Jonathan A Hyam1,2,3, Holly A Roy2,4, Yongzhi Huang3, Sean Martin3, Shouyan Wang1, Jodi Rippey5, Terry J Coyne6, Ian Stewart5, Graham Kerr5, Peter Silburn7,8, David J Paterson1, Tipu Z Aziz1,2,3, Alexander L Green9,10,11,12. 1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. 2. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. 3. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. 4. Neurosurgery Department, Derriford Hospital, Plymouth, PL6 8DH, UK. 5. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. 6. St. Andrews and Wesley Hospitals, Brisbane, Australia. 7. University of Queensland, Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, 4006, Australia. 8. Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. 9. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. alex.green@nds.ox.ac.uk. 10. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. alex.green@nds.ox.ac.uk. 11. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. alex.green@nds.ox.ac.uk. 12. Department of Neurosurgery, John Radcliffe Hospital, West Wing Level 3, Oxford, OX3 9DU, UK. alex.green@nds.ox.ac.uk.
Abstract
PURPOSE: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. METHODS: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. RESULTS: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). CONCLUSION: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.
PURPOSE:Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. METHODS: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. RESULTS: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). CONCLUSION: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.
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