CHICAGO – Deep brain stimulation of limbic relays within the basal ganglia circuitry reduced tic severity in patients with Tourette syndrome, according to data from a small double-blind, randomized crossover study.
In three patients with severe and medically refractory Tourette syndrome, researchers applied high-frequency bilateral deep brain stimulation to two structures that form part of the basal ganglia associative-limbic circuits–the centromedian-parafascicular complex (CM-Pf) of the thalamus and the ventromedial part of the globus pallidus interna (GPi).
Patients and investigators were blinded at evaluation to the four stimulation conditions–thalamic, pallidal, simultaneous thalamic and pallidal, and sham.
The greatest lessening of tics was achieved with ventromedial GPi stimulation, coinvestigator Dr. Luc Mallet said at the 12th International Congress of Parkinson's Disease and Movement Disorders. The total Yale Global Tic Severity Scale (YGTSS) score was reduced 65%, 96%, and 74% from baseline in patients 1, 2, and 3, respectively.
CM-Pf stimulation reduced tic severity by 64%, 30%, and 40%, respectively. Combining thalamic and pallidal stimulation did not improve tic reduction in the study (Arch. Neurol. 2008;65:952-7).
In patient No. 2, the best result was obtained after 1 month with stimulation, but the effects decreased after 2 months, even with increased voltage, said Dr. Mallet of Pitié-Salpêtrière Hospital, Paris.
Very good long-term effects were observed in patient No. 1, who was identified with borderline personality disorder before surgery.
The decrease in tic severity was accompanied by a dramatic reduction in self-injurious behaviors and impulsiveness, allowing the patient to start psychotherapy, to improve autonomy and social relationships, and to return to full-time work 2 years after surgery. Although tics are involuntary movements, they are influenced by emotional context, explained Dr. Mallet, who disclosed no conflicts of interest.
In patient No. 2, a stable reduction in tic severity was achieved 27 months after surgery using 20 hours of pallidal stimulation followed by 4 hours off. In patient 3, tic severity was reduced by 74% at 20 months without medication under pallidal and thalamic stimulation.
No neuropsychological, psychiatric, or other long-term adverse effects were observed.
The findings confirm those of open-label studies and case reports, and support the theory that Tourette results from dysfunction of the associative-limbic territories of the basal ganglia, Dr. Mallet said.
“We need further controlled studies to compare the two targets between the thalamus and the pallidum, but this is very encouraging for a proposed treatment for Tourette,” he said.
There is a large French multicenter study underway to evaluate ventromedial GPi stimulation in patients with Tourette.
Ventromedial GPi stimulation may be more efficient than CM-Pf because the GPi is a key structure for the output nucleus of the main basal ganglia pathway, whereas the CM-Pf is part of an indirect, internal loop of the basal ganglia circuitry, according to the investigators.
The current study was also by Dr. Marie-Laure Welter and was sponsored by the French National Institute for Health and Medical Research, the University of Pierre and Marie Curie in Paris, and the Public Assistance Hospital of Paris.