Pallidal Stimulation Research Articles

Microelectrode Neuronal Activity of the Internal Globus Pallidus in Dystonia Correlates with Postoperative Neuromodulation Effects and Placement of the Stimulation Electrode

BackgroundDeep 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. MethodsIn 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. ResultsThe 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. ConclusionThis 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.

P.012 Bilateral pallidal deep brain stimulation in a patient with chorea-acanthocytosis

Background: Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Methods: Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after deep brain stimulation (DBS) surgery. Results: Here we present a case of ChAc in a 31 year old male positive for VPS13A gene muations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. GPi-DBS using monopolar stimulation was associated with significant improvement in chorea and dysarthria. Conclusions: This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact of DBS in ChAc.

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia

ObjectiveFinding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients. MethodsEEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4–12 Hz) and beta band (13–30 Hz) peak coherences were studied. ResultsDystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3–10), TWSTRS: 22%, median 6.8 (IQR 4–9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit. ConclusionsPeak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity. SignificanceIMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.

Meta-Regression Analysis of the Long-Term Effects of Pallidal and Subthalamic Deep Brain Stimulation for the Treatment of Isolated Dystonia

The globus pallidus internus (GPi) and subthalamic nucleus (STN) are therapeutic targets for deep brain stimulation (DBS) in the treatment of isolated dystonia. We conducted a meta-regression analysis on long-term studies of bilateral DBS in the GPi and STN to compare the relative effects of the 2 approaches. We systematically searched the PubMed, Embase, and Cochrane Controlled Register of Trials databases to identify studies reporting the treatment outcomes of GPi DBS and STN DBS for isolated dystonia. The primary outcome measure was the change in the Burke-Fahn-Marsden dystonia rating scale movement score between the baseline and follow-up evaluations. We performed a regression analysis using a random effects model. A total of 42 follow-up evaluations (30 for GPi and 12 for STN) nested in 19 studies (16 of GPi and 3 of STN) were included in our analysis. The results from univariate regression analysis suggested that shorter disease duration and STN stimulation were associated with a greater standardized change in the Burke-Fahn-Marsden dystonia rating scale movement score. On combining the factors into 1 model, only the disease duration remained significant. The regression analysis results of the GPi and STN subgroups revealed more persistent improvement after STN stimulation. A shorter disease duration correlated positively with better DBS outcomes. The STN appeared to be an optimized stimulation target for the treatment of isolated dystonia, although randomized controlled trials are needed to compare the treatment efficacy of GPi DBS and STN DBS.

Update on current and emerging therapies for dystonia.

Treatment strategies for dystonia depend on the focal, segmental or generalized distribution of symptoms. Chemodenervation with botulinum toxin remains the treatment of choice for focal- or select-body regions in generalized and segmental dystonia. A potentially longer acting formulation of botulinum toxin is being investigated besides the currently available formulations. Electromyography increases toxin injection accuracy and may reduce injection number, frequency, side effects and costs by identifying dystonic muscle activity. Oral anticholinergics, baclofen and clonazepam are used off-label, but novel drugs in development include sodium oxybate, zonisamide and perampanel. Characterizing dystonia as a sensorimotor circuit disorder has prompted the use of noninvasive neuromodulation procedures. These techniques need further study but simultaneous rehabilitation techniques appear to also improve outcomes. Pallidal deep-brain stimulation is beneficial for medication-refractory primary generalized and possibly focal dystonia such as cervical dystonia. Certain genetic conditions are amenable to specific therapies and future gene-targeted therapies could benefit selected dystonia patients.

Long-term effect of subthalamic and pallidal deep brain stimulation for status dystonicus in children with methylmalonic acidemia and GNAO1 mutation

Status dystonicus (SD) is a rare and potentially life-threatening condition requiring intensive care management. Deep brain stimulation (DBS) has emerged as an effective treatment for SD refractory to medical management, but its application in this field is still limited. Here, we report the long-term outcome of four pediatric patients treated with DBS at the University Hospital of Padua, Italy, for SD refractory to medications. In addition, we present the results of a systematic literature review aimed at identifying published cases of SD treated with DBS, with focus on motor outcome. In our cohort,two children were affected by methylmalonic acidemia and suffered acute basal ganglia lesions, while the other two carried a pathogenic mutation in GNAO1 gene. DBS target was subthalamic nucleus (STN) in one case and globus pallidus internus (GPi) in three. All patients experienced SD resolution within 8-19days after surgery. Mean post-operative follow-up was 5years. We identified in the literature 53 additional SD cases treated with DBS (median age at DBS implantation: 12years) with reported positive outcome in 51 and resolution of SD in a mean of 17days after surgery. OurfindingsindicatethatDBS is an effective treatment for SD refractory to medications, even in patients with acute basal ganglia lesions; STN can be an appropriate target when GPi is damaged. Moreover, data from long-term follow-up show that SD recurrences can be significantly reduced in frequency or abolished after DBS implantation.

Amelioration of Dystonic Opisthotonus in Pantothenate Kinase-Associated Neurodegeneration Syndrome with Absent "Eye-of-the-Tiger" Sign Following Bilateral Pallidal Deep Brain Stimulation.

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Stimulation of the globus pallidus internus in the treatment of Parkinson's disease: Long-term results of a monocentric cohort

BackgroundPallidal deep brain stimulation (DBS) has shown to be beneficial in patients with advanced levodopa-responsive Parkinson's disease (PD) in several short-term studies. However, reported long-term outcomes of pallidal DBS for PD are limited and contradictory. MethodsEighteen consecutive PD patients were treated with unilateral or bilateral stimulation of the internal part of the globus pallidus (GPi). Assessments were carried out before and six months after neurosurgery, and annually thereafter for up to 16 years (mean follow-up time: 6 years). Primary outcomes included motor signs (Unified PD Rating Scale [UPDRS]-III), activities of daily living (ADL, UPDRS-II), and levodopa-induced motor complications (UPDRS-IV). ResultsThe results show that GPi stimulation improves levodopa-responsive PD motor signs (UPDRS-III), levodopa-induced motor complications (UPDRS-IV), and ADL (UPDRS-II) in advanced PD. Among motor signs, tremor showed the best response to pallidal stimulation. Levodopa-induced motor complications and tremor showed improvements for more than 10 years after neurosurgery. ConclusionsThe overall findings in our cohort demonstrate that pallidal stimulation is effective in reducing parkinsonian motor signs (UPDRS-III), particularly in the ‘off’-medication state. Although the beneficial effects on bradykinesia, rigidity and ADL may be limited to 5–6 years, the follow up results indicate that the improvements of levodopa-induced motor complications (UPDRS-IV) and tremor can be sustained for more than 10 years.

Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a multicentre imaging study.

Deep brain stimulation of the internal globus pallidus is a highly effective and established therapy for primary generalized and cervical dystonia, but therapeutic success is compromised by a non-responder rate of up to 25%, even in carefully-selected groups. Variability in electrode placement and inappropriate stimulation settings may account for a large proportion of this outcome variability. Here, we present probabilistic mapping data on a large cohort of patients collected from several European centres to resolve the optimal stimulation volume within the pallidal region. A total of 105 dystonia patients with pallidal deep brain stimulation were enrolled and 87 datasets (43 with cervical dystonia and 44 with generalized dystonia) were included into the subsequent 'normative brain' analysis. The average improvement of dystonia motor score was 50.5 ± 30.9% in cervical and 58.2 ± 48.8% in generalized dystonia, while 19.5% of patients did not respond to treatment (<25% benefit). We defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated (VTA) in normative atlas space and ranking voxel-wise for outcome distribution. We found a significant relation between motor outcome and the stimulation volume, but not the electrode location per se. The highest probability of stimulation induced motor benefit was found in a small volume covering the ventroposterior globus pallidus internus and adjacent subpallidal white matter. We then used the aggregated VTA-based outcome maps to rate patient individual VTAs and trained a linear regression model to predict individual outcomes. The prediction model showed robustness between the predicted and observed clinical improvement, with an r2 of 0.294 (P < 0.0001). The predictions deviated on average by 16.9 ± 11.6 % from observed dystonia improvements. For example, if a patient improved by 65%, the model would predict an improvement between 49% and 81%. Results were validated in an independent cohort of 10 dystonia patients, where prediction and observed benefit had a correlation of r2 = 0.52 (P = 0.02) and a mean prediction error of 10.3% (±8.9). These results emphasize the potential of probabilistic outcome brain mapping in refining the optimal therapeutic volume for pallidal neurostimulation and advancing computer-assisted planning and programming of deep brain stimulation.

Intrathecal Baclofen Pump Versus Globus Pallidus Interna Deep Brain Stimulation in Adult Patients with Severe Cerebral Palsy

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.

Subthalamic and pallidal oscillatory activity in patients with Neurodegeneration with Brain Iron Accumulation type I (NBIA-I)

