Weight and survival after deep brain stimulation for Parkinson's disease.

BACKGROUND: Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. OBJECTIVES: To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. METHODS: This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. RESULTS: There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). DISCUSSION: Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Functional characterization of the biogenic amine transporters on human macrophages.

Monocyte-derived macrophages (MDMs) are key players in tissue homeostasis and diseases regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but the mechanisms governing biogenic amine signaling in and around immune cells remain nebulous. In the CNS, biogenic amine transporters are regarded as the master regulators of neurotransmitter signaling. While we and others have shown that macrophages express these transporters, relatively little is known of their function in these cells. To address these knowledge gaps, we investigated the function of norepinephrine transporter (NET) and dopamine transporter (DAT) on human MDMs. We found that both NET and DAT are present and can uptake substrate from the extracellular space at baseline. Not only was DAT expressed in cultured MDMs, but it was also detected in a subset of intestinal macrophages in situ. Surprisingly, we discovered a NET-independent, DAT-mediated immunomodulatory mechanism in response to LPS. LPS induced reverse transport of dopamine through DAT, engaging an autocrine/paracrine signaling loop that regulated the macrophage response. Removing this signaling loop enhanced the proinflammatory response to LPS. Our data introduce a potential role for DAT in the regulation of innate immunity.

TNFα increases tyrosine hydroxylase expression in human monocytes.

Most, if not all, peripheral immune cells in humans and animals express tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Since TH is typically studied in the context of brain catecholamine signaling, little is known about changes in TH production and function in peripheral immune cells. This knowledge gap is due, in part, to the lack of an adequately sensitive assay to measure TH in immune cells expressing lower TH levels compared to other TH expressing cells. Here, we report the development of a highly sensitive and reproducible Bio-ELISA to quantify picogram levels of TH in multiple model systems. We have applied this assay to monocytes isolated from blood of persons with Parkinson's disease (PD) and to age-matched, healthy controls. Our study unexpectedly revealed that PD patients' monocytes express significantly higher levels of TH protein in peripheral monocytes relative to healthy controls. Tumor necrosis factor (TNFα), a pro-inflammatory cytokine, has also been shown to be increased in the brains and peripheral circulation in human PD, as well as in animal models of PD. Therefore, we investigated a possible connection between higher levels of TH protein and the known increase in circulating TNFα in PD. Monocytes isolated from healthy donors were treated with TNFα or with TNFα in the presence of an inhibitor. Tissue plasminogen activator (TPA) was used as a positive control. We observed that TNFα stimulation increased both the number of TH+ monocytes and the quantity of TH per monocyte, without increasing the total numbers of monocytes. These results revealed that TNFα could potentially modify monocytic TH production and serve a regulatory role in peripheral immune function. The development and application of a highly sensitive assay to quantify TH in both human and animal cells will provide a novel tool for further investigating possible PD immune regulatory pathways between brain and periphery.

Case Report: Deep Brain Stimulation of the Nucleus Basalis of Meynert for Advanced Alzheimer's Disease.

Patients with advanced Alzheimer's disease (AD) experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert (NBM-DBS) has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (Clinical Dementia Rating scale: 3.0 points) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination (MMSE) assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients. Clinical Trial Registration: ChiCTR1900022324.

Home Health Management of Parkinson Disease Deep Brain Stimulation: A Randomized Clinical Trial.

Importance: The travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy. Objective: To evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access. Design, Settings, and Participants: This open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain. Interventions: The home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care. Main Outcomes and Measures: The primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III. Results: Approximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices. Conclusions and Relevance: This study provides evidence supporting the safety and feasibility of postoperative home health DBS management. Trial Registration: ClinicalTrials.gov Identifier: NCT02474459.

Weight Change After Subthalamic Nucleus Deep Brain Stimulation in Patients With Isolated Dystonia.

