Globus Pallidus Internus Target Research Articles

Long-Term Outcomes of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series.

Among dystonia patients receiving globus pallidus internus (GPi) deep brain stimulation (DBS), long-term outcomes remain to be established. To report the long-term outcomes of GPi DBS in a patient cohort with idiopathic and acquired dystonia. In this long-term follow-up cohort, there were 4 patients with idiopathic dystonia and 2 patients with acquired dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale was used to evaluate 6 consecutive patients preoperatively and at 6months, 12months, and the last follow-up. The relationship between etiology and clinical improvement was analyzed. Stimulation parameters were evaluated for similarities and differences among these patients. The mean follow-up of our cohort was 65.3months (median 40.5months). The average improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (mean±SEM) were 56%±7.6, 67%±6.8 and 66%±9.7 at 6months, 12months, and the last follow-up, respectively. There was greater improvement during the long-term follow-up in the 4 patients with idiopathic dystonia than in the 2 patients with acquired dystonia. The 2 most ventral electrodes (contact 0 and 1) were activated in all 11 leads in this cohort. The average stimulation intensity, pulse width and frequency were 2.0±0.24mA, 252±43μs, and 99±6.0Hz, respectively. Isolated dystonia, either monogenic or idiopathic, usually responds better to GPi DBS than to acquired dystonia. Selection of patients by dystonia etiology, accurate placement of DBS leads in GPi targets, and proper stimulation programming are crucial to achieve better long-term outcomes.

Retrospective Multicenter Study on Outcome Measurement for Dyskinesia Improvement in Parkinson's Disease Patients with Pallidal and Subthalamic Nucleus Deep Brain Stimulation.

Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson’s disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-Ⅲ) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006).

Utility of GPI+VIM dual-lead deep brain stimulation for Parkinson's disease patients with significant residual tremor on medication.

Randomized controlled trials have demonstrated that deep brain stimulation (DBS) of both the globus pallidus internus (GPI) and subthalamic nucleus (STN) for Parkinson's disease (PD) is superior to the best medical therapy. Tremor is particularly responsive to DBS, with reports of 70%-80% improvement. However, a small number of patients do not obtain the expected response with both STN and GPI targets. Indeed, the authors' patient population had a similar 81.2% tremor reduction with a 9.6% failure rate. In an analysis of these failures, they identified patients with preoperative on-medication tremor who subsequently received a GPI lead as a subpopulation at higher risk for inadequate tremor control. Thereafter, STN DBS was recommended for patients with on-medication tremor. However, for the patients with symptoms and comorbidities that favored GPI as the target, dual GPI and ventral intermediate nucleus of the thalamus (VIM) leads were proposed. This report details outcomes for those patients. This is a retrospective review of patients with PD who met the criteria for and underwent simultaneous GPI+VIM DBS surgery from 2015 to 2020 and had available follow-up data. The preoperative Unified Parkinson's Disease Rating Scale scores were obtained with the study participants on and off their medication. Postoperatively, the GPI lead was kept on at baseline and scores were obtained with and without VIM stimulation. Thirteen PD patients with significant residual preoperative tremor on medication underwent simultaneous GPI+VIM DBS surgery (11 unilateral, 2 bilateral). A mean 90.6% (SD 15.0%) reduction in tremor scores was achieved with dual GPI+VIM stimulation compared to a 21.8% (SD 71.9%) reduction with GPI stimulation alone and a 30.9% (SD 37.8%) reduction with medication. Although rigidity and bradykinesia reductions were accomplished with just GPI stimulation, 13 of the 15 hemispheres required VIM stimulation to achieve excellent tremor control. GPI+VIM stimulation was required to adequately control tremor in all but 2 patients in this series, substantiating the authors' hypothesis that, in their population, medication-resistant tremor does not completely respond to GPI stimulation. Dual stimulation of the GPI and VIM proved to be an effective option for the patients who had symptoms and comorbidities that favored GPI as a target and had medication-resistant tremor.

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

IntroductionThe 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.MethodsThe 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.ResultsThere 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.ConclusionGPi 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.Electronic supplementary materialThe online version of this article (10.1007/s40120-020-00220-5) contains supplementary material, which is available to authorized users.

