Globus Pallidus Internus Stimulation Research Articles

Low-Frequency Stimulation of Globus Pallidus Internus for Axial Motor Symptoms of Parkinson's Disease.

Low-Frequency Stimulation of Globus Pallidus Internus for Axial Motor Symptoms of Parkinson's Disease.

Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial

Deep brain stimulation (DBS) has been proposed as a treatment option for severe Tourette's syndrome on the basis of findings from open-label series and small double-blind trials. We aimed to further assess the safety and efficacy of bilateral globus pallidus internus (GPi) DBS in patient's with severe Tourette's syndrome. In a randomised, double-blind, crossover trial, we recruited eligible patients (severe medically refractory Tourette's syndrome, age ≥20 years) from two clinics for tertiary movement disorders in the UK. Enrolled patients received surgery for GPi DBS and then were randomly assigned in a 1:1 ratio (computer-generated pairwise randomisation according to order of enrolment) to receive either stimulation on-first or stimulation off-first for 3 months, followed by a switch to the opposite condition for a further 3 month period. Patients and rating clinicians were masked to treatment allocation; an unmasked clinician was responsible for programming the stimulation. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) total score between the two blinded conditions, assessed with repeated measures ANOVA, in all patients who completed assessments during both blinded periods. After the end of the blinded crossover phase, all patients were offered continued DBS and continued to have open-label stimulation adjustments and objective assessments of tic severity until database lock 1 month after the final patient's final trial-related visit. This trial is registered with ClinicalTrials.gov, number NCT01647269. Between Nov 5, 2009, and Oct 16, 2013, we enrolled 15 patients (11 men, four women; mean age 34·7 years [SD 10·0]). 14 patients were randomly assigned and 13 completed assessments in both blinded periods (seven in the on-first group, six in the off-first group). Mean YGTSS total score in these 13 patients was 87·9 (SD 9·2) at baseline, 80·7 (SD 12·0) for the off-stimulation period, and 68·3 (SD 18·6) for the on-stimulation period. Pairwise comparisons in YGTSS total scores after Bonferroni correction were significantly lower at the end of the on-stimulation period compared with the off-stimulation period, with a mean improvement of 12·4 points (95% CI 0·1-24·7, p=0·048), equivalent to a difference of 15·3% (95% CI 5·3-25·3). All 15 patients received stimulation in the open-label phase. Overall, three serious adverse events occurred (two infections in DBS hardware at 2 and 7 weeks postoperatively, and one episode of deep-brain-stimulation-induced hypomania during the blinded on-stimulation period); all three resolved with treatment. GPi stimulation led to a significant improvement in tic severity, with an overall acceptable safety profile. Future research should concentrate on identifying the most effective target for DBS to control both tics and associated comorbidities, and further clarify factors that predict individual patient response. UK National Health Service.

Efficacy of deep brain stimulation in an adolescent patient with DYT11 myoclonus-dystonia

Myoclonus-dystonia is a movement disorder characterized by myoclonic jerks and dystonia. We herein report the case of an 18-year-old Japanese male patient with DYT11 myoclonus-dystonia who developed myoclonic jerks at 2 years-of-age. He harbored a novel heterozygous mutation in the major responsible gene, ε-sarcoglycan. As medication was ineffective and the myoclonus had become disabling, deep brain stimulation of the bilateral globus pallidus internus was carried out. After surgery, his symptoms showed overt improvement. Although reports of deep brain stimulation treatment in children or adolescents with myoclonus-dystonia are scarce, the treatment should be considered when symptoms, particularly myoclonus, become refractory, sustained and disabling.

Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation

BackgroundThere is a growing body of evidence demonstrating that deep brain stimulation (DBS) of globus pallidus internus (GPi DBS) and subthalamic nucleus (STN DBS) are effective treatment for patients with...

EPA-1587 - Functional outcome and quality of life in tourette’ s syndrome after deep brain stimulation of the posteroventrolateral globus pallidus internus: long-term follow-up

Introduction Deep brain stimulation (DBS) for Tourette’ s syndrome (TS) in various targets has been in the focus for some years. However, there are hardly any data on ‘psychosocial’ outcome after DBS for TS. Objectives The aim of the present study therefore was to focus on the functional outcome and ‘psychosocial changes’ in TS patients after DBS. Methods Six patients with treatment-refractory TS underwent GPi-DBS. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate symptomatic outcome. Psychosocial changes were assessed applying the Global Assessment of Functioning Scale (GAF) and the Gilles-de-la- Tourette-Syndrome Quality-of-Life scale (GTS-QOL) with additionally documenting psychosocial changes. Follow-up ranged between 12 and 72 months. Results In all symptomatic responders (4 of 6) we found a significant functional improvement (mean GAF increasing from 53.75 (± 7.5) preoperatively to 83.75 (± 7.5) at last follow-up) along with a positive correlation with the course of GTS-QOL (R2 = 0.62). Conclusions Treatment success should not only be assessed with the classic ‘tic-scales’, but also with the GAF and GTS-QOL. Although improvement of tics seems to be positively correlated with improved functional outcome, symptomatic improvement may lead to unexpected major psychosocial changes – which both the patient and the clinicians in charge – should be prepared for.

