Deep brain stimulation for Gilles de la Tourette syndrome in children and youth: a meta-analysis with individual participant data

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Gilles de la Tourette syndrome (GTS) is a disorder characterized by motor and vocal tics. Although by definition the onset of GTS is before age 18 years, clinical trials of deep brain stimulation (DBS) have been conducted only in adults. Using individual participant data (IPD) meta-analysis methodology, the current study investigated the safety and efficacy of DBS as a treatment for GTS in children and youth.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>A systematic review with no date or language restrictions was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Three electronic databases were searched: PubMed, EMBASE, and Web of Science. From 843 articles screened, the IPD of 58 children and youth (ages 12–21 years) extracted from 21 articles were collected and analyzed. A mixed-effects univariable analysis followed by multivariable hierarchical regression was performed using change in the Yale Global Tic Severity Scale (YGTSS) score as the primary outcome and reported measures of comorbidities as secondary outcomes.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>The authors’ results showed an average improvement of 57.5% ± 24.6% across studies on the YGTSS. They also found that comorbid depression and stimulation pulse width each correlated negatively with outcome (p &lt; 0.05). In patients with less severe GTS, greater improvements were evident following thalamic stimulation. More than one-quarter (n = 16, 27.6%) of participants experienced side effects, the majority of which were minor.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>DBS in the pediatric population may be an effective option with a moderate safety profile for treatment of GTS in carefully selected children and youth. Large, prospective studies with long-term follow-up are necessary to understand how DBS influences tic symptoms and may alter the natural course of GTS in children.</jats:p></jats:sec>

Deep brain stimulation for Tourette’s syndrome

“…The results showed that across patients, studies, and targets, DBS treatment was associated with a reduction in tic severity (YGTSS) by about 58% (SD = 25; p < 0.001). Moreover, DBS treatment was associated with a reduction in comorbid OCD symptoms (YBOCS) by 31% (SD = 45; p < 0.001) and anxiety (STAI) by 40% (SD = 20; p < 0.001) [70]. Although both targets were associated with significant tic improvements, greater improvements in tic severity were observed in thalamic stimulation compared to pallidal stimulation (YGTSS score improvement: thalamus: 69%; GPi: 53%; p = 0.0387), especially in patients with less severe TS symptoms at baseline.…”

“…Recently, a meta-analytis review of individual patient data from DBS studies with children and adolescents with refractory TS (N = 58; aged 12-21 years) has been published [70]. The studies reviewed targeted the thalamus or GPi regions.…”

“…In summary, DBS is a treatment option for adolescent patients who suffer from severe and intractable TS and have undergone careful assessment and selection by a multidisciplinary team [17,58,69,70]. Early DBS intervention in younger patients is still controversial, given the possibility of resolution of symptoms later in life without DBS.…”

Paediatric deep brain stimulation: ethical considerations in malignant Tourette syndrome

“…These included: transient blurry vision (8.6%), dysarthria (6.9%), infection (5.2%), anxiety (5.2%), worsening of pre-existing tremor (3.4%), dizziness (3.4%), agitation (3.4%) and a single patient each experienced haematoma, subcutaneous hydrops, hardware malfunction, lead tip cyst, lead fracture, tension headache, decreased memory, seizure-like episode, neck tightness, mild paraesthesia, light-headedness, parkinsonism, increased OCD, suicidal thoughts, seizure-like episode, disturbance of eye mobility and nausea. 19 Among these patients, the GPi was the most common location for electrode placement. 19 It is unclear whether any statistics gained from predominantly adult patient populations can be extrapolated to paediatric patient populations.…”

“…19 Among these patients, the GPi was the most common location for electrode placement. 19 It is unclear whether any statistics gained from predominantly adult patient populations can be extrapolated to paediatric patient populations. 4 Cognitive decline has neither reliably nor consistently been associated with DBS in patients with TS.…”