Deep Brain Stimulation for Tourette Syndrome

The first description of the “Maladie des Tics” in 1885 by the French neuropsychiatrist Georges Gilles de la Tourette has developed into a well-known syndrome bearing his name.1 It has historically been difficult to arrive at an accurate diagnostic criterion or devise optimal medical and pharmacological strategies for the treatment of Tourette syndrome (TS). The first neurosurgical procedures for TS were ablative, whereby Baker reported selective bifrontal transection of white matter in 1962. Stereotactic procedures were also reported in subsequent years, but their results were inconsistent.2 Deep brain stimulation (DBS) of the thalamus for TS was introduced in 1999 by Vandewalle et al.3 Since then, multiple case reports and series have demonstrated the viability of DBS as a potential surgical option for select cases of refractory TS. However, the small number of patients in individual centers and the heterogeneity of clinical protocols have hampered consensus on the general utility of DBS in TS.

The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry is a multinational collaborative effort designed to share data and improve the quality of outcomes research in the treatment of TS with DBS, recently described by Martinez-Ramirez et al in JAMA Neurology.4 The registry accumulated data from 171 patients between January 2012 and December 2016 across 31 institutions from 10 different countries. There was a greater prevalence of male gender (78.4%). The mean (standard deviation) age at symptom onset was 7.8 (3.5) yr, and the mean age at time of DBS surgery was 29.1 (10.8) yr. The most common comorbidities were obsessive-compulsive disorder (64.2%) and depression (47.3%). Stimulation sites included the centromedian thalamic region (57.1%), anterior globus pallidus internus (GPi; 25.2%), posterior GPi (15.3%), and the anterior limb of internal capsule (2.5%), although the latter was excluded from analysis due to small sample size.

The authors utilized the Yale Global Tic Severity Score (YGTSS) to compare clinical outcomes at 3 time points (presurgical baseline, 6-mo postoperative, and 12-mo postoperative) and between the 3 anatomical DBS targets. For the pooled data, there was a 40% improvement, from 75.01 (18.36) to 44.92 (19.01; P < .001), in the YGTSS total score at 6-mo. At 12-mo, this average gain increased to 45% (P < .001). Separate analysis of the motor and phonic components of the YGTSS yielded similar results. At 12-mo, this effect on the total YGTSS was significant for each DBS target, when analyzed separately, with no statistical difference observed for YGTSS scores between these 3 targets (P = .57). The most common adverse events seen with DBS were stimulation-related symptoms (30.4%), such as transient dysarthria and paresthesias.

The registry results mirror those described in a systematic review and meta-analysis of DBS for TS that was published in 2016.5 In that pooled analysis, 156 patients from 57 different studies met the inclusion criteria. There was a significant median improvement of 52.68% (IQR = 40.83; P < .001) for the total YGTSS, declining from a median score of 83 to 35 at the last available follow-up. The anatomic DBS targets analyzed in this meta-analysis were the same used in the International TS DBS Public Database and Registry, and similarly no difference was observed between targets (P = .496).5

Although not class 1 evidence, these data nonetheless should encourage movement disorder groups to consider treating refractory TS with DBS. The development of standardized surgical criteria through the collaborative effort of the registry participant centers will be helpful for identifying appropriate patients for evaluation. The fact that DBS of the centromedian thalamic region, anterior GPi and posterior GPi each appear to produce equivalent symptomatic improvement, with minimal complications, indicates a need to better understand the network physiology of TS. Exploration of the underlying basal ganglia-thalamocortical circuit neurophysiology in TS would be a welcome goal of future prospective clinical trials.