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Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus-nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus-parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically. Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences. Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis. Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses. Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.

SUBMITTER: Wehmeyer L

PROVIDER: S-EPMC8563609 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis.

Wehmeyer Laura L Schüller Thomas T Kiess Jana J Heiden Petra P Visser-Vandewalle Veerle V Baldermann Juan Carlos JC Andrade Pablo P

Frontiers in neurology 20211020

<b>Background:</b> Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus-nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus-parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and common ...[more]

PMID: 34744993

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Project description:To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Project description:BackgroundTourette syndrome (TS) is a neurological disorder characterized by tics, often associated with obsessive-compulsive disorder (OCD). Severe cases may require interventions such as deep brain stimulation (DBS) or repetitive transcranial magnetic stimulation (rTMS).MethodsA thorough search was performed across PubMed/Medline, Embase, (CENTRAL), and Google Scholar. Studies comparing DBS and rTMS efficacy for TS were included if they reported YGTSS before and after treatment. Two independent reviewers screened the search results, extracted data, and assessed study quality using standardized tools.Results22 studies met the inclusion criteria, with a total of 222 participants. Analysis of RCTs investigating post-intervention rTMS vs baseline showed a statistically insignificant decrease in YGTSS (MD = -5.01, 95% CI: [-10.8, 0.79], P= 0.090) but a statistically significant decrease in YBOCS (MD = -6.6; 95% CI: [-11.64, -1.55], P= 0.010). However, post-intervention rTMS in RCT and non-randomized trials vs baseline showed a significant decrease in YGTSS (MD = -11.6; 95% CI: [-18.25, -4.94], P < 0.001) and YBOCS (MD = -7.5; 95% CI: [-11.85, -3.15], P < 0.001). Post-intervention DBS in RCT and non-RCTs vs baseline showed a significant decrease in YGTSS (MD = -18.29; 95% CI: [-24.93, -11.64], P < 0.001) and YBOCS (MD = -4.76; 95% CI: [-7.30, -2.21], P < 0.001). Analysis of RCTs investigating Post-intervention DBS vs baseline showed a significant decrease in YGTSS (MD = -14.71; 95% CI: [-19.78, -9.63], P <0.001) and YBOCS (MD = -5.04; 95% CI: [-8.28, -1.80], P = 0.002).ConclusionOur analysis revealed both DBS and rTMS improved TS and OCD symptoms, however the effect of rTMS on TS in RCTs was insignificant, suggesting DBS stimulation is more effective. Despite this, clinicians may still opt for rTMS before DBS due to its less invasive nature, the limited number of high-quality RCTs, and the lack of studies directly comparing rTMS and DBS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023386856, identifier CRD42023386856.

Project description: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 < 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 > 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.

Dataset Information

Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis.

Publications

Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis.

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