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Objective: Postoperative delirium (POD) may cause cognitive morbidities and prolonged hospital stay. This study aimed to evaluate the risk factors associated with postoperative delirium in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD). Method: We retrospectively reviewed 83 patients with idiopathic PD who underwent bilateral DBS between 2016 and 2023. The target of DBS was the globus pallidus interna (Gpi) or the subthalamic nucleus (STN) in 84.3% and 15.7% of patients, respectively. Patients were evaluated using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and categorized into two groups: those with delirium and those without. Demographic features, disease duration, preoperative cognitive status (Mini-Mental State Examination) and silent ischemia, brain atrophy rates, DBS target location, surgical type and duration, Unified PD Rating Scale-3 scores, Hoehn and Yahr scores, postoperative perilead edema, and electrolyte imbalance were compared between patients with and without post-DBS delirium. Apart from univariate analysis, receiver operating characteristic (ROC) curve analysis for disease duration and multivariate logistic regression analyses were used to determine independent risk factors for post-DBS delirium. Results: Five out of the 83 patients (6%) developed post-DBS delirium. Age (> 68 years), disease duration, preoperative cerebral atrophy rates, and postoperative perilead edema were significantly higher in patients who developed delirium (p < 0.05 each). The ROC curve analysis revealed disease duration of ≥ 11 years as a risk factor for delirium (p = 0.001; odds ratio, OR: 58.4, 95% confidence interval, CI: 5.45–625.49). Age and disease duration were independent risk factors for post-DBS delirium (OR: 1.243, 95% CI: 1.070–1.592 and OR: 22.52, 95% CI: 1.21–383.96, respectively). Conclusions: Older age and longer disease duration are independent risk factors for postoperative delirium in patients with PD. This study highlights the need to identify high-risk patients when undertaking DBS to facilitate early diagnosis and timely management. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Cortico-striato-thalamo-cortical (CSTC) loops are fundamental organizing units in mammalian brains. CSTCs process limbic, associative, and sensorimotor information in largely separated but interacting networks. CTSC loops pass through paired striatal compartments, striosome (aka patch) and matrix, segregated pools of medium spiny projection neurons with distinct embryologic origins, cortical/subcortical structural connectivity, susceptibility to injury, and roles in behaviors and diseases. Similarly, striatal dopamine modulates activity in striosome and matrix in opposite directions. Routing CSTCs through one compartment may be an anatomical basis for regulating discrete functions. We used differential structural connectivity, identified through probabilistic diffusion tractography, to distinguish the striatal compartments (striosome-like and matrix-like voxels) in living humans. We then mapped compartment-specific projections and quantified structural connectivity between each striatal compartment, the globus pallidus interna (GPi), and 20 thalamic nuclei in 221 healthy adults. We found that striosome-originating and matrix-originating streamlines were segregated within the GPi: striosome-like connectivity was significantly more rostral, ventral, and medial. Striato-pallido-thalamic streamline bundles that were seeded from striosome-like and matrix-like voxels transited spatially distinct portions of the white matter. Matrix-like streamlines were 5.7-fold more likely to reach the GPi, replicating animal tract-tracing studies. Striosome-like connectivity dominated in six thalamic nuclei (anteroventral, central lateral, laterodorsal, lateral posterior, mediodorsal-medial, and medial geniculate). Matrix-like connectivity dominated in seven thalamic nuclei (centromedian, parafascicular, pulvinar-anterior, pulvinar-lateral, ventral lateral-anterior, ventral lateral-posterior, ventral posterolateral). Though we mapped all thalamic nuclei independently, functionally-related nuclei were matched for compartment-level bias. We validated these results with prior thalamostriate tract tracing studies in non-human primates and other species; where reliable data was available, all agreed with our measures of structural connectivity. Matrix-like connectivity was lateralized (left > right hemisphere) in 18 thalamic nuclei, independent of handedness, diffusion protocol, sex, or whether the nucleus was striosome-dominated or matrix-dominated. Compartment-specific biases in striato-pallido-thalamic structural connectivity suggest that routing CSTC loops through striosome-like or matrix-like voxels is a fundamental mechanism for organizing and regulating brain networks. Our MRI-based assessments of striato-thalamic connectivity in humans match and extend the results of prior tract tracing studies in animals. Compartment-level characterization may improve localization of human neuropathologies and improve neurosurgical targeting in the GPi and thalamus. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time. [ABSTRACT FROM AUTHOR]

Tardive dystonia (TD) is a disabling neurological disorder and is usually refractory to medical therapy. Over the past decade, several case reports and case series have demonstrated remarkable benefits of deep brain stimulation of the globus pallidus interna for the treatment of refractory TD. In this case report, we present an illustrative case of refractory TD treated with globus pallidus interna–deep brain stimulation, with long-term sustained improvement of the dystonia and psychiatric comorbidity. In addition, the patient had a dorsal cord schwannoma, producing pyramidal signs in the lower limbs, which highlights the need for meticulous clinical examination for optimum patient management.

