Double blind comparison of optimised Deep Brain Stimulation for severe Tourette syndrome

The aim of the project is to assess if optimised Deep Brain Stimulation (DBS) of the internal globus pallidum (GPi) reduces tic severity in patients with severe Tourette syndrome (TS).

TS is a condition presenting with chronic multiple motor and phonic tics starting in childhood. Although most patients have mild transient symptoms, a small number have severe motor and vocal tics unresponsive to conventional treatments. The violent character of the tics and the self-injuries that can be associated, can result in serious injuries.

In addition, patients also often suffer from comorbid depression, anxiety, obsessive compulsive symptoms, hyperactivity and are at risk of suicide. They can also have difficulties engaging in social interactions and in employment.

GPi DBS is a neurosurgical procedure which involves the placement of two electrodes into a part of the basal ganglia (GPi), that are then connected to an implantable pacemaker in the chest wall. The system can be programmed to deliver high frequency electrical stimulation. DBS is an accepted treatment for Parkinson’s disease, dystonia and tremor.

In experienced teams the risks are very low. A small number of patients with TS have previously benefited from DBS; nevertheless, more evidence is needed before DBS can be made available as an NHS treatment.

In this study, we are planning to recruit 20 adult patients with severe TS with a Yale Global Tic Severity Score (YGTSS) >50/100. Patients will be implanted with GPi DBS. Our innovative design involves a 6 months open-phase study for stimulation parameter adjustment.

In previous studies, this period was shorter and insufficient to obtain an optimal outcome. After these 6 months, patients will be randomized into two groups; one group will be kept with the stimulator on and the other will be switched off for up to two weeks. Tic severity will be re-assessed and patients will be switched to the other condition for another two weeks.

The tics are expected to come back within one to two days. Patients who find it difficult to tolerate one condition for two weeks will be assessed and switched to the other condition sooner. Patients and raters will be blind to the stimulation condition.

The primary outcome measure will be a validated clinical scale, the Tic Severity Score from the YGTSS. In addition, a video tic assessment will be conducted and rated by an independent blinded scorer using the Modified Rush Video Rating Scale.

Other scales assessing the impact of tics on quality of life, mood, anxiety, hyperactivity and obsessive-compulsive symptoms will be completed before surgery and at the end of the open-phase. The list of adverse events will also be collected. The mechanistic part of the study will seek to assess the potential variables (i.e. clinical, imaging and electrical) that could explain why some patients show better improvement than others.

We are planning a 6-month period for contracts and regulatory approvals, 20 months of recruitment and 39 months total duration.

The outcome of this study will be presented at conferences and published in high impact factor journals. This project has been discussed extensively with NHS England and we hope that it will lead to consideration to making DBS accessible for patients with very severe TS. The results will also be disseminated to patients and to the general public. A PPI group including 3 patients, 2 relatives and the CEO of Tourette’s Action is supporting our trial.