A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

Abstract

Objective: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi).

Results: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states.

Conclusions: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed.

Figure Random-effects meta-regression of the change in postural instability and gait disability (PIGD) and cardinal scores after deep brain stimulation (DBS) surgery across time The plots show the standardized difference between scores recorded at various time points postsurgery and the equivalent medication state presurgery. A change score <0 indicates an improvement, and >0 indicates a worsening. The blue data points are studies of globus pallidus interna (GPi) DBS and the red points are those of subthalamic nucleus (STN) DBS. The area of each point is proportional to the number of subjects. The number on the data point corresponds to the study number in table 1. Regression lines are split into STN (red) and GPi (blue). An asterisk (*) identifies when the coefficient of time was significant in the regression and corresponding coefficients of determination (R²) values are shown. (A) shows the change in PIGD scores post-pre DBS surgery OFF medication and (B) shows the difference in PIGD scores post-pre DBS surgery ON medication. (C) Shows the change in cardinal scores post-pre DBS surgery OFF medication and (D) shows the change in cardinal scores post-pre DBS surgery ON medication.