Project description:Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson's disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores at baseline and 6-12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.
Project description:ObjectiveTo compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease (PD).MethodsWe retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups.ResultsAt 12 months, the mean changes in the UPDRS total and part I-IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697).ConclusionThe patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.
Project description:BackgroundGlobus pallidus internus (GPi) and subthalamic nucleus (STN) are two common deep brain stimulation (DBS) targets. This meta-analysis was to compared the efficacy and safety of these two DBS targets for the treatment of Meige syndrome (MS).MethodsA systematic search was performed using EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov to identify DBS trials for MS. Review Manager 5.3 was used to perform meta-analysis and the mean difference (MD) was analyzed and calculated with a random effect model. Pearson's correlation coefficients and meta-regression analyses were utilized to identify relevant predictive markers.ResultsTwenty trials involving 188 participants with GPi-DBS and 110 individuals with STN-DBS were eligible. Both groups showed improvement of the Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFMDRS-M) and Disability (BFMDRS-D) scores (BFMDRS-M: MD = 10.57 [7.74-13.41] for GPi-DBS, and MD = 8.59 [4.08-13.11] for STN-DBS; BFMDRS-D: MD = 5.96 [3.15-8.77] for GPi-DBS, and MD = 4.71 [1.38-8.04] for STN-DBS; all P < 0.001) from baseline to the final follow-up, while no notable disparity in improvement rates was observed between them. Stimulation-related complications occurrence was also similar between two groups (38.54 ± 24.07% vs. 43.17 ± 29.12%, P = 0.7594). Simultaneously, preoperative BFMDRS-M score and disease duration were positively connected with the relative changes in BFMDRS-M score at the final visit.ConclusionBoth GPi-DBS and STN-DBS are effective MS therapies, with no differences in efficacy or the frequency of stimulation-related problems. Higher preoperative scores and longer disease duration probably predict greater improvement.
Project description:There is an ongoing debate about differential clinical outcome and associated adverse effects of deep brain stimulation (DBS) in Parkinson's disease (PD) targeting the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Given that functional connectivity profiles suggest beneficial DBS effects within a common network, the empirical evidence about the underlying anatomical circuitry is still scarce. Therefore, we investigate the STN and GPi-associated structural covariance brain patterns in PD patients and healthy controls. We estimate GPi's and STN's whole-brain structural covariance from magnetic resonance imaging (MRI) in a normative mid- to old-age community-dwelling cohort (n = 1184) across maps of grey matter volume, magnetization transfer (MT) saturation, longitudinal relaxation rate (R1), effective transversal relaxation rate (R2*) and effective proton density (PD*). We compare these with the structural covariance estimates in patients with idiopathic PD (n = 32) followed by validation using a reduced size controls' cohort (n = 32). In the normative data set, we observed overlapping spatially distributed cortical and subcortical covariance patterns across maps confined to basal ganglia, thalamus, motor, and premotor cortical areas. Only the subcortical and midline motor cortical areas were confirmed in the reduced size cohort. These findings contrasted with the absence of structural covariance with cortical areas in the PD cohort. We interpret with caution the differential covariance maps of overlapping STN and GPi networks in patients with PD and healthy controls as correlates of motor network disruption. Our study provides face validity to the proposed extension of the currently existing structural covariance methods based on morphometry features to multiparameter MRI sensitive to brain tissue microstructure.
Project description:AimSubthalamic nucleus deep brain stimulation (STN-DBS) has been reported to be effective in treating motor symptoms in Parkinson's disease (PD), which may be attributed to changes in the brain network. However, the association between brain morphology and initial STN-DBS efficacy, as well as the performance of prediction using neuroimaging, has not been well illustrated. Therefore, we aim to investigate these issues.MethodsIn the present study, 94 PD patients underwent bilateral STN-DBS, and the initial stimulation efficacy was evaluated. Brain morphology was examined by magnetic resonance imaging (MRI). The volume of tissue activated in the motor STN was measured with MRI and computed tomography. The prediction of stimulation efficacy was achieved with a support vector machine, using brain morphology and other features, after feature selection and hyperparameter optimization.ResultsA higher stimulation efficacy was correlated with a thicker right precentral cortex. No association with subcortical gray or white matter volumes was observed. These morphological features could estimate the individual stimulation response with an r value of 0.5678, an R2 of 0.3224, and an average error of 11.4%. The permutation test suggested these predictions were not based on chance.ConclusionOur results indicate that changes in morphology are associated with the initial stimulation motor response and could be used to predict individual initial stimulation-related motor responses.
