Globus Pallidus Internus Group Research Articles

The Effects of Deep Brain Stimulation on Mood and Quality of Life in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Deep brain stimulation (DBS) is extensively used to treat motor and non-motor symptoms in Parkinson's disease (PD). The aim of this study was to investigate the difference between subthalamic (STN) and globus pallidus internus (GPi) DBS on mood and quality of life with reference to minimal clinically important differences (MCID). A systematic literature search for articles published until November 2022 yielded 14 studies meeting the eligibility criteria, with a total of 1,088 patients undergoing STN (n=571) or GPi (n=517) stimulation. Baseline patient and clinical characteristics were comparable between the two groups. Results showed that GPi stimulation demonstrated a greater reduction in the Beck depression inventory (mean difference (MD)=1.68) than STN stimulation (MD=0.84). Hospital anxiety and depression scale showed a 2.69- and 3.48-point decrease by the GPi group in the depression and anxiety categories, respectively. The summary index (SI) of the PD questionnaire depicted a greater improvement in the GPi group from baseline (mean=41.01, 95% CI 34.89, 47.13) to follow-up (mean=30.85, 95% CI 22.08, 39.63) when compared to the STN group (baseline mean=42.43, 95% CI 34.50, 50.37; follow-up mean=34.21, 95% CI 25.43, 42.99). The emotions category also demonstrated a similar trend. However, STN stimulation showed greater reductions in motor symptoms and medication than GPi stimulation. This meta-analysis demonstrated that GPi stimulation seems to offer an advantage over STN stimulation in improving mood and quality of life in PD, but those effects must be further validated by larger studies.

Asleep Deep Brain Stimulation in Patients With Isolated Dystonia: Stereotactic Accuracy, Efficacy, and Safety

ObjectivesLead placement for deep brain stimulation (DBS) is routinely performed using neuroimaging or microelectrode recording (MER). Recent studies have demonstrated that DBS under general anesthesia using an imaging-guided target technique (“asleep” DBS) can be performed accurately and effectively with lower surgery complication rates than the MER-guided target method under local anesthesia (“awake” DBS). This suggests that asleep DBS may be a more acceptable method. However, there is limited direct evidence focused on isolated dystonia using this method. Therefore, this study aimed to investigate the clinical outcomes and targeting accuracy in patients with dystonia who underwent asleep DBS. Materials and MethodsWe examined 56 patients (112 leads) with isolated dystonia who underwent asleep DBS targeting in the globus pallidus internus (GPi) and subthalamic nucleus (STN). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were assessed preoperatively and at 12-month follow-up (12 m-FU). The lead accuracy was evaluated by comparing the coordinates of the preoperative plan with those of the final electrode implantation location. Other measures analyzed included stimulation parameters and adverse events (AEs). ResultsFor both GPi and STN cohorts, mean BFMDRS motor scores were significantly lower at 12 m-FU (8.9 ± 10.9 and 4.6 ± 5.7 points) than at baseline (22.6 ± 16.4 and 16.1 ± 14.1 points, p < 0.001). The mean difference between the planned target and the distal contact of the leads was 1.33 ± 0.54 mm for the right brain electrodes and 1.50 ± 0.57 mm for the left, determined by Euclidian distance. No perioperative complications or AEs related to the device were observed during the complete follow-up. However, AEs associated with stimulation occurred in 12 and 6 patients in the GPi and STN groups, respectively. ConclusionsAsleep DBS may be an accurate, effective, and safe method for treating patients with isolated dystonia regardless of the stimulation target.

STN Versus GPi Deep Brain Stimulation for Action and Rest Tremor in Parkinson's Disease.

