Deep Brain Stimulation In Parkinson's Disease Research Articles

Deep brain stimulation in Parkinson's disease: A scientometric and bibliometric analysis, trends, and research hotspots.

Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital remedy for refractory cases. This study performs a bibliometric analysis on DBS in PD, delving into research trends and study impact to offer comprehensive insights for researchers, clinicians, and policymakers, illuminating the current state and evolutionary trajectory of research in this domain. A systematic search on March 13, 2023, in the Scopus database utilized keywords like "Parkinson disease," "PD," "Parkinsonism," "Deep brain stimulation," and "DBS." The top 1000 highly cited publications on DBS in PD underwent scientometric analysis via VOS Viewer and R Studio's Bibliometrix package, covering publication characteristics, co-authorship, keyword co-occurrence, thematic clustering, and trend topics. The bibliometric analysis spanned 1984 to 2021, involving 1000 cited articles from 202 sources. The average number of citations per document were 140.9, with 31,854 references. "Movement Disorders" led in publications (n = 98), followed by "Brain" (n = 78) and "Neurology" (n = 65). The University of Oxford featured prominently. Thematic keyword clustering identified 9 core research areas, such as neuropsychological function and motor circuit electrophysiology. The shift from historical neurosurgical procedures to contemporary focuses like "beta oscillations" and "neuroethics" was evident. The bibliometric analysis emphasizes UK and US dominance, outlining 9 key research areas pivotal for reshaping Parkinson treatment. A discernible shift from invasive neurosurgery to DBS is observed. The call for personalized DBS, integration with NIBS, and exploration of innovative avenues marks the trajectory for future research.

Effects of Unilateral High Frequency Stimulation of the Subthalamic Nucleus on Risk-avoidant Behavior in a Partial 6-hydroxydopamine Model of Parkinson's Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.

1136 Risk Factors for Postoperative Urinary Retention After Deep Brain Stimulation Surgery: The Role of the Subthalamic Nucleus

INTRODUCTION: Deep brain stimulation (DBS) is a widely used neurosurgical procedure for treating Parkinson's disease (PD) and essential tremor (ET). Lower urinary tract dysfunction is a common complication in PD, and this study examines the risk factors for postoperative urinary retention (POUR) after DBS surgery in PD and ET patients to improve patient outcomes. METHODS: This retrospective study analyzed data from patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. Data on patient characteristics and surgical details were collected and analyzed using univariate and mixed-linear models. RESULTS: 350 patients underwent 1086 DBS or IPG surgeries, with 153 of them having PD and 197 having ET. The rate of POUR was 79/477 (16.6%), 19/295 (5.2%), and 1/246 (0.4%) for Part 1, Part 2, and IPG replacement. Optimal mixed linear modeling revealed history of urinary retention (OR = 10.2, p = .002), Part 1 surgery (OR = 3.6 compared to Part 2, p < .0003), male sex (OR = 2.5, p = .011), having an electrode placed or connected for the first time (OR = 1.8, p = .046), surgical time (OR 1.5 for each 30 min increase, p < .0001), CCI (OR = 1.4 per comorbidity, p= .006), and preoperative opioid use (OR 1.4 for each additional 10 MME, p = .022) to be significant risk factors for POUR. Having an electrode in STN was found to be protective of POUR (OR = 0.4, p = .030). CONCLUSIONS: While most identified risk factors for POUR in DBS are non-modifiable, they remain important for preoperative planning. Reducing opioid use and minimizing surgical time may help mitigate POUR risk. Targeting the STN during DBS may lead to decreased POUR rates, indicating the potential benefits of STN-targeted DBS for PD and ET patients.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Overlapping stimulation of subthalamic nucleus and dentato-rubro-thalamic tract in Parkinson's disease after deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt. A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains. Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR. DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.

7-Tesla Magnetic Resonance Imaging Scanning in Deep Brain Stimulation for Parkinson's Disease: Improving Visualization of the Dorsolateral Subthalamic Nucleus.

Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

Disparities in the treatment of movement disorders using deep brain stimulation.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

White matter connectivity of subthalamic nucleus and globus pallidus interna targets for deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking. The objective was to find STN and GPi structural connectivity patterns in order to better understand differences in DBS-activated brain circuits between these two stimulation targets and to guide optimal contact selection. The authors simulated DBS activation along the main axis of both the STN and GPi by using volume of activated tissue (VAT) modeling with known average stimulation parameters (2.8 V and 60 μsec for STN; 3.3 V and 90 μsec for GPi). The authors modeled VATs in the anterior, middle, and posterior STN and the anterior, midanterior, midposterior, and posterior GPi. The authors generated maps of the connections shared by the patients for each VAT by using probabilistic tractography of diffusion-weighted imaging data obtained in 46 PD patients who underwent DBS (26 with STN and 20 with GPi targeting), and differences between VATs for whole-brain and distal regions of interest (prefrontal cortex, supplementary motor area, primary motor cortex, primary sensory cortex, caudate, motor thalamus, and cerebellum) were generated from structural atlases. Differences between maps were quantified and compared. VATs across the STN and GPi had different structural connectivity patterns. The authors found significant connectivity differences between VATs for all regions of interest. Posterior and middle STN showed stronger connectivity to the primary motor cortex and supplementary motor area (SMA) (p < 0.001). Posterior STN had the strongest connectivity to the primary sensory cortex and motor thalamus (p < 0.001). Posterior GPi showed stronger connectivity to the primary motor cortex (p < 0.001). Connectivity to the SMA was similar for the posterior and midposterior GPi (p > 0.05), which was greater than that for the anterior GPi (p < 0.001). When both nuclei were compared, posterior and middle STN had stronger connectivity to the SMA, cerebellum, and motor thalamus than GPi (all p < 0.001). Posterior GPi and STN had similar connectivity to the primary sensory cortex. On patient-specific imaging, structural connectivity differences existed between GPi and STN DBS, as measured with standardized electrical field modeling of the DBS targets. These connectivity differences may correlate with the differential clinical benefits obtained by targeting each of the two nuclei with DBS for PD. Prospective work is needed to relate these differences to clinical outcomes and to inform targeting and programming.

The Five-Factor Modified Frailty Index as a Predictor of Outcomes in Deep Brain Stimulation Surgery for Parkinson's Disease.

Introduction Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Though there are many pharmacological therapeutics approved today for PD, surgical interventions such as deep brain stimulation (DBS) have shown convincing symptom mitigation and minimal complication rates in aggregate. Recently, the concept of frailty - defined as reduced physiologic reserve and function affecting multiple systems throughout the patient - has gained traction as a predictor of short-term postoperative morbidity and mortality. As such, the Modified Frailty Index-5 (mFI-5) is a postoperative morbidity predictor based on five factors and has been used in neurosurgical subspecialties such as tumor, vascular, and spine. Yet, there is minimal literature assessing frailty in the field of functional neurosurgery. With the prevalence of DBS in PD, this study evaluated the mFI-5 as a predictor of postoperative complications in a selected patient population. Methods The American College of Surgeons National Surgical Quality Improvement Program 2010-2019 Database was queried for Current Procedural Terminology (CPT) codes, as well as the International Classification of Diseases (ICD)-9 and ICD-10 codes pertaining to DBS procedures in PD patients. Each patient was scored by the mFI-5 protocol and stratified into groups of No Frailty (mFI-5=0), Moderate Frailty (mFI-5=1), and Significant Frailty (mFI-5≥2). The No Frailty group was used as a reference in multivariate and univariate analyses of the groups. Results A total of 1,645 subjects were included in the study and were subcategorized into groups of No Frailty (N=877), Moderate Frailty (N=561), and Significant Frailty (N=207) based on their frailty scores. The subjects' mean age was 65.8±9.4 years. Overall, 1,161 (70.6%) were male, while 484 (29.4%) were female. With reference to the No Frailty group in multivariate analysis, patients with moderate frailty experienced greater unplanned readmission (OR 2.613, 95% CI 1.143-5.973, p=0.023), while those with significant frailty experienced greater unplanned readmission (OR 3.723, 95% CI 1.376-10.073, p=0.010), any readmission (OR 2.396, 95% CI 1.098-5.230, p=0.028), non-home discharge (OR 4.317, 95% CI 1.765-10.562, p<0.001), and complications in aggregate (OR 2.211, 95% CI 1.285-3.806, p=0.004). Conclusions Until now, the available clinical tools were limited in providing accurate predictions with minimal information for postoperative outcomes in DBS for PD patients. Our data give clinicians insight into the relationship between frailty and surgical outcomes and will assist physicians in preparing for postoperative care by predicting outcomes of significantly frail PD patients receiving DBS therapy.

