title: Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial.
abstract: BACKGROUND
  Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment.
  
  
  METHODS
  In this randomised, sham-controlled trial, we recruited patients with cervical dystonia from centres in Germany, Norway, and Austria. Eligible patients (ie, those aged 18-75 years, disease duration ≥3 years, Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score ≥15 points) were randomly assigned (1:1) to receive active neurostimulation (frequency 180 Hz; pulse width 120 μs; amplitude 0·5 V below adverse event threshold) or sham stimulation (amplitude 0 V) by computer-generated randomisation lists with randomly permuted block lengths stratified by centre. All patients, masked to treatment assignment, were implanted with a deep brain stimulation device and received their assigned treatment for 3 months. Neurostimulation was activated in the sham group at 3 months and outcomes were reassessed in all patients after 6 months of active treatment. Treating physicians were not masked. The primary endpoint was the change in the TWSTRS severity score from baseline to 3 months, assessed by two masked dystonia experts using standardised videos, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148889.
  
  
  RESULTS
  Between Jan 19, 2006, and May 29, 2008, we recruited 62 patients, of whom 32 were randomly assigned to neurostimulation and 30 to sham stimulation. Outcome data were recorded in 60 (97%) patients at 3 months and 56 (90%) patients at 6 months. At 3 months, the reduction in dystonia severity was significantly greater with neurostimulation (-5·1 points [SD 5·1], 95% CI -7·0 to -3·5) than with sham stimulation (-1·3 [2·4], -2·2 to -0·4, p=0·0024; mean between-group difference 3·8 points, 1·8 to 5·8) in the intention-to-treat population. Over the course of the study, 21 adverse events (five serious) were reported in 11 (34%) of 32 patients in the neurostimulation group compared with 20 (11 serious) in nine (30%) of 30 patients in the sham-stimulation group. Serious adverse events were typically related to the implant procedure or the implanted device, and 11 of 16 resolved without sequelae. Dysarthria (in four patients assigned to neurostimulation vs three patients assigned to sham stimulation), involuntary movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression (one vs two) were the most common non-serious adverse events reported during the course of the study.
  
  
  CONCLUSIONS
  Pallidal neurostimulation for 3 months is more effective than sham stimulation at reducing symptoms of cervical dystonia. Extended follow-up is needed to ascertain the magnitude and stability of chronic neurostimulation effects before this treatment can be recommended as routine for patients who are not responding to conventional medical therapy.
  
  
  BACKGROUND
  Medtronic.
authors.affiliation: Department of Neurology, Christian Albrechts University, Kiel, Germany. Electronic address: volkmann_j@ukw.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Volkmann
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Joerg
authors.initials: J
authors.lastname: Mueller
authors.affiliation: Department of Neurology, Christian Albrechts University, Kiel, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Kühn
authors.affiliation: Department of Neurosurgery, Medical School Hannover, Hannover, Germany.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Timmermann
authors.affiliation: Department of Neurosurgery, Christian Albrechts University, Kiel, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Falk
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.affiliation: Department of Neurology, Charité Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kivi
authors.affiliation: Department of Neurosurgery, Charité Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany.
authors.forename: Gerd-Helge
authors.initials: GH
authors.lastname: Schneider
authors.affiliation: Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Schnitzler
authors.affiliation: Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Martin
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authors.lastname: Südmeyer
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany.
authors.forename: Jürgen
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authors.lastname: Voges
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wolters
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wittstock
authors.affiliation: Department of Neurosurgery, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Jan-Uwe
authors.initials: JU
authors.lastname: Müller
authors.affiliation: Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Sascha
authors.initials: S
authors.lastname: Hering
authors.affiliation: Department of Neurosurgery, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Eisner
authors.affiliation: Division of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Vesper
authors.affiliation: Division of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prokop
authors.affiliation: Department of Neurosurgery, Christian Albrechts University, Kiel, Germany; Division of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Pinsker
authors.affiliation: Department of Neurology, Medical School Hannover, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schrader
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Kloss
authors.affiliation: Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Kiening
authors.affiliation: Department of Neurology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Boetzel
authors.affiliation: Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Mehrkens
authors.affiliation: Department of Neurology, University of Oslo, Oslo, Norway.
authors.forename: Inger Marie
authors.initials: IM
authors.lastname: Skogseid
authors.affiliation: Department of Neurosurgery, University of Oslo, Oslo, Norway.
authors.forename: Jon
authors.initials: J
authors.lastname: Ramm-Pettersen
authors.affiliation: Section of Biostatistics, Department of Psychiatry, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Kemmler
authors.affiliation: Institute of Neurology, University College London, London, UK.
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jerrold L
authors.initials: JL
authors.lastname: Vitek
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Benecke
mesh_terms: D000368:Aged; D001317:Austria; D046690:Deep Brain Stimulation / Q000295:instrumentation / Q000379:methods*; D004185:Disability Evaluation; D005500:Follow-Up Studies; D005858:Germany; D005917:Globus Pallidus / Q000502:physiology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D010919:Placebos; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014103:Torticollis / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D010919:Placebos