ObjectiveTo investigate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi), deep brain stimulation (DBS) on individual action tremor/postural tremor (AT) and rest tremor (RT) in Parkinson’s disease (PD). Randomized DBS studies have reported marked benefit in tremor with both GPi and STN and DBS, however, there is a paucity of information available on AT vs RT when separated by the surgical target.MethodsWe retrospectively reviewed the 1-year clinical outcome of PD patients treated with STN and GPi DBS at the University of Florida. We specifically selected patients with moderate to severe AT. Eighty-eight patients (57 STN and 31 GPi) were evaluated at 6 and 12 months for changes in AT and RT in the OFF-medication/ON stimulation state. A comparison of “response” was performed and defined as greater than or equal to a 2-point decrease in tremor score.ResultsSTN and GPi DBS both improved AT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). The STN DBS group experienced a greater improvement in AT at 6 months compared to the GPi group (p = 0.005) but not at the 12 months follow-up (p = 0.301). Both STN and GPi DBS also improved RT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). There was no difference in RT scores between the two groups at 6 months (p = 0.23) or 12 months (p = 0.74). The STN group had a larger proportion of patients who achieved a “response” in AT at 6 months (p < 0.01), however, this finding was not present at 12 months (p = 0.23). A sub-analysis revealed that in RT, the STN group had a larger percentage of “responders” when followed through 12 months (p < 0.01).ConclusionBoth STN and GPi DBS reduced PD associated AT and RT at 12 months follow-up. There was no advantage of either brain target in the management of RT or AT. One nuance of the study was that STN DBS was more effective in suppressing AT in the early postoperative period, however, this effect diminished over time. Clinicians should be aware that it may take longer to achieve a similar tremor outcome when utilizing the GPi target.

Subthalamic nucleus and globus pallidus internus stimulation for the treatment of Parkinson's disease: A systematic review.

ObjectiveDeep brain stimulation (DBS) for treatment of advanced Parkinson’s disease (PD) has two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). The clinical effectiveness of these two stimulation targets was compared in the present study.MethodsA systematic review and meta-analysis was performed to evaluated the postoperative changes in the United Parkinson’s Disease Rating Scale (UPDRS) on- and off-phase, on-stimulation motor scores; activities of daily living score (ADLS); and levodopa equivalent dose (LED) after STN and GPI stimulation. Randomized and nonrandomized controlled trials of PD treated by STN and GPI stimulation were considered for inclusion.ResultsEight published reports of eligible studies involving 599 patients met the inclusion criteria. No significant differences were observed between the STN and GPI groups in the on-medication, on-stimulation UPDRS motor score [mean difference, 2.15; 95% confidence interval (CI), −0.96–5.27] or ADLS (mean difference, 3.40; 95% CI, 0.95–7.76). Significant differences in favor of STN stimulation were noted in the off-medication, on-stimulation UPDRS motor score (mean difference, 1.67; 95% CI, 0.98–2.37) and LED (mean difference, 130.24; 95% CI, 28.82–231.65).ConclusionThe STN may be the preferred target for DBS in consideration of medication reduction, economic efficiency, and motor function improvement in the off phase. However, treatment decisions should be made according to the individual patient’s symptoms and expectations.

Mental Health-Related Healthcare Use Following Bilateral Deep Brain Stimulation For Parkinson's Disease.

The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are both effective targets for deep brain stimulation (DBS) to relieve motor symptoms of Parkinson's disease. However, studies have reported varied effects on mental health-related adverse events and depressed mood following DBS. The current observational study sought to compare mental health healthcare utilization and costs for three years following STN or GPi DBS. For a cohort of Veterans (n = 161) with Parkinson's disease who participated in a larger multi-site randomized trial, we compared mental health outpatient visits, medication use, inpatient admissions, and associated costs by DBS target site (STN vs. GPi). Neither group nor time differences were significant for mental health outpatient or inpatient utilization following DBS. Overall costs associated with mental health visits and medications did not differ by time or by group. However, the percentage of patients with mental health medication use increased in the 6-month and 6 to 12 month periods post-surgery. The STN group had significantly greater increase in medication use at 6 to 12 months post-surgery compared to the GPi group (p < 0.05). Despite a brief increase in medication use following surgery, this study suggests that mental health healthcare use and costs are stable over time and similar between DBS targets. Prior research findings of mental health-related adverse events and mood following DBS did not translate to greater mental health service utilization in our cohort. The changes seen in the year following surgery may reflect temporary adjustments with stabilization over time.

Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease

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. 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. 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. 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.

GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease

ObjectivesTo compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities. MethodsWe conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32–34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case–control study. ResultsA total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131). ConclusionsThe overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.

