Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome.

BACKGROUND: There are still no sufficient data regarding the use of deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) and no agreement on optimal target. OBJECTIVE: To compare efficacy and safety of bilateral DBS of thalamus (centromedian-ventro-oral internus, CM-Voi) versus posteroventral lateral globus pallidus internus (pvl GPi)) versus sham stimulation, and baseline in severe medically refractory GTS. METHODS: In this randomized double-blind sham stimulation-controlled trial (RCT), 10 patients (3 women, mean age = 29.4 ± 10.2 SD, range 18-47) underwent three blinded periods each lasting three months including (i) sham, (ii) pvl GPi (on-GPi), and (iii) thalamic stimulation (on-thal) followed by an open uncontrolled long-term follow-up (up to 9 years) with individually determined target and stimulation settings. RESULTS: Nine patients completed the RCT. At group level, on-GPi - but not on-thal - resulted in a significant tic reduction compared to baseline, but had no effect on premonitory urges and psychiatric comorbidities. Direct comparisons of targets resulted in inconsistent or negative (compared to sham) findings. During follow-up, we found no improvement of tics, comorbidities, and quality of life at group level, however, single patients benefitted continuously from thalamic DBS. At last follow-up 89.9 months (mean) after surgery, 50% of patients had discontinued DBS. Hardware infections occurred in 3/10 patients. CONCLUSION: Our data suggest that the initial effect of pvl GPi DBS is superior to thalamic (CM-Voi) DBS. While half of the patients discontinued treatment, single patients benefitted from thalamic DBS even after years. It is likely that outcome is influenced by various factors beyond the mere change in tic severity.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.