scholarly journals Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study

2019 ◽  
Vol 90 (10) ◽  
pp. 1078-1090 ◽  
Author(s):  
Kara A Johnson ◽  
P Thomas Fletcher ◽  
Domenico Servello ◽  
Alberto Bona ◽  
Mauro Porta ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Tourette Syndrome ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Large Cohort ◽  
Obsessive Compulsive ◽  
Compulsive Behaviour ◽  
Clinical Responses ◽  
Over Time ◽  
Deep Brain

BackgroundDeep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.MethodsWe collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.ResultsTics and obsessive–compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.ConclusionThe results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

scholarly journals Deep Brain Stimulation for Gilles de la Tourette Syndrome: Toward Limbic Targets

2020 ◽  
Vol 10 (5) ◽  
pp. 301 ◽  
Author(s):  
Domenico Servello ◽  
Tommaso Francesco Galbiati ◽  
Roberta Balestrino ◽  
Guglielmo Iess ◽  
Edvin Zekaj ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Clinical Response ◽  
Tourette Syndrome ◽  
Brain Stimulation ◽  
Clinical Picture ◽  
Effective Therapy ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Over Time ◽  
Deep Brain

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by tics and, frequently, psychiatric and behavioral comorbidities. Above all, obsessive compulsive disorder/behavior (OCD/OCB) influences the clinical picture and has a severe impact on quality of life, eventually more than the tics themselves. Deep brain stimulation (DBS) is an effective therapy in selected, refractory cases. Clinical response to DBS may vary according to the clinical picture, comorbidities, and to the anatomical target. This retrospective study compares the results obtained from DBS in the ventralis oralis/centromedian-parascicular nucleus of the thalamus (Voi-Cm/Pf) (41 patients) and antero-medial Globus Pallidus internus (am-GPi) (14 patients), evaluating clinical response over time by means of Yale Global Tic Severity Scale (YGTSS) and Yale–Brown Obsessive-Compulsive Scale (YBOCS) scores over a period of 48 months. A significant and stable improvement in the YGTSS and YBOCS has been obtained in both groups (p < 0.001). There was a significant difference in YBOCS improvement over time between the am-GPi group and the Voi-Cm/Pf group, indicating a better and faster control of OCD/OCB symptoms in the former group. The ratio of hardware removal was 23% and limited to 13 patients in the Voi-Cm/Pf group. These results confirm that DBS is an effective therapy in treating GTS and suggest that the am-GPi might be superior to Voi-Cm/Pf in alleviating comorbid OCD/OCB.

scholarly journals Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome

Brain ◽  
2020 ◽  
Vol 143 (8) ◽  
pp. 2607-2623 ◽  
Author(s):  
Kara A Johnson ◽  
Gordon Duffley ◽  
Daria Nesterovich Anderson ◽  
Jill L Ostrem ◽  
Marie-Laure Welter ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Clinical Outcomes ◽  
Tourette Syndrome ◽  
Brain Stimulation ◽  
Cross Validation ◽  
Structural Connectivity ◽  
Obsessive Compulsive ◽  
Compulsive Behaviour ◽  
Deep Brain ◽  
Correlated Networks

Abstract Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P &lt; 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P &gt; 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

scholarly journals Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder

2019 ◽  
Author(s):  
Ningfei Li ◽  
Juan Carlos Baldermann ◽  
Astrid Kibleur ◽  
Svenja Treu ◽  
Harith Akram ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Clinical Improvement ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Anterior Cingulate ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Fiber Tracts ◽  
Deep Brain

AbstractMultiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.

Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained

2019 ◽  
Vol 90 (7) ◽  
pp. 805-812 ◽  
Author(s):  
Daniel Huys ◽  
Sina Kohl ◽  
Juan Carlos Baldermann ◽  
Lars Timmermann ◽  
Volker Sturm ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Nucleus Accumbens ◽  
Executive Functions ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Obsessive Compulsive ◽  
Open Label ◽  
Compulsive Disorder ◽  
Deep Brain

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.

scholarly journals The role of diffusion tensor imaging and tractography for deep brain stimulation planning in treatment of obsessive-compulsive disorder

2019 ◽  
Vol 98 (Suppl) ◽  
pp. 13-13
Author(s):  
Mario Minor Murakami Junior ◽  
Fabio Luiz Franceschi Godinho ◽  
Paula Ricci Arantes ◽  
Eberval Gadelha Figueiredo ◽  
Rubens Gisbert Cury ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Diffusion Tensor ◽  
Region Of Interest ◽  
Internal Capsule ◽  
Future Perspective ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Deep Brain

Introduction: Obsessive-compulsive disorder (OCD) is a common, chronic and long-lasting mental disorder. The current first-line therapy for OCD is high doses of selective serotonin reuptake inhibitor (SSRI) and cognitive-behavioral psychotherapy. For patients with refractory symptoms, studies demonstrated that they may respond well to Deep Brain Stimulation (DBS), a technique that can modulate altered neuronal activity. Some stimulation sites are currently being used as targets to DBS and showed good response, but further analyses are necessary to improve the location of the electrodes since some patients demonstrated a poor outcome. Neuroimaging that assess white matter such as diffusion tensor image and tractography can evaluate the quality of the targets and assess the tracts that are affected by the electric field of the electrodes used in the surgery. Our hypothesis is that the patient outcome depends on the trajectory of the tracts that are affected by the electric field.Objectives: Our aim is to investigate which tracts connected with the stimulation sites contribute to clinical improvement effects and weather is possible to predict the outcomes based on connectivity.Methodology: We analyzed 4 patients (2 female) with treatment-refractory obsessive-compulsive disorder undergoing deep brain stimulation targeting the anterior limb of the internal capsule/ nucleus accumbens (ALIC). We will perform tractography analysis of the fibers using the volume of active tissue (VTA) as the region of interest. We will relate the alteration in OCD symptom severity on Yale-Brown obsessive-compulsive scale (Y-BOCS) between the condition before surgery and one-year follow-up with the tracts involved with the stimulation sites using DTI data such as fractal anisotropy and mean diffusivity.Partial Results: Half of the patients did show great improvement and the other two maintained a bad outcome. We found that active stimulation of the ALIC more lateral and posterior of the nucleus was associated with a better outcome. Currently, the description of the tracts involved in patients with better outcomes is performed. The tracts involved with this result will be determined by analysis of DTI and tractography.Discussion and Conclusion: For a future perspective, the results will be important to improve the stimulation sites in DBS surgery resulting in better outcomes.

scholarly journals Deep brain stimulation for Tourette syndrome: a single-center series

2018 ◽  
Vol 128 (2) ◽  
pp. 596-604 ◽  
Author(s):  
Richard S. Dowd ◽  
Michael Pourfar ◽  
Alon Y. Mogilner
Keyword(s):  
Deep Brain Stimulation ◽  
Tourette Syndrome ◽  
Brain Stimulation ◽  
Behavioral Therapy ◽  
Obsessive Compulsive ◽  
Average Decrease ◽  
Tic Severity ◽  
Average Position ◽  
Deep Brain

OBJECTIVETourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS.METHODSThe authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient's pre- and postoperative images.RESULTSPatients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up.CONCLUSIONSThe authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

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