Pallidal Deep Brain Stimulation Research Articles

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial.

Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD. A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores. Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported. STN or GPi DBS are ineffective on dystonia related to WD.

Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.

Pallidal and Thalamic Deep Brain Stimulation in the Treatment of Unilateral Dystonia: A Prospective Assessment.

The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking. To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia. Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously. DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations. This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach.

Pilot Study of Acute Behavioral Effects of Pallidal Burst Stimulation in Parkinson's Disease.

Burst-patterned pallidal deep brain stimulation (DBS) in an animal model of Parkinson's disease (PD) yields significantly prolonged therapeutic benefit compared to conventional continuous DBS, but its value in patients remains unclear. The aims were to evaluate the safety and tolerability of acute (<2 hours) burst DBS in PD patients and to evaluate preliminary clinical effectiveness relative to conventional DBS. Six PD patients were studied with DBS OFF, conventional DBS, and burst DBS. Unified Parkinson's Disease Rating Scale III (UPDRS-III) and proactive inhibition (using stop-signal task) were evaluated for each condition. Burst and conventional DBS were equally tolerated without significant adverse events. Both stimulation patterns provided equivalent significant UPDRS-III reduction and increased proactive inhibition relative to DBS OFF. This pilot study supports the safety and tolerability of burst DBS, with acute effects similar to conventional DBS. Further larger-scale studies are warranted given the potential benefits of burst DBS due to decreased total energy delivery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

Pallidal deep brain stimulation for patients with myoclonus-dystonia without SGCE mutations.

Pallidal deep brain stimulation (GPi-DBS) is effective for treating myoclonus and dystonia caused by SGCE mutations (DYT-SGCE, DYT11). However, it is unknown whether GPi-DBS is effective for the treatment of myoclonus-dystonia which is not associated with the SGCE gene mutations. In this study, we investigated the efficacy of GPi-DBS in treating myoclonus-dystonia in SGCE mutation-negative cases. Three patients with myoclonus-dystonia without SGCE mutations who underwent GPi-DBS were evaluated preoperatively and 6months postoperatively using the Unified Myoclonus Rating Scale (UMRS) and Fahn-Marsden Dystonia Rating Scale (FMDRS) for myoclonus and dystonia, respectively. In two of the three patients, myoclonus was more evident during action. Myoclonus was predominant at rest in the other patient, and he was unaware of his dystonia symptoms. The results were compared with those of the four DYT-SGCE cases. The mean UMRS score in patients with myoclonus-dystonia without SGCE mutations improved from 61.7 to 33.7 pre- and postoperatively, respectively, and the mean FMDRS score improved from 7.2 to 4.5. However, the degree of improvement in myoclonus-dystonia in patients without SGCE mutations was inferior to that in patients with DYT-SGCE (the UMRS score improved by 45% and 69%, respectively). GPi-DBS is effective for treating myoclonus-dystonia in patients with and without SGCE mutations. GPi-DBS should be considered as a treatment option for myoclonus-dystonia without SGCE mutations.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.

Pallidal versus subthalamic deep brain stimulation for Meige syndrome: A systematic review and meta-analysis

BackgroundGlobus pallidus internus (GPi) and subthalamic nucleus (STN) are two common deep brain stimulation (DBS) targets. This meta-analysis was to compared the efficacy and safety of these two DBS targets for the treatment of Meige syndrome (MS). MethodsA systematic search was performed using EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov to identify DBS trials for MS. Review Manager 5.3 was used to perform meta-analysis and the mean difference (MD) was analyzed and calculated with a random effect model. Pearson's correlation coefficients and meta-regression analyses were utilized to identify relevant predictive markers. ResultsTwenty trials involving 188 participants with GPi-DBS and 110 individuals with STN-DBS were eligible. Both groups showed improvement of the Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFMDRS-M) and Disability (BFMDRS-D) scores (BFMDRS-M: MD = 10.57 [7.74–13.41] for GPi-DBS, and MD = 8.59 [4.08–13.11] for STN-DBS; BFMDRS-D: MD = 5.96 [3.15–8.77] for GPi-DBS, and MD = 4.71 [1.38–8.04] for STN-DBS; all P < 0.001) from baseline to the final follow-up, while no notable disparity in improvement rates was observed between them. Stimulation-related complications occurrence was also similar between two groups (38.54 ± 24.07% vs. 43.17 ± 29.12%, P = 0.7594). Simultaneously, preoperative BFMDRS-M score and disease duration were positively connected with the relative changes in BFMDRS-M score at the final visit. ConclusionBoth GPi-DBS and STN-DBS are effective MS therapies, with no differences in efficacy or the frequency of stimulation-related problems. Higher preoperative scores and longer disease duration probably predict greater improvement.

