Subthalamic deep brain stimulation for refractory Gilles de la Tourette's syndrome: clinical outcome and functional connectivity

Abstract

Background: Deep brain stimulation (DBS) is a promising novel approach for managing refractory Gilles de la Tourette's syndrome (GTS). The subthalamic nucleus (STN) is the most common DBS target for treating movement disorders, and smaller case studies have reported the efficacy of bilateral STN-DBS treatment for relieving tic symptoms. However, management of GTS and treatment mechanism of STN-DBS in GTS remain to be elucidated.

Methods: Ten patients undergoing STN-DBS were included. Tics severity was evaluated using the Yale Global Tic Severity Scale. The severities of comorbid psychiatric symptoms of obsessive-compulsive behavior (OCB), attention-deficit/hyperactivity disorder, anxiety, and depression; social and occupational functioning; and quality of life were assessed. Volumes of tissue activated were used as seed points for functional connectivity analysis performed using a control dataset.

Results: The overall tics severity significantly reduced, with 62.9% ± 26.2% and 58.8% ± 27.2% improvements at the 6- and 12-months follow-up, respectively. All three patients with comorbid OCB showed improvement in their OCB symptoms at both the follow-ups. STN-DBS treatment was reasonably well tolerated by the patients with GTS. The most commonly reported side effect was light dysarthria. The stimulation effect of STN-DBS might regulate these symptoms through functional connectivity with the thalamus, pallidum, substantia nigra pars reticulata, putamen, insula, and anterior cingulate cortices.

Conclusions: STN-DBS was associated with symptomatic improvement in severe and refractory GTS without significant adverse events. The STN is a promising DBS target by stimulating both sensorimotor and limbic subregions, and specific brain area doses affect treatment outcomes.

Keywords: Clinical outcome; Deep brain stimulation; Functional connectivity; Gilles de la Tourette’s syndrome; Psychiatric comorbidity; Subthalamic nucleus.

Fig. 1

Tic severity over time. a Line chart of motor and vocal tics and b box plot of overall tic severity evaluated based on the YGTSS total scores at baseline and at the 3-, 6-, and 12-month follow-ups. Error bars indicate standard deviations of the scores. Note: ^*p < 0.05. ^**p < 0.01 (relative to baseline). Abbreviation: YGTSS Yale Global Tic Severity Scale

Fig. 2

Psychiatric comorbidities and quality of life over time. a Line chart of OCB evaluated using the Y-BOCS. b–d Box plot of anxiety, quality of life, and adaptive functioning evaluated using the HAMA-14, GTS-QOL, and GAF, respectively. Note: ^*p < 0.05; ^**p < 0.01 (relative to baseline). Abbreviations: GAF Global Assessment of Functioning scale, GTS-QOL Gilles de la Tourette Syndrome-Quality of Life Scale, HAMA-14 14 items of the Hamilton Anxiety Scale, Y-BOCS Yale-Brown Obsessive Compulsive Scale

Fig. 3

Reconstruction of DBS electrode placement using Lead-DBS software. All the active contacts reached the dorsal part of the subthalamic nucleus. Abbreviations: DBS deep brain stimulation

Fig. 4

The average profile of functional electrode connectivity in multiple whole-brain regions. Positive correlations are presented in warm colors, and negative correlations are shown in cool colors