Globus Pallidus Internus Deep Brain Stimulation Research Articles

Are there gender differences between subthalamic or globus pallidus internus DBS in Parkinson’s disease? Results from a single center

Are there gender differences between subthalamic or globus pallidus internus DBS in Parkinson’s disease? Results from a single center

Long-Term Globus Pallidus Internus Deep Brain Stimulation in Pediatric Non-Degenerative Dystonia: A Cohort Study and a Meta-Analysis.

The evidence in the effectiveness of deep brain stimulation in children with medication-refractory non-degenerative monogenic dystonia is heterogeneous and long-term results are sparse. The objective is to describe long-term outcomes in a single-center cohort and compare our results with a meta-analysis cohort form literature. We performed a retrospective single-center cohort study including consecutive pediatric patients with non-degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual-patient data meta-analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M) score. The clinical cohort included 25 patients with a mean study follow-up of 11.4 years. The meta-analysis cohort included 224 patients with a mean follow-up of 3 years. Overall, the BFMDRS-M mean improvements at 1 year and at last follow-up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta-analysis cohort, respectively. TOR1A-dystonia showed the greatest and most stable BFMDRS-M improvement in both cohorts at 1 year and at last follow-up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta-analysis cohort), followed by SGCE-dystonia (63% and 63.9% in the meta-analysis cohort). THAP1-dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta-analysis cohort) and KMT2B-dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta-analysis cohort) showed a less pronounced or sustained response. Globus pallidus deep brain stimulation long-term treatment seems effective with a possible gene-specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Stimulation-induced Sensory Side Effects from Globus Pallidus Internus Deep Brain Stimulation? (P2-3.013)

Stimulation-induced Sensory Side Effects from Globus Pallidus Internus Deep Brain Stimulation? (P2-3.013)

Electrode position and cognitive outcome following deep brain stimulation surgery

OBJECTIVE Subthalamic nucleus (STN) and globus pallidus internus (GPI) deep brain stimulation (DBS) effectively treat motor symptoms in Parkinson’s disease (PD) but may be associated with cognitive and psychiatric changes in some patients. Evaluation of changes in cognitive and psychiatric symptoms following DBS is complicated by changes in these symptoms that occur as part of the natural disease course. The aim of this study was to evaluate whether electrode position was associated with changes in neurocognitive symptoms in patients who underwent STN and GPI DBS. METHODS A single-institution retrospective cohort study was conducted on patients with PD who underwent DBS from 2008 to 2019. Cognitive and psychiatric outcomes included Beck Depression Inventory II (BDI-II) score, presence of impulsive-compulsive behavior (ICB), Mini-Mental State Examination (MMSE) score, and overall cognitive status grade determined by comprehensive neuropsychology testing (normal, mild impairment, moderate impairment, and dementia). Pre- and postoperative comparisons were performed using a Wilcoxon signed-rank test or paired t-test. Patients with and without cognitive decline were compared using a Mann-Whitney U-test or unpaired t-test. A chi-square test was used for categorical comparisons. RESULTS One hundred thirty patients were included (mean age 62.5 ± 7.9 years). At a mean postoperative follow-up from DBS of 13.0 ± 12.7 (range 6–66) months, there was an improvement in ICB (26.3% preoperatively vs 15.0% postoperatively, p = 0.017), but a decline in MMSE score (28.6 ± 1.6 vs 27.6 ± 2.0, p < 0.001) and overall cognitive status (normal: 66.2% vs 39.2%; mild: 12.3% vs 17.7%; moderate: 21.5% vs 33.1%; dementia: 0.0% vs 10.0%; p < 0.001). Patients undergoing STN DBS had a worse decline in overall cognitive status than patients who underwent GPI DBS (p = 0.006). Postoperative cognitive decline was associated with a more medial electrode position only for patients who underwent STN DBS. CONCLUSIONS Cognitive change was observed in some patients with PD who underwent both GPI and STN DBS, likely due partly to underlying disease progression. Compared with GPI DBS, STN DBS was associated with a greater likelihood of cognitive decline. In STN but not GPI DBS, cognitive decline was associated with medialized electrode position, suggesting modulation of nonmotor STN divisions may contribute to cognitive changes following STN DBS.

Impacts of Deep Brain Stimulation of the Globus Pallidus Internus on Swallowing: A Retrospective, Cross-Sectional Study.