No differential effects of subthalamic nucleus vs. globus pallidus deep brain stimulation in Parkinson’s disease: Speech acoustic and perceptual findings

BackgroundDeep Brain Stimulation (DBS) in the Subthalamic Nucleus (STN) or the Globus Pallidus Interna (GPI) is well-established as a surgical technique for improving global motor function in patients with idiopathic Parkinson’s Disease (PD). Previous research has indicated speech deterioration in more than 30% of patients after STN-DBS implantation, whilst speech outcomes following GPI-DBS have received far less attention. Research comparing speech outcomes for patients with PD receiving STN-DBS and GPI-DBS can inform pre-surgical counseling and assist with clinician and patient decision-making when considering the neural targets selected for DBS-implantation. The aims of this pilot study were (1) to compare perceptual and acoustic speech outcomes for a group of patients with PD receiving bilateral DBS in the STN or the GPI with DBS stimulation both ON and OFF, and (2) examine associations between acoustic and perceptual speech measures and clinical characteristics. MethodsTen individuals with PD receiving STN-DBS and eight individuals receiving GPI-DBS were audio-recorded reading a passage. Three listeners blinded to neural target and stimulation condition provided perceptual judgments of intelligibility and overall speech severity. Speech acoustic measures were obtained from the recordings. Acoustic and perceptual measures and clinical characteristics were compared for the two neural targets and stimulation conditions. ResultsIntelligibility and speech severity were not significantly different across neural target or stimulation conditions. Generally, acoustic measures were also not statistically different for the two neural targets or stimulation conditions. Acoustic measures reflecting more varied speech prosody were associated with improved intelligibility and lessened severity. Convergent correlations were found between UPDRS-III speech scores and perceptual measures of intelligibility and severity. ConclusionThis study reports a systematic comparison of perceptual and acoustic speech outcomes following STN-DBS and GPI-DBS. Statistically significant differences in acoustic measures for the two neural targets were small in magnitude and did not yield group differences in perceptual measures. The absence of robust differences in speech outcomes for the two neural targets has implications for pre-surgical counseling. Results provide preliminary support for reliance on considerations other than speech when selecting the target for DBS in patients with PD.

Deep brain stimulation for Tourette syndrome: modulation of the limbic-motor interface network.

Deep brain stimulation (DBS) is an effective treatment for medically refractory Tourette syndrome (TS). Several effective targets have been reported, but there is still controversy about the networks involved in the efficacy of DBS for TS. Here, the authors aimed to identify the basal ganglia-thalamo-cortical networks associated with tic and obsessive-compulsive behavior (OCB) improvement and the network link between the two main targets for TS. A retrospective analysis of 21 patients treated with pallidal and thalamic DBS was performed. Tics and OCB scores were recorded before and after DBS. The authors localized the electrodes in standard MNI (Montreal Neurological Institute) space and calculated the volume of tissue activated with the settings at the last follow-up to obtain areas of maximal improvement ("sweet spots") among all patients for the pallidal and thalamic targets. Tractography was used to show the white matter pathways associated with maximal tic and OCB improvement. Ten patients treated with pallidal DBS and 11 patients treated with thalamic DBS were included. Responder rates were 80% in the pallidal and 64% in the thalamic target groups. Sweet spots for tics and OCB clustered in several areas across the basal ganglia and thalamus delineated two main networks. Tic reduction in the pallidal target mapped to a limbic pallidothalamic network and in the thalamic target to the premotor thalamocortical network. Putting these two networks together will form the main output of the so-called limbic-motor interface network. However, OCB reduction mapped a dorsomedial prefrontal cortex/dorsal anterior cingulate (dmPFC/dACC) network. The authors demonstrated the involvement of the limbic-motor interface network during effective DBS for tics in patients with TS. OCB redution was associated with the additional involvement of dmPFC/dACC connections passing dorsal to the head of the globus pallidus pars externa on its way to the thalamus and midbrain.

BOLD frequency-dependent alterations in resting-state functional connectivity by pallidal deep brain stimulation in patients with Parkinson's disease.

