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Marie-Laure Welter, MD, PhD; Luc Mallet, MD, PhD; Jean-Luc Houeto, MD, PhD; Carine Karachi, MD, PhD; Virginie Czernecki, PhD; Philippe Cornu, MD; Soledad Navarro, MD; Bernard Pidoux, MD; Didier Dormont, MD, PhD; Eric Bardinet, PhD; Jérôme Yelnik, MD; Philippe Damier, MD, PhD; Yves Agid, MD, PhD

Arch Neurol. 2008;65(7):952-957.

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.

Trial Registration  clinicaltrials.gov Identifier: NCT00139308

Author Affiliations: National Institute of Health and Medical Research (INSERM), Unit 679, Pierre et Marie Curie University-Paris 6, Clinical Investigation Centre, Federation of Nervous System Diseases (Drs Welter, Karachi, Czernecki, Yelnik, and Agid), Department of Neurosurgery (Drs Karachi, Cornu, and Navarro), Federation of Clinical Neurophysiology (Dr Pidoux), Department of Neuroradiology (Drs Dormont and Bardinet), and National Centre of Research and Health, UPR640 (Drs Dormont and Bardinet), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital; and INSERM, Equipe AVENIR Group IFR-70 (Dr Mallet), Paris, France; Department of Neurology, Centre Hopitalier Universitaire Poitiers, Poitiers, France (Dr Houeto); and Clinical Investigation Centre, Department of Neurology, Laennec Hospital, Centre Hopitalier Universitaire Nantes, Nantes, France (Dr Damier).

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