Deep brain stimulation (DBS) is a common treatment for motor symptoms of Parkinson disease (PD), a condition associated with increased risk of dysphagia. The effect of DBS on swallowing function has not been comprehensively evaluated using gold-standard imaging techniques, particularly for globus pallidus internus (GPi) DBS. The objective of this retrospective, cross-sectional study was to identify differences in swallowing safety and timing kinematics among PD subjects with and without GPi DBS. We investigated the effects of unilateral and bilateral GPi DBS as well as the relationship between swallowing safety and DBS stimulation parameters, using retrospective analysis of videofluoroscopy recordings (71 recordings from 36 subjects) from electronic medical records. Outcomes were analyzed by surgical status (pre-surgical, unilateral DBS, bilateral DBS). The primary outcome was percent of thin-liquid bolus trials rated as unsafe, with Penetration-Aspiration Scale scores of 3 or higher. Secondary analyses included swallowing timing measures, relationships between swallowing safety and DBS stimulation parameters, and Dynamic Imaging Grade of Swallowing Toxicity ratings. Most subjects swallowed all boluses safely (19/29 in the pre-surgical, 16/26 in the unilateral DBS, and 10/16 in the bilateral DBS conditions). Swallowing safety impairment did not differ among stimulation groups. There was no main effect of stimulation condition on timing metrics, though main effects were found for sex and bolus type. Stimulation parameters were not correlated with swallowing safety. Swallowing efficiency and overall impairment did not differ among conditions. These results provide evidence that GPi DBS does not affect pharyngeal swallowing function. Further, prospective, investigations are needed.

Increased electrode impedance as an indicator for early detection of deep brain stimulation (DBS) hardware Infection: Clinical experience and in vitro study

BackgroundWhen deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. MethodsA stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. ResultsThe mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3–6 (p = 0.003). ConclusionThis study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.

Rescue subthalamic stimulation after unsatisfactory outcome of pallidal stimulation in Parkinson's disease: a case series and review.

Subthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson's disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients' characteristics have not been well described and this phenomenon has not been well reviewed. This monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries. Eight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved. Our findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.

Case report: Lingual dystonia symptoms treated with botulinum toxin in patients with THAP1 mutation

Background: THAP1 mutation dystonia is a known genetic cause of generalized dystonia. THAP1 mutation frequently presents with clinical features of bulbar dysfunction, including oromandibular and lingual dystonia. Patients complain of significant speech, chewing, and swallowing difficulties leading to major occupational and social disabilities. While bilateral globus pallidus internus deep brain stimulation (DBS) is powerful therapy for generalized dystonia and improves dystonia symptoms in the cervical and limb region, it may not improve speech despite multiple adjustments to the stimulation parameters. Treating lingual dystonia symptoms with oral medications is commonly unsatisfactory. Botulinum toxin injection, a potent therapy for focal forms of dystonia is currently underutilized in clinical practice for treating lingual dystonia.Cases: We present two patients with THAP1 mutation reporting lingual dystonia symptoms. The first patient did not meet the eligibility criteria for DBS therapy due to significant psychiatric symptoms. The second patient received DBS with improvements in cervical, limb, and trunk symptoms but complained of severe speech difficulties that did not improve despite multiple programming sessions. These patients were treated with botulinum toxin injections every 12 weeks for more than 3 years, with speech improvements lasting most of the cycle. For the most part they tolerated botulinum toxin without bothersome side effects. Along with the clinical histories, we present objective perceptual analysis of speech samples collected before and after botulinum toxin injections in one of the treatment cycles.Conclusion: Botulinum toxin injections that are clinically beneficial for mitigating lingual dystonia symptoms should be utilized to address symptoms of THAP1 mutation dystonia that may not be amenable to other therapies, such as the DBS.

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

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

Bilateral globus pallidus internus (GPi) deep brain stimulation for cervical dystonia: Effects on motor and non-motor symptoms within 5 years follow

BackgroundCervical Dystonia (“CD”) is a movement disorder characterised by sustained muscle contractions in the neck, causing involuntary posturing. Deep brain stimulation (“DBS”) of the globus pallidal internus (GPi) is advanced treatment for pharmaco-refractory patients. As CD is a rare disease, cohort studies are often limited to patients of heterogenous disease profile, small sample size or short follow-up. This study firstly aimed to measure the efficacy of GPi-DBS on motor and non-motor symptoms of CD. A secondary aim was to evaluate if clinical factors – such as age, disease duration and baseline disease severity – influence variability of motor outcomes. Methods37 idiopathic CD patients were recruited from movement disorders clinics at The Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and 1 year, 3 years and 5 years post-operatively with the following clinical scales: Toronto Western Spasmodic Torticollis Rating Scale (“TWSTRS”), Hospital Anxiety and Depression Scale and EuroQuol-5D. ResultsGPI-DBS significantly improved overall TWSTRS scores by 57% from baseline to 5Y FU (p < 0.001). It also significantly improved TWSTRS severity, disability, and pain sub-scores by 72%, 59% and 46% respectively. We did not find a significant improvement in mood or quality of life scores at 5 years. Similarly, clinical factors at baseline did not correlate with variability in motor outcome. ConclusionWe concluded that GPi-DBS is an effective treatment for motor symptoms and pain in CD. There was limited effect on mood and QoL, and no clinical predictive factors of outcome were identified.

