title: Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.
abstract: BACKGROUND
  High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease.
  
  
  METHODS
  We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948.
  
  
  RESULTS
  Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study.
  
  
  CONCLUSIONS
  The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinson's disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects.
  
  
  BACKGROUND
  Boston Scientific.
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany. Electronic address: lars.timmermann@uk-koeln.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Timmermann
authors.affiliation: Boston Scientific, Neuromodulation, Valencia, CA, USA.
authors.forename: Roshini
authors.initials: R
authors.lastname: Jain
authors.affiliation: Boston Scientific, Neuromodulation, Valencia, CA, USA.
authors.forename: Lilly
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Maarouf
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Barbe
authors.affiliation: Neurological Rehabilitation Center, Godeshoehe, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Allert
authors.affiliation: Wilhelminenspital, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brücke
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Iris
authors.initials: I
authors.lastname: Kaiser
authors.affiliation: Wilhelminenspital, Vienna, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beirer
authors.affiliation: Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sejio
authors.affiliation: Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Suarez
authors.affiliation: Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lozano
authors.affiliation: Centre Hospitalier Universitait du Rennes, Service de Neurochirurgie, Rennes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Haegelen
authors.affiliation: Service de Neurologie, Hôpital Pontchaillou, Rennes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Vérin
authors.affiliation: Department of Functional Neurosurgery, IRCCS Galeazzi Hospital, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Porta
authors.affiliation: Department of Functional Neurosurgery, IRCCS Galeazzi Hospital, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Servello
authors.affiliation: Department of Neurosurgery, Southmead Hospital, Bristol, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Gill
authors.affiliation: Department of Neurology, Southmead Hospital, Bristol, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Whone
authors.affiliation: Boston Scientific, Neuromodulation, Maastricht, Netherlands.
authors.forename: Nic
authors.initials: N
authors.lastname: Van Dyck
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Francois
authors.initials: F
authors.lastname: Alesch
mesh_terms: D000328:Adult; D000368:Aged; D046690:Deep Brain Stimulation / Q000295:instrumentation* / Q000379:methods*; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000628:therapy*; D011446:Prospective Studies; D020531:Subthalamic Nucleus / Q000502:physiology*; D016896:Treatment Outcome