Project description:ObjectiveTo compare the efficacy of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on reducing levodopa-induced dyskinesia (LID) in Parkinson's disease, and to explore the potential underlying mechanisms.MethodsWe retrospectively assessed clinical outcomes in 43 patients with preoperative LID who underwent DBS targeting the STN (20/43) or GPi (23/43). The primary clinical outcome was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) and secondary outcomes included changes in the total daily levodopa equivalent dose, the drug-off Unified Parkinson Disease Rating Scale Part Ⅲ at the last follow-up (median, 18 months), adverse effects, and programming settings. Correlation analysis was used to find potential associated factors that could be used to predict the efficacy of DBS for dyskinesia management.ResultsCompared to baseline, both the STN group and the GPi group showed significant improvement in LID with 60.73 ± 40.29% (mean ± standard deviation) and 93.78 ± 14.15% improvement, respectively, according to the UDysRS score. Furthermore, GPi-DBS provided greater clinical benefit in the improvement of dyskinesia (P < 0.05) compared to the STN. Compared to the GPi group, the levodopa equivalent dose reduction was greater in the STN group at the last follow-up (43.81% vs. 13.29%, P < 0.05). For the correlation analysis, the improvement in the UDysRS outcomes were significantly associated with a reduction in levodopa equivalent dose in the STN group (r = 0.543, P = 0.013), but not in the GPi group (r = -0.056, P = 0.801).InterpretationBoth STN and GPi-DBS have a beneficial effect on LID but GPi-DBS provided greater anti-dyskinetic effects. Dyskinesia suppression for STN-DBS may depend on the reduction of levodopa equivalent dose. Unlike the STN, GPi-DBS might exert a direct and independent anti-dyskinesia effect.
Project description:BackgroundMutations in the G-protein subunit alpha o1 (GNAO1) gene have recently been shown to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. The clinical manifestations of GNAO1-associated movement disorders are highly heterogeneous. However, the genotype-phenotype correlations in this disease remain unclear, and the treatments for GNAO1-associated movement disorders are still limited.ObjectiveThe objective of this study was to explore diagnostic and therapeutic strategies for GNAO1-associated movement disorders.MethodsThis study describes the cases of three Chinese patients who had shown severe and progressive dystonia in the absence of epilepsy since early childhood. We performed genetic analyses in these patients. Patients 1 and 2 underwent globus pallidus internus (GPi) deep brain stimulation (DBS) implantation, and Patient 3 underwent subthalamic nucleus (STN) DBS implantation. In addition, on the basis of a literature review, we summarized and discussed the clinical characteristics and outcomes after DBS surgery for all reported patients with GNAO1-associated movement disorders.ResultsWhole-exome sequencing (WES) analysis revealed de novo variants in the GNAO1 gene for all three patients, including a splice-site variant (c.724-8G > A) in Patients 1 and 3 and a novel heterozygous missense variant (c.124G > A; p. Gly42Arg) in Patient 2. Both GPi and STN DBS were effective in improving the dystonia symptoms of all three patients.ConclusionDBS is effective in ameliorating motor symptoms in patients with GNAO1-associated movement disorders, and both STN DBS and GPi DBS should be considered promptly for patients with sustained refractory GNAO1-associated dystonia.
