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1. Axial impairment and falls in Parkinson’s disease: 15 years of subthalamic deep brain stimulation

Author

Alessandro Zampogna, Francesco Cavallieri, Francesco Bove, Antonio Suppa, Anna Castrioto, Sara Meoni, Pierre Pélissier, Emmanuelle Schmitt, Amélie Bichon, Eugénie Lhommée, Andrea Kistner, Stephan Chabardès, Eric Seigneuret, Valerie Fraix, and Elena Moro

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract In this retrospective study, we longitudinally analyzed axial impairment and falls in people with Parkinson’s disease (PD) and subthalamic nucleus deep brain stimulation (STN-DBS). Axial scores and falling frequency were examined at baseline, and 1, 10, and 15 years after surgery. Preoperative demographic and clinical data, including PD duration and severity, phenotype, motor and cognitive scales, medications, and vascular changes on neuroimaging were examined as possible risk factors through Kaplan–Meier and Cox regression analyses. Of 302 individuals examined before and at 1 year after surgery, 102 and 57 were available also at 10 and 15 years of follow-up, respectively. Axial scores were similar at baseline and at 1 year but worsened at 10 and 15 years. The prevalence rate of frequent fallers progressively increased from baseline to 15 years. Preoperative axial scores, frontal dysfunction and age at PD onset were risk factors for axial impairment progression after surgery. Axial scores, akinetic/rigid phenotype, age at disease onset and disease duration at surgery predicted frequent falls. Overall, axial signs progressively worsened over the long-term period following STN-DBS, likely related to the progression of PD, especially in a subgroup of subjects with specific risk factors.

Published
2022
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2. Does Motor Symptoms Asymmetry Predict Motor Outcome of Subthalamic Deep Brain Stimulation in Parkinson's Disease Patients?

Author

Francesco Bove, Francesco Cavallieri, Anna Castrioto, Sara Meoni, Emmanuelle Schmitt, Amélie Bichon, Eugénie Lhommée, Pierre Pélissier, Andrea Kistner, Eric Chevrier, Eric Seigneuret, Stephan Chabardès, Franco Valzania, Valerie Fraix, and Elena Moro

Subjects
deep brain stimulation, motor asymmetry, motor outcome, Parkinson's disease, predictors, subthalamic nucleus, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

BackgroundIn Parkinson's disease (PD), the side of motor symptoms onset may influence disease progression, with a faster motor symptom progression in patients with left side lateralization. Moreover, worse neuropsychological outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) have been described in patients with predominantly left-sided motor symptoms. The objective of this study was to evaluate if the body side of motor symptoms onset may predict motor outcome of bilateral STN-DBS.MethodsThis retrospective study included all consecutive PD patients treated with bilateral STN-DBS at Grenoble University Hospital from 1993 to 2015. Demographic, clinical and neuroimaging data were collected before (baseline condition) and 1 year after surgery (follow-up condition). The predictive factors of motor outcome at one-year follow-up, measured by the percentage change in the MDS-UPDRS-III score, were evaluated through univariate and multivariate linear regression analysis.ResultsA total of 233 patients were included with one-year follow-up after surgery [143 males (61.40%); 121 (51.90 %) right body onset; 112 (48.10%) left body onset; mean age at surgery, 55.31 ± 8.44 years; mean disease duration, 11.61 ± 3.87]. Multivariate linear regression analysis showed that the left side of motor symptoms onset did not predict motor outcome (β = 0.093, 95% CI = −1.967 to 11.497, p = 0.164).ConclusionsIn this retrospective study, the body side of motor symptoms onset did not significantly influence the one-year motor outcome in a large cohort of PD patients treated with bilateral STN-DBS.

