Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial.

Autor:	Lhommée E; Movement Disorder Unit, Neurology Department, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, University Grenoble Alpes, Grenoble Institut des Neurosciences (GIN), and Institut National de Santé et en Recherche Médicale (INSERM) U1216, Grenoble, France., Wojtecki L; Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Czernecki V; Sorbonne University, Pierre and Marie Curie University Paris 6, Paris, France; Brain and Spine Institute, Paris, France; Neurology Department, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris (APHP), INSERM, Institut du Cerveau et de la Moelle Epinière, and Centre d'Investigation Clinique (CIC) 1422, Paris, France., Witt K; Department of Neurology, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany., Maier F; Department of Neurology, University of Cologne, Cologne, Germany., Tonder L; Medtronic, Minneapolis, MN, USA., Timmermann L; Department of Neurology, University of Cologne, Cologne, Germany; Department of Neurology, Philipps University of Marburg, Marburg, Germany., Hälbig TD; NeuroCure Clinical Research Center (NCRC), Charité University Medical Center, Charité (Campus Mitte), Berlin, Germany., Pineau F; Sorbonne University, Pierre and Marie Curie University Paris 6, Paris, France; Brain and Spine Institute, Paris, France; Neurology Department, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris (APHP), INSERM, Institut du Cerveau et de la Moelle Epinière, and Centre d'Investigation Clinique (CIC) 1422, Paris, France., Durif F; Service de Neurologie, CHU Clermont-Ferrand, Université Clermont Auvergne, Clermont-Ferrand, France., Witjas T; Neurology, Assistance Publique Hôpitaux de Marseille, Marseille, France., Pinsker M; Department of Neurosurgery, University Hospital, Freiburg, Germany., Mehdorn M; Department of Neurosurgery, Universitätsklinikum Schlsewig-Holstein, Kiel, Germany., Sixel-Döring F; Department of Neurology, Philipps University of Marburg, Marburg, Germany; Paracelsus-Elena-Klinik, Kassel, Germany., Kupsch A; Department of Neurology and Stereotactic Neurosurgery, University of Magdeburg, and Neurology Moves, Medical Center Bismarck Karrée, Berlin, Germany., Krüger R; Center of Neurology, and Hertie Institute for Clinical Brain Research, University Hospital, Tübingen, Germany; Luxembourg Centre for Systems Biology, University of Luxembourg, Luxembourg City, Luxembourg; Department of Neurology, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg., Elben S; Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Chabardès S; Department of Neurosurgery, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, University Grenoble Alpes, Grenoble Institut des Neurosciences (GIN), and Institut National de Santé et en Recherche Médicale (INSERM) U1216, Grenoble, France., Thobois S; Movement Disorder Unit, Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France; Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Cognitives, Centre de Neurosciences Cognitives, Bron, France; Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France., Brefel-Courbon C; Neurology Department and Centre Expert Parkinson, University Hospital Toulouse, Toulouse France; INSERM Toulouse NeuroImaging Centre, Toulouse France., Ory-Magne F; Neurology Department and Centre Expert Parkinson, University Hospital Toulouse, Toulouse France; INSERM Toulouse NeuroImaging Centre, Toulouse France., Regis JM; Department of Functional Neurosurgery, Assistance Publique Hôpitaux de Marseille, Aix-Marseille University, Marseille, France., Maltête D; Department of Neurology, Rouen University Hospital, INSERM U1073, Rouen Faculty of Medicine, Rouen, France., Sauvaget A; Addictology and Liaison-Psychiatry Department, CIC 0004, CHU de Nantes, Hôtel Dieu, Nantes, France., Rau J; Coordinating Centre for Clinical Trials of the Philipps-University of Marburg, Marburg, Germany., Schnitzler A; Department of Neurology and Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Schüpbach M; Neurology Department, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris (APHP), INSERM, Institut du Cerveau et de la Moelle Epinière, and Centre d'Investigation Clinique (CIC) 1422, Paris, France; Department of Neurology, University Hospital Bern, Bern, Switzerland; University of Bern, Bern, Switzerland., Schade-Brittinger C; Coordinating Centre for Clinical Trials of the Philipps-University of Marburg, Marburg, Germany., Deuschl G; Department of Neurology, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany., Houeto JL; Department of Neurology, CIC-INSERM 1402, CHU de Poitiers; Université de Poitiers, Poitiers, France., Krack P; Movement Disorder Unit, Neurology Department, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, University Grenoble Alpes, Grenoble Institut des Neurosciences (GIN), and Institut National de Santé et en Recherche Médicale (INSERM) U1216, Grenoble, France; Department of Clinical Neurosciences (Neurology), Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Paul.krack@hcuge.ch.
Jazyk:	angličtina
Zdroj:	The Lancet. Neurology [Lancet Neurol] 2018 Mar; Vol. 17 (3), pp. 223-231.
DOI:	10.1016/S1474-4422(18)30035-8
Abstrakt:	Background: Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. Methods: We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Findings: Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p<0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p<0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. Interpretation: In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications. Funding: German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic. (Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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