OBJECTIVE: Deep Brain Stimulation (DBS) was approved by Food and Drug Administration for Parkinson's Disease, essential tremor, primary generalized or segmental dystonia and obsessive-compulsive disorder treatment. The exact mechanism of DBS remains unclear which causes side effects. The aim of this review was to assess variables causing stimulation-induced chronic psychiatric/ personality-changing side effects.
METHODS: The analysis of scientific database (PubMed, Cochrane Library, EMBASE) was conducted. The included articles had to be research study or case report and DBS to be conducted in therapeutic purposes. The researches with mental disorders in patients' medical histories were excluded.
RESULTS: 17 articles were used in the review. In the group of movement disorders the characteristic of side effects was strongly related to the placement of the electrode implantation. Tiredness/ fatigue was correlated with DBS in thalamus. Implantations in subthalamic nucleus were mostly followed by affective side effects such as depression or suicide. The higher voltage of electrode was connected with more severe depression after implantation. The analysis of affective disorder contained only 3 articles - 2 about obsessive-compulsive disorder and 1 about depression. Forgetfulness and word-finding problems as activities connected with cognition may be an inevitable side effect if obsessive thoughts are to be inhibited.
CONCLUSION: DBS of subthalamic nucleus should be seen as the most hazardous place of implantation. As a result there is a strong need of "gold standards" based on the connectivity research and closer cooperation of scientists and clinicians.
OBJECTIVE Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson's disease(PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets,their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objectiveof this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS ofGPi or STN at various time points, including 36 months of follow-up.METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registriesfor clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched.Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through databasesearch, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independentlyand in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidenceprofile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of dailyliving, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and theproportion of male patients within a study (post hoc) were explored as potential subgroups.RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily livingwas identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference[WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantlybetter with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99-4.06 p = 0.001). The motor benefits of GPi and STN DBSfor PD are similar.CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for agreater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This differenceis sustained at 36 months. Further long-term studies are necessary.
BACKGROUND: Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS.
METHODS: A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows).
RESULTS: Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11).
CONCLUSIONS: There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.
QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores?
RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I).
QUESTION 2: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease?
RECOMMENDATION: When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I).
QUESTION 3: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease?
RECOMMENDATION: There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I).
QUESTION 4: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease?
RECOMMENDATION: When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I).
QUESTION 5: Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease?
RECOMMENDATION: If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I).
QUESTION 6: Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson's disease?
RECOMMENDATION: If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I).
QUESTION 7: Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson's disease?
RECOMMENDATION: There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events. The full guideline can be found at: https://www.cns.org/guidelines/deep-brain-stimulation-parkinsons-disease.
Objective Deep 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. Methods A 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. Results Eight 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). Conclusion The 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.
The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow-up periods: 6-15, 24-48 and >48 months. For the medication (Med)-Off/stimulation(Stim)-On condition compared with baseline Med-Off, STN-DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). Pre-operative levodopa responsiveness of UPDRS-III and Med-Off severity of gait were the predictors of this beneficial effect. STN-DBS significantly improved FOG for the Med-Off/Stim-On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med-On/Stim-On condition. This meta-analysis showed a robust improvement of gait and FOG by STN-DBS for more than 4 years in the Med-Off/Stim-On condition. No beneficial effect was found for the On state of medication. Pre-operative levodopa responsiveness of global motor performance (UPDRS-III) is the strongest predictor of the effect of deep brain stimulation on gait.
Objective: To evaluate the efficacy and safety of subthalamic nucleus deep brain stimulation (STN-DBS) combined with drug therapy for treating Parkinson's disease (PD). Methods: Retrieve relevant randomized controlled trials (RCTs) from online databases (January 1, 1980-October 1, 2016) as PubMed, EBMASE/SCOPUS and Cochrane Library with key words: subthalamic nucleus, deep brain stimulation, DBS, STN, Parkinson disease, random. Selection of studies was performed according to pre-designed inclusion and exclusion criteria. Quality of studies was evaluated by using Jadad Scale and Cochrane Handbook for Systematic Reviews of Interventions. All data were pooled by RevMan 5.2 software for Meta-analysis. Results: The research enrolled 3245 articles, from which 6 studies with Jadad score ≥ 4 were chosen after excluding duplicates and those not meeting the inclusion criteria. A total of 958 PD patients were included. Meta-analysis showed that comparing with best medical treatment (BMT), STN-DBS combined with drug therapy significantly reduced the scores of Unified Parkinson's Disease Rating Scale (UPDRS)III in the "on" phase (SMD =-0.570, 95%CI:-0.710-- 0.430; P = 0.000) and in the "off" phase (SMD =-1.170, 95%CI:-1.500--0.850; P = 0.000), UPDRS I score (SMD =-0.150, 95%CI:-0.290--0.010; P = 0.030), and 39-Item Parkinson's Disease Questionnaire (PDQ-39) score (SMD =-0.510, 95%CI:-0.660--0.370; P = 0.000). But it can increase the occurrence of severe adverse events (RD = 0.140, 95% CI: 0.090-0.190; P = 0.000) and dysarthria (RD = 0.070, 95%CI: 0.010-0.120; P = 0.020), while decrease the occurrence of dyskinesia (RR = 0.450, 95% CI: 0.330-0.620; P = 0.000). Conclusions: Subthalamic nucleus deep brain stimulation combined with drug therapy could greatly improve motor function, mental status and quality of life of PD patients, however, clinicians should pay more attention to the increased risk of severe adverse events and dysarthria after operation.