Published
2022
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3. Deep brain stimulation of the subthalamic nucleus in obsessive-compulsives disorders: long-term follow-up of an open, prospective, observational cohort

Author

Thierry Bougerol, Jérôme Yelnik, Luc Mallet, Alim-Louis Benabid, Sara Fernandez Vidal, Olivier David, Stephan Chabardes, Paul Krack, Mircea Polosan, Brigitte Piallat, Eric Seigneuret, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Bern University Hospital [Berne] (Inselspital), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, University of Geneva [Switzerland], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], and Université de Genève = University of Geneva (UNIGE)

Subjects
Male, Obsessive-Compulsive Disorder, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Deep Brain Stimulation, Anxiety, Severity of Illness Index, Cohort Studies, ddc:616.89, 0302 clinical medicine, Quality of life, Basal ganglia, Prospective Studies, Prospective cohort study, 0303 health sciences, Anxiety/etiology, Middle Aged, 3. Good health, Psychiatry and Mental health, Subthalamic nucleus, Mania, Treatment Outcome, Cohort, Female, Cohort study, Adult, medicine.medical_specialty, Deep brain stimulation, Neurosurgery, 610 Medicine & health, Deep Brain Stimulation/adverse effects, behavioral disciplines and activities, 03 medical and health sciences, Subthalamic Nucleus, Internal medicine, Deep Brain Stimulation/methods, Severity of illness, mental disorders, medicine, Humans, 030304 developmental biology, business.industry, Mania/etiology, nervous system, Obsessive-Compulsive Disorder/therapy, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

BackgroundObsessive–compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD.MethodWe analysed, in a prospective, observational, monocentric, open label cohort, the effect of chronic non-motor STN-DBS in 19 patients with treatment-resistant OCD consecutively operated in a single centre. Severity of OCD was evaluated using the Yale and Brown Obsessive–Compulsive Scale (YBOCS). YBOCS scores at 6, 12 and 24 months postoperatively were compared with baseline. Responders were defined by >35% improvement of YBOCS scores. Global Assessment Functioning (GAF) scale was used to evaluate the impact of improvement.ResultsAt a 24-month follow-up, the mean YBOCS score improved by 53.4% from 33.3±3.5 to 15.8±9.1 (95% CI 11.2–20.4; pConclusionChronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management.

Published
2020
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4. Asymmetric STN DBS for FOG in Parkinson's disease: A pilot trial

Author

Sara Meoni, Anna Castrioto, Elena Moro, Eric Seigneuret, Bettina Debȗ, Pierre Pelissier, Stephan Chabardes, Valérie Fraix, Emma Scelzo, Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Male, 0301 basic medicine, Parkinson's disease, Deep brain stimulation, genetic structures, Deep Brain Stimulation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pilot Projects, Stimulation, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Refractory, Subthalamic Nucleus, medicine, Humans, Gait Disorders, Neurologic, Aged, Cross-Over Studies, business.industry, Parkinson Disease, Middle Aged, medicine.disease, Gait, Clinical trial, Subthalamic nucleus, Treatment Outcome, surgical procedures, operative, 030104 developmental biology, Neurology, Gait analysis, Anesthesia, Female, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract

Background In Parkinson's disease (PD), freezing of gait (FOG) is a highly disabling gait disorder. Though deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment for advanced PD, the management of STN DBS refractory FOG remains challenging. Objective To evaluate the long-term impact on FOG of unilateral stimulation reduction in PD treated with bilateral STN DBS. Methods Patients with bilateral STN DBS for at least one year and refractory FOG were included in a randomized, double blind, cross-over clinical trial. They were randomized to chronic (CHR) vs. experimental (EXP) stimulation (30% amplitude reduction contralateral to the least affected body side), each condition for 4 weeks. Gait and FOG were assessed both in the OFF and ON medication conditions. Primary outcome was the difference in the FOG percentage during gait assessment and in a composite gait score in CHR vs. EXP stimulation. Results The study was stopped early for futility. Of the 12 patients included, eight dropped out because of re-emerging of PD symptoms. In the four patients who sustained the experimental condition, the FOG percentage did not improve, whether in the OFF (CHR: 13.4% vs. EXP: 16.8%) or in the ON (CHR: 19.5% vs. EXP: 19.8%) medication condition. There was no change in the composite gait score (CHR: 5.5 ± 1.3 vs. EXP: 6.3 ± 3.3). Conclusions Most patients did not tolerate the unilateral amplitude reduction of STN DBS in the long-term. Moreover, this strategy failed to improve FOG in patients who could sustain the procedure. Clinicaltrial.gov identifier NCT02704195.