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

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

Deep Brain Stimulation Management of Essential Tremor with Dystonic Features

<strong>Clinical Vignette:</strong> A 64-year-old female with essential tremor (ET) presents for evaluation of deep brain stimulation (DBS) candidacy. Examination revealed subtle dystonic features as well as a disabling postural-action tremor. <strong>Clinical Dilemma:</strong> Can dystonia occur in the setting of the diagnosis of ET and can its presence alter DBS target selection? <strong>Clinical Solution:</strong> Unilateral DBS implantation of the ventralis intermedius (Vim) led to improvement in both tremor and dystonic posturing. <strong>Gap in Knowledge:</strong> Case reports of DBS in dystonic tremor suggest Vim, globus pallidus internus (GPi), and subthalamic targets may all be effective, to varying degrees, in improving both tremor and dystonia. More rigorous studies are needed to identify the optimal target(s). <strong>Expert Commentary:</strong> This case underscores the limited evidence available to guide a clinician’s choice of DBS targets in patients with ET and dystonia. The severity of the dystonia and the presence of more generalized dystonia may alter the thinking about optimal targeting. Vim, GPi, and subthalamic targets appear potentially acceptable options, though Vim is usually the first target attempted when postural-action tremor is the chief complaint. Occasionally, a second rescue DBS lead may be necessary.

Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease.

Recent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution. PD patients undergoing awake or asleep bilateral GPi or STN DBS were prospectively monitored. The primary outcome measure was stimulation-induced change in motor function off medication 6 months postoperatively, measured using the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Secondary outcomes included change in quality of life, measured by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), change in levodopa equivalent daily dosage (LEDD), stereotactic accuracy, stimulation parameters, and adverse events. Six-month outcome data were available for 133 patients treated over 45 months (78 GPi [16 awake, 62 asleep] and 55 STN [14 awake, 41 asleep]). UPDRS-III score improvement with stimulation did not differ between awake and asleep groups for GPi (awake, 20.8 points [38.5%]; asleep, 18.8 points [37.5%]; p = 0.45) or STN (awake, 21.6 points [40.3%]; asleep, 26.1 points [48.8%]; p = 0.20) targets. The percentage improvement in PDQ-39 and LEDD was similar for awake and asleep groups for both GPi (p = 0.80 and p = 0.54, respectively) and STN cohorts (p = 0.85 and p = 0.49, respectively). In PD patients, bilateral GPi and STN DBS using the asleep method resulted in motor, quality-of-life, and medication reduction outcomes that were comparable to those of the awake method.

STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice.

When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson's disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient's outcome? and 2- Should this patient's DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson's disease cases (Figure 1). This bilateral STN "one-size-fits-all" approach was challenged by an editorial entitled "STN vs. GPi: The Rematch," which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi 'rematch' studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson's disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific approach will be proposed to optimize outcomes of PD DBS therapy. Finally, the importance of an interdisciplinary care team for screening and effective management of DBS patients will be reaffirmed. Interdisciplinary teams can facilitate the proposed patient-specific DBS treatment planning and provide a more thorough analysis of the risk-benefit ratio for each patient.

Weight Changes in Subthalamic Nucleus vs Globus Pallidus Internus Deep Brain Stimulation: Results From the COMPARE Parkinson Disease Deep Brain Stimulation Cohort

Parkinson's patients, on average, gain weight after deep brain stimulation (DBS). To determine potential differences in weight gain when comparing the subthalamic nucleus and the globus pallidus internus target. A retrospective analysis was performed on the prospective, randomized cohort of National Institutes of Health COMPARE trial DBS patients who received unilateral subthalamic nucleus or globus pallidus internus DBS. Baseline weights were recorded before DBS surgery and at 6, 12, and 18 months postoperatively. Relationships between weight change and changes in Beck Depression Inventory score, Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III) (also the dyskinesia duration and disability subscores from UPDRS IV), and Hoehn-Yahr stage were determined via Spearman's rank-order correlation coefficients. Regression analyses were performed to investigate the effects of potential factors on weight change over time. Patients in the COMPARE DBS cohort gained a significant amount of weight, a mean of 4.86 lb (standard deviation = 8.73) (P = .001), but there was no significant difference between subthalamic nucleus and globus pallidus internus targets (weight gain of 4.29 ± 6.79 and 5.38 ± 10.32 lb, respectively; P = .68). Weight gain did not correlate with Beck Depression Inventory score change, UPDRS motor score, dyskinesia duration, dyskinesia disability change, or the Hoehn-Yahr stage (P = .62, .21, and .31, respectively). No specific variable was associated with weight gain, and there were no differences in binge eating post-surgery in either target. There were significant changes in weight over time after DBS therapy. However, neither Beck Depression Inventory score change nor UPDRS score change or dyskinesia was correlated with weight gain. No significant factor was associated with the weight change.

