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Title: Effect of pedunculopontine nucleus deep brain stimulation in reducing falls, improving gait and postural control in Parkinson's disease
Author: Naushahi, Mohammad Jawad
ISNI:       0000 0004 7232 6034
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Keywords: deep brain stimulation (DBS), subthalamic nucleus (STN), pedunculopontine nucleus (PPN), Parkinson’s disease (PD) Objective: To determine the advantage of bilateral PPN-DBS in reducing falls, improving gait and postural control in patients with advanced PD. Background: In recent years, PPN-DBS has been explored to address the axial motor symptoms of gait freezing and loss of postural control (adding to tremor, rigidity and bradykinesia as drivers of disease burden in advanced PD). However, the role of PPN-DBS remains unclear. Methods: A prospective, four-phase, within-subject cross-over, double-blinded study where bilateral STN (Med. 3389) and PPN-DBS (Med. 3387) electrodes were implanted in six patients with advanced PD and axial motor symptoms while on optimal medical therapy. The primary endpoint was the reduction in falls and improvement in gait. Performance was recorded on optimal medical therapy only (open-label phase), bilateral STN or PPN-DBS and simultaneous bilateral STN & PPN-DBS (ALL neurostimulation in conjunction with optimal medical therapy; 6- months each). The study received local ethics approval and informed written consent was obtained from all patients. Results: There was 100% decrease (Wilcoxon signed-ranks test; p < 0.05) in ICNG Index (falls / 1000 steps) with simultaneous bilateral STN (at 2.6 ± 0.2 V, 140 Hz, 60 μs) & PPN-DBS (at 1.5 ± 0.2 V, 20 Hz, 60 μs) in conjunction with optimal medical therapy compared to optimal medical therapy only. PPN-DBS was generally well tolerated and only induced momentary ipsilateral oscillopsia at commencement on ≥ 2.0 V with rapid habituation, consistent with previous findings. No other complications were reported with PPN-DBS. Conclusion: In appropriately selected patients, simultaneous bilateral STN & PPNDBS, in conjunction with optimal medical therapy, targeting the mid-lower PPN with the aid of DWI / DTI scans with PDT analysis and resultant saccadic modulation coupled with performance changes in the relevant axial motor segments, offers the possibility of ameliorating both the axial motor symptoms as well as the limb motor symptoms of advanced PD. DWI / DTI scans with PDT analysis of the PPN region may be used as a pre-operative tool to localise the electrode placement site, and they may also be useful as a post-operative tool to reassess electrode position.
Supervisor: Bain, Peter ; Bronstein, Adolfo ; Nandi, Dipankar Sponsor: Medical Research Council ; Medtronic Ltd (Firm)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral