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Research paper
Subthalamic stimulation and neuropsychiatric symptoms in Parkinson’s disease: results from a long-term follow-up cohort study
  1. Marie Abbes1,
  2. Eugénie Lhommée1,2,3,
  3. Stéphane Thobois4,5,6,
  4. Hélène Klinger4,5,6,
  5. Emmanuelle Schmitt1,2,3,
  6. Amélie Bichon1,2,3,
  7. Anna Castrioto1,2,3,
  8. Jing Xie7,
  9. Valérie Fraix1,2,3,
  10. Andrea Kistner1,2,3,
  11. Pierre Pélissier1,2,3,
  12. Éric Seigneuret8,
  13. Stéphan Chabardès2,3,8,
  14. Patrick Mertens9,
  15. Emmanuel Broussolle4,5,6,
  16. Elena Moro1,2,3,
  17. Paul Krack1,2,3,10
  1. 1Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation, CHU Grenoble Alpes, Grenoble, France
  2. 2Grenoble Institut des Neurosciences, Université Grenoble Alpes, Grenoble, France
  3. 3Inserm U1216, Grenoble, France
  4. 4Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Université de Lyon 1, Université de Lyon, Lyon, France
  5. 5Neurologie C, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France
  6. 6Centre de Neurosciences Cognitives, CNRS, UMR 5229, Bron, France
  7. 7Institut du vieillissement, Hospices Civils de Lyon, Hôpital des Charpennes, Lyon, France
  8. 8Department of Neurosurgery, CHU Grenoble Alpes, Grenoble, France
  9. 9Neurochirurgie A, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France
  10. 10Department of Clinical Neuroscience, Faculty University of Geneva, Hôpitaux Universitaires de Genève, Geneva, Switzerland
  1. Correspondence to Professor Paul Krack, Neurology Division, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva 1205, Switzerland; Paul.Krack{at}


Background Reports on behavioural outcomes after subthalamic nucleus deep brain stimulation in Parkinson’s disease are controversial and limited to short-term data. Long-term observation in a large cohort allows a better counselling and management.

Methods To determine whether a long-term treatment with subthalamic stimulation induces or reduces impulse control behaviours, neuropsychiatric fluctuations and apathy, 69 patients treated with subthalamic stimulation are prospectively and retrospectively assessed using Ardouin Scale of Behavior in Parkinson’s Disease before and after 3–10 years of stimulation.

Results At a mean follow-up of 6 years, all impulse control disorders and dopaminergic addiction were significantly decreased, apart from eating behaviour and hypersexuality. Neuropsychiatric fluctuations also significantly improved (ON euphoria: 38% of the patients before surgery and 1% after surgery, P<0.01; OFF dysphoria: 39% of the patients before surgery and 10% after surgery, P<0.01). However, apathy increased (25% of the patients after surgery and 3% before, P<0.01). With the retrospective analysis, several transient episodes of depression, apathy, anxiety and impulse control disorders occurred.

Conclusions Bilateral subthalamic nucleus stimulation was overall very effective in improving impulse control disorders and neuropsychiatric fluctuations in parkinsonian patients in the long term despite a counteracting frequent apathy. Transient episodes of impulse control disorders still occurred within the follow-up. These findings recommend a close follow-up in parkinsonian patients presenting with neuropsychiatric symptoms before deep brain stimulation surgery.

Clinical trial registration NCT01705418;Post-results.

  • apathy
  • dopamine
  • impulse control disorder
  • Parkinson’s disease
  • subthalamic nucleus

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  • MA and EL contributed equally.

  • Contributors Research project: (A) Conception: EL, PK. (B) Organisation: AK, PP. (C) Execution: MA, EL, ST, HK, ESchmitt, AB, JX, VF, AK, ÉSeigneuret, SC, PM, EB, PK. Statistical analysis: (A) Design: EL, PK. (B) Execution: MA. (C) Review and critique: EL, ST, HK, ESchmitt, AB, AC, JX, VF, AK, PP, ÉSeigneuret, SC, PM, EB, EM, PK. Manuscript preparation: (A) Writing of the first draft: MA, EL. (B) Review and critique: MA, ST, HK, ESchmitt, AB, AC, JX, VF, AK, PP, ÉSeigneuret, SC, PM, EB, EM, PK. Final approval of the version published: MA, EL, ST, HK, ESchmitt, AB, AC, JX, VF, AK, PP, ÉSeigneuret, SC, PM, EB, EM, PK. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: MA, EL, ST, HK, ESchmitt, AB, AC, JX, VF, AK, PP, ÉSeigneuret, SC, PM, EB, EM, PK.

  • Funding This research received funding from the Programme Hospitalier de Recherche Clinique Interrégional and Servier Pharmaceutical company NCT01705418.

  • Competing interests ST has received grant from Fondation pour la Recherche Médicale, France Parkinson, and ANR; honoraria, travel grant from Boston, Medtronic, Teva, UCB, AbbVie and Aguettant. AC has received granted funds from Edmond J & Lily Safra Foundation; reimbursement of travel expenses to scientific meetings from Orkyn, Elivie, AbbVie, Medtronic and Boston Scientific. VF has received travel grants from Zambon and AbbVie (World PD congress and MD congress); honoraria from UCB, Medtronic for lecturing; honoraria from AbbVie for participation in scientific committee. JX recieved honoraria and travel grant from Teva, UCB and Aguettant. EL received travel grant from Medtronic. EB reports financial support during the past year outside the submitted work from AbbVie (travel expenses, congress registration, consultant), Medtronic (technical support in our hospital for improving DBS therapy and care of patients with movement disorders), Aguettant (consultant and research project) and public financial support from Agence Régionale de Santé Auvergne et Rhône-Alpes (research project on Parkinson’s disease). HK received reimbursement of registration fees and travel expenses to participate in training session from Medtronic. SC received consultancy fees from Medtronic and Boston Scientific and travel reimbursement from Medtronic and Boston Scientific. ES received travel and congress fees from Medtronic, St Jude and Boston Scientific. PK reports grants from the French Ministry of Health (PHRC Programme de Recherche Hospitalier Clinique Interrégional), and Euthérapie during the conduct of the study; grants and personal fees from Medtronic, Boston Scientific, Movement Disorder Society, UCB; grants from St Jude Medical France, Edmond J & Lily Safra Foundation, INSERM (French National Institute of Health and Research in Medicine), France Parkinson, Swiss National Science Foundation, ROGER DE SPOELBERCH Foundation, Centre National Recherche Scientifique, Orkyn, Homeperf; personal fees from European Society Stereotactic Functional Neurosurgery, outside the submitted work. PM received consultancy fees from Medtronic and congress fees and travel reimbursements from Medtronic and St Jude companies. EM has received honoraria from Medtronic for lecturing and scientific board services. She has also received grant support from Merz.

  • Patient consent Obtained. However, detail has been removed from two of the case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The Ethics Committee of the Grenoble University Hospital approved the study.

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

  • Data sharing statement The data belong to the Grenoble University Hospital.