[Display omitted] • D1R and D2R neurons in the GPi show distinct electrophysiological properties. • D2R neurons exhibit altered action potential responses in 6-OHDA-lesioned mice. • Alterations in D2R neuron electrophysiology may contribute to PD pathophysiology. Parkinson's disease (PD) ranks as the second most prevalent and rapidly growing neurodegenerative disorder. As a primary output nucleus within the basal ganglia (BG), the globus pallidus interna (GPi) is a key structure in BG information processing. It is also a key target for deep brain stimulation (DBS) to alleviate motor symptoms of PD. Previous studies have identified PD patients exhibiting abnormal neuronal activity in the GPi. On the other hand, various types of dopamine receptor (DR)-positive neurons have been identified within the GPi. However, the electrophysiological properties of specific DR-positive neurons within the GPi and their alterations in PD have not been addressed. In the present study, we used whole-cell patch-clamp recordings to identify two neuronal subpopulations within the GPi, dopamine D1 receptor (D1R)-positive, and dopamine D2 receptor (D2R)-positive neurons, which exhibited distinct electrophysiological properties. Additionally, significant alterations of electrophysiological properties of D2R-positive neurons within the GPi were observed in 6-hydroxydopamine (6-OHDA)-lesioned mice. These data suggest that the distinct electrophysiological properties of specific DR-positive neurons and their abnormal alteration in the GPi may be associated with PD's pathogenesis. [ABSTRACT FROM AUTHOR]

Every decision that we make involves a conflict between exploiting our current knowledge of an action’s value or exploring alternative courses of action that might lead to a better, or worse outcome. The sub-cortical nuclei that make up the basal ganglia have been proposed as a neural circuit that may contribute to resolving this explore-exploit ‘dilemma’. To test this hypothesis, we examined the effects of neuromodulating the basal ganglia’s output nucleus, the globus pallidus interna, in patients who had undergone deep brain stimulation (DBS) for isolated dystonia. Neuromodulation enhanced the number of exploratory choices to the lower value option in a two-armed bandit probabilistic reversal-learning task. Enhanced exploration was explained by a reduction in the rate of evidence accumulation (drift rate) in a reinforcement learning drift diffusion model. We estimated the functional connectivity profile between the stimulating DBS electrode and the rest of the brain using a normative functional connectome derived from heathy controls. Variation in the extent of neuromodulation induced exploration between patients was associated with functional connectivity from the stimulation electrode site to a distributed brain functional network. We conclude that the basal ganglia’s output nucleus, the globus pallidus interna, can adaptively modify decision choice when faced with the dilemma to explore or exploit.

ObjectiveWe 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.MethodsWe 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.ResultsAt 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.ConclusionBilateral 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.

