Article Text

Download PDFPDF
Original research
A prospective, controlled study of non-motor effects of subthalamic stimulation in Parkinson’s disease: results at the 36-month follow-up
  1. Stefanie Theresa Jost1,
  2. Anna Sauerbier1,2,
  3. Veerle Visser-Vandewalle3,
  4. Keyoumars Ashkan2,
  5. Monty Silverdale4,
  6. Julian Evans4,
  7. Philipp A Loehrer5,
  8. Alexandra Rizos2,
  9. Jan Niklas Petry-Schmelzer1,
  10. Paul Reker1,
  11. Gereon Rudolf Fink1,
  12. Jeremy Franklin6,
  13. Michael Samuel2,
  14. Alfons Schnitzler7,
  15. Michael Thomas Barbe1,
  16. Angelo Antonini8,9,
  17. Pablo Martinez-Martin10,
  18. Lars Timmermann5,
  19. K Ray-Chaudhuri2,11,
  20. Haidar S Dafsari1
  21. On behalf of EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group
  1. 1 Department of Neurology, University Hospital Cologne, Cologne, Germany
  2. 2 Parkinson Foundation International Centre of Excellence, King's College Hospital, London, UK
  3. 3 Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany
  4. 4 Department of Neurology and Neurosurgery, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Greater Manchester, UK
  5. 5 Department of Neurology, University Hospital of Giessen and Marburg, Campus Marburg, Marburg, Hessen, Germany
  6. 6 Institute of Medical Statistics and Computational Biology (IMSB), University of Cologne, Köln, Nordrhein-Westfalen, Germany
  7. 7 Department of Neurology, Center for Movement Disorders and Neuromodulation, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
  8. 8 Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy
  9. 9 University of Padua, Padova, Veneto, Italy
  10. 10 Center for Networked Biomedical Research on Neurodegenerative Diseases, Madrid, Spain
  11. 11 Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
  1. Correspondence to Dr Haidar S Dafsari, Department of Neurology, University Hospital Cologne, Cologne 50937, Germany; haidar.salimi-dafsari{at}


Objective To examine 36-month effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS) compared with standard-of-care medical treatment (MED) in Parkinson’s disease (PD).

Methods Here we report the 36-month follow-up of a prospective, observational, controlled, international multicentre study of the NILS cohort. Assessments included NMSScale (NMSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). Propensity score matching resulted in a pseudo-randomised sub-cohort balancing baseline demographic and clinical characteristics between the STN-DBS and MED groups. Within-group longitudinal outcome changes were analysed using Wilcoxon signed-rank and between-group differences of change scores with Mann-Whitney U test. Strength of clinical responses was quantified with Cohen’s effect size. In addition, bivariate correlations of change scores were explored.

Results Propensity score matching applied on the cohort of 151 patients (STN-DBS n=67, MED n=84) resulted in a well-balanced sub-cohort including 38 patients per group. After 36 months, STN-DBS significantly improved NMSS, PDQ-8, SCOPA-motor examination and -complications and reduced LEDD. Significant between-group differences, all favouring STN-DBS, were found for NMSS, SCOPA-motor complications, LEDD (large effects), motor examination and PDQ-8 (moderate effects). Furthermore, significant differences were found for the sleep/fatigue, urinary (large effects) and miscellaneous NMSS domains (moderate effects). NMSS total and PDQ-8 change scores correlated significantly.

Conclusions This study provides Class IIb evidence for beneficial effects of STN-DBS on NMS at 36-month follow-up which also correlated with quality of life improvements. This highlights the importance of NMS for DBS outcomes assessments.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors STJ: data analysis, drafting of the manuscript and figures; ASa, MSi, PAL, AR, JNP-S, PR, GRF, MTB and AA: data acquisition, critical revision of the manuscript; VV-V, KA and JE: surgical intervention, critical revision of the manuscript; JF, MSa and ASc: critical revision of the manuscript; PM-M, LT, KR-C and HSD: study concept and design, data acquisition, critical revision of the manuscript.

  • Funding This paper is independent research funded by the German Research Foundation (Grant KFO 219).

  • Competing interests STJ has received a travel grant from the German Academic Exchange Service. ASa reports no financial disclosures. VV-V is a member of the advisory boards and reports consultancies for Medtronic, Boston Scientific and St. Jude Medical. She received a grant from SAPIENS Steering Brain Stimulation. KA has received honoraria for educational meetings, travel and consultancy from Medtronic, St. Jude Medical and Boston Scientific. MSi has received honoraria from Bial, Britannia and Medtronic. JE reports no financial disclosures. PAL was funded by the Konrad-Adenauer-Foundation and the Koeln-Fortune Program. He reports travel grants from AbbVie. AR has received honorarium from UCB and was supported by a grant from Medtronic. JNP-S has received travel grants from Boston Scientific. PR has received a travel grant from AbbVie. GRF reports no financial disclosures. JF reports no financial disclosures. MSa has received honoraria for educational meetings/travel/accommodation from Medtronic, St. Jude Medical and UCB, grants from Parkinson's UK and Ipsen, and has acted as a consultant for Medtronic and St. Jude Medical. ASc reports personal consultancy and lecture fees from Medtronic Inc, Abbott and Boston Scientific, lecture fees from UCB, Teva Pharma, Bial and Zambon, and through his institution funding for his research from the German Research Council, the German Federal Ministry of Education and Health. MTB reports grants from Boston Scientific and Medtronic. AA reports personal consultancy fees from Zambon, AbbVie, Boehringer Ingelheim, GE, Neuroderm, Biogen, Bial, EVER Neuro Pharma, Therevance, Vectura grants from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020 - PD_Pal Grant 825785, Ministry of Education University and Research (MIUR) Grant ARS01_01081, owns Patent WO2015110261-A1, owns shares from PD Neurotechnology Limited. PM-M has received honoraria from Editorial Viguera and Movement Disorder Society for lecturing in courses; from AbbVie for speaking in experts' meetings and from AbbVie and Zambon for participating in the advisory board of epidemiological studies. License fee payments for the King’s Parkinson’s Disease Pain Scale, and grants from the International Parkinson and Movement Disorder Society for development and validation of the MDS-Non-motor Symptom Scale. LT reports grants, personal fees and non-financial support from SAPIENS Steering Brain Stimulation, Medtronic, Boston Scientific and St. Jude Medical. KR-C has received funding from Parkinson's UK, National Institute of Health Research, UCB and the European Union; he received honoraria from UCB, Abbott, Britannia, US Worldmeds and Otsuka Pharmaceuticals, and acted as a consultant for AbbVie, UCB and Britannia. HSD work was funded by the Prof. Klaus Thiemann Foundation and the Felgenhauer Foundation and has received honoraria by Boston Scientific and Medtronic.

  • Patient consent for publication Not required.

  • Ethics approval Medical ethics committees of the participating centres approved the study protocol (master votes for Germany: Cologne, study number: 12-145, German Clinical Trials Register: DRKS00006735, and for the United Kingdom: National Research Ethics Service South East London REC 3, 10/H0808/141; National Institute of Health Research portfolio, number: 10084).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data included in this study are available on request to the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of the participants.