ObjectivesNeurodegeneration with Brain Iron Accumulation type I (NBIA-I) is a rare hereditary neurodegenerative disorder with pallidal degeneration leading to disabling generalized dystonia and parkinsonism. Pallidal or subthalamic deep brain stimulation can partially alleviate motor symptoms. Disease-specific patterns of abnormally enhanced oscillatory neuronal activity recorded from the basal ganglia have been described in patients with movement disorders undergoing deep brain stimulation (DBS). Here we studied oscillatory activity recorded from the internal globus pallidus (GPi) and the subthalamic nucleus (STN) to characterize neuronal activity patterns in NBIA-I. MethodsWe recorded local field potentials (LFP) from DBS electrodes in 6 juvenile patients with NBIA-I who underwent functional neurosurgery. Four patients were implanted in the STN and two patients in the GPi. Recordings were performed during wakeful rest. An FFT-based approach was used to analyze the power spectrum in the target area. ResultsIn all patients we found distinct peaks in the low frequency (7–12 Hz) and in 5 out 6 also in the beta frequency range (15–30 Hz) with the largest beta peak in the patient that presented with the most prominent bradykinesia. No distinct peaks occurred in the gamma frequency range (35–100 Hz). The oscillatory pattern did not differ between STN and GPi. ConclusionsHere we show for the first time the oscillatory activity pattern in the STN and the GPi in juvenile patients with dystonia plus syndrome due to NBIA-I. The low frequency peak we found is in line with previous studies in patients with isolated idiopathic dystonia. In our cohort, the pallidal beta band activity may be related to more severe motor slowing in dystonia plus syndrome such as NBIA-I. SignificanceOur results further support the link between hyperkinetic motor symptoms such as dystonia and enhanced basal ganglia low frequency activity irrespective of the underlying etiology of dystonia.

Mortality Following Long-Term Subthalamic and Pallidal Deep Brain Stimulation in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis

Mortality Following Long-Term Subthalamic and Pallidal Deep Brain Stimulation in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis

Effect of pallidal deep-brain stimulation on articulation rate in dystonia.

Pallidal deep-brain stimulation of the internal globus pallidus (GPi-DBS) is an effective treatment for dystonia. However, GPi-DBS may cause important stimulation-induced side effects such as hypokinetic dysarthria, which is particularly manifested by articulation rate abnormalities. However, little data regarding the effect of the location of the electrode and stimulation parameters for pallidal stimulation on articulation rate in dystonia is available. Speech data were acquired from 18 dystonic patients with GPi-DBS and 18 matched healthy controls. Each of dystonic patients was tested twice within 1day in both the GPi-DBS ON and GPi-DBS OFF stimulation conditions. Compared to healthy controls, the decreased diadochokinetic rate and slower articulation rate in dystonic patients were observed in both stimulation conditions. No significant differences in speech rate measures between stimulation conditions were detected with no relation to contact localization and stimulation intensity. Our findings do not support the use articulation rate as a surrogate marker of stimulation-induced changes to the speech apparatus in dystonia.

Motor Cortical Plasticity Relates to Symptom Severity and Clinical Benefit From Deep Brain Stimulation in Cervical Dystonia

To investigate the relationship between motor cortical plasticity, intracortical inhibition, and clinical response to pallidal deep brain stimulation (DBS) in patients with cervical dystonia (CD). Response to paired associative stimulation (PAS) and short interval intracortical inhibition (SICI) were assessed in patients with CD before and after three months of DBS and correlated with severity of dystonic symptoms as assessed by Toronto-Western-Spasmodic Torticollis Rating Scale (TWSTRS) severity score. Relations of electrophysiological parameters with clinical improvement were explored with correlation analysis. Patients with higher levels of plasticity before surgery showed higher symptom severity (R = 0.83, p = 0.008) but had also the larger clinical benefit following DBS (R = 0.88, p = 0.003). This correlation was independent from preoperative (preOP) TWSTRS motor score as revealed by partial correlation analysis. Intracortical inhibition was not altered in CD and not related to clinical outcome after DBS. Our findings indicate that a high degree of preOP plasticity is associated with higher symptom severity, underlining the role of abnormal plasticity in the pathophysiology of dystonia. At the same time individual degree of plasticity may drive reestablishment of normal motor programs, leading to better clinical outcome with DBS. The latter suggests that individual PAS-response may indicate the susceptibility for neuromodulatory processes as an important factor for clinical DBS effects. It might therefore serve as a neurophysiological marker to predict outcome and guide patient selection.

Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism

Background: X-linked dystonia parkinsonism (XDP) causes adult-onset progressive dystonia and parkinsonism, which may not respond to pharmacotherapy. Objective: Previous case reports have reported beneficial effects from bilateral pallidal (GPi) deep brain stimulation (DBS). Here, we report the long-term clinical outcomes of 3 patients treated at our center. Methods: All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson’s Disease Rating Scale (UPDRS). Adverse events were recorded. Results: The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other. Conclusion: Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms.