Background: Device‐assisted and neuromodulatory therapies are the standard of care for Parkinson's disease (PD) with disabling motor complications. We aimed to compare and rank the currently available advanced therapies for PD on patient relevant outcomes. Methods: We searched various databases for randomized controlled trials that studied subthalamic nucleus deep brain stimulation (STN‐DBS), globus pallidus interna (GPi) DBS, pallidotomy, subthalamotomy, continuous subcutaneous apomorphine infusion (CSAI), or intrajejunal levodopa infusion (IJLI), in patients with PD and motor complications. Primary outcome was the quality of life (QOL) at 6 months. Secondary outcomes included Unified Parkinson's Disease Rating Scale III and II, ON time, OFF time, levodopa equivalent daily doses, and adverse events (AE). Data were pooled using a Bayesian network meta‐analysis, summarized as mean difference (MD) with 95% credibility intervals (CrI) and visualized in forest plots/league tables. Surface under the cumulative ranking curve plots determined the ranking probability. Results: We identified 6745 citations and included 26 trials. STN‐DBS (MD, −8.0; 95% CrI, −11, −5.8), GPi‐DBS (MD, −7.1; 95% CrI, −11, −2.9), and IJLI (MD, −7.0; 95% CrI, −12, −1.8) led to better QOL than medical therapy alone, without significant differences among them. STN‐DBS had the highest probability of being ranked the best treatment for QOL (79.6%), followed by IJLI (63.5%) and GPi‐DBS (62.8%). Conclusions: In advanced PD, STN‐DBS alleviates more patient and clinician relevant outcomes, followed by GPi‐DBS and IJLI. In resource limited settings, unilateral pallidotomy may improve motor symptoms and activities of daily living, although overall QOL may not be improved. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Tardive dystonia (TD) is a disabling neurological disorder and is usually refractory to medical therapy. Over the past decade, several case reports and case series have demonstrated remarkable benefits of deep brain stimulation of the globus pallidus interna for the treatment of refractory TD. In this case report, we present an illustrative case of refractory TD treated with globus pallidus interna-deep brain stimulation, with long-term sustained improvement of the dystonia and psychiatric comorbidity. In addition, the patient had a dorsal cord schwannoma, producing pyramidal signs in the lower limbs, which highlights the need for meticulous clinical examination for optimum patient management. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) can lead to psychosocial and functional improvement in medically refractory cervical, segmental, or generalized moderate to severe dystonia. After treatment with DBS in women with dystonia, pregnancy can be planned. However, in the literature, there are no standardized clinical guidelines for the management of movement disorder treated with DBS during pregnancy. Herein, we report a 24-year-old female patient with cervical dystonia (CD) who have an implanted bilateral globus pallidus interna (GPi)-DBS. The patient got pregnant during the 5-year follow-up period after DBS surgery and then delivered a healthy baby via cesarean section under general anesthesia. A patient with CD who have a DBS system with a rechargeable battery could be managed safely during pregnancy and childbirth.

Background: The up‐to‐date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson's disease (PD) is lacking. Objective: To address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS. Methods: We used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted. Results: The STN‐DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS‐III at both 6‐ and 12‐month follow‐ups (P < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow‐up times. For the sub‐scores of UPDRS‐III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor (P = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS‐III total score at a median follow‐up of 12 months (P = 0.030). Conclusion: The current study confirmed the value of preoperative levodopa responsiveness for prediction of the short‐term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short‐term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long‐term motor outcomes were highlighted by this study. [ABSTRACT FROM AUTHOR]

Background: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson’s Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. Objective: We explored whether recovery of the H-reflex—an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD—could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. Methods: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. Results: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. Conclusion: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

IntroductionPrevious studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms.MethodsIn this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med–STN+GPi–, (2) Med–STN–GPi+, (3) Med+STN+GPi–, and (4) Med+STN–GPi+.ResultsEight patients had completed 30 trials of assessment. Compared with the preoperative Med– state, in the Med–STN+GPi– condition, the cardinal symptoms in both sides of the body were all improved. In the Med–STN–GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi– state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN–GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med– and Med+ states. No side effects associated with this study were seen.ConclusionsImprovement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.

Introduction: Previous studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms. Methods: In this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med–STN+GPi–, (2) Med–STN–GPi+, (3) Med+STN+GPi–, and (4) Med+STN–GPi+. Results: Eight patients had completed 30 trials of assessment. Compared with the preoperative Med– state, in the Med–STN+GPi– condition, the cardinal symptoms in both sides of the body were all improved. In the Med–STN–GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi– state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN–GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med– and Med+ states. No side effects associated with this study were seen. Conclusions: Improvement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side. [ABSTRACT FROM AUTHOR]

Cervical dystonia is a non-degenerative movement disorder characterized by dysfunction of both motor and sensory cortico-basal ganglia networks. Deep brain stimulation targeted to the internal pallidum is an established treatment, but its specific mechanisms remain elusive, and response to therapy is highly variable. Modulation of key dysfunctional networks via axonal connections is likely important. Fifteen patients underwent preoperative diffusion-MRI acquisitions and then progressed to bilateral deep brain stimulation targeting the posterior internal pallidum. Severity of disease was assessed preoperatively and later at follow-up. Scans were used to generate tractography-derived connectivity estimates between the bilateral regions of stimulation and relevant structures. Connectivity to the putamen correlated with clinical improvement, and a series of cortical connectivity-based putaminal parcellations identified the primary motor putamen as the key node (r = 0.70, P = 0.004). A regression model with this connectivity and electrode coordinates explained 68% of the variance in outcomes (r = 0.83, P = 0.001), with both as significant explanatory variables. We conclude that modulation of the primary motor putamen-posterior internal pallidum limb of the cortico-basal ganglia loop is characteristic of successful deep brain stimulation treatment of cervical dystonia. Preoperative diffusion imaging contains additional information that predicts outcomes, implying utility for patient selection and/or individualized targeting. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson's disease (PD). Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively. Results: Pearson's correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R 2 = 0.283, p = 0.016) but not on the non-tremor total score (R 2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R 2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R 2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R 2 = 0.290, p = 0.021), but not on the total score (R 2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R 2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor. Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets., Methods: In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson's Disease Rating Scale [UPDRS]-III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach., Results: The authors' findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi-globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies., Conclusions: Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.