Functional outcome and quality of life in Tourette's syndrome after deep brain stimulation of the posteroventrolateral globus pallidus internus: long-term follow-up

Objectives. Deep brain stimulation (DBS) for Tourette's syndrome (TS) in various targets has been in the focus for some years. However, there are hardly any data on “psychosocial” outcome after DBS for TS. The aim of the present study therefore was to focus on the functional outcome and “psychosocial changes” in TS patients after DBS. Methods. Six patients with treatment-refractory TS underwent GPi-DBS. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate symptomatic outcome. Psychosocial changes were assessed applying the Global Assessment of Functioning Scale (GAF) and the Gilles-de-la-Tourette-Syndrome Quality-of-Life scale (GTS-QOL) with additionally documenting psychosocial changes. Follow-up ranged between 12 and 72 months. Results. In all symptomatic responders (4 of 6) we found a significant functional improvement (mean GAF increasing from 53.75 (± 7.5) pre-operatively to 83.75 (± 7.5) at last follow-up) along with a positive correlation with the course of GTS-QOL (R2 = 0.62). Conclusions. Treatment success should not only be assessed with the classic “tic-scales”, but also with the GAF and GTS-QOL. Although improvement of tics seems to be positively correlated with improved functional outcome, symptomatic improvement may lead to unexpected major psychosocial changes – which both the patient and the clinicians in charge – should be prepared for.

Deep brain stimulation in children and young adults with secondary dystonia: the Children's Hospital Los Angeles experience

Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. It can be classified as primary or secondary. There is no cure for dystonia and the goal of treatment is to provide a better quality of life for the patient. Surgical intervention is considered for patients in whom an adequate trial of medical treatment has failed. Deep brain stimulation (DBS), specifically of the globus pallidus interna (GPi), has been shown to be extremely effective in primary generalized dystonia. There is much less evidence for the use of DBS in patients with secondary dystonia. However, given the large number of patients with secondary dystonia, the significant burden on the patients and their families, and the potential for DBS to improve their functional status and comfort level, it is important to continue to investigate the use of DBS in the realm of secondary dystonia. The objective of this study is to review a series of cases involving patients with secondary dystonia who have been treated with pallidal DBS. A retrospective review of 9 patients with secondary dystonia who received treatment with DBS between February 2011 and February 2013 was performed. Preoperative and postoperative videos were scored using the Barry-Albright Dystonia Scale (BADS) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) by a neurologist specializing in movement disorders. In addition, the patients' families completed a subjective questionnaire to assess the perceived benefit of DBS. The average age at DBS unit implantation was 15.1 years (range 6-20 years). The average time to follow-up for the BADS evaluation from battery implantation was 3.8 months (median 3 months). The average time to follow-up for the subjective benefit evaluation was 10.6 months (median 9.5 months). The mean BADS scores improved by 9% from 26.5 to 24 (p = 0.04), and the mean BFMDRS scores improved by 9.3% (p = 0.055). Of note, even in patients with minimal functional improvement, there seemed to be decreased contractures and spasms leading to improved comfort. There were no complications such as infections or hematoma in this case series. In the subjective benefit evaluation, 3 patients' families reported "good" benefit, 4 reported "minimal" benefit, and 1 reported no benefit. These early results of GPi stimulation in a series of 9 patients suggest that DBS is useful in the treatment of secondary generalized dystonia in children and young adults. Objective improvements in BADS and BFMDRS scores are demonstrated in some patients with generalized secondary dystonia but not in others. Larger follow-up studies of DBS for secondary dystonia, focusing on patient age, history, etiology, and patterns of dystonia, are needed to learn which patients will respond best to DBS.

Intraoperative dopamine release during globus pallidus internus stimulation in Parkinson's disease

It is still unclear whether dopamine (DA) levels correlate with Parkinson's disease (PD) severity or play a role in the mechanisms of high-frequency stimulation (HFS). We have used microdialysis to record pallidal DA in 5 patients with PD undergoing microelectrode-guided pallidotomy. We found that patients with more severe disease and, consequently, lower pallidal DA did poorly after pallidal lesions. In the operating room, 4 of 5 patients had a significant increase in DA levels during HFS (600%, on average). To test the hypothesis that DA was important for the effects of stimulation, we correlated the amelioration in rigidity observed in the operating room with pallidal DA release. Though rigidity was 56% better during stimulation, no correlation was found between such an improvement and DA release. These findings suggest that additional mechanisms not directly dependent on pallidal DA release may be involved in the clinical effects of HFS of the globus pallidus internus.

