<b>OBJECTIVE: </b>To assess the neuropsychological outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN) for advanced Parkinson disease.<b>METHODS: </b>We randomly assigned patients to receive either GPi DBS or STN DBS. Standardized neuropsychological tests were performed at baseline and after 12 months. Patients and study assessors were masked to treatment allocation.<b>RESULTS: </b>Univariate analysis of change scores indicated group differences on Stroop word reading and Stroop color naming (confidence interval [CI] 1.9-10.0 and 2.1-8.8), on Trail Making Test B (CI 0.5-10.3), and on Wechsler Adult Intelligence Scale similarities (CI -0.01 to 1.5), with STN DBS showing greater negative change than GPi DBS. No differences were found between GPi DBS and STN DBS on the other neuropsychological tests. Older age and better semantic fluency at baseline predicted cognitive decline after DBS.<b>CONCLUSIONS: </b>We found no clinically significant differences in neuropsychological outcome between GPi DBS and STN DBS. No satisfactory explanation is available for the predictive value of baseline semantic fluency for cognitive decline.<b>Classification Of Evidence: </b>This study provides Class I evidence that there is no large difference in neuropsychological outcome between GPi DBS and STN DBS after 12 months. The study lacks the precision to exclude a moderate difference in outcomes.
OBJECTIVES: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. METHODS: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson’s Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. RESULTS: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] 16.4 to 10.8; <i>p</i> < 0.001) and STN (42.5 to 29.7; 95% CI 15.8 to 9.4; <i>p</i> = 0.001); improvements were similar between targets and stable over time (<i>p</i> = 0.59). Health-related quality of life improved at 6 months on all subscales (all <i>p</i> values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (<i>p</i> = 0.01); other neurocognitive measures showed gradual decline overall. CONCLUSIONS: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Object. Difficulty with step initiation, called "start hesitation," is related to gait bradykinesia and is an early hallmark of gait freezing in Parkinson disease (PD). Authors of this study investigated the effects of deep brain stimulation (DBS) and levodopa on step initiation before and 6 months after DBS surgery in 29 patients with PD who were randomized to either the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) as the DBS site. Methods. The authors measured the amplitude and duration of anticipatory postural adjustments (APAs), the feed-forward postural preparation that precedes the onset of voluntary step initiation, based on center-of-pressure displacements on a force plate. They also measured the length and velocity of the first step using a motion analysis system to study kinematics. Some of the patients (22) were from a large, multicenter, double-blind clinical trial, and all patients in the study (29, PD-DBS group) were randomized to DBS in either the bilateral STN (15 patients) or bilateral GPi (14 patients). Differences in step initiation were investigated in 2 conditions before surgery (off/on levodopa) and in 4 conditions after surgery (off/on levodopa combined with off/on DBS). Twenty-eight elderly healthy control volunteers (CTRL group) were also tested, and 9 control volunteers with PD who met the criteria for DBS (PD-C group) were tested at baseline and 6 months later. Results. Patients in the PD-DBS group had smaller amplitudes and longer durations of APAs compared with those in the 28 healthy control volunteers in all conditions. Before surgery, APAs improved with levodopa. After surgery, the APAs were significantly worse than in the best-treatment state before surgery (DOPA condition), and responsiveness to levodopa decreased. No differences in APAs were detected between the STN and GPi groups. A comparison with PD control volunteers who did not undergo DBS surgery confirmed that a deterioration in step preparation was not related to disease progression. Step length and velocity were smaller in the PD-DBS group than in controls in all conditions. Before surgery, levodopa improved the length and velocity of the first step. Both step length and velocity were unchanged in the best-treatment state before surgery (DOPA condition) as compared with after surgery (DBS+DOPA), with only step velocity in the STN group getting worse after surgery. Conclusions. Six months of DBS in the STN or GPi impaired anticipatory postural preparation for step initiation, the opposite effect as with levodopa. Deep brain stimulation disrupted postural preparation more than step execution, suggesting independent motor pathways for preparation and execution of gait. Although turning the stimulators on after surgery combined with levodopa benefited the postural preparation to step, a comparison of pre- and postsurgery conditions suggests that either the surgery itself or 6 months of continuous stimulation may lead to an alteration of circuits or plastic changes that impair step initiation.
Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.
BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa- induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials arc limited. OBJECTIVE: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD. DESIGN: This study represents the combined results from our previously published, randomized, blinded, parallel-group pilot study and additional patients enrolled in our single-center extension study. SETTING: Oregon Health and Science University in Portland. PATIENTS: Twenty-three patients with idiopathic PD, levodopa- induced dyskinesia, and response fluctuations were randomized 10 implantation of bilateral GPi or STN stimulators. Patients and evaluating clinicians were blinded 10 stimulation site. All patients were tested preoperatively while taking and not taking medications and after 3, 6. and 12 months of DBS. MAIN OUTCOME MEASURES: Postoperatively, response of symptoms to DBS, medication, and combined medication and DBS was evaluated. Twenty patients (10 in the GPi group and 10 in the STN group) completed 12-month follow-up. RESULTS: Off-medication Unified Parkinson's Disease Rating Scale motor scores were, improved after 12 months of both GPi and STN stimulation (39% vs 48%). Bradykinesia tended to improve more with STN than GPi stimulation. No improvement in on-medication function was observed in either group. Levodopa dose was reduced by 38% in STN stimulation patients compared with 3% in GPi stimulation patients (P=.08). Dyskinesia was reduced by stimulation at both GPi and STN (89% vs 62%). Cognitive and behavioral complications were observed only in combination with STN stimulation. CONCLUSION: Stimulation of cither the GPi or STN improves many features of advanced PD. It is premature to exclude GPi as an appropriate target for DBS in patients with advanced disease. (PsycInfo Database Record (c) 2023 APA, all rights reserved)
To assess the neuropsychological outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN) for advanced Parkinson disease.
METHODS:
We randomly assigned patients to receive either GPi DBS or STN DBS. Standardized neuropsychological tests were performed at baseline and after 12 months. Patients and study assessors were masked to treatment allocation.
RESULTS:
Univariate analysis of change scores indicated group differences on Stroop word reading and Stroop color naming (confidence interval [CI] 1.9-10.0 and 2.1-8.8), on Trail Making Test B (CI 0.5-10.3), and on Wechsler Adult Intelligence Scale similarities (CI -0.01 to 1.5), with STN DBS showing greater negative change than GPi DBS. No differences were found between GPi DBS and STN DBS on the other neuropsychological tests. Older age and better semantic fluency at baseline predicted cognitive decline after DBS.
CONCLUSIONS:
We found no clinically significant differences in neuropsychological outcome between GPi DBS and STN DBS. No satisfactory explanation is available for the predictive value of baseline semantic fluency for cognitive decline.Classification Of Evidence: This study provides Class I evidence that there is no large difference in neuropsychological outcome between GPi DBS and STN DBS after 12 months. The study lacks the precision to exclude a moderate difference in outcomes.