Keywords: deep brain stimulation; chorea; inherited movement disorder; globus pallidus interna EN deep brain stimulation chorea inherited movement disorder globus pallidus interna 401 403 3 04/05/22 20220401 NES 220401 Chorea is a hyperkinetic movement disorder characterized by involuntary brief, random, and irregular muscle contractions conveying a feeling of restlessness.1 Inherited choreas constitute a significant portion of choreas, including neuroacanthocytosis (NA), I GNAO1 i -associated movement disorder (GNAO1), Huntington's disease, dentatorubral-pallidoluysian atrophy, Wilson's disease, familial paroxysmal kinesigenic choreoathetosis, and intracerebral calcifications. Currently, chorea is not an approved indication for DBS; however, reports of off-label globus pallidus interna (GPi) DBS for genetic choreas demonstrate generally satisfactory outcomes. [Extracted from the article]

Deep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes. Five patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences. The mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead. The imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location. [ABSTRACT FROM AUTHOR]

Magnetic resonance guided focused ultrasound (MRgFUS) of the globus pallidus interna (GPi) has shown promise in the treatment of drug-resistant Parkinson's disease, though direct visualization of the GPi remains challenging with MRI. The purpose of this study was to compare various preoperative MR imaging techniques and to evaluate the utility of quantitative susceptibility imaging (QSM) in the depiction of the GPi prior to MRgFUS ablation. Six patients with medication refractory advanced idiopathic Parkinson's disease were referred for preoperative MR imaging prior to MRgFUS pallidotomy. Axial T1WI and T2WI, Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR), and QSM sequences were acquired. DTI tractography was performed to delineate the corticospinal tracts. Qualitative visualization scores and contrast to noise ratios (CNR) were recorded and measured on all images. QSM had significantly higher median qualitative visualization scores (3.00) compared with the T1WI (1.00), T2WI (1.50), and FGATIR sequences (1.50) (p < 0.05). QSM provided superior CNR for GPi depiction in each category (GPi-GPe and GPi-IC), respectively. For GPi-GPe, median CNR for T1WI, T2WI, FGATIR, and QSM was 1.13, 1.68, 0.79, and 10.78. For GPi-IC, median CNR for T1WI, T2WI, FGATIR, and QSM was 1.48, 4.63, 4.24, and 40.26, respectively (p < 0.05). QSM offers improved visualization of the GPi compared with the traditional and currently recommended MR sequences prior to MRgFUS ablation in patients with Parkinson's disease. These results suggest that QSM should be considered as part of all preoperative imaging protocols prior to MRgFUS pallidotomy. • QSM can provide increased contrast and conspicuity of the GPi and its borders relative to standard MRI sequences that are currently recommended • Delineation of the GPi borders is critical to a safe and successful ablation for patients with Parkinson disease [ABSTRACT FROM AUTHOR]

Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response. We explored whether recovery of the H-reflex—an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD—could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation. Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities. Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization. H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD. • The H-reflex is an easily measured electrical analogue of the stretch reflex. • H-reflex recovery is altered in Parkinson's Disease (PD). • H-reflex recovery is predictably modulated during STN or GPi DBS for PD. • Normalization of H-reflex is maximal with optimized intraoperative macrostimulation. • H-reflex recovery is a promising biomarker of optimal DBS electrode placement in PD. [ABSTRACT FROM AUTHOR]

