title: Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT): Study Protocol of a Randomized Controlled Feasibility Trial.
abstract: BACKGROUND
  Essential tremor is a movement disorder that can result in profound disability affecting the quality of life. Medically refractory essential tremor can be successfully reduced by deep brain stimulation (DBS) traditionally targeting the thalamic ventral intermediate nucleus (Vim). Although this structure can be identified with magnetic resonance (MR) imaging nowadays, Vim-DBS electrodes are still implanted in the awake patient with intraoperative tremor testing to achieve satisfactory tremor control. This can be attributed to the fact that the more effective target of DBS seems to be the stimulation of fiber tracts rather than subcortical nuclei like the Vim. There is evidence that current coverage of the dentatorubrothalamic tract (DRT) results in good tremor control in Vim-DBS. Diffusion tensor MR imaging (DTI) tractography-assisted stereotactic surgery targeting the DRT would therefore not rely on multiple trajectories and intraoperative tremor testing in the awake patient, bearing the potential of more patient comfort and reduced operation-related risks. This is the first randomized controlled trial comparing DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia with stereotactic surgery of thalamic/subthalamic region as conventionally used.
  
  
  OBJECTIVE
  This clinical pilot trial aims at demonstrating safety of DTI tractography-assisted stereotactic surgery in general anesthesia and proving its equality compared to conventional stereotactic surgery with intraoperative testing in the awake patient.
  
  
  METHODS
  The Deep Brain Stimulation for Tremor Tractographic Versus Traditional (DISTINCT) trial is a single-center investigator-initiated, randomized, controlled, observer-blinded trial. A total of 24 patients with medically refractory essential tremor will be randomized to either DTI tractography-assisted stereotactic surgery targeting the DRT in general anesthesia or stereotactic surgery of the thalamic/subthalamic region as conventionally used. The primary objective is to assess the tremor reduction, obtained by the Fahn-Tolosa-Marin Tremor Rating Scale in the 2 treatment groups. Secondary objectives include (among others) assessing the quality of life, optimal electrode contact positions, and safety of the intervention. The study protocol has been approved by the independent ethics committee of the University of Freiburg.
  
  
  RESULTS
  Recruitment to the DISTINCT trial opened in September 2015 and is expected to close in June 2017. At the time of manuscript submission the trial is open to recruitment.
  
  
  CONCLUSIONS
  The DISTINCT trial is the first to compare DTI tractography-assisted stereotactic surgery with target point of the DRT in general anesthesia to stereotactic surgery of the thalamic/subthalamic region as conventionally used. It can serve as a cornerstone for the evolving technique of DTI tractography-assisted stereotactic surgery.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02491554; https://clinicaltrials.gov/ct2/show/NCT02491554 (Archived by WebCite at http://www.webcitation.org/6mezLnB9D). German Clinical Trials Register DRKS00008913; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00008913 (Archived by WebCite at http://www.webcitation.org/6mezCtxhS).
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Bastian Elmar Alexander
authors.identifier: http://orcid.org/0000-0002-2836-0046
authors.initials: BE
authors.lastname: Sajonz
authors.affiliation: Department of Neurology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.identifier: http://orcid.org/0000-0002-5064-9882
authors.initials: F
authors.lastname: Amtage
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Peter Christoph
authors.identifier: http://orcid.org/0000-0003-1691-546X
authors.initials: PC
authors.lastname: Reinacher
authors.affiliation: Clinical Trials Unit Freiburg, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Carolin
authors.identifier: http://orcid.org/0000-0002-8478-0045
authors.initials: C
authors.lastname: Jenkner
authors.affiliation: Department of Neurology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Tobias
authors.identifier: http://orcid.org/0000-0001-5334-4710
authors.initials: T
authors.lastname: Piroth
authors.affiliation: Clinical Trials Unit Freiburg, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.identifier: http://orcid.org/0000-0003-3360-7813
authors.initials: J
authors.lastname: Kätzler
authors.affiliation: Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Horst
authors.identifier: http://orcid.org/0000-0001-7264-4807
authors.initials: H
authors.lastname: Urbach
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Volker Arnd
authors.identifier: http://orcid.org/0000-0002-1703-6283
authors.initials: VA
authors.lastname: Coenen
keywords: deep brain stimulation; essential tremor; magnetic resonance tractographic-assisted implantation