    Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.
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    Understanding the human pedunculopontine nucleus in Parkinson's disease
    (Springer, 2016-07) Fytagoridis, Anders; Silburn, Peter; Coyne, Terry; Thevathasan, Wesley
    This paper presents the Brisbane experience of pedunculopontine nucleus (PPN) deep brain stimulation (DBS) in Parkinson's disease (PD). Clinical outcomes along with studies of the mechanisms and neurophysiology of PPN in PD patients with severe freezing of gait (FoG) and postural imbalance (PI) are summarised and presented. Our results indicate that PPN DBS improves FoG and falls in the relatively uncommon group of PD patients who respond well to medication other than for continuing on time FoG and falls. Our studies indicate that bilateral DBS is more beneficial than unilateral DBS, and that the more caudal region of the PPN seems preferable for stimulation. There is evidence that rapid-release programs for initiation and correction of gait and posture are modulated by the PPN, possibly to some extent independently of the cerebral cortex. These functions were found to be impaired in PD patients with severe FoG/PI, but to some extent corrected by bilateral PPN DBS.
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    Where and what is the PPN and what is its role in locomotion?
    (Oxford University Press on behalf of the Guarantors of Brain, 2015-05-01) Windels, Francois; Thevathasan, Wesley; Silburn, Peter; Sah, Pankaj
    This scientific commentary refers to ‘The integrative role of the pedunculopontine nucleus in human gait’, by Lau et al. (doi:10.1093/brain/awv047).