To determine the effects of globus pallidus interna (GPi) deep brain stimulation (DBS) on speech and voice quality of patients with primary, medically refractory dystonia. Voices of 14 patients aged ≥18 years (males = 7 and females = 7) with primary dystonia (DYT1 gene mutation dystonia = 4, cervical dystonia = 6, and generalized dystonia = 4) with bilateral GPi DBS were assessed. Five blinded raters (two fellowship-trained laryngologists and three speech/language pathologists) evaluated audio recordings of each patient pre- and post-DBS. Perceptual voice quality was rated using the Grade, Roughness, Breathiness, Asthenia, and Strain scale and changes in speech intelligibility were assessed with the Clinical Global Impression scale of Severity instrument. Inter-rater and intrarater reliability rates for perceptual voice ratings were assessed using the kappa coefficient. Voice quality parameters showed mean improvements in Grade (P < 0.0001), Roughness (P = 0.0043), and Strain (P < 0.0001) 12 months post-DBS. Asthenia increased from baseline to 6 months (P = 0.0022) and declined significantly from 6 to 12 months (P = 0.0170). Breathiness did not change significantly over time. Speech intelligibility also improved from 6 to 12 months (P = 0.0202) and from pre-DBS to 12 months post-DBS (P = 0.0022). Grade and Strain ratings had nearly perfect and substantial inter-rater agreement (0.84 and 0.71 , respectively). Voice and speech intelligibility improved after bilateral GPi DBS for dystonia. GPi DBS may emerge as a potential treatment option for patients with medically refractory laryngeal dystonia. [ABSTRACT FROM AUTHOR]

Background: The role of deep brain stimulation (DBS) in the management of motor symptoms in patients with Parkinson's disease is well defined. However, it is becoming increasingly clear that DBS can either improve or worsen a number of non‐motor phenomena. Objectives: We examined the published literature to better understand the effects on autonomic symptoms following DBS of the subthalamic nucleus and the globus pallidus interna. Methods: We conducted a PubMed search of studies regarding the effects of DBS on the autonomic system published from January 2001. We searched for the following terms and their combinations: Parkinson's disease, deep brain stimulation, subthalamic nucleus, globus pallidus interna, autonomic dysfunction. Results: Most studies reported in the literature focus on DBS targeting the subthalamic nucleus, with particular emphasis on favorable outcomes regarding gastrointestinal function and bladder control. However, the emergence or worsening of autonomic symptoms in subgroups of patients has also been documented. More controversial is the effect of stimulation on the cardiovascular, pulmonary, and thermo‐regulatory systems as well as sexual functioning. Data regarding the influence of DBS on the autonomic system when the target is the globus pallidus interna is less forthcoming, with target selection varying according to centre and clinical indication. Conclusions: DBS appears to affect the autonomic nervous system, with varying degrees of influence, which may or may not be clinically beneficial for the patient. A better understanding of these effects could help personalize stimulation for individual patients with autonomic disorders and/or avoid autonomic symptoms in susceptible patients. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) can lead to psychosocial and functional improvement in medically refractory cervical, segmental, or generalized moderate to severe dystonia. After treatment with DBS in women with dystonia, pregnancy can be planned. However, in the literature, there are no standardized clinical guidelines for the management of movement disorder treated with DBS during pregnancy. Herein, we report a 24-year-old female patient with cervical dystonia (CD) who have an implanted bilateral globus pallidus interna (GPi)-DBS. The patient got pregnant during the 5-year follow-up period after DBS surgery and then delivered a healthy baby via cesarean section under general anesthesia. A patient with CD who have a DBS system with a rechargeable battery could be managed safely during pregnancy and childbirth. [ABSTRACT FROM AUTHOR]

Objective To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson’s disease (PD). Methods We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups. Results At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697). Conclusion The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.

IntroductionCognitive symptoms from Parkinson’s disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson’s disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3–8 Hz) and/or beta (10–30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Abstract Introduction Previous studies found subthalamic nucleus deep brain stimulation (STN‐DBS) has clinical effect on Parkinson's disease, dystonia, and obsessive compulsive disorder. It is noteworthy that only a few studies report the STN‐DBS for Tourette's syndrome (TS). Globus pallidus interna (GPi)‐DBS is the one of the most common targets for TS. So, this paper aims to investigate the neural oscillations in STN and GPi as well as the DBS effect between these two targets in same patients. Methods The local field potentials (LFPs) were simultaneously recorded from the bilateral GPi and STN in four patients with TS. The LFPs were decomposed into neural oscillations, and the frequency and time–frequency characteristics of the neural oscillations were analyzed across the conditions of resting, poststimulation, and movement. Results No difference of resting LFP was found between the two targets. The poststimulation period spectral power revealed the high beta and gamma oscillations were recovered after GPi‐DBS but remained attenuated after STN‐DBS. The STN beta oscillation has fewer changes during tics than voluntary movement, and the gamma oscillation was elevated when the tics appeared. Conclusion The high beta and gamma oscillations in GPi restored after GPi‐DBS, but not STN‐DBS. High beta and gamma oscillations may have physiological function in resisting tics in TS. The cortex compensation effect might be interfered by the STN‐DBS due to the influence on the hyper‐direct pathway but not GPi‐DBS.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) have been proven to be equally effective in improving motor-symptoms for advanced Parkinson's disease (PD) patients. However, it is unclear that which target stimulation is more effective in reducing dyskinesia. We conducted the meta-analysis to evaluate the efficacy of STN and GPi-DBS in the dyskinesia.Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Controlled trials about the dyskinesia comparing the efficacy of GPi and STN DBS were included. Clinical data of dyskinesia and levodopa equivalent doses (LED) were collected for the meta-analysis.Results: Eight eligible trials containing a total of 822 patients were included in this meta-analysis. Our results showed that GPi DBS offered a greater reduction of dyskinesia than STN DBS at 12 months after surgery, with an overall pooled SMD of 0.32 (95% CI = 0.06 to 0.59, P = 0.02). Treatment of STN DBS was associated with a greater reduction of LED compared with GPi DBS, with a change score of −320.55 (95% CI = −401.36 to −239.73, P < 0.00001).Conclusion: GPi DBS is superior to reduce dyskinesia than STN DBS at 12 months after surgery for advanced PD patients. Further studies should focus on the different mechanism for dyskinesia reduction by GPi or STN DBS.