Purpose: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment method for advanced Parkinson's disease (PD) and isolated dystonia and provides marked improvement of major motor symptoms. In addition, non-motor effects have been reported including weight gain (WG) in patients with PD after STN-DBS. However, it is still unclear whether patients with isolated dystonia also experience WG. Methods: Data from 47 patients with isolated dystonia who underwent bilateral STN-DBS surgery between October 2012 and June 2019 were retrospectively collected. The severity of dystonia was assessed via the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Changes in the body mass index (BMI) and BFMDRS score were analyzed using paired Student's t-tests. Regression analysis was performed to identify factors that affected the BMI after surgery. Results: Postoperative WG was observed in 78.7% of patients. The percentage of overweight and obese patients increased from 25.5% (before STN-DBS) to 48.9% (at the last follow-up). The mean BMI and mean percentage change in BMI increased by 1.32 ± 1.83 kg/m2 (P < 0.001) and 6.28 ± 8.34%, respectively. BMI increased more in female than in male patients. At the last follow-up, BFMDRS movement and disability scores improved by 69.76 ± 33.23% and 65.66 ± 31.41%, respectively (both P < 0.001). The final regression model analysis revealed that sex and preoperative BMI alone were independently associated with BMI change (P < 0.05). Conclusions: STN-DBS is associated with postoperative WG with patients with isolated dystonia. WG is more prominent in female patients and is associated with preoperative weight but not with the efficacy of STN-DBS on motor symptoms.

Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary.

INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

Cognitive Outcomes for Essential Tremor Patients Selected for Thalamic Deep Brain Stimulation Surgery Through Interdisciplinary Evaluations.

Objective: Deep brain stimulation (DBS) targeted to the ventral intermediate (VIM) nucleus of the thalamus is effective for motor symptoms in essential tremor (ET), but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients (pre-DBS and 1+ year after DBS). Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function. Results: We identified 50 ET DBS patients; 29 (58%) males; the mean age of tremor onset was 35.84 (±21.50) years with a median age of 38 years. The mean age at DBS was 68.18 (±10.07) years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment (pre vs. post) and age of tremor onset (<38 vs. >38 years); F (1,30) = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment (pre vs. post) and complications vs. no complications subgroups; F (1,45) = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant. Conclusion: In this large cohort of ET patients with (>30% improvements), DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS.

Long-term Parkinson's disease quality of life after staged DBS: STN vs GPi and first vs second lead.

Deep brain stimulation (DBS) for Parkinson's disease (PD) improves quality of life (QoL), but longitudinal follow-up data are scarce. We sought to quantify long-term benefits of subthalamic nucleus (STN) vs globus pallidus internus (GPi), and unilateral vs staged bilateral PD-DBS on postoperative QoL. This is a retrospective, longitudinal, non-randomized study using the PD QoL questionnaire (PDQ)-39 in patients with STN- or GPi-DBS, and with unilateral (N = 191) or staged bilateral (an additional contralateral lead implant) surgery (N = 127 and 156 for the first and second lead, respectively). Changes in PDQ-39 summary index (PDQ-39SI) and subscores throughout 60 months of follow-up were used as the primary analysis. We applied mixed models that included levodopa and covariates that differed at baseline across groups. For unilateral implantation, we observed an initial improvement in PDQ-39SI of 15.55 ± 3.29% (µ ± SE) across both brain targets at 4 months postoperatively. Unilateral STN patients demonstrated greater improvement in PDQ-39SI than GPi patients at 4 and 18 months postoperatively. Analysis of patients with staged bilateral leads revealed an initial 25.34 ± 2.74% (µ ± SE) improvement in PDQ-39SI at 4 months after the first lead with further improvement until 18 months, with no difference across targets. Scores did not improve after the second lead with gradual worsening starting at 18 months postoperatively. STN-DBS provided greater short-term QoL improvement than GPi-DBS for unilateral surgery. For staged bilateral DBS, overall QoL improvement was explained primarily by the first lead. Decision-making for patients considering DBS should include a discussion surrounding the potential risks and benefits from a second DBS lead.

Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes.

OBJECTIVE: We aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making. METHODS: This single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes. RESULTS: For the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes. CONCLUSION: Bilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.

Hospital Management of Parkinson Disease Patients.