A Technique of Deep Brain Stimulation of the Globus Pallidus Interna for Dystonia Under General Anesthesia With Sevoflurane.

Background Globus pallidus interna (GPi) deep brain stimulation (DBS) is an established surgical procedure that confers a benefit in medication refractory dystonia. Patients with generalized dystonia require general anesthesia (GA) for the surgery as their movements may hinder the surgical procedure. General anesthetics tend to dampen the microelectrode recordings (MERs) from the GPi. Methods We describe our experience with a series of consecutive patients with dystonia who underwent bilateral GPi DBS using standard DBS and MER under GA using sevoflurane as the maintenance general anesthetic drug. All patients had Medtronic 3,387 leads implanted and connected to an RC battery. Patients underwent sequential programming of the DBS after the surgery. Results The mean age of the 13 patients who underwent DBS of the GPi for dystonia was 46.5 years with a range from 29 to 71 years. Every patient in our case series received various doses of(1.37% to 2.11%) inhaled sevoflurane for anesthesia maintenance. Sevoflurane provided adequate anesthesia and allowed accurate MERs from the GPi.No adverse effects were encountered. On follow-up and sequential DBS programming, patients had significant improvements in dystoniaattesting to the accuracy of the electrode placements. Conclusions We report our experience using sevoflurane for maintenance of GA for bilateral GPi DBS for dystonia. The main benefits identified have been adequate anesthesia and reduction of dystonia-related movements to allow the performance of the DBS surgery. The MER signals from the GPi were not suppressed by sevoflurane. This allowed accurate mapping and placement of the DBS implants in the GPi.

Surgical treatment of movement disorders in neurometabolic conditions.

Refractory movement disorders are a common feature of inborn errors of metabolism (IEMs), significantly impacting quality of life and potentially leading to life-threatening complications such as status dystonicus. Surgical techniques, including deep brain stimulation (DBS) and lesioning techniques, represent an additional treatment option. However, the application and benefits of these procedures in neurometabolic conditions is not well understood. This results in challenges selecting surgical candidates and counseling patients preoperatively. In this review, we explore the literature of surgical techniques for the treatment of movement disorders in IEMs. Globus pallidus internus DBS has emerged as a beneficial treatment option for dystonia in Panthotate-Kinase-associated Neurodegeneration. Additionally, several patients with Lesch-Nyhan Disease have shown improvement following pallidal stimulation, with more robust effects on self-injurious behavior than dystonia. Although there are numerous reports describing benefits of DBS for movement disorders in other IEMs, the sample sizes have generally been small, limiting meaningful conclusions. Currently, DBS is preferred to lesioning techniques. However, successful use of pallidotomy and thalamotomy in neurometabolic conditions has been reported and may have a role in selected patients. Surgical techniques have also been used successfully in patients with IEMs to treat status dystonicus. Advancing our knowledge of these treatment options could significantly improve the care for patients with neurometabolic conditions.

Intraoperative electrophysiological monitoring determines the final electrode position for pallidal stimulation in dystonia patients.