Project description:INTRODUCTION:Previous studies found subthalamic nucleus deep brain stimulation (STN-DBS) has clinical effect on Parkinson's disease, dystonia, and obsessive compulsive disorder. It is noteworthy that only a few studies report the STN-DBS for Tourette's syndrome (TS). Globus pallidus interna (GPi)-DBS is the one of the most common targets for TS. So, this paper aims to investigate the neural oscillations in STN and GPi as well as the DBS effect between these two targets in same patients. METHODS:The local field potentials (LFPs) were simultaneously recorded from the bilateral GPi and STN in four patients with TS. The LFPs were decomposed into neural oscillations, and the frequency and time-frequency characteristics of the neural oscillations were analyzed across the conditions of resting, poststimulation, and movement. RESULTS:No difference of resting LFP was found between the two targets. The poststimulation period spectral power revealed the high beta and gamma oscillations were recovered after GPi-DBS but remained attenuated after STN-DBS. The STN beta oscillation has fewer changes during tics than voluntary movement, and the gamma oscillation was elevated when the tics appeared. CONCLUSION:The high beta and gamma oscillations in GPi restored after GPi-DBS, but not STN-DBS. High beta and gamma oscillations may have physiological function in resisting tics in TS. The cortex compensation effect might be interfered by the STN-DBS due to the influence on the hyper-direct pathway but not GPi-DBS.
Project description:Deep-brain stimulation (DBS) is an effective treatment for patients with Meige syndrome. The globus pallidus interna (GPi) and the subthalamic nucleus (STN) are accepted targets for this treatment. We compared 12-month outcomes for patients who had undergone bilateral stimulation of the GPi or STN. Forty-two Asian patients with primary Meige syndrome who underwent GPi or STN neurostimulation were recruited between September 2017 and September 2019 at the Department of Neurosurgery, Peking University People's Hospital. The primary outcome was the change in motor function, including the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) and disability subscale (BFMDRS-D) at 3 days before DBS (baseline) surgery and 1, 3, 6, and 12 months after surgery. Secondary outcomes included health-related quality of life, sleep quality status, depression severity, and anxiety severity at 3 days before and 12 months after DBS surgery. Adverse events during the 12 months were also recorded. Changes in BFMDRS-M and BFMDRS-D scores at 1, 3, 6, and 12 months with DBS and without medication did not significantly differ based on the stimulation target. There were also no significant differences in the changes in health-related quality of life (36-Item Short-Form General Health Survey) and sleep quality status (Pittsburgh Sleep Quality Index) at 12 months. However, there were larger improvements in the STN than the GPi group in mean score changes on the 17-item Hamilton depression rating scale (- 3.38 vs. - 0.33 points; P = 0.014) and 14-item Hamilton anxiety rating scale (- 3.43 vs. - 0.19 points; P < 0.001). There were no significant between-group differences in the frequency or type of serious adverse events. Patients with Meige syndrome had similar improvements in motor function, quality of life and sleep after either pallidal or subthalamic stimulation. Depression and anxiety factors may reasonably be included during the selection of DBS targets for Meige syndrome.
Project description:ObjectiveThe subthalamic nucleus (STN) and internal globus pallidus (GPi) are the most effective targets in deep brain stimulation (DBS) for Parkinson's disease (PD). However, the common and specific effects on brain connectivity of stimulating the 2 nuclei remain unclear.MethodsPatients with PD receiving STN-DBS (n = 27, 6 women, mean age 64.8 years) or GPi-DBS (n = 28, 13 women, mean age 64.6 years) were recruited for resting-state functional magnetic resonance imaging to assess the effects of STN-DBS and GPi-DBS on brain functional dynamics.ResultsThe functional connectivity both between the somatosensory-motor cortices and thalamus, and between the somatosensory-motor cortices and cerebellum decreased in the DBS-on state compared with the off state (p < 0.05). The changes in thalamocortical connectivity correlated with DBS-induced motor improvement (p < 0.05) and were negatively correlated with the normalized intersection volume of tissues activated at both DBS targets (p < 0.05). STN-DBS modulated functional connectivity among a wider range of brain areas than GPi-DBS (p = 0.009). Notably, only STN-DBS affected connectivity between the postcentral gyrus and cerebellar vermis (p < 0.001) and between the somatomotor and visual networks (p < 0.001).InterpretationOur findings highlight common alterations in the motor pathway and its relationship with the motor improvement induced by both STN- and GPi-DBS. The effects on cortico-cerebellar and somatomotor-visual functional connectivity differed between groups, suggesting differentiated neural modulation of the 2 target sites. Our results provide mechanistic insight and yield the potential to refine target selection strategies for focal brain stimulation in PD. ANN NEUROL 2021;90:670-682.