Comparison of subthalamic unilateral and bilateral theta burst deep brain stimulation in Parkinson's disease.

High-frequency, conventional deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is usually applied bilaterally under the assumption of additive effects due to interhemispheric crosstalk. Theta burst stimulation (TBS-DBS) represents a new patterned stimulation mode with 5 Hz interburst and 200 Hz intraburst frequency, whose stimulation effects in a bilateral mode compared to unilateral are unknown. This single-center study evaluated acute motor effects of the most affected, contralateral body side in 17 PD patients with unilateral subthalamic TBS-DBS and 11 PD patients with bilateral TBS-DBS. Compared to therapy absence, both unilateral and bilateral TBS-DBS significantly improved (p < 0.05) lateralized Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) scores. Bilateral TBS-DBS revealed only slight, but not significant additional effects in comparison to unilateral TBS-DBS on total lateralized motor scores, but on the subitem lower limb rigidity. These results indicate that bilateral TBS-DBS has limited additive beneficial effects compared to unilateral TBS-DBS in the short term.

Subthalamic and nigral neurons are differentially modulated during parkinsonian gait.

The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.

Comparison of Shod and Unshod Gait in Patients With Parkinson's Disease With Subthalamic and Nigral Stimulation.

Background: The Parkinsonian [i.e., Parkinson's disease (PD)] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus (STN DBS) and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra (STN+SN DBS) and environmental rehabilitative factors as footwear on gait kinematics. Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with PD with medication in different DBS conditions (i.e., STIM OFF, STN DBS, and STN+SN DBS) during different gait tasks (i.e., normal gait, fast gait, and gait during dual task) and compared gait characteristics to healthy controls. Notably, 15 patients participated in the study, and 11 patients were analyzed after a dropout of four patients due to DBS-induced side effects. Results: Gait was modulated by both factors, namely, footwear and DBS mode, in patients with PD. Footwear impacted gait characteristics in patients with PD similarly to controls with longer step length, lower cadence, and shorter single-support time. Interestingly, DBS exerted specific effects depending on gait tasks with increased cognitive load. STN+SN DBS was the most efficient DBS mode compared to STIM OFF and STN DBS with intense effects as step length increment during dual task. Conclusion: The PD gait disorder is a multifactorial symptom, impacted by environmental factors as footwear and modulated by DBS. DBS effects on gait were specific depending on the gait task, with the most obvious effects with STN+SN DBS during gait with increased cognitive load.

A New Stimulation Mode for Deep Brain Stimulation in Parkinson's Disease: Theta Burst Stimulation.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. METHODS: In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. RESULTS: There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode. CONCLUSIONS: Theta burst stimulation is a safe and effective stimulation mode with potential future application opportunities. © 2020 International Parkinson and Movement Disorder Society.