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for refractory dystonia. Neuroradiological target and stimulation electrode trajectory planning with intraoperative microelectrode recordings (MER) and stimulation are used. With improving neuroradiological techniques, the need for MER is in dispute mainly because of the suspected risk of hemorrhage and the impact on clinical post DBS outcome. The aim of the study is to compare the preplanned GPi electrode trajectories with final trajectories selected for electrode implantation after electrophysiological monitoring and to discuss the factors potentially responsible for differences between preplanned and final trajectories. Finally, the potential association between the final trajectory selected for electrode implantation and clinical outcome will be analyzed. Forty patients underwent bilateral GPi DBS (right-sided implants first) for refractory dystonia. The relationship between preplanned and final trajectories (MicroDrive system) was correlated with patient (gender, age, dystonia type and duration) and surgery characteristics (anesthesia type, postoperative pneumocephalus) and clinical outcome measured using CGI (Clinical Global Impression parameter). The correlation between the preplanned and final trajectories together with CGI was compared between patients 1-20 and 21-40 for the learning curve effect. The trajectory selected for definitive electrode implantation matched the preplanned trajectory in 72.5% and 70% on the right and left side respectively; 55% had bilateral definitive electrodes implanted along the preplanned trajectories. Statistical analysis did not confirm any of the studied factors as predictor of the difference between the preplanned and final trajectories. Also no association between CGI and final trajectory selected for electrode implantation in the right/left hemisphere has been proven. The percentages of final electrodes implanted along the preplanned trajectory (the correlation between anatomical planning and intraoperative electrophysiology results) did not differ between patients 1-20 and 21-40. Similarly, there were no statistically significant differences in CGI (clinical outcome) between patients 1-20 and 21-40. The final trajectory selected after electrophysiological study differed from the preplanned trajectory in a significant percentage of patients. No predictor of this difference was identified. The anatomo-electrophysiological difference was not predictive of the clinical outcome (as measured using CGI parameter).

Are Cognitively Impaired Patients Selectively Recruited to Pallidal Deep Brain Stimulation (DBS) in Parkinson’s Disease (PD)? (P5-11.016)

<h3>Objective:</h3> To determine whether demographic cognitive selection bias exists when choosing between STN and GPi as targets for DBS. <h3>Background:</h3> Though globus pallidus interna (GPi) is reportedly similarly effective to subthalamic nucleus (STN) DBS, offers primary dyskinesia reduction, and has been associated with less postoperative cognitive decline, STN is more frequently selected at many sites. This could be due to an impression that STN is more effective or programmable in practice. We hypothesized this could result in patients thought to be at greater cognitive risk, or with fewer comorbidities, selectively being recruited to GPi vs STN DBS. <h3>Design/Methods:</h3> We analyzed the pre-DBS demographic and baseline cognitive data of 127 patients who underwent neuropsychological evaluation. We compared performance in global functioning, verbal learning, verbal memory, confrontation naming, phonemic fluency, and semantic fluency between the STN and GPi groups using t tests. <h3>Results:</h3> 95 STN &amp; 32 GPi implants comprised our cohort. The pre-DBS GPi population was younger (57.6 ± 9.5) compared to STN (63.3 ± 8.6), p = .005. STN patients performed better in semantic fluency as measured by T scores, 50.75 versus 44.28 for the GPi group (p = 0.01). We found no significant difference in disease duration or other cognitive domains analyzed. <h3>Conclusions:</h3> We found that subjects selected for GPi DBS had worse semantic fluency performance, but other cognitive measures did not differ. Global cognitive performance does not appear to drive DBS selection at our center. Patients selected for GPi targets did not differ in disease duration or severity; however, they were younger. Further investigation will be required to see if phenotype, or psychiatric or medical comorbidities, affect selection. The many preoperative variables (cognition, mood, medication burden, dyskinesia) highlight the importance of an interdisciplinary approach to target selection and a comprehensive analysis of symptoms and risk-benefit profile. <b>Disclosure:</b> Dr. Marmol has nothing to disclose. Dr. Feldman has nothing to disclose. Dr. Harcourt has nothing to disclose. Annelly Buré-Reyes has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Luca has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Luca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Signant Health. Jonathan Jagid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic Inc. The institution of Jonathan Jagid has received research support from Boston Scientific. The institution of Jonathan Jagid has received research support from Medtronic Inc. The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson’s Foundation. The institution of Dr. Haq has received research support from NIMH. Dr. Haq has a non-compensated relationship as a consultant with Medtronics that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Boston Scientific that is relevant to AAN interests or activities. Dr. Haq has a non-compensated relationship as a consultant with Abbott that is relevant to AAN interests or activities. Dr. Sarno has nothing to disclose.