Published
2019
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5. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease

Author

Stéphane Thobois, Marie Vidailhet, Stéphane Derrey, Andrea Kistner, Philippe Damier, Daniel Weiss, W.M. Michael Schuepbach, Günther Deuschl, Thomas D. Hälbig, Tobias Wächter, Andreas Kupsch, Michael T. Barbe, Jan Vesper, Carmen Schade-Brittinger, Christine Brefel-Courbon, G.R. Fink, Jean-Luc Houeto, Friederike Sixel-Döring, Alireza Gharabaghi, Jens Volkmann, Karina Knudsen, David Maltête, Andrea A. Kühn, Andrea Falk, Patrick Mertens, Gerd-H. Schneider, Lars Timmermann, Alfons Schnitzler, Eric Seigneuret, Fabienne Ory-Magne, Pascal Derkinderen, Patrick Chaynes, Tatiana Witjas, Joern Rau, Valérie Fraix, S. Paschen, J. Regis, Lisa Tonder, Lars Wojtecki, Marcus O. Pinsker, Paul Krack, Haidar S. Dafsari, Andreas Hartmann, Fanny Pineau, Laura Paschen, Claudia Trenkwalder, Yves Agid, Universität Bern [Bern] (UNIBE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medtronic [Minneapolis, MI, USA], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Geneva [Switzerland], Centre de coordination des essais cliniques, Philipps-University, Marburg, Allemagne., Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NeuroCure Clinical Research Center (NCRC), Charité University Medical Center, Charité (Campus Mitte), Berlin, Germany., Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Department of Neuroscience, Karolinska institutet, Stockholm, Sweden, Department of Neuroscience, Karolinska institutet, Department of Neurology, University Medical Center Schleswig-Holstein, Arnold-Heller-Street 3, Kiel 24105, Germany., Department of Neurology, Christian-Albrechts-University, Kiel, Germany., Christian-Albrechts-Universität zu Kiel (CAU), University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany., National Parkinson Foundation Centre of Excellence, King's College Hospital, London, UK., Department of Neurology, University of Cologne, Cologne, Germany., Department of Neurology, Movement Disorder and Neuromodulation Unit, Charité-Universitätsmedizin, Berlin, Germany., NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Neurology & Neurosurgery, Charite University Medicine Berlin, Campus Virchow Klinikum & Benjamin Franklin, Berlin, Germany., Centre Hospitalier Universitaire [Grenoble] (CHU), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), UM des troubles du mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d'Anatomie et Cytopathologie [Toulouse], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique de Toulouse (CIC 1436), Department of Functional Neurosurgery and Stereotaxy, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany., Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Clinique neurologique, Hôpital Laennec, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paracelsus-Elena-Klinik, Kassel, Germany., Department of Neurology, Philipps University Marburg, Germany., Paracelsus Elena Klinik, Centre for Parkinson's Disease & Movement Disorders, Department of Neurosurgery, University of Tuebingen, Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, University of Vermont [Burlington], Stereotactic and Functional Neurosurgery Service and Gamma Knife Unit CHU Timone Marseille, France., AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Service de Neurologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service Public de Wallonie, Department of Nuclear Medicine and PET Centre Aarhus University Hospital, Institute of Clinical Medicine Aarhus University, Norrebrogade 44, Building 10, 8000, Aarhus C, Denmark., Somnomar, Sleep Research Institute, Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Toulouse, Service de Pharmacologie Médicale et Clinique, CHU Toulouse [Toulouse], University of Vermont College of Medicine [Burlington, VT, USA], Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universität Bern [Bern], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité Hospital, Humboldt Universität zu Berlin, and Service de neurochirurgie [Rouen]

Subjects
0301 basic medicine, medicine.medical_specialty, Parkinson's disease, Deep brain stimulation, medicine.medical_treatment, 610 Medicine & health, Disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, Rating scale, law, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Clinical endpoint, Medicine, ddc:610, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 10. No inequality, ComputingMilieux_MISCELLANEOUS, business.industry, medicine.disease, humanities, 3. Good health, nervous system diseases, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Subthalamic nucleus, 030104 developmental biology, Neurology (clinical), business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

ObjectiveTo investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.MethodsWe performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson’s Disease Rating Scale (UPDRS) (UPDRS-III “off” and “on” medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.ResultsPDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.ConclusionImpaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.Clinicaltrials.gov identifierNCT00354133.

