Internal pallidal and thalamic stimulation in patients with Tourette syndrome

Background: Tourette syndrome ( TS) is thought to result from dysfunction of the associative- limbic territories of the basal ganglia, and patients with severe symptoms of TS respond poorly to medication. High- frequency stimulation has recently been applied to patients with TS in open studies using the centromedian- parafascicular complex ( CM- Pf) of the thalamus, the internal globus pallidus ( GPi), or the anterior limb of the internal capsule as the principal target. Objective: To report the effect of high- frequency stimulation of the CM- Pf and/ or the GPi, 2 associative- limbic relays of the basal ganglia, in patients with TS. Design: Controlled, double-blind, randomized crossover study. Setting: Medical research. Patients: Three patients with severe and medically refractory TS. Intervention: Bilateral placement of stimulating electrodes in the CM- Pf ( associative- limbic part of the thalamus) and the GPi ( ventromedial part). Main Outcome Measures: Effects of thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation on neurologic, neuropsychological, and psychiatric symptoms. Results: A dramatic improvement on the Yale Global Tic Severity Scale was obtained with bilateral stimulation of the GPi ( reduction in tic severity of 65%, 96%, and 74% in patients 1, 2, and 3, respectively). Bilateral stimulation of the CM-Pf produced a 64%, 30%, and 40% reduction in tic severity, respectively. The association of thalamic and pallidal stimulation showed no further reduction in tic severity ( 60%, 43%, and 76%), whereas motor symptoms recurred during the sham condition. No neuropsychological, psychiatric, or other long-term adverse effect was observed. Conclusions: High-frequency stimulation of the associativelimbic relay within the basal ganglia circuitry may be an effective treatment of patients with TS, thus heightening the hypothesis of a dysfunction in these structures in the pathophysiologic mechanism of the disorder. Trial Registration: clinicaltrials. gov Identifier: NCT00139308