Combined Stimulation of the Substantia Nigra and the Subthalamic Nucleus for the Treatment of Refractory Gait Disturbances in Parkinson’s Disease: A Preliminary Study

Abstract

Deep brain stimulation of the subthalamic nucleus is efficient for the treatment of motor symptoms (i.e., tremors) in patients with Parkinson’s disease. Gait disorders usually appear during advanced stages of idiopathic Parkinson’s disease in up to 80% of patients and have an important impact on their quality of life. The effects of deep brain stimulation of the subthalamic nucleus on gait and balance are still controversial. For this reason, alternative targets have been considered, such as stimulation of the pedunculopontine nucleus and the pars reticulata of substantia nigra, involved in the integration of the functional connections for gait. Due to the proximity of the subthalamic nucleus to the substantia nigra, their combined stimulation is feasible and may lead to better outcomes, improving axial symptoms. Our objective was to prospectively compare simultaneous stimulation of both structures versus conventional subthalamic stimulation in improving gait disorders. In ten patients with advanced Parkinson’s disease, deep brain stimulation leads (eight linear contacts) were implanted, and gait analysis was performed 6 months after surgery in off-stimulation and after 4 weeks of dual or single subthalamic stimulation. An improvement in gait parameters was confirmed with both stimulation conditions, with better results with combined substantia nigra and subthalamic stimulation compared with conventional subthalamic stimulation. Further studies are needed to determine if this effect remains after long-term dual-target stimulation.

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

“…The concomitant heterogeneity of (semi)quantitative gait assessment methods used in these studies further account for the inconclusive findings on SNr-DBS induced effects that include improvement in a freezing assessment score [18] or the freezing item of UPDRS [14], increased step length [15,17] and a higher fraction of normal gait cycles [13]. Similar, we found improvement in standard kinematic parameters [32], Avecillas atlas [34], and CIT168 atlas [35].…”

“…Horn and colleagues [ 15 ] report increased step length with STN+SNr-DBS compared to STN-DBS that was more pronounced during increased cognitive load under dual tasking. Wagner and colleagues report a reduction of step-time variability for STN+SNr-DBS compared to STN and OFF DBS [ 17 ] without specific gait-related inclusion criteria, similar to Villadóniga and colleagues [ 13 ] who report a significantly higher fraction of normal gait cycles as determined by deceleration, reversing and acceleration, yet the clinical significance of this finding remains speculative. Thus, gait related motor symptoms were variable across and within trials, which may explain the heterogeneity of results.…”

“…To date, effects of combined stimulation of STN and SNr on gait disability have been reported in 5 cohorts with a total of 51 patients [ 13–15, 17, 18 ]. Across these studies, the interval for which combined DBS was applied before clinical or kinematic assessments varied from 30 min [ 18 ] up to 3 months [ 14 ].…”

“…Across these studies, the interval for which combined DBS was applied before clinical or kinematic assessments varied from 30 min [ 18 ] up to 3 months [ 14 ]. The concomitant heterogeneity of (semi)quantitative gait assessment methods used in these studies further account for the inconclusive findings on SNr-DBS induced effects that include improvement in a freezing assessment score [ 18 ] or the freezing item of UPDRS [ 14 ], increased step length [ 15, 17 ] and a higher fraction of normal gait cycles [ 13 ]. Similar, we found improvement in standard kinematic parameters with STN-DBS in our cohort.…”

“…While DBS of only the SNr was insufficient to control both axial and segmental symptoms [11,12], studies using combined stimulation of STN and SNr for intervals from 30 min to 4 months have reported heterogeneous improvements of gait performance [13][14][15][16][17] or during freezing assessments [18,19]. Latest technical advances with sensing devices have pushed the field of closed loop DBS paradigms, thereby expanding the potential for dynamically addressing specific symptoms [20][21][22].…”