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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.
Lancet Neurol. 2015 Jul; 14(7):693-701.LN

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.

FINDINGS

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.

INTERPRETATION

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.

FUNDING

Boston Scientific.

Authors+Show Affiliations

Department of Neurology, University Hospital Cologne, Cologne, Germany. Electronic address: lars.timmermann@uk-koeln.de.Boston Scientific, Neuromodulation, Valencia, CA, USA.Boston Scientific, Neuromodulation, Valencia, CA, USA.Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.Department of Neurology, University Hospital Cologne, Cologne, Germany.Neurological Rehabilitation Center, Godeshoehe, Germany.Wilhelminenspital, Vienna, Austria.Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.Wilhelminenspital, Vienna, Austria.Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.Servicio de Neurocirugía, Instituto de Neurociencias, Hospital Universitario Central de Asturias, Oviedo, Spain.Centre Hospitalier Universitait du Rennes, Service de Neurochirurgie, Rennes, France.Service de Neurologie, Hôpital Pontchaillou, Rennes, France.Department of Functional Neurosurgery, IRCCS Galeazzi Hospital, Milan, Italy.Department of Functional Neurosurgery, IRCCS Galeazzi Hospital, Milan, Italy.Department of Neurosurgery, Southmead Hospital, Bristol, UK.Department of Neurology, Southmead Hospital, Bristol, UK.Boston Scientific, Neuromodulation, Maastricht, Netherlands.Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26027940

Citation

Timmermann, Lars, et al. "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." The Lancet. Neurology, vol. 14, no. 7, 2015, pp. 693-701.
Timmermann L, Jain R, Chen L, et al. 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. Lancet Neurol. 2015;14(7):693-701.
Timmermann, L., Jain, R., Chen, L., Maarouf, M., Barbe, M. T., Allert, N., Brücke, T., Kaiser, I., Beirer, S., Sejio, F., Suarez, E., Lozano, B., Haegelen, C., Vérin, M., Porta, M., Servello, D., Gill, S., Whone, A., Van Dyck, N., & Alesch, F. (2015). 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. The Lancet. Neurology, 14(7), 693-701. https://doi.org/10.1016/S1474-4422(15)00087-3
Timmermann L, et al. 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. Lancet Neurol. 2015;14(7):693-701. PubMed PMID: 26027940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Timmermann,Lars, AU - Jain,Roshini, AU - Chen,Lilly, AU - Maarouf,Mohamed, AU - Barbe,Michael T, AU - Allert,Niels, AU - Brücke,Thomas, AU - Kaiser,Iris, AU - Beirer,Sebastian, AU - Sejio,Fernando, AU - Suarez,Esther, AU - Lozano,Beatriz, AU - Haegelen,Claire, AU - Vérin,Marc, AU - Porta,Mauro, AU - Servello,Domenico, AU - Gill,Steven, AU - Whone,Alan, AU - Van Dyck,Nic, AU - Alesch,Francois, Y1 - 2015/05/28/ PY - 2014/11/04/received PY - 2015/04/14/revised PY - 2015/05/08/accepted PY - 2015/6/2/entrez PY - 2015/6/2/pubmed PY - 2015/8/27/medline SP - 693 EP - 701 JF - The Lancet. Neurology JO - Lancet Neurol VL - 14 IS - 7 N2 - 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Boston Scientific. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/26027940/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(15)00087-3 DB - PRIME DP - Unbound Medicine ER -