Introduction: Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods: We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results: Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3–8 Hz) and/or beta (10–30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion: Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Intraoperative extracellular microelectrode recordings (MER) are considered as the standard electrophysiological method for the precise positioning of the DBS electrode into the target brain structure. Accurate targeting of the permanent stimulation electrode into the Globus Pallidus internus (GPi) is key to positive long-term effects. The suitability of the location is peroperatively assessed by microelectrodes that register single-unit neuronal activity. The aim of this article is to analyse electrophysiological recordings of patient's neuronal activity with a focus on the identification of markers relevant to the patient's clinical state. In this study, 13 patients chronically treated with double-sided DBS GPi were examined with a microrecording. The signal (24 kHz) processing, included bandpass filtering (0.5–5 kHz), automated detection of artefacts and feature extraction. Pre-processed signals were analysed by means of statistical learning. The results show that the GPi was distinguished from its vicinity with p < 0.001 and 3 machine learning models AUCs had an accuracy of higher than 0.87. The observed biomarker, Hjort mobility, additionally correlated with the long-term neuromodulation effect (rho = −0.4; p < 0.05). Furthermore, we revealed a change of neural activity associated with the active distal DBS contact localization along the medio-lateral direction. This paper demonstrates the quantitative relationship between electrophysiological findings and the clinical effects of pallidal stimulation in dystonia and suggested objectification predictors of the effectiveness of this therapy. • Unambiguous criteria for DBS implantation performance in dystonia are not yet known. • The methodology for processing microrecording signals has been implemented. • Microelectrode recordings were evaluated in 13 dystonic patients with GPi-DBS. • The electrophysiological biomarker is correlated with the long-term neuromodulation effect. • Contact localization along the medio-lateral direction may affect postoperative DBS effect. [ABSTRACT FROM AUTHOR]

There is no consensus on a standardized approach to spasticity or dystonia management of cerebral palsy (CP). This study aimed to investigate clinical outcomes and compare therapeutic responses for pallidal stimulation versus intrathecal baclofen (ITB) therapy in adult patients with severe CP. We retrospectively reviewed patients with CP treated with deep brain stimulation (DBS) of the globus pallidus internus (GPi) or implantation of ITB pump between June 2003 and April 2017. Patients were included if they were clinically diagnosed with medically intractable CP and had >12 months of postprocedural follow-up data. Patients were assessed before and 12 months post-treatment using the visual analogue scale, Burke–Fahn–Marsden Dystonia Rating Scale, self-rating improvement scale, and 36-Item Short-Form General Health Survey Questionnaire. Patients (n = 22) were divided into GPi DBS (n = 12) and ITB therapy (n = 10) groups. For the Burke–Fahn–Marsden Dystonia Rating Scale, DBS group movement scores and ITB group disability scores were significantly improved post-treatment. Although visual analogue scales did not differ between groups, self-rating improvement scores differed significantly between groups. For quality of life, physical functioning, body pain, vitality, social functioning, and mental health significantly improved in ITB group 12 months post-treatment compared with those of preoperative period. Only mental health differed significantly between groups. Despite retrospective design and relatively low number of cases, this study indicated that ITB therapy was less invasive and more effective in improving the quality of life compared with GPi DBS. ITB therapy should be considered an alternative treatment for patients with severe CP. [ABSTRACT FROM AUTHOR]

