Internal pallidal and thalamic stimulation in patients with Tourette syndrome

Marie-Laure Welter, Luc Mallet, Jean-Luc Houeto, Carine Karachi, Virginie Czernecki, Philippe Cornu, Soledad Navarro, Bernard Pidoux, Didier Dormont, Eric Bardinet, Jérôme Yelnik, Philippe Damier, Yves Agid
Archives of Neurology 2008, 65 (7): 952-7

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 associative-limbic 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.

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