Management of patients with Parkinson disease (PD) during inpatient hospital stays is complex and poses unique challenges for physicians and ancillary staff. Patients with PD have a high risk of complications, encephalopathy, and prolonged hospital stay. Early recognition of complications and implementation of rehabilitation strategies along with appropriate management of medications are critical to improve outcomes. Patients with PD can exhibit worsening mobility and balance, insomnia, orthostatic hypotension, multiple neuropsychiatric symptoms, and gastrointestinal dysfunction while hospitalized. This review summarizes the specific in-hospital concerns observed in patients with PD and discusses potential treatment approaches.

Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies.

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson's Disease.

INTRODUCTION: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson's disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear. We examined in detail the DBS electrode position and stimulation parameters in two patients with uncontrollable laughter during programming after STN-DBS surgery and illustrated the anatomical correlates of the acute mood changes with STN stimulation. CASE REPORT: Unilateral STN-DBS induced uncontrollable laughter with activation of the most ventral contacts in both patients. However, the location of the electrodes responsible for this adverse effect differed between the patients. In the first patient, the DBS lead was placed more inferiorly and medially within the STN. In the second patient, the DBS lead was implanted more anteriorly and inferiorly than initially planned at the level of the substantia nigra reticulata (SNr). CONCLUSION: Unilateral STN-DBS can induce acute uncontrollable laughter with activation of electrodes located more anterior, medial, and inferior in relationship with the standard stereotactic STN target. We suggest that simulation of ventral and medial STN, surrounding limbic structures or the SNr, is the most plausible anatomical substrate responsible for this acute mood and behavioral change. Our findings provide insight into the complex functional neuroanatomical relationship of the STN and adjacent structures important for mood and behavior. DBS programming with more dorsal and lateral contacts within the STN should be entertained to minimize the emotional side effects.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary.

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.

Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease: A Review.

Importance: Selection of the best deep brain stimulation (DBS) target-subthalamic nucleus (STN) or globus pallidus interna (GPi)-for treatment of motor complications in Parkinson disease remains a matter of debate. Observations: Increasing evidence from randomized clinical trials indicates that motor benefit is similar between both targets, including an effect on dyskinesia and improvement in quality of life. Deep brain stimulation of the STN offers consistently greater dopaminergic medication reduction, possible mild benefit in nonmotor domains, and potential economic advantage. Deep brain stimulation of the GPi provides a probable advantage in dyskinesia suppression, management of symptoms with unilateral leads, and flexibility in medications and programming adjustments. Overall, STN DBS is at potentially higher or equal risk for neuropsychiatric changes compared with GPi DBS. Conclusions and Relevance: Both GPi and STN DBS provide similar, consistent, marked motor benefits, but subtle target differences exist. Target selection should be tailored to each patient's clinical presentation, neuropsychiatric profile, and goals of surgery, allowing customization of this therapy and improved individual outcomes.

A Comparison of Unilateral Deep Brain Stimulation (DBS), Simultaneous Bilateral DBS, and Staged Bilateral DBS Lead Accuracies.

BACKGROUND: Accuracy of lead placement within the brain can affect the outcome of deep brain stimulation (DBS) surgery. Whether performing unilateral lead implantation, simultaneous bilateral lead implantation, or staged bilateral lead implantation affects accuracy has not yet been assessed. We compare lead placement errors to evaluate whether one approach affords greater lead accuracy. METHODS: We retrospectively reviewed 205 leads placed in 125 DBS surgeries. The accuracy of lead placement, defined by differences in x, y, and z coordinates and error vector magnitudes, was compared between three surgery groups: unilateral leads, bilateral leads placed simultaneously, and bilateral leads placed in staged surgeries. We also compared accuracies between first and second leads within each bilateral cohort and between second leads of the bilateral cohorts. Finally, we examined the effect of target and age on accuracy. RESULTS: The accuracy of lead placement was comparable among unilateral, simultaneous bilateral, and staged bilateral leads. Timing of placement of the second lead in bilateral cases was not found to affect accuracy. The mean number of microelectrode trajectories was greater for first leads in simultaneous bilateral DBS (p = 0.032). No significant correlation between either age or target and accuracy was found. CONCLUSION: Although there may be other important reasons for performing DBS in a staged fashion, our study finds that neither laterality nor timing of second lead placement, patient age, or target site have significant impact on DBS lead accuracy, a finding that indicates with appropriate approach selection based on patient factors, accuracy does not have to be significantly compromised.