Abstract
Freezing of gait (FOG) is a devastating motor symptom of Parkinson's disease that leads to falls, reduced mobility, and decreased quality of life. Reliably eliciting FOG has been difficult in the clinical setting, which has limited discovery of pathophysiology and/or documentation of the efficacy of treatments, such as different frequencies of subthalamic deep brain stimulation (STN DBS). In this study we validated an instrumented gait task, the turning and barrier course (TBC), with the international standard FOG questionnaire question 3 (FOG-Q3, r = 0.74, p < 0.001). The TBC is easily assembled and mimics real-life environments that elicit FOG. People with Parkinson's disease who experience FOG (freezers) spent more time freezing during the TBC compared to during forward walking (p = 0.007). Freezers also exhibited greater arrhythmicity during non-freezing gait when performing the TBC compared to forward walking (p = 0.006); this difference in gait arrhythmicity between tasks was not detected in non-freezers or controls. Freezers' non-freezing gait was more arrhythmic than that of non-freezers or controls during all walking tasks (p < 0.05). A logistic regression model determined that a combination of gait arrhythmicity, stride time, shank angular range, and asymmetry had the greatest probability of classifying a step as FOG (area under receiver operating characteristic curve = 0.754). Freezers' percent time freezing and non-freezing gait arrhythmicity decreased, and their shank angular velocity increased in the TBC during both 60 Hz and 140 Hz STN DBS (p < 0.05) to non-freezer values. The TBC is a standardized tool for eliciting FOG and demonstrating the efficacy of 60 Hz and 140 Hz STN DBS for gait impairment and FOG. The TBC revealed gait parameters that differentiated freezers from non-freezers and best predicted FOG; these may serve as relevant control variables for closed loop neurostimulation for FOG in Parkinson's disease.
Highlights
Gait impairment and freezing of gait (FOG) are common in Parkinson’s disease, and lead to falls, [1,2,3] resulting in injury, loss of independence, institutionalization, and even death [4,5]
Gait impairment is characterized by the loss of rhythmic alternating cycles of forward motion of one leg during the stance phase of the other leg, which are represented by the variability of stride time and the angular velocity of the lower leg during the swing phase, respectfully
Subjects were classified as a freezer or non-freezer based on the FOG questionnaire (FOG-Q) question 3 (FOG-Q3): Do you feel that your feet get glued to the floor while walking, turning or when trying to initiate walking? The scores were as follows: 0 –never, 1 –about once a month, 2 –about once a week, 3 –about once a day, 4 –whenever walking
Summary
Gait impairment and freezing of gait (FOG) are common in Parkinson’s disease, and lead to falls, [1,2,3] resulting in injury, loss of independence, institutionalization, and even death [4,5]. Understanding and treating gait impairment and FOG are paramount unmet needs and were given the highest priority at the National Institute of Neurological Disorders and Stroke 2014 PD conference [7]. Both gait impairment and FOG have unpredictable responses to dopaminergic medication and continuous high frequency open loop subthalamic deep brain stimulation (DBS) [8,9]. A closed loop, adaptive system that can adjust stimulation appropriately may be able to improve therapy for FOG and impaired gait. Before this goal can be attained, it is important to determine which gait parameters are associated with freezing behavior, which predict freezing events, and the effect of different DBS frequencies on gait impairment and FOG
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