Zachary J Conway1, Peter A Silburn2,3, Wesley Thevathasan4,5,6, Karen O' Maley3, Geraldine A Naughton7, Michael H Cole1. 1. School of Behavioural and Health Sciences Australian Catholic University Brisbane Queensland Australia. 2. Asia-Pacific Centre for Neuromodulation, Queensland Brain Institute The University of Queensland Brisbane Queensland Australia. 3. Neurosciences Queensland Brisbane Queensland Australia. 4. The Bionics Institute East Melbourne Victoria Australia. 5. Department of Neurology Royal Melbourne and Austin Hospitals Melbourne Victoria Australia. 6. Department of Medicine University of Melbourne Parkville Victoria Australia. 7. School of Behavioural and Health Sciences Australian Catholic University Melbourne Victoria Australia.
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: Of the 21 included studies, 17 investigated the effect of alternate stimulation frequencies, five examined alternate stimulation amplitudes, and two studied changes in pulse width. Given the available data, meta-analyses were only possible for alternate stimulation frequencies. Analysis of the heterogeneity amongst the included studies indicated significant variability between studies and, on the basis of the GRADE framework, the pooled evidence from the meta-analysis studies was of very low quality due to the significant risks of bias. CONCLUSIONS: 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.
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: Of the 21 included studies, 17 investigated the effect of alternate stimulation frequencies, five examined alternate stimulation amplitudes, and two studied changes in pulse width. Given the available data, meta-analyses were only possible for alternate stimulation frequencies. Analysis of the heterogeneity amongst the included studies indicated significant variability between studies and, on the basis of the GRADE framework, the pooled evidence from the meta-analysis studies was of very low quality due to the significant risks of bias. CONCLUSIONS: 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.
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