Functional MRI (fMRI) has been used to investigate the therapeutic mechanisms underlying deep brain stimulation (DBS) for Parkinson's disease (PD). However, the alterations in stimulation site-seeded functional connectivity induced by DBS at the internal globus pallidus (GPi) remain unclear. Furthermore, whether DBS-modulated functional connectivity is differentially affected within particular frequency bands remains unknown. The present study aimed to reveal the alterations in stimulation site-seeded functional connectivity induced by GPi-DBS and to examine whether there exists a frequency band effect in blood oxygen level-dependent (BOLD) signals related to DBS. Patients with PD receiving GPi-DBS (n = 28) were recruited for resting-state fMRI with DBS on and DBS off under a 1.5-T MR scanner. Age- and sex-matched healthy controls (n = 16) and DBS-naïve PD patients (n = 24) also received fMRI scanning. The alterations in stimulation site-seeded functional connectivity in the stimulation-on state versus stimulation-off state, as well as the relationship between alterations in connectivity and improvement in motor function induced by GPi-DBS, were examined. Furthermore, the modulatory effect of GPi-DBS on the BOLD signals within the 4 frequency subbands (slow-2 to slow-5) was investigated. Finally, the functional connectivity of the motor-related network, consisting of multiple cortical and subcortical regions, was also examined among the groups. In this study, p < 0.05 with Gaussian random field correction indicates statistical significance. Functional connectivity seeding from the stimulation site (i.e., the volume of tissue activated [VTA]) increased in the cortical sensorimotor areas and decreased in the prefrontal regions with GPi-DBS. Alterations in connectivity between the VTA and the cortical motor areas were correlated with motor improvement by pallidal stimulation. The alterations in connectivity were dissociable between the frequency subbands in the occipital and cerebellar areas. The motor network analysis indicated decreased connectivity among most cortical and subcortical regions but increased connectivity between the motor thalamus and the cortical motor area in patients with GPi-DBS compared with those in DBS-naïve patients. The DBS-induced decrease in several cortical-subcortical connectivities within the slow-5 band correlated with motor improvement with GPi-DBS. These findings indicate that the alterations in functional connectivity from the stimulation site to the cortical motor areas, as well as multiple connectivities among the motor-related network, were associated with the efficacy of GPi-DBS for PD. Furthermore, the changing pattern of functional connectivity within the 4 BOLD frequency subbands is partially dissociable.

A case report of deleterious SGCE myoclonus: dystonia successfully treated with pallidal deep brain stimulation

SGCE (epsilon (ε)-sarcoglycan gene) myoclonus-dystonia (SGCE M-D) is a pleiotropic neuropsychiatric disorder with an autosomal dominant mode of inheritance, variable severity, and incomplete penetrance. There have been few reports of patients with SGCE M-D who have been successfully treated with deep brain stimulation (DBS). This case report presents a missense mutation (c.289&gt;T) inherited in a Northeastern Asian family affected by SGCE M-D. The individuals with the condition exhibited clinical manifestations of generalized myoclonus accompanied by sustained cervical dystonia. A 38-year-old woman had a history of generalized dystonia myoclonus with paroxysmal jerks for the past 10 years. The symptoms gradually worsened over the years, affecting her entire body and interfering with most of her daily activities. Genetic testing identified a single base deletion in exon 3 of the SGCE gene, which was considered the genotype underlying her phenotypic symptoms. After failed attempts with oral medications as an outpatient, she underwent DBS targeting the globus pallidus internus (GPI). Her symptoms significantly improved after the activation of the stimulator. Our case supports the beneficial effect of GPI-targeted DBS in patients who are unresponsive to oral medications and have a genetically confirmed M-D phenotype.

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation.

Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation in dystonia: The added value of neuropsychological assessments.

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication-refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre- and post-DBS assessment (mean age 51 years; range 20-70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre-DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre-DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post-DBS neuropsychological evaluations should be made on a case-by-case basis.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease

BackgroundSleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. MethodsWe directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. ResultsPallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. ConclusionOur findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Assess stimulation-induced dyskinesia and its potential physiological mechanism using phase-amplitude coupling

With the increasing use of deep brain stimulation (DBS) on clinical treatment of Parkinsons diseases, stimulation-induced dyskinesia (SID) becomes more and more common. SID was often detected shortly after DBS treatment on patients. However, the pathogenesis of SID and exact region of SID remains unclear. The aim of this paper is to review the studies of stimulation-induced dyskinesia and try to propose a new method to study and quantify SID, which is phase-amplitude coupling. phase-amplitude coupling (PAC) has been widely used in many other studies of brain-related illness and therapies. It is believed to have a profound relationship with our brain activities. Because of the features of PAC itself, the anatomical regions related to SID after pallidal DBS in Parkinson's disease (PD) patients can be possibly found, and the value of PAC can be served as a biomarker for us to assess the stimulation-induced dyskinesia. However, further researches on patients should be done to verify this method. It is very important to understand how SID is formed and its pathogenesis because it may help us find the appropriate parameters of deep brain stimulation and reduce the damage caused by the implant of electrode