A closer look at unilateral versus bilateral deep brain stimulation: results of the National Institutes of Health COMPARE cohort

In this paper, the authors' aim was to examine reasons underpinning decisions to undergo, or alternatively forgo, a second-sided deep brain stimulation (DBS) implantation in patients with Parkinson disease (PD). Fifty-two patients with Parkinson disease (PD) were randomized to receive DBS to the subthalamic nucleus or globus pallidus internus (GPi) as part of the COMPARE trial. Forty-four patients had complete data sets. All patients were offered a choice at 6 months after unilateral implantation whether to receive a contralateral DBS implant. All patients had advanced PD. The mean patient age was 59.8 years (range 43-76 years), and the mean duration of disease was 12.2 years (range 5-21 years). The mean baseline Unified Parkinson's Disease Rating Scale (UPDRS)-III motor score was 42.7. The main outcome measures used in this study were the UPDRS-III Motor Scale and the UPDRS-IV Dyskinesia Scale. Twenty-one (48%) of the 44 patients in the cohort did not undergo bilateral implantation and have been successfully treated for an average of 3.5 years; of these, 14 (67%) had a GPi target. The most common reason for adding a second side was inadequacy to address motor symptoms. Patient satisfaction with motor outcomes after unilateral DBS implantation was the most common reason for not undergoing bilateral implantation. Those who chose a second DBS procedure had significantly higher baseline UPDRS-III motor and ipsilateral UPDRS-III scores, and a significantly lower asymmetrical index. The logistic regression analysis revealed that the odds of proceeding to bilateral DBS was 5.2 times higher for STN than for GPi DBS. For every 1% increase in asymmetry, the odds of bilateral DBS decreased [corrected] by 0.96. Unilateral DBS is an effective treatment for a subset of patients with PD. Baseline asymmetry is an important factor in the effectiveness and decision-making process between unilateral and bilateral DBS. Patients with GPi DBS in this cohort were more likely to choose to remain with unilateral implantation.

Risks of intracranial hemorrhage in patients with Parkinson's disease receiving deep brain stimulation and ablation

Objectives This study analyzed risk factors for hemorrhage in a large series of deep brain stimulation (DBS) and ablation procedures in patients with advanced Parkinson's disease (PD). Methods Six hundred and forty four subjects with advanced PD treated with DBS or ablation procedures between March 1999 and December 2007 were enrolled in the study. Procedures were performed by the same surgeon, and included DBS in 126 patients, ablation in 507 patients and DBS after prior unilateral ablation procedures in 11 patients. Of 796 target procedures, 207 were DBS including 202 subthalamic nucleus (STN) targets, 3 ventralis intermedius nucleus (Vim) targets and 2 globus pallidus internus (GPi) targets, and the others were 589 ablation procedures including 474 GPi targets and 115 Vim targets. Postoperative CT or MRI was performed in all patients within 24 h of lead implantation or ablation treatment. Statistical correlation analysis of risk factors for intracranial hemorrhage (ICH) was performed by stepwise logistic regression. Explanatory variables were patient age, sex, blood pressure, anatomical targets, the number of microelectrode recording (MER) penetrations and surgical modality. Results Postoperative symptomatic ICH occurred in 10 cases (8 pallidotomy and 2 thalamotomy) and asymptomatic ICH in 14 cases (9 pallidotomy, 4 thalamotomy and 1 DBS). Hypertension and surgical modality were significant factors contributing to hemorrhage (both P < 0.05). The likelihood of hemorrhage in hypertensive patients was 2.5 times that in normotensive patients. The risk of hemorrhage during ablation was 5.4 times that in DBS. The number of MER trajectories did not significantly correlate with ICH occurrence ( P = 0.07). No statistically significant difference was found in age, sex and anatomical targets. Conclusion This study demonstrated that hypertension is a risk factor for ICH in PD patients. DBS is generally a safe surgical modality as compared with ablation. Increasing microelectrode trajectories seemed to increase the risk of ICH, but no statistically significant difference was found ( P = 0.07).