Effects of Pedunculopontine Area and Pallidal DBS on Gait Ignition in Parkinson's Disease

BackgroundFreezing of gait is a disabling feature of Parkinson's disease, and so far no established treatment exists. Deep brain stimulation of the pedunculopontine area has been proposed to treat refractory gait disorders, yet data on measurable effects, especially in combination with stimulation of other targets, are scarce. MethodsAcute effects of either low frequency pedunculopontine stimulation or high frequency stimulation of the posteroventral lateral globus pallidus internus and a combination of both in a 66-year-old man with advanced Parkinson's disease were assessed. Four weeks after the intervention, the gait was examined with patient blinded in each condition using computerized gait analysis. ResultsIsolated pedunculopontine or pallidal stimulation had a mild impact on gait ignition and freezing of gait, but combined stimulation had a marked effect. ConclusionsCombined multifocal stimulation may be a promising option for gait ignition and freezing of gait in advanced Parkinson's disease.

Pallidal deep brain stimulation relieves camptocormia in primary dystonia

Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

Effect of Subthalamic Nucleus or Globus Pallidus Interna Stimulation on Oculomotor Function in Patients with Parkinson’s Disease

Background: Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson’s disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. Objective: We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. Methods: Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. Results: As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. Conclusion: Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function.

Deep brain stimulation improves quality of life in pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is an uncommon extrapyramidal movement disorder characterized by the progressive incapacitating dystonia. Medical management is often incapable of reversing the dystonic symptoms. In recent years, stereotactic procedure like deep brain stimulation has been found effective in resolving the disabling dystonia and improving the quality of life. There are few cases in the world literature highlighting the usefulness of this technique. We report a case of 10-year-old girl who underwent bilateral Globus pallidus internus stimulation for PKAN.

Unilateral Deep Brain Stimulation of the Right Globus Pallidus Internus in Patients with Tourette's Syndrome: Two Cases with Outcomes After 1 Year and a Brief Review of the Literature

Tourette's syndrome is a complex neuropsychiatric disorder, characterized by tics. Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) has been considered to be an effective treatment for refractory Tourette's syndrome. Postoperative outcomes are described after 12 months' follow-up in a 41-year-old male patient and a 22-year-old male patient with Tourette's syndrome, both of whom underwent unilateral electrode implantations into the right GPi for DBS. These patients were diagnosed with Tourette's syndrome in childhood and, despite long-term therapy with a range of antipsychotic medications, continued to experience disabling tics in adulthood. Improvements in tic severity of 58.5% and 53.1% were observed at 12 months in the older and younger patient, respectively; improvements were determined by the Yale Global Tic Severity Scale. Both patients also experienced reductions in tic frequency and reported improvements in their health-related quality of life. Improvements in tics were similar to previous reports involving patients who underwent bilateral GPi DBS. These cases suggest that unilateral DBS of the right GPi is effective and might be a viable surgical choice for some patients with Tourette's syndrome.

Long Disease Duration Interferes With Therapeutic Effect of Globus Pallidus Internus Pallidal Stimulation in Primary Cervical Dystonia

We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. At last follow-up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed-rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). Bilateral GPi-DBS is an effective long-term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.

Deep Brain Stimulation in Children with Dystonia: Experience from a Tertiary Care Center (S28.006)