Improvement in Cervical Dystonia – Outcomes of a Prospective, Multicenter, International Registry of Deep Brain Stimulation (DBS) (P11-11.002)

<h3>Objective:</h3> To report real-world outcomes of Dystonia patients implanted with a Multiple Independent Current Control (MICC)-based Directional DBS system. <h3>Background:</h3> Management of dystonia using Deep Brain Stimulation (DBS) is a well-established therapeutic approach. However, optimal DBS target sites in patients with cervical (focal) versus generalized dystonia are thought to diverge and be specific for particular connections (Horn 2022). DBS devices equipped with capabilities such as directionality and Multiple Independent Current Control (MICC) may offer potential for improved clinical outcomes. Here, we report a sub-analysis of patients with cervical dystonia only or dystonia with cervical involvement from an on-going, multicenter registry. <h3>Design/Methods:</h3> In this prospective, on-label, multi-center, international registry (ClinicalTrials.gov Identifier: NCT02686125) of dystonia, enrolled subjects received MICC-based directional DBS systems (Vercise, Boston Scientific). Subjects were followed up to 3 years (post-implant). Several study assessments evaluating their dystonia symptoms (e.g., TWSTRS), quality of life (GIC) and overall satisfaction were administered. Adverse Events were also collected. <h3>Results:</h3> A total of 43-patients (mean age 56.9-years, 58% females) with focal (cervical) dystonia only and 83-patients (mean 41.95-years, 61% females) with generalized or segmental dystonia with cervical involvement who underwent pallidal DBS were prospectively evaluated. Both groups reported significant improvement in overall TWSTRS scores – however the extent varied. In the cervical only cohort, a 19.9-point improvement was noted at 6-months (n=25) and sustained up to 1-year (23.2-point improvement, n=20). In those with generalized or segmental dystonia (with cervical involvement), a 9.7-point. and 7.3-improvement in overall TWSTRS scores was noted at 6- (n = 50) and 12-months (n = 38), respectively. <h3>Conclusions:</h3> This registry represents the first comprehensive, large-scale collection of real-world outcomes associated with dystonia patients implanted with a directional DBS system capable of MICC. Preliminary results demonstrate significant improvement in patients with cervical dystonia (either alone or with other regions involved) following DBS. <b>Disclosure:</b> Dr. Albanese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific. Dr. Albanese has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Publishing Group. Dr. Albanese has a non-compensated relationship as a President-Elect with International Association on Parkinsonism and Related Disorders that is relevant to AAN interests or activities. Roshini Jain has received personal compensation for serving as an employee of Boston Scientific. Roshini Jain has received stock or an ownership interest from Boston Scientific. Lilly Chen has received personal compensation for serving as an employee of Boston Scientific . Joachim Krauss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inomed. Joachim Krauss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for aleva. Joachim Krauss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston.

Pallidal Beta Activity Is Linked to Stimulation-Induced Slowness in Dystonia.

Pallidal deep brain stimulation (DBS) effectively alleviates symptoms in dystonia patients, but may induce movement slowness as a side-effect. In Parkinson's disease, hypokinetic symptoms have been associated with increased beta oscillations (13-30 Hz). We hypothesize that this pattern is symptom-specific, thus accompanying DBS-induced slowness in dystonia. In 6 dystonia patients, pallidal rest recordings with a sensing-enabled DBS device were performed and tapping speed was assessed using marker-less pose estimation over 5 time points following cessation of DBS. After cessation of pallidal stimulation, movement speed increased over time (P < 0.01). A linear mixed-effects model revealed that pallidal beta activity explained 77% of the variance in movement speed across patients (P=0.01). The association between beta oscillations and slowness across disease entities provides further evidence for symptom-specific oscillatory patterns in the motor circuit. Our findings might help DBS therapy improvements, as DBS-devices able to adapt to beta oscillations are already commercially available. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A convergent subcortical signature to explain the common efficacy of subthalamic and pallidal deep brain stimulation.

This scientific commentary refers to 'Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease', by Johnson et al. (https://doi.org/10.1093/braincomms/fcad025).

Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.