Prognostic value of globus pallidus internus volume in primary dystonia treated by deep brain stimulation

Given that improvement is variable from one patient to another, the authors analyzed the impact of globus pallidus internus (GPi) volume on the result of deep brain stimulation (DBS) by comparing highly and less improved patients with primary dystonodyskinetic syndromes. A stereotactic model was developed to visualize and quantify the relationship between the isofield lines generated by the DBS lead and GPi target. The model was used in 30 right-handed selected patients with primary dystonodyskinetic syndromes who had been treated using bilateral stimulation of the sensorimotor GPi. Ten healthy control individuals were also included in the study. First, the authors compared the GPi volumes between patients and healthy controls. Second, the stimulated GPi volumes, that is, the intersection between the volume of each isofield value and the GPi volumes, were compared between less improved and highly improved patients. Improvement in the Burke-Fahn-Marsden Dystonia Rating Scale's motor score was rated > 90% in 20 patients (97 +/- 4.6%) and < 60% in 10 patients (56.9 +/- 6%). The mean volume of the right (461.8 +/- 81.8 mm(3)) and left (406.6 +/- 113.2 mm(3)) GPi in patients showing less response to DBS was significantly smaller than the GPi volume of patients who responded well (right 539.9 +/- 86.6 mm(3), left 510.6 +/- 88.7 mm(3)) and healthy controls (right 557.8 +/- 109.1 mm(3), left 525.1 +/- 40.8 mm(3)). On the left side, the mean stimulated volumes (isofield line range 0.2-1 V/mm) were significantly larger in highly improved than in less improved patients. In this model, the threshold for functional effect was calculated at 0.2 V/mm.

Posteroventral pallidotomy in medically intractable postapoplectic monochorea: case report

Background Posteroventral pallidotomy is a widely accepted surgical procedure for treating medically intractable Parkinson’s disease and Levo-dopa induced dyskinesia. In the surgical treatment of hyperkinetic movement disorders, generalized dystonia has recently become a favorable indication of posteroventral pallidotomy. However, a commonly recognized surgical procedure for treating choreiform movement disorders has not yet been established. Here we present an unusual experience of a posteroventral pallidotomy performed to treat a medically intractable monochorea caused by a vascular insult on the basal ganglia. Case presentation A 63-year-old female presented with choreiform movement of the left upper limb that she had suffered for 5 months. She was found to have a hemorrhagic infarction in the right putaminal area. No other abnormal lesions were shown by magnetic resonance imaging except for a widening of the right cerebellopontine cistern because of an acoustic neurinoma removed 5 years previously. Despite medication with a dopamine antagonist, choreiform movement of the left limb had not improved, and the patient complained of rigidity and slowness of ambulation owing to the side effects of the medicine. A right posteroventral pallidotomy was performed with macrostimulation for a physiologic confirmation of the globus pallidus internus (GPi), which is the conventional target for Parkinson’s disease. After coagulating the GPi target, the choreiform movement of the contralateral upper limb was completely abolished. The postoperative course was uneventful and no recurrence of chorea was observed over a follow-up period of 6 months. Conclusion Stereotactic surgery for hyperkinetic movement disorders is not as common a procedure as that used for treating Parkinson’s disease. Furthermore, there have been few reports of pallidal surgery for treating the chorea caused by an ischemic insult. However, on the basis of the current concept that varying types of hyperkinetic disorders may have a common pathophysiological mechanism, a posteroventral pallidotomy may be an alternative surgical procedure for treating medically intractable postapoplectic chorea like in an occasion of dystonia.