Double blind, nonrandomized crossover study of active recharge biphasic deep brain stimulation for primary dystonia

BackgroundDeep brain stimulation (DBS) of the globus pallidus interna (GPi) is an effective therapy for select patients with primary dystonia. DBS programming for dystonia is often challenging due to variable time to symptomatic improvement or stimulation induced side effects (SISE) such as capsular or optic tract activation which can prolong device optimization. ObjectiveTo characterize the safety and tolerability of active recharge biphasic DBS (bDBS) in primary dystonia and to compare it to conventional clinical DBS (clinDBS). MethodsTen subjects with primary dystonia and GPi DBS underwent a single center, double blind, nonrandomized crossover study comparing clinDBS versus bDBS. The testing occurred over two-days. bDBS and clinDBS were administered on separate days and each was activated for 6 h. Rating scales were collected by video recording and scored by four blinded movement disorders trained neurologists. ResultsThe bDBS paradigm was safe and well-tolerated in all ten subjects. There were no persistent SISE reported. The mean change in the Unified Dystonia Rating Scale after 4 h of stimulation was greater in bDBS when compared to clinDBS (−6.5 vs 0.3, p < 0.04). ConclusionIn this pilot study, we demonstrated that biphasic DBS is a novel stimulation paradigm which can be administered safely. The biphasic waveform revealed a greater immediate improvement. Further studies are needed to determine whether this immediate improvement persists with chronic stimulation or if clinDBS will eventually achieve similar levels of improvement to bDBS over time.

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).

Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson's disease.

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation (N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus (N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor (N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes (P = 0.9) but a higher frequency (P = 0.009) and a higher number of peaks (P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes (P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease.

Theta/Alpha Band Suppression and Clinical Outcomes During Globus Pallidus Internus Deep Brain Stimulation in Huntington's Disease.

Theta/Alpha Band Suppression and Clinical Outcomes During Globus Pallidus Internus Deep Brain Stimulation in Huntington's Disease.

Bilateral globus pallidus interna deep brain stimulation in Parkinson's disease: Therapeutic effects and motor outcomes prediction in a short-term follow up.

We aimed to compare the motor effect of bilateral globus pallidus interna (GPi) deep brain stimulation (DBS) on motor subtypes of Parkinson's disease (PD) patients and identify preoperative predictive factors of short-term motor outcome. We retrospectively investigated bilateral GPi DBS clinical outcomes in 55 PD patients in 1 year follow up. Motor outcome was measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III before and 1 year after surgery. Clinical outcomes were compared among different motor subtypes. Preoperative predictors of motor outcome were assessed by performing univariate and multivariate linear regression and logistic regression analyses. At 1 year following implantation, GPi DBS significantly improved the off-medication MDS-UPDRS III scores in all motor subtype cohorts, with prominent improvement in tremor. No significant difference of postoperative motor symptoms changes was found except greater tremor improvement achieved in both the tremor-dominant (TD) and indeterminate (IND) patients compared to the postural instability and gait difficulty (PIGD) patients. High percentage of PIGD patients were weak responders to DBS. Better levodopa responsiveness and more severe tremor predicted greater overall improvement of motor function in the entire cohort. Similarly, both levodopa responsiveness and tremor improvement were confirmed as predictors for motor improvement in PIGD patients. Bilateral GPi DBS could effectively improve motor outcomes in PD patients regardless of motor subtypes. Both TD and IND patients obtained larger tremor improvement. The intensity of levodopa responsiveness and the severity of tremor could serve as predictors of motor improvement 1 year after GPi DBS.

Bilateral Pallidal Deep Brain Stimulation in Meige Syndrome: Effects on Motor Function, Neuropsychological Status, and Mood.

Bilateral pallidal deep brain stimulation (DBS) has been broadly accepted as a feasible surgical procedure for treating various forms of dystonia, but its effects on motor function, neuropsychological status, and mood in patients with Meige syndrome have rarely been examined. To evaluate the effects of bilateral globus pallidus internus DBS (GPi-DBS) on the motor performance, quality of life, neuropsychological status, and mood of patients with primary Meige syndrome. Between January 2015 and April 2019, the database of 35 patients with Meige syndrome who underwent bilateral GPi-DBS in our institution was retrospectively reviewed. The severity of dystonia, health-related quality of life, cognitive function, and mood were assessed using standardized and validated rating scales at baseline. Repeat assessment of the same domains was performed at 1 year and 3 years after neurostimulation in a similar manner. One year and 3 years after bilateral GPi-DBS, Burke-Fahn-Marsden Dystonia Rating Scale movement scores were improved by 65% and 72% and Burke-Fahn-Marsden Dystonia Rating Scale disability scores were improved by 49% and 57%, respectively. The significant improvement in health-related quality of life observed at 1 year was sustained at 3 years. Relative to baseline and to the 1-year assessment, cognitive functions and mood remained stable after 3 years of neurostimulation. No deaths or life-threatening events were reported over the study period. Bilateral GPi-DBS is a safe and effective approach for medically refractory Meige syndrome that can improve motor function and quality of life without cognitive and mood side effects.