The effects of subthalamic and pallidal deep brain stimulation on postural responses in patients with Parkinson disease

The effect of deep brain stimulation (DBS) for Parkinson disease (PD) on balance is unclear. The goal of this study was to investigate how automatic postural responses (APRs) were affected in patients randomized to either subthalamic nucleus (STN) or globus pallidus internus (GPi) surgery. The authors tested 24 patients with PD who underwent bilateral DBS, 9 control patients with PD who did not undergo DBS, and 17 age-matched control volunteers. The electrode placement site was randomized and blinded to the patients and to the experimenters. Kinematic, kinetic, and electromyographic recordings of postural responses to backward disequilibrium via forward translations of the standing surface were recorded in the week prior to surgery while the patients were off (OFF) and on (ON) antiparkinsonian medication (levodopa), and then 6 months after surgery in 4 conditions: 1) off medication with DBS switched off (OFF/OFF); 2) off medication with DBS on (DBS); 3) on medication with DBS off (DOPA); and 4) with both medication and DBS on (DBS+DOPA). Stability of the automatic postural response (APR) was measured as the difference between the displacement of the center of pressure and the projected location of the center of body mass. Patients with PD had worse APR stability than controls. Turning the DBS on at either site improved APR stability compared with the postoperative OFF condition by lengthening the tibialis response, whereas medication did not show an appreciable effect. The STN group had worse APR stability in their best functional state (DBS+DOPA) 6 months after the DBS procedure compared with their best functional state (ON levodopa) before the DBS procedure. In contrast, the GPi group and the PD control group showed no change over 6 months. The APR stability impairment in the STN group was associated with smaller tibialis response amplitudes, but there was no change in response latency or coactivation with gastrocnemius. Turning the DBS current on improved APR stability for both STN and GPi sites. However, there was a detrimental DBS procedural effect for the STN group, and this effect was greater than the benefit of the stimulating current, making overall APR stability functionally worse after surgery for the STN group.

Site of deep brain stimulation and jaw velocity in Parkinson disease

While deep brain stimulation (DBS) has proven to be an effective treatment for many symptoms of Parkinson disease (PD), a deterioration of axial symptoms frequently occurs, particularly for speech and swallowing. These unfavorable effects of DBS may depend on the site of stimulation. The authors made quantitative measures of jaw velocity to compare the relative effectiveness of DBS in the globus pallidus internus (GPi) or the subthalamic nucleus (STN). This was a randomized, double-blind, and longitudinal study, with matched healthy controls. The peak velocities of self-scaled and externally scaled jaw movements were studied in 27 patients with PD before and after 6 months of bilateral DBS in the GPi or the STN. A mixed-effects model was used to identify differences in jaw velocity before DBS surgery (baseline) while off and on levodopa therapy, and after 6 months of DBS (postoperative) during 4 treatment conditions (off- and on-levodopa states with and without DBS). Self-scaled jaw velocity was impaired by the DBS procedure in the STN; velocity was significantly decreased across all postoperative conditions compared with either the off- or on-levodopa baseline conditions. In contrast, the postoperative velocity in the GPi group was generally faster than the baseline off-levodopa state. Turning the DBS off and on had no effect on jaw velocity in either group. Unlike baseline, levodopa therapy postoperatively no longer increased jaw velocity in either group, and this lack of effect was not related to postoperative changes in dose. The externally scaled jaw velocity was little affected by PD, but DBS still slightly affected performance, with the STN group significantly slower than the GPi group for most conditions. The authors' results suggest that either the electrode implant in STN or the subsequent period of continuous STN stimulation negatively affected voluntary jaw velocity, including the loss of the preoperative levodopa-induced improvement. While the GPi group showed some improvement in voluntary jaw velocity postoperatively, their performance during the combination of DBS and levodopa was not different from their best medical management presurgery. The results have implications for DBS target selection, particularly for those patients with oromotor dysfunctions.