Objective: To investigate the efficacy and safety of deep brain stimulation (DBS) of globus pallidus internus (GPi) in children with dystonia. Background Deep brain stimulation (DBS) is an effective treatment for medically refractory dystonia. A few studies in children have shown utility of DBS in primary > secondary dystonia. More studies are needed. Design/Methods: IRB approved retrospective chart review of patients (≤21 years) with dystonia who underwent DBS of GPi. Optimal stimulation parameters and complications were recorded. Outcome measures assessed were change in the Burke-Fahn-Marsden-Dystonia-Rating-Scale and functional status post-surgery. Results: Eight patients underwent DBS for dystonia. Mean age of onset of dystonia was 7.5 ± 4.8, 7 were male. Mean age at DBS was 14.1 ± 4.6 years. Etiology of dystonia was primary in 6 [DYT-1+ (1), DYT-11 + (1), idiopathic DYT-1 negative (4)], and secondary in 2 [mitochondrial disorder (1), traumatic brain injury (1)]. Six had generalized dystonia, 1 hemidystonia, 1 cranio-cervical dystonia. All underwent GPi implantation, 1 unilateral and the rest bilateral. Mean follow-up was 6.7 ± 2.6 years, 1 lost to follow-up. Mean Burke-Fahn-Marsden-Dystonia-Rating-Scale was 62 ± 32.3 prior to surgery followed by improvement at 6 months (44± 27), 12 months (33± 24.7) and at last follow-up (31.5± 24). Mean DBS parameters at the time of maximal improvement of dystonia-rating-scale were: amplitude 3.2±0.7 volts, pulse width 170± 68 microseconds and frequency 102± 35 Hz. Three patients who were nonambulatory prior to surgery were able to ambulate without assistance after DBS. Hardware problems (electrode dislocation and breakage of cable) were observed in 2 and infection was noted in 1; no other therapy-related morbidity was observed. Conclusions: DBS of the GPi is an effective and safe therapy in pediatric patients with primary as well as selected cases of secondary dystonia. Early neurosurgical intervention seems to be crucial to prevent irreversible impairment of motor function. Disclosure: Dr. Ghosh has nothing to disclose. Dr. Machado has received personal compensation for activities with Intelect Medical, Boston scientific, ATI Pharmacology, Cardionomics and Monteris Medical as a consultant. Dr. Deogaonkar has received personal compensation for activities with Medtronic as a consultant. Dr. Deogaonkar has received (royalty or license fee or contractual rights) payments from Autonomic Technology Inc. Dr. Ghosh has received personal compensation for activities with Merz Pharma as a consultant.

GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease

ObjectivesTo compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities. MethodsWe conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32–34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case–control study. ResultsA total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131). ConclusionsThe overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.

Effects of Relative Low-Frequency Bilateral Globus Pallidus Internus Stimulation for Treatment of Cervical Dystonia

Objective: To assess the effect of relative lower amplitude and frequency for globus pallidus internus (GPi) deep brain stimulation (DBS) of cervical dystonia (CD). Materials and Methods: Between February 2005 and October 2008, 14 patients diagnosed with CD underwent bilateral GPi DBS and all the patients received low-frequency stimulation and were followed for more than 2 years. We activated the implantable pulse generator 3–4 days postoperatively and initial amplitude, pulse width, and frequency were set at 1.5 V, 120 µs, and 70 Hz. The Toronto Western Spasmodic Torticolis Rating Scale (TWSTRS) was applied preoperatively and at 1, 6, 12 and 24 months postoperatively. Results: The overall TWSTRS scores improved 71.2% 2 years postoperatively (p = 0.001). The mean improvement was 78.4% in severity subscores, 68.4% in disability, and 66.8% in pain scores for the 2-year follow-up period. The TWSTRS scores were significantly reduced (p < 0.05), suggesting that the most significant improvement of the TWSTRS scores occurred within 1 month. The final amplitude was 2.9/2.7 V with the pulse width of 147.9/147.9 µs and the frequency of 101.1/100 Hz. Conclusion: According to our results, the initial settings of low amplitude and especially relatively low frequency are safe and effective for treatment of CD.

Deep brain stimulation of the globus pallidus internus and Gilles de la Tourette syndrome: Toward multiple networks modulation

Background:Gilles de la Tourette's syndrome (GTS) is a complex neuropsychiatric disorder characterized by disabling motor and vocal tics. The pathophysiology of GTS remains poorly understood. Conventional treatment consists in pharmacological and behavioral treatment. For patients suffering severe adverse effects or not responding to pharmacological treatment, deep brain stimulation (DBS) presents an alternative treatment. However, the optimal target choice in DBS for GTS remains a divisive issue.Methods:A PubMed search from 1999 to 2012 was conducted. Thirty-three research articles reporting on DBS in patients with GTS were selected and analyzed.Results:Eighty-eight patients with Tourette's syndrome were treated since 1999 with DBS. The majority of patients received thalamic stimulation. Significantly fewer patients were treated with globus pallidus internus stimulation. Occasionally, the anterior limb of the internal capsule and the nucleus accumbens were implanted. The subthalamic nucleus was selected once. All targets were reported with positive results, but of variable extent. Only 14 patients exhibited level 1 evidence.Conclusion:In light of the wide spectrum of associated behavioral co-morbidities in GTS, multiple networks modulation may result in the most efficacious treatment strategy. The optimal locations for DBS within the cortico-basal ganglia-thalamocortical circuits remain to be established. However, at the current stage, comparison between targets should be done with great caution. Significant disparity between number of patients treated per target, methodological variability, and quality of reporting renders a meaningful comparison between targets difficult. Randomized controlled trials with larger cohorts and standardization of procedures are urgently needed.

Deep brain stimulation for medically refractory life-threatening status dystonicus in children

Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders.

Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism

Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.