Introduction: X-linked dystonia-parkinsonism (XDP/DYT3/Lubag) patients had improved dystonia and parkinsonism with bilateral pallidal deep brain stimulation (DBS) in the literature.Method: We reviewed eleven XDP patients who underwent bilateral pallidal DBS from October 2009 to September 2018. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Unified Parkinson's Disease Rating Scale (UPDRS)-III scores were reviewed from baseline up to the longest follow-up together with the demographic and clinical data. The published case reports on DBS in XDP were also reviewed.Results: The mean age was 39 ± 9.2 years with a mean disease duration of 3 years (range 1-9 years). An immediate response for dystonia post-DBS (1 month) was seen in all cases, with a mean BFMDRS score of 23.3 ± 12.12 [from a mean baseline of 36.3 ± 12.1] and a small change in the mean UPDRS-III score of 20 ± 10.39 [from a mean baseline of 24.04 ± 8.74]. At 12 months (n = 10), the mean BFMDRS score was 13.7 ± 10.63 and the mean UPDRS-III score was 19 ± 13.19. There was improvement in the clinical and functional stage of the patients, with majority in Stage 1 (n = 3) and Stage 2 (n = 5) at their last follow-up.Conclusion: Bilateral pallidal DBS should be considered as a treatment option for XDP. It is effective in the first 12 months in controlling dystonia with variable response in controlling parkinsonism. It may be effective in up to 72-84 months, as seen in three patients. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) have been proven to be equally effective in improving motor-symptoms for advanced Parkinson's disease (PD) patients. However, it is unclear that which target stimulation is more effective in reducing dyskinesia. We conducted the meta-analysis to evaluate the efficacy of STN and GPi-DBS in the dyskinesia. Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Controlled trials about the dyskinesia comparing the efficacy of GPi and STN DBS were included. Clinical data of dyskinesia and levodopa equivalent doses (LED) were collected for the meta-analysis. Results: Eight eligible trials containing a total of 822 patients were included in this meta-analysis. Our results showed that GPi DBS offered a greater reduction of dyskinesia than STN DBS at 12 months after surgery, with an overall pooled SMD of 0.32 (95% CI = 0.06 to 0.59, P = 0.02). Treatment of STN DBS was associated with a greater reduction of LED compared with GPi DBS, with a change score of −320.55 (95% CI = −401.36 to −239.73, P < 0.00001). Conclusion: GPi DBS is superior to reduce dyskinesia than STN DBS at 12 months after surgery for advanced PD patients. Further studies should focus on the different mechanism for dyskinesia reduction by GPi or STN DBS. [ABSTRACT FROM AUTHOR]

There is converging evidence that bilateral basal ganglia motor networks jointly support normal movement behaviors including unilateral movements. The extent and manner in which these networks interact during lateralized movement remains unclear. In this study, simultaneously recorded bilateral Globus Pallidus interna (GPi) local field potentials (LFP) were examined from 19 subjects with idiopathic Parkinson disease (PD), while undergoing awake deep brain stimulation (DBS) implantation. Recordings were carried out during two behavioral states; rest and cued left hand movement (finger tapping). The state-dependent effects on α- β oscillatory power and β phase-encoded phase amplitude coupling (PAC), including symmetrical and assymetrical changes between hemispheres, were identified. Unilateral hand movement resulted in symmetrical oscillatory power suppression within bilateral GPi at α (8–12 Hz) and high β (21–35 Hz) and increase in power of high frequency oscillations (HFO, 200–300 Hz) frequency bands. Asymmetrical attenuation was also observed at both low β (13–20 Hz) and low γ (40–80 Hz) bands within the contralateral GPi (P = 0.009). In addition, unilateral movement effects on PAC were confined to the contralateral GPi with attenuation of both low β-low γ and β-HFO PAC (P < 0.05). Further analysis showed that the lateralized attenuation of low β and low γ power did not correlate with low β-low γ PAC changes. The overall coherence between bilateral GPi was not significantly altered with unilateral movement, however the preferred phase difference in the high β range increased from 0.23 (±1.31) radians during rest to 1.99 (±0.78) radians during movement execution. Together, the present results suggest that unilateral motor control involves bilateral basal ganglia networks with movement features differentially encoded by distinct frequency bands. The lateralization of low β and low γ attenuation with movement suggests that these frequency bands are specific to the motor act whereas symmetrical expression of α, high β, and HFO oscillations best correspond to motor state. The restriction of movement-related PAC modulation to the contralateral GPi indicates that cross-frequency interactions appear to be associated with lateralized movements. Despite no significant movement-related changes in the interhemispheric coherence, the increase in phase difference suggests that the communication between bilateral GPi is altered with unilateral movement.