Do patient's get angrier following STN, GPi, and thalamic deep brain stimulation

Objective The objective of the study was to examine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), the globus pallidus internus (GPi), and/or the ventralis intermedius thalamic nucleus (Vim) was associated with making patients angrier pre to post-surgical intervention. Background Secondary outcome analysis of the NIH COMPARE Parkinson's Disease DBS trial revealed that participants were angrier and had more mood and cognitive side effects following DBS. Additionally blinded on/off analysis did not change anger scores. The sample size was small but suggested that STN DBS may have been worse than GPi in provoking anger. We endeavored to examine this question utilizing a larger dataset (the UF INFORM database), and also we included a third surgical target (Vim), which has been utilized for a different disease, essential tremor. Methods Consecutive patients from the University of Florida Movement Disorders Center who were implanted with unilateral DBS for Parkinson's disease (STN or GPi) or essential tremor (Vim) were included. Patients originally implanted at outside institutions were excluded. Pre-operative and 4- to 6-month post-operative Visual Analog Mood Scale (VAMS) scores for all three groups were compared; additionally, pre-operative and 1- to 3-month scores were compared for STN and GPi patients. A linear regression model was utilized to analyze the relationship between the VAMS anger score and the independent variables of age, years with symptoms, Mini-Mental Status Examination (MMSE) score, handedness, ethnicity, gender, side of surgery, target of surgery, baseline Dementia Rating Scale (DRS) total score, baseline Beck Depression Index (BDI) score, micro- and macroelectrode passes, and years of education. Levodopa equivalent dosages and dopamine agonist use were analyzed for a potential impact on anger scores. Results A total of 322 unilateral DBS procedures were analyzed, with STN ( n = 195), Vim ( n = 71), and GPi ( n = 56) making up the cohort. An ANOVA was used to detect significant differences among the three targets in the changes pre- to post-operatively. Similar to the COMPARE dataset, at 4 months, the only subscore of VAMS to reveal a significant difference between the three targets was the angry subscore, with GPi revealing a mean (standard) change of 2.38 (9.53); STN, 4.82 (14.52); and Vim, −1.17 (11.51) ( p = 0.012). At 1–3 months post-operation, both STN and GPi groups were significantly angrier ( p = 0.004), but there was no significant difference between the two groups. However, GPi patients were significantly more confused as compared to STN patients ( p = 0.016). The linear regression model which sought independent explanatory variables revealed a relationship between the VAMS anger score and the surgical target and the disease duration. The mean changes for STN and GPi DBS pre- to post-operation were 11.67 ( p = 0.001) and 8.21 ( p = 0.022) units more than those with Vim, respectively. For every year added of disease duration, the VAMS anger score increased by 0.24 ( p = 0.022). For the GPi and STN groups, number of microelectrode passes was significantly associated with angry score changes ( p = 0.014), with the anger score increasing 2.29 units per microelectrode pass. Independent variables not associated with the VAMS anger score included the surgery side, handedness, gender, ethnicity, education, age at surgery, MMSE, DRS, and BDI scores. Although the STN group significantly decreased in LED when compared to GPi, there was no relationship to anger scores. Similarly, dopamine agonist use was not different between STN and GPi groups and did not correlate with the VAMS anger score changes. Conclusions STN and GPi DBS for Parkinson's disease were associated with significantly higher anger scores pre- to post-DBS as compared to Vim for essential tremor. Anger score changes in STN and GPi patients seem to be associated with microelectrode passes, suggesting that it may be a lesional effect. PD patients with longer disease duration may be particularly susceptible, and this should be kept in mind when discussing the potential of DBS surgery for an individual patient. Essential tremor patients who on average have much longer disease durations did not get angrier. The changes in anger scores were not related to LED change or dopamine agonist use. Whether the induction of anger is disease-specific or target-specific is not currently known; however, our data would suggest that PD patients implanted in STN or GPi are at a potential risk. Finally, on closer inspection of the COMPARE DBS data, VAMS anger scores did not change on or off DBS, suggesting that anger changes may be more of a lesional effect rather than a stimulation induced one (Okun et al., 2009).

STN vs. Pallidal Stimulation in Parkinson Disease: Improvement With Experience and Better Patient Selection

Objectives. This is a prospective study to determine the outcomes of subthalamic nucleus (STN) vs. globus pallidus internus (GPi) deep brain stimulation (DBS) at our institution. Materials and Methods. We studied a total of 39 patients - 29 with STN and 10 with GPi DBS over a period of up to 6years. Mean ages in the two groups were similar (59 and 60years, respectively) and disease duration prior to implantation was similar (9.6 and 11.7years, respectively). Unified Parkinson Disease Rating Scale (UPDRS) was recorded preoperatively and at follow-up (at least at 6-month intervals). Medications also were recorded, and each patient's levodopa equivalent units (LEU) were calculated. Results were analyzed using a paired Student's t-test. Results. LEU reduced significantly (p<0.05) in the STN group (5.7 to 3.7) but not the GPi group. Both targets significantly improved part 3 and part 4 scores of the UPDRS but GPi DBS did not improve part 2 scores (activities of daily living). STN DBS had much better outcome on the motor "off" scores of the UPDRS, whereas GPi only improved tremor. A comparison of the "earliest 10" and "most recent 10" STN patients showed a significant improvement in outcome in the most recent cases. Conclusions. In our group, STN was more effective for alleviating the symptoms of Parkinson disease, even in older patients with significant dyskinesias. Better patient selection and greater experience have led to more improvement in the more recent patients.