DIPS (Dystonia Image-based Programming of Stimulation: a prospective, randomized, double-blind crossover trial)

Abstract

Introduction: Deep brain stimulation of the internal globus pallidus is an effective treatment for dystonia. However, there is a large variability in clinical outcome with up to 25% non-responders even in highly selected primary dystonia patients. In a large cohort of patients we recently demonstrated that the variable clinical outcomes of pallidal DBS for dystonia may result to a large degree by the exact location and stimulation volume within the pallidal region. Here we test a novel approach of programing based on these insights: we first defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated of > 80 patients collected in a multicentre effort. We subsequently modified the algorithms to be able to test all possible stimulation settings of de novo patients in silico based on the expected clinical outcome and thus potentially predict the best possible stimulation parameters for the individual patients.

Methods: Within the framework of a BMBF-funded study, this concept of a computer-based prediction of optimal stimulation parameters for patients with dystonia will be tested in a randomized, controlled crossover study. The main parameter for clinical efficacy and primary endpoint is based on the blinded physician rating of dystonia severity reflected by Clinical Dystonia Rating Scales for both interventions (best clinical settings and model predicted settings) after 4 weeks of continuous stimulation. The primary endpoint is defined as "successful treatment with model predicted settings" (yes or no). The value is "yes" if the motor symptoms with model predicted settings are equal or better (tolerance 5% of absolute difference in percentages) to clinical settings. Secondary endpoints will include measures of quality of life, calculated energy consumption of the neurostimulation system and physician time for programming.

Perspective: We envision, that computer-guided deep brain stimulation programming in silico might provide optimal stimulation settings for patients with dystonia without the burden of months of programming sessions. The study protocol is designed to evaluate which programming method is more effective in controlling motor symptom severity and improving quality of life in dystonia (best clinical settings and model predicted settings). Trial registration Registered with ClinicalTrials.gov on Oct 27, 2021 (NCT05097001).

Keywords: Deep brain stimulation; Dystonia; Imaging-guided DBS programming.

Conflict of interest statement

FL, MMR and JV have received commercial funding prior to this study. The remaining authors declare that any research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors declare that this study has not received any industrial funding.

© 2021. The Author(s).

Figures

Fig. 1

provides an overview of the course of study. Patients first undergo baseline visit and programming visit, then are randomized and blinded to two arms and receive either the computer-generated or the clinically generated program for 4 weeks. In the first motor visit, the patients are examined and then—still blinded—receive the other program for four weeks. Subsequently, in the second motor visit, the program is evaluated and the patients end the study with the choice of the better program

Fig. 2

gives an overview of the examinations per visit. The visits are represented as a row below each other, the respective examinations as marked columns on the right-hand side