Long-term neuropsychological outcomes of deep brain stimulation in early-stage Parkinson's disease

IntroductionThe pilot trial of deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) randomized 30 patients (medication duration 0.5–4 years; without dyskinesia or motor fluctuations) to receive optimal drug therapy alone (early ODT) or subthalamic nucleus (STN) DBS plus ODT (early DBS + ODT). This study reports long-term neuropsychological outcomes from the early DBS pilot trial. MethodsThis is an extension of an earlier study that examined two-year neuropsychological outcomes in the pilot trial. The primary analysis was conducted on the five-year cohort (n = 28), and a secondary analysis was conducted on the 11-year cohort (n = 12). Linear mixed effects models for each analysis compared overall trend in outcomes for randomization groups. All subjects who completed the 11-year assessment were also pooled to evaluate long-term change from baseline. ResultsThere were no significant differences between groups in either the five- or 11-year analyses. Across all PD patients who completed the 11-year visit, there was significant decline in Stroop Color and Color-Word and Purdue Pegboard from baseline to 11 years. ConclusionsPrevious significant differences between the groups in phonemic verbal fluency and cognitive processing speed showing more decline for early DBS + ODT subjects one year after baseline diminished as PD progressed. No cognitive domains were worse for early DBS + ODT subjects compared to standard of care subjects. There were shared declines across all subjects on cognitive processing speed and motor control, likely reflecting disease progression. More study is needed to understand the long-term neuropsychological outcomes associated with early DBS in PD.

Oscillatory beta dynamics inform biomarker-driven treatment optimization for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons and dysregulation of the basal ganglia. Cardinal motor symptoms include bradykinesia, rigidity, and tremor. Deep brain stimulation (DBS) of select subcortical nuclei is standard of care for medication-refractory PD. Conventional open-loop DBS delivers continuous stimulation with fixed parameters that do not account for a patient's dynamic activity state or medication cycle. In comparison, closed-loop DBS, or adaptive DBS (aDBS), adjusts stimulation based on biomarker feedback that correlates with clinical state. Recent work has identified several neurophysiological biomarkers in local field potential recordings from PD patients, the most promising of which are 1) elevated beta (∼13-30 Hz) power in the subthalamic nucleus (STN), 2) increased beta synchrony throughout basal ganglia-thalamocortical circuits, notably observed as coupling between the STN beta phase and cortical broadband gamma (∼50-200 Hz) amplitude, and 3) prolonged beta bursts in the STN and cortex. In this review, we highlight relevant frequency and time domain features of STN beta measured in PD patients and summarize how spectral beta power, oscillatory beta synchrony, phase-amplitude coupling, and temporal beta bursting inform PD pathology, neurosurgical targeting, and DBS therapy. We then review how STN beta dynamics inform predictive, biomarker-driven aDBS approaches for optimizing PD treatment. We therefore provide clinically useful and actionable insight that can be applied toward aDBS implementation for PD.

Comparison of intraoperative imaging guided versus microelectrode recording guided deep brain stimulation for Parkinson's disease: A meta-analysis

BackgroundTraditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD). MethodsPubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site. ResultsSix studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were −0.45 (95% confidence interval, CI=−1.11 to 0.20), −0.18 (95% CI=−0.41 to 0.06), 3.40 (95% CI=−5.36 to 12.16), and 5.00 (95% CI=−1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques. ConclusionsBoth IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment.

Identifying the Sources of Racial Disparity in the Treatment of Parkinson's Disease With Deep Brain Stimulation.