Published
2019
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6. Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease MRI-Based Anatomoclinical Correlations and Optimal Target

Author

Carina Maineri, Napoleon Torres, Manik Bhattacharjee, Alexandre Krainik, Alim-Louis Benabid, Daniela Nosko, Olivier David, M.U. Ferraye, Martin Parent, Brigitte Piallat, Eric Seigneuret, Albert J. Fenoy, Valérie Fraix, André Parent, Bettina Debû, Stephan Chabardes, Laurent Goetz, Pierre Pollak, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université Laval [Québec] (ULaval), CHU Grenoble, Italian Hospital of Buenos Aires, Örebro University Hospital [Örebro, Sweden], The University of Texas Health Science Center at Houston (UTHealth), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Michael J. Fox Foundation, Fondation de France, CentreHospitalier Universitaire de Grenoble Alpes, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, Reticular formation, Midbrain, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), Medicine, Pedunculopontine Tegmental Nucleus, Pedunculopontine nucleus, medicine.diagnostic_test, Freezing of gait, business.industry, Mesencephalic reticular formation, Magnetic resonance imaging, Parkinson disease, Cuneiform nucleus, 030220 oncology & carcinogenesis, Surgery, Neurology (clinical), Brainstem, business, Mesencephalic locomotor region, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.

Published
2019
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7. Pallidal deep brain stimulation for dystonia: a long term study

Author

Elena Moro, Alim-Louis Benabid, Eric Seigneuret, Sara Meoni, Pierre Pollak, Valérie Fraix, Eric Chevrier, Paul Krack, Laurent Vercueil, Stephan Chabardes, and Anna Castrioto

Subjects
Adult, Male, 0301 basic medicine, Deep brain stimulation, Deep Brain Stimulation, medicine.medical_treatment, Globus Pallidus, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Motor score, Retrospective Studies, Dystonia, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Globus pallidus internus, nervous system diseases, ddc:616.8, Psychiatry and Mental health, Treatment Outcome, 030104 developmental biology, Long term learning, Globus pallidus, Dystonic Disorders, Anesthesia, Female, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Dystonic disorder, Follow-Up Studies
Abstract

Pallidal deep brain stimulation (globus pallidus internus (GPi) DBS) is the best therapeutic option for disabling isolated idiopathic (IID) and inherited (INH) dystonia. Acquired dystonia (AD) may also benefit from GPi DBS. Efficacy and safety in the long-term remained to be established.To retrospectively assess long-term clinical outcomes and safety in dystonic patients who underwent GPi DBS.Patients were videotaped and assessed preoperatively and postoperatively (1-year and at last available follow-up) using the Burke-Fahn-Marsden Dystonia Rating Scale (motor score (BFMDRS-M); disability score (BFMDRS-D)).Sixty-one patients were included (follow-up 7.9±5.9 years; range 1-20.7). In IID and INH (n=37), the BFMDRS-M improved at first (20.4±24.5; p0.00001) and last (22.2±18.2; p0.001) follow-ups compared with preoperatively (50.5±28.0). In AD (n=19), the BFMDRS-M ameliorated at 1-year (40.8±26.5; p0.02) and late follow-ups (44.3±24.3; p0.04) compared with preoperatively (52.8±24.2). In INH dystonia with other neurological features (n=4) there was no motor benefit. In IID and INH, the BFMDRS-D improved at 1-year (9.5±7.5; p0.0002) and late follow-ups (10.4±7.8; p0.016) compared with preoperatively (13.3±6.9). In AD, the BFMDRS-D reduced at 1-year (12.0±8.1; p0.01) and late follow-ups (12.7 ±6.1; p=0.2) compared with preoperatively (14.35±5.7). Most adverse events were hardware related.GPi DBS is an effective and safe treatment in most patients with dystonia.

