Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation
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.
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.
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).
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.
KeywordsPedunculopontine nucleus Deep brain stimulation Parkinson disease Postural hypotension Autonomic nervous system
We would like to thank Amanda Rojek, Nor Faizal Ahmad Bahuri and John-Stuart Brittain for their support in data collection. This study was supported by a research grant from Medtronic Europe S.A. and grants from the Oxford Biomedical Research Centre of the UK NIHR, the Norman Collisson Foundation, the Wolfson Charitable Trust and the National Health and Medical Research Council (Australia).
Conception of project: JAH, ALG, DJP, TZA. Study design: JAH, ALG, DJP, GK, PS. Data collection: JAH, JSB, SW, NFAB, JR, IS. Insertion of DBS electrodes: ALG, TZA, TC. Analysis and manuscript composition: JAH, HAR, YH, ALG, GK. Manuscript feedback: all authors
Compliance with ethical standards
Conflict of interest
JA Hyam, TJ Coyne, TZ Aziz and AL Green have received honoraria from Medtronic Inc. and St. Jude Medical. No author is employed or has investment in either company. Prof Green is on an Executive Advisory Board (Movement Disorders) for Abbott and holds a consultancy agreement with Abbott. He also has a Consultancy agreement with Renishaw plc. He has given Expert testimony (unrelated) and receives Royalties from Oxford University Press (unrelated). He holds an MRC grant (unrelated to this project).
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