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.

Tourette syndrome research highlights from 2022

“…Several targets have been used for DBS in TS, and the question of the optimal target is still debated. Dai and colleagues report the outcomes of dorsal (sensorimotor) STN DBS in 10 patients with TS and showed an overall reduction of 62.9% of tics at six months and 58.8% at 12 months, with an improvement in quality-of-life measures and OCD ( Dai et al . 2022 ).…”

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation

“…Network correlates to restore functionality in TS are less established, especially not via the more recent application of subthalamic DBS 16 , 17 . Here, the most highly weighted hyperdirect streamlines showed connectivity to M1 and SMA.…”

“…Indeed, targeting the same nucleus has proven an effective therapy for a heterogeneous spectrum of disorders that includes Parkinson’s disease (PD) 11 , dystonia (DYT) 12 , 13 , obsessive-compulsive disorder (OCD) 14 , 15 and Tourette’s syndrome (TS) 16 , 17 . At first glance, it may appear paradoxical that applying electrical stimulation to a subcortical structure of such constrained extent could alleviate symptoms in four disorders that manifest as differently from one another at a phenotypical level.…”

Mapping Dysfunctional Circuits in the Frontal Cortex Using Deep Brain Stimulation

“…Network correlates to restore functionality in TS are less established, especially not via the more recent application of subthalamic DBS 15,16 . Here, the most highly weighted hyperdirect fibers originated in M1 and SMA, which align with tic-related alterations 76,77 and have been associated with tic reduction under thalamic 78,79 or pallidal DBS 27,80 .…”

“…The STN – with a volume of only ∼240 mm 3 9 – is much smaller than the striatum, but nonetheless receives efference copies of projections from the entire frontal cortex 3 , rendering it an ideal access node to modulate large-scale brain networks using small electrodes. Indeed, the nucleus has been successfully targeted by deep brain stimulation (DBS) to treat diseases as different as Parkinson’s disease (PD) 10 , dystonia (DYT) 11,12 , obsessive-compulsive disorder (OCD) 13,14 , and Tourette’s syndrome (TS) 15,16 .…”