Deep Brain Stimulation of Anteromedial Globus Pallidus Interna for Severe Tourette's Syndrome
ABSTRACT Multiple anatomical targets for deep brain stimulation (DBS) have been proposed for the treatment of severe Tourette's syndrome. In this open study, the authors evaluated the effectiveness of DBS of the anteromedial globus pallidus interna on tic severity and common comorbidities.
Eleven patients (eight of them men, mean age=39 years) with severe and medically intractable Tourette's syndrome underwent implantation of Medtronic quadripolar electrodes in the globus pallidus interna bilaterally. The primary outcome measure was the Yale Global Tic Severity Scale. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, the Gilles de la Tourette Syndrome-Quality of Life Scale, and the Global Assessment of Functioning Scale. Follow-up occurred at 1 month and then at a mean of 14 months after surgery (range=4-30 months).
Ten patients (91%) reported improvement in tic severity soon after DBS. Overall, there was a 48% reduction in motor tics and a 56.5% reduction in phonic tics at final follow-up. Six patients (54.5%) had a more than 50% reduction, sustained for at least 3 months, in Yale Global Tic Severity Scale score. Only two patients required ongoing pharmacotherapy for tics after surgery, and patients improved significantly on all secondary measures. One patient did not tolerate DBS and discontinued treatment after 3 months. Greater anxiety in two patients and hardware malfunction in three patients were noteworthy adverse outcomes.
The results suggest anteromedial globus pallidus interna DBS for Tourette's syndrome is an effective and well-tolerated treatment for a subgroup of patients with severe Tourette's syndrome.
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ABSTRACT: Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR) stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g., for the treatment of Parkinson's disease (PD), is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incorporated a detailed numerical representation of 2 · 10(4) simulated neurons. We simulated the subthalamic nucleus (STN) and the globus pallidus externus (GPe). Connections within the STN were governed by spike-timing dependent plasticity (STDP). In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological) activity to strongly desynchronized (healthy) activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward toward a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.Frontiers in Computational Neuroscience 11/2014; 8:154. DOI:10.3389/fncom.2014.00154 · 2.23 Impact Factor
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ABSTRACT: Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient-specific outcomes, and the risk of surgery- and stimulation-related serious adverse events. This report describes our open-label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS). Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit). Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication-refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement.01/2013; 3.
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ABSTRACT: Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes. Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD). A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age. The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry. Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences.01/2013; 2:207. DOI:10.12688/f1000research.2-207.v1