A Prospective Randomized Double-blind Trial of Bilateral Thalamic Deep Brain Stimulation in Adults with Tourette Syndrome

As part of the first randomized double-blind trial of deep brain stimulation (DBS) of the globus pallidus (GPi) in Tourette syndrome, we examined the effect of stimulation on response initiation and inhibition. A total of 14 patients with severe Tourette syndrome were recruited and tested on the stop signal task prior to and after GPi-DBS surgery and compared to eight age-matched healthy controls. Tics were significantly improved following GPi-DBS. The main measure of reactive inhibition, the stop signal reaction time did not change from before to after surgery and did not differ from that of healthy controls either before or after GPi-DBS surgery. This suggests that patients with Tourette syndrome have normal reactive inhibition which is not significantly altered by GPi-DBS.

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What Patients With Gilles de la Tourette Syndrome Should Be Treated With Deep Brain Stimulation and What Is the Best Target?

Neurosurgery ◽

10.1227/neu.0b013e3182535a00 ◽

2012 ◽

Vol 71 (1) ◽

pp. 173-192 ◽

Cited By ~ 37

Author(s):

John Carlo Pansaon Piedad ◽

Hugh Edward Rickards ◽

Andrea Eugenio Cavanna

Keyword(s):

Deep Brain Stimulation ◽

Tourette Syndrome ◽

Brain Stimulation ◽

Case Reports ◽

Neurodevelopmental Disorder ◽

Case Series ◽

Current Evidence ◽

Double Blind ◽

Randomized Controlled Studies ◽

Deep Brain

AbstractBACKGROUND:Gilles de la Tourette syndrome (GTS) is a chronic neurodevelopmental disorder characterized by tics and associated behavioral symptoms. Over the past decade, deep brain stimulation (DBS) has been increasingly advocated as a reversible and controllable procedure for selected cases of GTS.OBJECTIVE:We set out to answer 2 clinically relevant questions: what patients with GTS should be treated with DBS and what is the best target?METHODS:We conducted a systematic literature review of the published studies of DBS in GTS and critically evaluated the current evidence for both patient and target selection.RESULTS:Since 1999, up to 99 cases of DBS in GTS have been reported in the scientific literature, with varying selection criteria, stimulation targets, and assessment protocols. The vast majority of studies published to date are case reports or case series reporting successful outcomes in terms of both tic severity improvement and tolerability. The reviewed studies suggest that the best candidates are patients with significant functional impairment related to the tic symptoms, who did not respond to conventional pharmacological and behavioral interventions. The globus pallidus internus and thalamus appear to be the safest and most effective targets, especially for patients with “pure” GTS and patients with comorbid obsessive-compulsive symptoms, anxiety, and depression.CONCLUSION:DBS is a promising treatment option for severe cases of GTS. There is a need to reach consensus on the definition of “treatment-refractoriness” and to conduct larger double-blind randomized controlled studies on the most promising targets.

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Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome

Journal of Neurosurgery ◽

10.3171/jns-07/11/1004 ◽

2007 ◽

Vol 107 (5) ◽

pp. 1004-1014 ◽

Cited By ~ 191

Author(s):

Robert J. Maciunas ◽

Brian N. Maddux ◽

David E. Riley ◽

Christina M. Whitney ◽

Mike R. Schoenberg ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Tourette Syndrome ◽

Outcome Measures ◽

Brain Stimulation ◽

Rating Scale ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Double Blind ◽

Exact Test ◽

Deep Brain

Object The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. Methods Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. Results In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. Conclusions Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

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Faculty Opinions recommendation of Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727745626.793535474 ◽

2017 ◽

Author(s):

Jonathan Mink ◽

Shannon Dean

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Controlled Trial ◽

Tourette's Syndrome ◽

Tourette’S Syndrome ◽

Double Blind ◽

Pallidal Deep Brain Stimulation ◽

Deep Brain

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A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder

Translational Psychiatry ◽

10.1038/s41398-021-01307-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip E. Mosley ◽

François Windels ◽

John Morris ◽

Terry Coyne ◽

Rodney Marsh ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Adverse Events ◽

Brain Stimulation ◽

Stria Terminalis ◽

Treatment Resistant ◽

Obsessive Compulsive ◽

Double Blind ◽

Bed Nucleus ◽

Compulsive Disorder ◽

Deep Brain

AbstractDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

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