GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities.

OBJECTIVE: To describe the response of a medication-refractory, 16-year old male with severe Tourette syndrome (TS) and typical co-morbidities to bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi). BACKGROUND: Case reports suggest efficacy of DBS in treating severe TS. A medication-refractory, 16-year old male with severe Tourette syndrome (TS) and typical co-morbidities underwent DBS of the globus pallidus interna (GPi). METHODS: Pre-surgical neuropsychological, psychiatric, and neurological evaluations were compared to 6 month follow-up evaluations. Measures included Yale Global Tic Severity Scale (YGTSS), Tic Symptom Self Report (TSSR), Modified Rush Video-Based Tic Rating Scale (VTRS) scored by an independent, “blinded” rater, behavior rating scales (BASC-2, BRIEF), Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), a quality of life measure (SF-36v2), and neurocognitive tests. RESULTS: YGTSS improved by 84% (from 90 to 14), TSSR improved by 88% (from 94 to 11), and VTRS improved by 21% (from 14 to 11). BASC-2 showed marked reduction in co-morbid symptoms including depression (120 to 41, Z-score 7.83), anxiety (94 to 42, Zscore 5.12), and hyperactivity (93 to 50, Z-score 4.21). Mild social introversion and withdrawal remained at 6 months. The Behavioral Regulation Index improved from 87 to 49 (Z-score 3.47), the Metacognition Index improved from 80 to 61 (Z-score 1.64), and the Global Executive Composite improved from 86 to 57 (Z-score 2.60). CY-BOCS improved by 69% (from 16 to 5). Neurocognitive testing showed improved verbal reasoning, psychomotor speed, mental flexibility, and visual-perception, with somewhat poorer performance on a test of memory. The SF-36v2 improved by 65% (from 86 to 142). He returned to school part-time. CONCLUSIONS: Both tics and comorbid conditions including OCD, depression, anxiety, and AD/HD improved following bilateral GPi DBS, resulting in markedly improved quality of life. The residual mild social avoidance may have been a result of learned/reinforced pre-surgical behavior patterns. Careful selection of patients, experience with DBS, and comprehensive assessments at baseline and at follow-up visits are essential for successful outcome of DBS in TS. Tourette syndrome (TS) is characterized by vocal and motor tics, along with varying degrees of psychiatric co-morbidities including attention-deficit (+/hyperactivity) disorder (ADHD), obsessivecompulsive disorder (OCD), anxiety, depression, and oppositional defiant disorder (Jankovic, 2001). The majority of patients experience significant improvement in or remission by the late teenage years (Leckman et al, 1998), although many will have milder, persistent tics and OCD even into adulthood (Pappert et al, 2003; Bloch et al, 2006). A subset experience a dramatic, debilitating worsening of symptoms that may persist into adulthood. Recent years have seen growing interest in the management of neuropsychiatric conditions with deep brain stimulation (DBS) (Kopell et al, 2004). Several cases of marked improvement of severe TS symptoms have been reported with DBS (Table 1). Here, we describe our rationale for and experience with DBS of the bilateral globus pallidus interna (GPi) in a 16-year-old boy with severe, medication-refractory TS. The GPi (motor) was chosen as the target for the following reasons: Increased parvalbumin-staining neurons in the GPi of TS patients is associated with an increase in GPi volume (Kalanithi et al, 2005). Irregular firing patterns in the GPi of TS patients have been observed. The GPi has connections to the prefrontal cortex (PFC), an area that influences cognition and mood (Yoshida et al, 1993; Middleton and Strick, 2002). Previous successful treatment of severe TS with GPi DBS (Table 1). INTRODUCTION Table 1. Previous reports of deep brain stimulation in medication refractory TS* Ref. N [age, yrs] Target F/U Outcomes Adverse Events