Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson's Disease

Marlieke Scholten, Johannes Klemt, Melanie Heilbronn, Christian Plewnia, Bastiaan R Bloem, Friedemann Bunjes, Rejko Krüger, Alireza Gharabaghi, Daniel Weiss, Marlieke Scholten, Johannes Klemt, Melanie Heilbronn, Christian Plewnia, Bastiaan R Bloem, Friedemann Bunjes, Rejko Krüger, Alireza Gharabaghi, Daniel Weiss

Abstract

Conventional subthalamic deep brain stimulation for Parkinson's disease (PD) presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG). Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr) area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN) stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i) Off stimulation, (ii) STN stimulation (alone), and (iii) SNr stimulation (alone). SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer) attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability) and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry). Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.

Keywords: Parkinson’s disease; freezing of gait; gait; nigral stimulation; subthalamic nucleus deep brain stimulation.

Figures

Figure 1
Figure 1
Score of the total UPDRS III (left), segmental score (sum of items 20–26 + 31, only upper and lower limbs), and gait and posture subscore (sum of items 27–30) during subthalamic nucleus (STN), substantia nigra pars reticulate (SNr), and Off stimulation. Significant differences (p < 0.05) are denoted by horizontal square brackets. Both STN and SNr stimulations could significantly improve the segmental and gait and posture subscore.
Figure 2
Figure 2
Boxplot representing median values, 25–75% range (box) and min–max range (bars) of swing time asymmetry. Differences were computed with the Wilcoxon signed rank test and are denoted by horizontal square brackets. Abbreviations: STN, subthalamic nucleus deep brain stimulation; SNr, substantia nigra deep brain stimulation; ll, leg length; CV, coefficient of variation.
Figure 3
Figure 3
Medio-lateral location of electrode of the most caudal contact is associated with the improvement of peak angular velocity variability by substantia nigra pars reticulate (SNr) stimulation. Both electrode position and CV of PAV are obtained from the dominant side. A more medial electrode position is associated with more regular gait induced by SNr stimulation (r = −0.594; p = 0.042). Abbreviations: CV, coefficient of variation; PAV, peak shank angular velocity.

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