Kinematic Effects of Combined Subthalamic and Dorsolateral Nigral Deep Brain Stimulation in Parkinson's Disease.

Background:Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson's disease (PD). Objective:This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulation sites within the SNr. Methods:In a double-blinded crossover design, 10 patients with PD and gait impairment underwent clinical examination and kinematic assessment with STN DBS, combined STN+SNr DBS and OFF DBS 30 minutes after reprogramming. To confirm stimulation within the SNr, electrodes, active contacts, and stimulation volumes were modeled in a common space and overlap with atlases of SNr was computed. Results:Overlap of stimulation volumes with dorsolateral SNr was confirmed for all patients. UPDRS III, scoring of freezing during turning and transitioning, stride length, stride velocity, and range of motion of shank, knee, arm, and trunk as well as peak velocities during turning and transitions and turn duration were improved with STN DBS compared to OFF. On cohort level, no further improvement was observed with combined STN+SNr DBS but additive improvement of spatiotemporal gait parameters was observed in individual subjects. Conclusions:Combined high frequency DBS of the STN and dorsolateral SNr did not consistently result in additional short-term kinematic or clinical benefit compared to STN DBS. Stimulation intervals, frequency, and patient selection for target symptoms as well as target region within the SNr need further refinement in future trials.