Parkinson’s disease (PD) is a neurodegenerative condition, which compromises the motor functions and causes the alteration of some executive brain functions. The presence of changes in cognitive symptoms in PD could be due to the procedure of deep brain stimulation (DBS). We searched in several databases for studies that compared performance in executive function tests before and after the DBS procedure in PE and then performed a meta-analysis. After the initial search, there were 15 articles that specifically evaluated the functions of verbal fluency, working memory, cognitive flexibility, abstract thinking, and inhibition. It was found that there were differences in the evaluation of the cognitive functions in terms of the protocols, which generated heterogeneity in the results of the meta-analysis. Likewise, a tendency to diminish functions like verbal fluency and inhibition was found, being this consistent with similar studies. In the other functions evaluated, no difference was found between pre- and postsurgery scores. Monitoring of this type of function is recommended after the procedure.
Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). We aim to evaluate the efficacy of GPi (globus pallidus internus), STN (subthalamic nucleus)-DBS and medical therapy for PD. We conducted a systematic review and multiple-treatments meta-analysis to investigate the efficacy of neurostimulation and medical therapy for PD patients. Sixteen eligible studies were included in this analysis. We pooled the whole data and found obvious difference between GPi-DBS versus medical therapy and STN-DBS versus medical therapy in terms of UPDRS scores (Unified Parkinson's Disease Rating Scale). Meanwhile, we found GPi-DBS had the similar efficacy on the UPDRS scores when compared with STN-DBS. What is more, quality of life, measured by PDQ-39 (Parkinson's disease Questionnaire) showed greater improvement after GPi-DBS than STN-DBS. Five studies showed STN-DBS was more effective for reduction in medication than GPi-DBS. Overall, either GPi-DBS or STN-DBS was an effective technique to control PD patients' symptoms and improved their functionality and quality of life. Meanwhile, the UPDRS scores measuring parkinsonian symptoms revealed no significant difference between GPi-DBS and STN-DBS. STN-DBS was more effective for reduction in medication than GPi-DBS. Alternatively, GPi-DBS was more effective for improving the PDQ-39 score than STN-DBS.
Deep brain stimulation (DBS) is the surgical procedure for patients with advanced Parkinson's disease. Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the most targeted locations for the procedure. To investigate the variable efficiencies for the two different locations, we conducted a meta-analysis to compare both stimulation sites. MATERIALS AND METHODS: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Randomized controlled trials comparing the efficacies of GPi and STN DBS were included. Clinical outcomes of motor function, nonmotor function, and quality of life (QOL) were collected for the meta-analysis. RESULTS: Ten eligible trials with 1,034 patients were included in the analysis. Unified Parkinson's disease rating scale III (UPDRS-III) scores were collected at 6, 12, and 24 months postsurgery separately to assess the motor function of the patients. A statistically significant effect in favor of the GPi DBS was obtained in the off-medication/on-stimulation phase of UPDRS-III at 12 months (mean difference [MD] =6.87, 95% confidence interval [95% CI]: 3.00-10.74, P=0.57, I (2)=0%). However, GPi DBS showed an opposite result at 24 months (MD =-2.46, 95% CI: -4.91 to -0.02, P=0.05, I (2)=0%). In the on-medication/on-stimulation phase, GPi DBS obtained a worse outcome compared with STN DBS (MD =-2.90, 95% CI: -5.71 to -0.09, P=0.05, I (2)=0%). Compared with STN DBS, increased dosage of levodopa equivalent doses was needed in GPi DBS (standardized MD =0.60, 95% CI: 0.46-0.74, P<0.00001, I (2)=24%). Meanwhile, Beck Depression Inventory II scores demonstrated that STN has a better performance (standardized MD =-0.31, 95% CI: -0.51 to -0.12, P=0.002, I (2)=0%). As for neurocognitive phase postsurgery, GPi DBS showed better performance in three of the nine tests, especially in verbal fluency. Use of GPi DBS was associated with a greater effect in eight of the nine subscales of QOL. CONCLUSION: GPi and STN DBS significantly improve advanced Parkinson's patients' symptoms, functionality, and QOL. Variable therapeutic efficiencies were observed in both procedures, GPi and STN DBS. GPi DBS allowed greater recovery of verbal fluency and provided greater relief of depression symptoms. Better QOL was also obtained using GPi DBS. Meanwhile, GPi DBS was also associated with increased dosage of levodopa equivalent doses. The question regarding which target is superior remained open for discussion. An understanding of the target selection still depends on individual symptoms, neurocognitive/mood status, therapeutic goals of DBS (eg, levodopa reduction), and surgical expertise.
Deep Brain Stimulation (DBS) was approved by Food and Drug Administration for Parkinson's Disease, essential tremor, primary generalized or segmental dystonia and obsessive-compulsive disorder treatment. The exact mechanism of DBS remains unclear which causes side effects. The aim of this review was to assess variables causing stimulation-induced chronic psychiatric/ personality-changing side effects.
METHODS:
The analysis of scientific database (PubMed, Cochrane Library, EMBASE) was conducted. The included articles had to be research study or case report and DBS to be conducted in therapeutic purposes. The researches with mental disorders in patients' medical histories were excluded.
RESULTS:
17 articles were used in the review. In the group of movement disorders the characteristic of side effects was strongly related to the placement of the electrode implantation. Tiredness/ fatigue was correlated with DBS in thalamus. Implantations in subthalamic nucleus were mostly followed by affective side effects such as depression or suicide. The higher voltage of electrode was connected with more severe depression after implantation. The analysis of affective disorder contained only 3 articles - 2 about obsessive-compulsive disorder and 1 about depression. Forgetfulness and word-finding problems as activities connected with cognition may be an inevitable side effect if obsessive thoughts are to be inhibited.
CONCLUSION:
DBS of subthalamic nucleus should be seen as the most hazardous place of implantation. As a result there is a strong need of "gold standards" based on the connectivity research and closer cooperation of scientists and clinicians.
