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Background: Treating medication-refractory freezing of gait (FoG) in Parkinson’s disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS).Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson's disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off-and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1-8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD.

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Gait impairment and increased gait variability are common among individuals with Parkinson’s disease (PD) and have been associated with increased risk for falls. The development of composite scores has gained interest to aggregate multiple aspects of gait into a single metric. The Enhanced Gait Variability Index (EGVI) was developed to compare an individual’s gait variability to the amount of variability in a healthy population, yet the EGVI’s individual parts may also provide important information that may be lost in this conversion. We sought to contrast individual gait measures as predictors of fall frequency and the EGVI as a single predictor of fall frequency in individuals with PD. 273 patients (189M, 84F; 68 ± 10 yrs) with idiopathic PD walked over an instrumented walkway and reported fall frequency over three months (never, rarely, monthly, weekly, or daily). The predictive ability of gait velocity, step length, step time, stance time, and single support time and the EGVI was assessed using regression techniques to predict fall frequency. The EGVI explained 15.1% of the variance in fall frequency (p<0.001, r = 0.389). Although the regression using the combined spatiotemporal measures to predict fall frequency was significant (p=0.002, r = 0.264), none of the components reached significance (gait velocity: p=0.640, step length: p=0.900, step time: p=0.525, stance time: p=0.532, single support time: p=0.480). The EGVI is a better predictor of fall frequency in persons with PD than its individual spatiotemporal components. Patients who fall more frequently have more variable gait, based on the interpretation of the EGVI. While the EGVI provides an objective measure of gait variability with some ability to predict fall frequency, full clinical interpretations and applications are currently unknown.

Bullock, GS, Schmitt, AC, Chasse, PM, Little, BA, Diehl, LH, and Butler, RJ. The relationship between trunk rotation, upper quarter dynamic stability, and pitch velocity. J Strength Cond Res 32(1): 261-266, 2018-Understanding the relationship between upper quarter mobility, dynamic stability, and pitching velocity may be beneficial in elucidating underlying factors that affect pitching performance. The purpose of this study was to investigate upper trunk rotation mobility and upper quarter dynamic stability and their correlation to pitch velocity in NCAA Division I collegiate pitchers. We hypothesized that collegiate pitchers with greater upper trunk rotation mobility and upper extremity dynamic stability would exhibit higher pitching velocity. Trunk rotation and the Upper Quarter Y-Balance Test (YBT-UQ) were measured using standardized protocols. Collegiate pitchers (N = 30) then proceeded to complete their team prescribed dynamic and throwing warm-up followed by a pitching session from regulation distance at 100% effort. Each pitch was recorded for velocity and pitch type, only fastballs were used in analysis. The relationships between trunk rotation and fastball velocity, and YBT-UQ scores and fastball velocity were assessed using a series of 2-tail Pearson's correlations (p< 0.05). Throwing and nonthrowing sides (69.6 ± 9.5°, 70.7 ± 9.4°) had similar trunk rotation mobility. No statistically significant correlation between upper trunk rotation mobility and pitch velocity was found (throwing arm: r = 0.131; p < 0.491; nonthrowing arm: r = 0.135; p < 0.478). There was also no correlation between the YBT-UQ and fastball velocity. In this study of Division I baseball pitchers, we found no relationship between trunk rotational mobility, upper quarter dynamic stability, and pitching velocity. This suggests that increased upper extremity stability and trunk mobility are not directly related to fastball velocity. Understanding factors that associate to velocity may be helpful in predicting pitching performance.