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zeng, Huang, Lin, Pan, Wan, Zhang, Sun and Li.)

Objective: To compare subthalamic nucleus (STN) deep brain stimulation (DBS) with globus pallidus interna (GPi) DBS for tremor suppression in Parkinson disease (PD).Background: DBS is an effective surgical therapy that has been shown to provide significant benefit for motor symptoms in PD. Currently, two main structures targeted to treat motor complications in PD are the STN and GPi. Although some groups traditionally favor STN over GPi for tremor suppression, evidence demonstrating superiority in long-term tremor control is limited.Methods: We performed a systematic review for all randomized trials comparing STN vs GPi DBS in PD that were published before March 2017. Five studies were examined in a random effects model meta-analysis. We conducted moderator variable analysis to determine if there was a treatment effect difference for STN versus GPi.Results: We compared DBS ON versus OFF and found a significant overall standardized difference mean effect: Effect Size = 0.36; 95% CI = 0.316-0.395; P < 0.0001. These findings indicate that DBS reduced tremor symptoms in PD patients with a medium effect size. Moderator variable analysis of STN vs GPI revealed two significant standardized effect sizes: STN effect size = 0.38 and GPi effect size = 0.35. A Z-test showed that effect sizes between the STN and GPi were not significantly different (P = 0.56).Conclusions: DBS is effective in reducing tremor in PD patients regardless of stimulation target. However, the degree of tremor suppression in STN DBS versus GPi DBS was equivalent. [ABSTRACT FROM AUTHOR]

There is converging evidence that bilateral basal ganglia motor networks jointly support normal movement behaviors including unilateral movements. The extent and manner in which these networks interact during lateralized movement remains unclear. In this study, simultaneously recorded bilateral Globus Pallidus interna (GPi) local field potentials (LFP) were examined from 19 subjects with idiopathic Parkinson disease (PD), while undergoing awake deep brain stimulation (DBS) implantation. Recordings were carried out during two behavioral states; rest and cued left hand movement (finger tapping). The state-dependent effects on α- β oscillatory power and β phase-encoded phase amplitude coupling (PAC), including symmetrical and assymetrical changes between hemispheres, were identified. Unilateral hand movement resulted in symmetrical oscillatory power suppression within bilateral GPi at α (8–12 Hz) and high β (21–35 Hz) and increase in power of high frequency oscillations (HFO, 200–300 Hz) frequency bands. Asymmetrical attenuation was also observed at both low β (13–20 Hz) and low γ (40–80 Hz) bands within the contralateral GPi (P = 0.009). In addition, unilateral movement effects on PAC were confined to the contralateral GPi with attenuation of both low β-low γ and β-HFO PAC (P < 0.05). Further analysis showed that the lateralized attenuation of low β and low γ power did not correlate with low β-low γ PAC changes. The overall coherence between bilateral GPi was not significantly altered with unilateral movement, however the preferred phase difference in the high β range increased from 0.23 (±1.31) radians during rest to 1.99 (±0.78) radians during movement execution. Together, the present results suggest that unilateral motor control involves bilateral basal ganglia networks with movement features differentially encoded by distinct frequency bands. The lateralization of low β and low γ attenuation with movement suggests that these frequency bands are specific to the motor act whereas symmetrical expression of α, high β, and HFO oscillations best correspond to motor state. The restriction of movement-related PAC modulation to the contralateral GPi indicates that cross-frequency interactions appear to be associated with lateralized movements. Despite no significant movement-related changes in the interhemispheric coherence, the increase in phase difference suggests that the communication between bilateral GPi is altered with unilateral movement. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson’s disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic. Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest. Results: In all PD patients, we noted excessive beta band activity (13-30Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200-400Hz, indicating the presence of beta-HFO CFC. In all 3 TS patients at rest, we observed theta band activity (4-7Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200-400Hz) and gamma band (35-200Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5-10Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects. Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5-10Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present.

Medical therapies in patients with Meige syndrome, including botulinum toxin injection, have been limited because of incomplete response or adverse side effects. We evaluated a patient with Meige syndrome who was successfully treated with deep brain stimulation (DBS) in the globus pallidus interna (GPi). This case report and other previous reports suggest that bilateral GPi DBS may be an effective treatment for medically refractory Meige syndrome, without significant adverse effects.

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 dystonia attesting 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, AlMajali et al.)

Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic. Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest. Results: In all PD patients, we noted excessive beta band activity (13-30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4-7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200-400 Hz) and gamma band (35-200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5-10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects. Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5-10 Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present. [ABSTRACT FROM AUTHOR]