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. Neurology Balance and gait are gradually, and inevitably, impaired as Parkinson disease (PD) progresses, resulting in significant impairment of mobility. Mobility disability is one of the most important causes of diminished quality of life, morbidity, and mortality in patients with PD.1,2 Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or globus pallidus interna (GPi) is an increasingly common therapy for mid-to late-stage PD. With optimized stimulation settings, DBS typically lessens the motor symptoms of tremor, limb rigidity, bradykinesia, and akinesia. However, the long-term effects on balance, locomotion, and speech, often referred to as axial motor signs, are debated.Despite improvements in clinical ratings of PIGD immediately after DBS surgery, patients tend to fall more.3 These seemingly contradictory findings are not altogether surprising given that balance and gait are complex behaviors consisting of many sensorimotor subsystems that may not be fully characterized by the PIGD items in the Unified Parkinson's Disease Rating Scale (UPDRS). So although posture and gait are affected by bradykinesia, rigidity, and to a lesser extent tremor, other sensorimotor systems underlying posture and gait, such as setdependent flexibility, 4 sensory integration, 5 and postural synergies, 6 do not show the same responsiveness to levodopa. Therefore, each subsystem underl...

Interactive effects of GPI stimulation and levodopa on postural control in Parkinson's disease

“…Although some studies have suggested that GPI-DBS is less effective than STN stimulation for axial symptoms [24], a recent randomised double-blind study comparing the outcomes after stimulation at the two sites found that balance confidence and clinical balance scores were superior with GPI-DBS [11]. In addition, a meta-regression analysis of long-term studies suggested that GPI-DBS may provide more sustained benefit in preventing long-term decline in PIGD [10]. The mechanisms by which GPI-DBS improves postural control are uncertain, but it has been suggested that it may be due to descending effects on the pedunculopontine nucleus or other non-dopaminergic centres in the mesencephalic locomotor area [25].…”

“…GPI stimulation in combination with levodopa has been shown to improve PIGD scores [9], as well as alleviating the other cardinal signs of IPD [10]. Most recently, the combined effect of medication and DBS was found to improve subjective balance and gait scores more than either therapy alone [11].…”

Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease

“…With optimized stimulation settings, DBS reduces the motor symptoms of tremor, limb rigidity, bradykinesia, and akinesia. 43 Two brain regions, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), have been stimulated to treat PD. Earlier studies performed in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a model of PD showed that MPTP prominently increased in the lateral segment of the GPi and the STN.…”

Are the Effects of Community-Based Dance on Parkinson Disease Severity, Balance, and Functional Mobility Reduced with Time? A 2-Year Prospective Pilot Study

“…However, postural instability and gait difficulty are improved by deep brain stimulation to the same extent as the other cardinal symptoms of PD. 13 As such, nonpharmacologic and nonsurgical interventions are needed to address balance and gait deficits for patients with PD.…”