Neurostimulation in tardive dystonia/dyskinesia: A delayed start, sham stimulation-controlled randomized trial

Doreen Gruber; Martin Südmeyer; Günther Deuschl; Daniela Falk; Joachim K Krauss; Joerg Mueller; Jan-Uwe Müller; Werner Poewe; Gerd-Helge Schneider; Christoph Schrader; Jan Vesper; Jens Volkmann; Christine Winter; Andreas Kupsch; Alfons Schnitzler; DBS study group for dystonia

doi:10.1016/j.brs.2018.08.006

Neurostimulation in tardive dystonia/dyskinesia: A delayed start, sham stimulation-controlled randomized trial

Brain Stimul. 2018 Nov-Dec;11(6):1368-1377. doi: 10.1016/j.brs.2018.08.006. Epub 2018 Sep 11.

Authors

Affiliations

¹ Departments of Neurology and Neurosurgery, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Movement Disorders Clinic, Beelitz-Heilstaetten, Germany; Department of Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Magdeburg, Germany.
² Department of Neurology and Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany.
³ Departments of Neurology and Neurosurgery, Christian-Albrechts-University, Kiel, Germany.
⁴ Departments of Neurology and Neurosurgery, Medical School Hannover, Hannover, Germany.
⁵ Department of Neurology, Vivantes Hospital Berlin-Spandau, Berlin, Germany.
⁶ Department of Neurosurgery, University of Greifswald, Greifswald, Germany.
⁷ Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
⁸ Departments of Neurology and Neurosurgery, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
⁹ Department of Neurology and Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany; Division of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany.
¹⁰ Departments of Neurology and Neurosurgery, Christian-Albrechts-University, Kiel, Germany; Department of Neurology, University of Wuerzburg, Wuerzburg, Germany.
¹¹ Departments of Neurology and Neurosurgery, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus MItte, Berlin, Germany.
¹² Departments of Neurology and Neurosurgery, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany; Department of Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Magdeburg, Germany; Neurology Moves, Movement Disorder Center Berlin, Germany. Electronic address: kupsch@neurologie-bewegt.de.

PMID: 30249417
DOI: 10.1016/j.brs.2018.08.006

Abstract

Introduction: Growing evidence suggests that pallidal deep brain stimulation represents a potential new therapeutic avenue in tardive dystonia/dyskinesia, but controlled and blinded randomized studies (RCT) are missing. The present RCT compares dystonia/dyskinesia severity of pallidal neurostimulation in patients with tardive dystonia using a delayed-start design paradigm.

Methods: Dystonia/dyskinesia severity was assessed via blinded videos following pallidal neurostimulation at 3 (blinded phase) and 6 months (open extension phase). Primary endpoint was the percentage change of dystonia severity (Burke-Fahn-Marsden-Dystonia-Rating-Scale, BFMDRS) at 3 months between active vs. sham neurostimulation using blinded-video assessment. Secondary endpoints comprised clinical rating scores for movement disorders. Clinicaltrials.gov NCT00331669.

Results: Twenty-five patients were randomized (1:1) to active (n = 12) or sham neurostimulation (n = 13). In the intention-to-treat analyses the between group difference of dystonia severity (BFMDRS) between active vs. sham stimulation was not significant at 3 months. Three months post-randomisation dystonia severity improved significantly within the neurostimulation by 22.8% and non-significantly within the sham group (12.0%) compared to their respective baseline severity. During the open-label extension with both groups being actively treated, significant and pronounced improvements of 41.5% were observed via blinded evaluation. Adverse events (n = 10) occurred in 10/25 of patients during the 6 months, mostly related to surgical implantation of the device; all resolved without sequelae.

Conclusion: The primary endpoint of this randomized trial was not significant, most likely due to incomplete recruitment. However, pronounced improvements of most secondary endpoints at 3 and 6 months provide evidence for efficacy and safety of pallidal neurostimulation in tardive dystonia.

Keywords: Deep brain stimulation; Generalized and segmental dystonia; Globus pallidus; Neurostimulation; Stereotactic surgery; Tardive dystonia.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Deep Brain Stimulation / instrumentation
Deep Brain Stimulation / methods*
Dystonia / diagnosis
Dystonia / physiopathology
Dystonia / therapy*
Female
Globus Pallidus / physiology
Humans
Implantable Neurostimulators*
Male
Middle Aged
Single-Blind Method
Tardive Dyskinesia / diagnosis
Tardive Dyskinesia / physiopathology
Tardive Dyskinesia / therapy*
Time Factors
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT00331669