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Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

ABSTRACT: INTRODUCTION:Personalized, scheduled deep brain stimulation in Tourette syndrome (TS) may permit clinically meaningful tic reduction while reducing side effects and increasing battery life. Here, we evaluate scheduled DBS applied to TS at two-year follow-up. METHODS:Five patients underwent bilateral centromedian thalamic (CM) region DBS. A cranially contained constant-current device delivering stimulation on a scheduled duty cycle, as opposed to the standard continuous DBS paradigm was utilized. Baseline vs. 24-month outcomes were collected and analyzed, and a responder analysis was performed. A 40% improvement in the Modified Rush Tic Rating Scale (MRTRS) total score or Yale Global Tic Severity Scale (YGTSS) total score defined a full responder. RESULTS:Three of the 4 patients followed to 24 months reached full responder criteria and had a mean stimulation time of 1.85 h per day. One patient lost to follow-up evaluated at the last time point (month 18) was a non-responder. Patients exhibited improvements in MRTRS score beyond the improvements previously reported for the 6 month endpoint; on average, MRTRS total score was 15.6% better at 24 months than at 6 months and YGTSS total score was 14.8% better. Combining the patients into a single cohort revealed significant improvements in the MRTRS total score (-7.6 [5.64]; p = 0.02). CONCLUSION:Electrical stimulation of the centromedian thalamic region in a scheduled paradigm was effective in suppressing tics, particularly phonic tics. Full responders were able to achieve the positive DBS effect with a mean of 2.3 ± 0.9 (SEM) hours of DBS per day.

SUBMITTER: Rossi PJ

PROVIDER: S-EPMC4969169 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

Rossi P Justin PJ Opri Enrico E Shute Jonathan B JB Molina Rene R Bowers Dawn D Ward Herbert H Foote Kelly D KD Gunduz Aysegul A Okun Michael S MS

Parkinsonism & related disorders 20160607

<h4>Introduction</h4>Personalized, scheduled deep brain stimulation in Tourette syndrome (TS) may permit clinically meaningful tic reduction while reducing side effects and increasing battery life. Here, we evaluate scheduled DBS applied to TS at two-year follow-up.<h4>Methods</h4>Five patients underwent bilateral centromedian thalamic (CM) region DBS. A cranially contained constant-current device delivering stimulation on a scheduled duty cycle, as opposed to the standard continuous DBS paradig ...[more]

PMID: 27297737

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Project description:ObjectiveTo examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders.MethodsData from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9-69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression-Improvement score assessed by masked evaluators.ResultsThe presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction.ConclusionsPresence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication.Clinicaltrialsgov identifiersThe child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively).Classification of evidenceThis study provides Class I evidence that CBIT is effective in reducing tic severity across subgroups of patients with chronic tic disorders, although the difference between treatments was smaller for participants on tic-suppressing medications, suggesting reduced efficacy in this subgroup.

Project description:Tics are sudden stereotyped movements or vocalizations. Cases of lesion-induced tics are invaluable, allowing for causal links between symptoms and brain structures. While a lesion network for tics has recently been identified, the degree to which this network translates to Tourette syndrome has not been fully elucidated. This is important given that patients with Tourette syndrome make up a large portion of tic cases; therefore, existing and future treatments should apply to these patients. The aim of this study was to first localize a causal network for tics from lesion-induced cases and then refine and validate this network in patients with Tourette syndrome. We independently performed 'lesion network mapping' using a large normative functional connectome (n = 1000) to isolate a brain network commonly connected to lesions causing tics (n = 19) identified through a systematic search. The specificity of this network to tics was assessed through comparison to lesions causing other movement disorders. Using structural brain coordinates from prior neuroimaging studies (n = 7), we then derived a neural network for Tourette syndrome. This was done using standard anatomical likelihood estimation meta-analysis and a novel method termed 'coordinate network mapping', which uses the same coordinates, yet maps their connectivity using the aforementioned functional connectome. Conjunction analysis was used to refine the network for lesion-induced tics to Tourette syndrome by identifying regions common to both lesion and structural networks. We then tested whether connectivity from this common network is abnormal in a separate resting-state functional connectivity MRI data set from idiopathic Tourette syndrome patients (n = 21) and healthy controls (n = 25). Results showed that lesions causing tics were distributed throughout the brain; however, consistent with a recent study, these were part of a common network with predominant basal ganglia connectivity. Using conjunction analysis, coordinate network mapping findings refined the lesion network to the posterior putamen, caudate nucleus, globus pallidus externus (positive connectivity) and precuneus (negative connectivity). Functional connectivity from this positive network to frontal and cingulate regions was abnormal in patients with idiopathic Tourette syndrome. These findings identify a network derived from lesion-induced and idiopathic data, providing insight into the pathophysiology of tics in Tourette syndrome. Connectivity to our cortical cluster in the precuneus offers an exciting opportunity for non-invasive brain stimulation protocols.

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Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

Publications

Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

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