Deep brain stimulation (DBS) is a highly efficacious treatment for appropriately selected patients with advanced, medically refractory Parkinson's disease (PD). It is severely underutilized in Black patients-constituting a major treatment gap. The source of this disparity is unknown, but its identification and correction are necessary to provide equitable care. To identify sources of racial disparity in DBS for PD. We predicted the demographics of potential DBS candidates by synthesizing published data on PD and race. We retrospectively examined the clinical course of a cohort including all patients with PD evaluated for DBS at our center from 2016 to 2020, testing whether the rate of DBS use and time from evaluation to surgery differed by race. We also tested whether the geographic distribution of patient catchment was biased relative to racial demographics. Far fewer Black patients were evaluated for DBS than would be expected, given regional demographics. There was no significant difference in the rate at which Black patients evaluated in our clinic were treated with DBS, compared with White patients. Fewer patients were recruited from portions of the surrounding area with larger Black populations. The known underuse of DBS in Black patients with PD was replicated in this sample from a center in a racially diverse metropolitan area, but was not attributable to the presurgical workup. Future work should examine the transition from medical management to surgical evaluation where drivers of disparity are potentially situated. Surgical practices should increase outreach to physicians managing PD in underserved areas.

Gender-specific outcomes of deep brain stimulation for Parkinson’s disease — results from a single movement disorder center

Introduction and goalThe investigation of gender differences in treatment response is crucial for effective personalized therapies. With only 30%, women are underrepresented in trials for deep brain stimulation (DBS) in Parkinson’s disease (PD). It is therefore important to evaluate gender-specific outcomes of DBS in PD in order to improve therapeutic counseling.MethodsWe analyzed clinical outcome parameters of 203 patients with PD that underwent DBS surgery targeting the subthalamic nucleus (STN) at our movement disorder center. A total of 27.6% of patients were female and 72.4% male. Motor and non-motor scores were compared before and 1 year after DBS surgery (1y FU) using Wilcoxon signed-rank tests and gender specific outcomes were analyzed with chi-square tests.ResultsAt 1y FU, we found significant improvement in UPDRS II, UPDRS III (35.78 ± 36.14% MedOFF vs. StimON-MedOFF), UPDRS IV, depression (BDI-II), and health-related disability as (ADL) that showed no gender-specific differences. No significant change was revealed for UPDRS I, QUIP, and DemTect for the entire cohort. However, when analyzing both groups separately, only women improved in general cognition (plus 1.26 ± 3.03 DemTect points, p = 0.014*), whereas only men ameliorated in depression (minus 1.97 ± 6.92 BDI-II points, p = 0.002**) and impulsivity (minus 2.80 ± 7.27 QUIP points, p = 0.004**). Chi-square tests, however, revealed no significant differences between genders.Conclusion and outlookSTN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in non-motor-domains like cognition, depressive symptoms, and impulsivity. To explore this in more detail, larger cohorts need to be investigated in multicenter trials.

Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease

ObjectiveThe deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5–4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial. Materials and MethodsAttempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures. ResultsTwelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson’s Disease Rating Scale [UPDRS]–IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; pinteraction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire–39 (PDQ-39), and levodopa equivalent daily dose (LEDD). ConclusionsEleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016). Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT00282152.

Deep Brain Stimulation for Advanced Parkinson Disease in Developing Countries: A Cost-Effectiveness Study From China.

The cost-effectiveness of deep brain stimulation (DBS) is more favorable than best medical treatment (BMT) for advanced Parkinson disease (PD) in developed countries. However, it remains unclear in developing countries, where the cost of DBS may not be reimbursed by health care system. To model and evaluate the long-term cost-effectiveness of DBS for advanced PD in China from a patient payer perspective. We developed a Markov model representing the clinical progress of PD to predict the disease progression and related medical costs in a 15-year time horizon. The incremental cost-effectiveness ratio (ICER) and net benefit were used to evaluate the cost-effectiveness of DBS vs BMT. DBS treatment led to discounted total costs of ¥370 768 ($56 515.20) (95% CI, ¥369 621.53-371 914.88), compared with ¥48 808 ($7439.68) (95% CI, ¥48 502.63-49 114.21) for BMT, with an additional 1.51 quality-adjusted life years gained, resulting in an ICER of ¥213 544 ($32 549.96)/quality-adjusted life years (95% CI, ¥208 177.35-218 910.10). Sensitivity analysis showed that DBS-related cost has the most substantial impact on ICER. Nation-wide net benefit of BMT and DBS were ¥33 819 ($5154.94) (95% CI, ¥30 211.24-37 426) and ¥30 361 ($4627.85) (95% CI, ¥25 587.03-39 433.66), respectively. Patient demographic analysis showed that more favorable DBS cost-effectiveness was associated with younger age and less severe disease stage. DBS is cost-effective for patients with advanced PD over a 15-year time horizon in China. However, compared with developed countries, DBS remains a substantial economic burden for patients when no reimbursement is provided. Our findings may help inform cost-effectiveness-based decision making for clinical care of PD in developing countries.

