Objective: In this trial we will assess the efficacy and safety of pallidal deep brain stimulation (DBS) versus botulinum toxin A (BoNT A) therapy in cervical dystonia (CD). We hypothesize that DBS is safe and superior to BoNT A in controlling motor symptoms and restoring quality of life.

Background: The current mainstay treatment for CD is selective injections of BoNt A in affected muscles. Pallidal DBS is an effective therapy, but currently restricted to patients with BoNT A resistant symptoms. As BoNT A is effective but not satisfactory in a relevant proportion of patients(1), earlier DBS surgery might be advantageous in providing stable symptom control and preventing disability(2).

Methods: Within this trial, 66 subjects with ≥2 years of CD (severity ≥20 TWSTRS total) will be recruited into a double-blind comparison of pallidal DBS versus BoNT A from 12 DBS centres in Germany. Eligible patients need ≥25% motor score reduction 4 weeks after BoNT A injection, but are willing to undergo DBS surgery due to unsatisfactory symptom control. All patients will be implanted with an ACTIVA PC system (Medtronic Inc., Minneapolis), then randomized into 2 groups: First group will receive effective neurostimulation (best clinical practice; 90µs, 130Hz) + regular sham injections (saline) in dystonic muscles. Second group will receive regular BoNT A injections (2 cycles; best clinical practice) in dystonic muscles + sham-stimulation (0V generator output). Primary outcome: change in TWSTRS total score between baseline and 6 months of therapy. Secondary outcomes: changes in TWSTRS motor, Tsui, CDQ24, SF36. Safety will be assessed by spontaneously reported adverse effects. In-depth statistical analysis includes analysis based on ITT and PP populations, analysis based on imputation of missing values, analysis adjusting for differences in baseline TWSTRS total. After 6 months sham-controlled period all patients will receive open-label neurostimulation and follow-up for 12 months.

Results: The study has been approved by the institutional review boards and the German regulatory agency. Recruitment will start in 2017. First results are anticipated for 2018.

Conclusions: We will assess if pallidal DBS is a safe and effective alternative to BoNT A in CD, which may be offered earlier in the treatment algorithm based on patient preference.

References: EudraCT registration number: 2016-001378-13.

1. Misra, V.P., et al., Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study. BMJ Open, 2012.

2. Volkmann J, et al. Pallidal neurostimulation in patients with medication-refractory cervical dystonia – a sham-controlled randomized trial. Lancet Neurology 2014.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/design-of-a-randomized-sham-controlled-trial-of-pallidal-neurostimulation-versus-botulinum-toxin-treatment-for-cervical-dystonia-stimtox-cd/