Benefits of pallidal stimulation in dystonia are linked to cerebellar volume and cortical inhibition

Clinical benefits of pallidal deep brain stimulation (GPi DBS) in dystonia increase relatively slowly suggesting slow plastic processes in the motor network. Twenty-two patients with dystonia of various distribution and etiology treated by chronic GPi DBS and 22 healthy subjects were examined for short-latency intracortical inhibition of the motor cortex elicited by paired transcranial magnetic stimulation. The relationships between grey matter volume and intracortical inhibition considering the long-term clinical outcome and states of the GPi DBS were analysed. The acute effects of GPi DBS were associated with a shortening of the motor response whereas the grey matter of chronically treated patients with a better clinical outcome showed hypertrophy of the supplementary motor area and cerebellar vermis. In addition, the volume of the cerebellar hemispheres of patients correlated with the improvement of intracortical inhibition which was generally less effective in patients than in controls regardless of the DBS states. Importantly, good responders to GPi DBS showed a similar level of short-latency intracortical inhibition in the motor cortex as healthy controls whereas non-responders were unable to increase it. All these results support the multilevel impact of effective DBS on the motor networks in dystonia and suggest potential biomarkers of responsiveness to this treatment.

Modulation of inhibitory plasticity in basal ganglia output nuclei of patients with Parkinson's disease

Deep brain stimulation of certain target structures within the basal ganglia is an effective therapy for the management of the motor symptoms of Parkinson's disease. However, its mechanisms, as well as the pathophysiology of Parkinson's disease, are varied and complex. The classical model of Parkinson's disease states that symptoms may arise as a result of increased neuronal activity in the basal ganglia output nuclei due to downregulated GABAergic striato-nigral/-pallidal projections. We sought to investigate the stimulation and levodopa induced effects on inhibitory synaptic plasticity in these basal ganglia output nuclei, and to determine the clinical relevance of altered plasticity with respect to patients' symptoms. Two closely spaced microelectrodes were advanced into the substantia nigra pars reticulata (potential novel therapeutic target for axial motor symptoms) or globus pallidus internus (conventional therapeutic target) in each of 28 Parkinson's disease patients undergoing subthalamic or pallidal deep brain stimulation surgery. Sets of 1 Hz test-pulses were delivered at different cathodal pulse widths (25, 50, 100, 150, 250 μs) in randomized order, before and after a train of continuous high frequency stimulation at 100 Hz. Increasing the pulse width led to progressive increases in both the amplitudes of extracellular focally evoked inhibitory field potentials and durations of neuronal silent periods. Both of these effects were augmented after a train of continuous high frequency stimulation. Additionally, reductions in the baseline neuronal firing rate persisted beyond 1 min after high frequency stimulation. We found greater enhancements of plasticity in the globus pallidus internus compared to the substantia nigra pars reticulata, and that intraoperative levodopa administration had a potent effect on the enhancement of nigral plasticity. We also found that lower levels of nigral plasticity were associated with higher severity motor symptoms. The findings of this study demonstrate that the efficacy of inhibitory synaptic transmission may be involved in the pathophysiology of Parkinson's disease, and furthermore may have implications for the development of novel stimulation protocols, and advancement of DBS technologies.

Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment.

Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Corticopallidal Connectome of the Globus Pallidus Externus in Humans: An Exploratory Study of Structural Connectivity Using Probabilistic Diffusion Tractography.

Electrophysiologic abnormalities of the globus pallidus externus have been shown in several disease processes including Parkinson disease, dystonia, and Huntington disease. However, the connectivity, nuclear structure, and function of the globus pallidus externus are still not well-understood. Increasing evidence for the existence of direct corticopallidal connections challenges traditional understanding of the connectivity of the globus pallidus externus; nevertheless, these corticopallidal connections have yet to be fully characterized in humans. The objective of this study was to assess the corticopallidal connections of the globus pallidus externus by means of probabilistic diffusion-weighted MR imaging tractography using high-resolution, multishell data. Imaging data from the open-access Human Connectome Project data base were used to perform probabilistic tractography between the globus pallidus externus and the cerebral cortex using 34 distinct cortical regions. Group averages were calculated for normalized percentages of tracts reaching each of the cortical targets, and side-to-side comparison was made. Cortical connectivity was demonstrated between the globus pallidus externus and multiple cortical regions, including direct connection to putative sensorimotor, associative, and limbic areas. Connectivity patterns were not significantly different between the right and left hemispheres with the exception of the frontal pole, which showed a greater number of connections on the right (P = .004). Our in vivo study of the human globus pallidus externus using probabilistic tractography supports the existence of extensive corticopallidal connections and a tripartite functional division, as found in animal studies. A better understanding of the connectivity of the globus pallidus externus may help to understand its function and elucidate the effects of programming the higher contacts in pallidal deep brain stimulation.

Long-term outcomes of pallidal deep brain stimulation in X-linked dystonia parkinsonism (XDP): Up to 84 months follow-up and review of literature

IntroductionX-linked dystonia-parkinsonism (XDP/DYT3/Lubag) patients had improved dystonia and parkinsonism with bilateral pallidal deep brain stimulation (DBS) in the literature. MethodWe 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. ResultsThe 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. ConclusionBilateral 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.