Comparison of intraoperative imaging guided versus microelectrode recording guided deep brain stimulation for Parkinson's disease: A meta-analysis

BackgroundTraditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD). MethodsPubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site. ResultsSix studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were −0.45 (95% confidence interval, CI=−1.11 to 0.20), −0.18 (95% CI=−0.41 to 0.06), 3.40 (95% CI=−5.36 to 12.16), and 5.00 (95% CI=−1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques. ConclusionsBoth IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment.

Complications of Deep Brain Stimulation for Parkinson Disease and Relationship between Micro-electrode tracks and hemorrhage: Systematic Review and Meta-Analysis

Deep brain stimulation is a common treatment for Parkinson's disease (PD). Despite strong efficacy in well-selected patients, complications can occur. Intraoperative micro-electrode recording (MER) can enhance efficacy by improving lead accuracy. However, there is controversy as to whether MER increases risk of hemorrhage. To provide a comprehensive systematic review and meta-analysis reporting complication rates from deep brain stimulation in PD. We also interrogate the association between hemorrhage and MER. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were implemented while querying the Pubmed, Embase, and Cochrane databases. All included studies were randomized controlled trials and prospective case series with 5 or more patients. Primary outcomes included rates of overall revision, infection, lead malposition, surgical site and wound complications, hardware-related complications, and seizure. The secondary outcome was the relationship between number of MER tracks and hemorrhage rate. 262 articles with 21,261 patients were included in the analysis. Mean follow-up was 25.8months (range 0-133). Complication rates were: revision 4.9%, infection 4.2%, lead malposition 3.3%, surgical site complications 2.8%, hemorrhage 2.4%, hardware-related complications 2.4%, and seizure 1.9%. While hemorrhage rate did not increase with single-track MER (odds ratio, 3.49; P= 0.29), there was a significant non-linear increase with each additional track. Infection and lead malposition were the most common complications. Hemorrhage risk increases with more than one MER track. These results highlight the challenge of balancing surgical accuracy and perioperative risk.

Clinical factors and dopamine transporter availability for the prediction of outcomes after globus pallidus deep brain stimulation in Parkinson’s disease

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson’s disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [18F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson’s Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD.

Deep brain stimulation in the globus pallidus alleviates motor activity defects and abnormal electrical activities of the parafascicular nucleus in parkinsonian rats.

Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease (PD). The most common sites targeted for DBS in PD are the globus pallidus internal (GPi) and subthalamic nucleus (STN). However, STN-DBS and GPi-DBS have limited improvement in some symptoms and even aggravate disease symptoms. Therefore, discovering new targets is more helpful for treating refractory symptoms of PD. Therefore, our study selected a new brain region, the lateral globus pallidus (GP), as the target of DBS, and the study found that GP-DBS can improve motor symptoms. It has been reported that the thalamic parafascicular (PF) nucleus is strongly related to PD pathology. Moreover, the PF nucleus and GP have very close direct and indirect fiber connections. However, whether GP-DBS can change the activity of the PF remains unclear. Therefore, in this study, we monitored the activity changes in the PF nucleus in PD rats during a quiet awake state after GP-DBS. We found that GP-DBS could reverse the electrical activity of the PF nucleus in PD model rats, including the discharge pattern of the neurons and the local field potential (0.7–12 and 12–70 Hz). Based on the results mentioned above, PF activity in PD model rats could be changed by GP-DBS. Thus, the normalization of PF neuronal activity may be a potential mechanism for GP-DBS in the treatment of PD; these findings lay the foundation for PD treatment strategies.