Bilateral Globus Pallidus Externus Deep Brain Stimulation for the Treatment of Refractory Tourette Syndrome: An Open Clinical Trial

Abstract

ObjectivesWe have previously proposed that Tourette syndrome (TS) is the clinical expression of the hyperactivity of globus pallidus externus (GPe) and various cortical areas. This study was designed to test this hypothesis by verifying the efficacy and safety of bilateral GPe deep brain stimulation (DBS) for treating refractory TS. Materials and MethodsIn this open clinical trial, 13 patients were operated on. Target coordinates (center of GPe) were obtained by direct visualization. Physiological mapping was performed with macrostimulation and microrecording. Primary and secondary outcome measures were, respectively, responder and improvement rates of TS and comorbidities, according to pre- and postoperative scores on the following assessment instruments: Yale Global Tic Severity Scale, Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory/Hamilton Depression Rating Scale, Beck Anxiety Inventory/Hamilton Anxiety Rating Scale, and Concentrated Attention test. ResultsIntraoperative stimulation (100 Hz/5.0V) did not produce any adverse effects or impact on tics. Microrecording revealed bursting cells discharging synchronously with tics in the central part of the dorsal half of GPe. Patients were followed up for a mean of 61.46±48.50 months. Responder rates were 76.9%, 75%, 71.4%, 71.4%, and 85.7%, respectively, for TS, obsessive-compulsive disorder (OCD), depression, anxiety, and attention deficit hyperactivity disorder. Mean improvements among responders in TS, OCD, depression, and anxiety were 77.4%, 74.7%, 89%, and 84.8%, respectively. After starting stimulation, tic improvement was usually delayed, taking up to ten days to manifest. Afterward, it increased over time, usually reaching its maximum at approximately one year postoperatively. The best stimulation parameters were 2.3V to 3.0V, 90 to 120 μsec, and 100 to 150 Hz, and the most effective contacts were the two dorsal ones. Two complications were registered: reversible impairment of previous depression and transient unilateral bradykinesia. ConclusionsBilateral GPe-DBS proved to be low risk and quite effective for treating TS and comorbidities, ratifying the pathophysiological hypothesis that led to this study. Moreover, it compared favorably with DBS of other targets currently in use.