Published
2017

8. Analysis of Injury Mechanisms in Head Injuries in Skiers and Snowboarders

Author

Catherine Masson, Sanae Afquir, Jean-Baptiste Delay, Nicolas Bailly, Pierre-Jean Arnoux, Eric Seigneuret, Jean-Dominique Laporte, Dominique Savary, Thierry Donnadieu, Anthony Melot, SALOMON Corporation, Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel, Association Médecins de Montagne, Hôpital Nord [CHU - APHM], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Traumatic brain injury, HEAD INJURY, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Crash, Occupational safety and health, CONCUSSION, SPORT, Head trauma, Young Adult, 03 medical and health sciences, 0302 clinical medicine, HELMET, TETE, Skiing, Brain Injuries, Traumatic, Injury prevention, Concussion, medicine, Craniocerebral Trauma, Humans, Orthopedics and Sports Medicine, BLESSURE, 030212 general & internal medicine, Child, CORPS HUMAIN, business.industry, Head injury, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 030229 sport sciences, Middle Aged, medicine.disease, SKI, CASQUE, CHOC, Physical therapy, Accidental Falls, Female, Head Protective Devices, France, business, human activities, SNOWBOARD
Abstract

Mechanisms of injury and description of head impacts leading to traumatic brain injury (TBI) in skiers and snowboarders have not been extensively documented. We investigate snow sport crashes leading to TBI 1) to identify typical mechanisms leading to TBI to better target prevention measures and 2) to identify the injury mechanisms and the head impact conditions.The subjects were skiers and snowboarders diagnosed of TBI and admitted between 2013 and 2015 to one of the 15 medical offices and three hospital centers involved in the study. The survey includes the description of the patients (age, sex, practice, skill level, and helmet use), the crash (type, location, estimated speed, causes, and fall description), and the injuries sustained (symptoms, head trauma scores, and other injuries). Sketches were used to describe the crash and impact locations. Clustering methods were used to distinguish profiles of injured participants.A total of 295 skiers and 71 snowboarders were interviewed. The most frequent type of mechanism was falls (54%), followed by collision between users (18%) and jumps (15%). Collision with obstacle (13%) caused the most serious TBI. Three categories of patients were identified. First, men age 16-25 yr are more involved in crash at high speed or in connection with a jump. Second, women, children (16 yr), and beginners are particularly injured in collisions between users. Third, those older than 50 yr, usually nonhelmeted, are frequently involved in falls. Ten crash scenarios were identified. Falling head first is the most frequent of skiers' falls (28%).Crash scenarios leading to TBI were identified and associated with profiles of injured participants. Those results should help to better target TBI prevention and protection campaigns.

Published
2017
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9. DOPAMINE AND THE BIOLOGY OF CREATIVITY: LESSONS FROM PARKINSON’S DISEASE

Author

Eugénie Lhommée, Alina Batir, Claire Ardouin, Paul Krack, Eric Seigneuret, Jean-Louis Quesada, Stephan Chabardes, Valérie Fraix, Pierre Pollak, and Alim-Louis Benabid

Subjects
Levodopa, Parkinson's disease, Deep brain stimulation, STN-DBS, medicine.medical_treatment, Dopamine, Dopamine agonist, lcsh:RC346-429, Creativity, Dmpulse control disorders, medicine, creativity, lcsh:Neurology. Diseases of the nervous system, Original Research, Dopaminergic, medicine.disease, ddc:616.8, STN DBS, Impulse Control Disorders, Neurology, Dopamine receptor, Parkinson’s disease, Neurology (clinical), medicine.symptom, Psychology, Mania, Neuroscience, Stn dbs, medicine.drug
Abstract

Background: Parkinson’s disease (PD) is characterized by reduced flexibility, conceptualization, and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists. Methods: Eleven consecutive creative PD patients were selected from candidates for subthalamic nucleus deep brain stimulation (STN DBS) surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III), cognition (Frontal score, Mattis scale), and behavior (Ardouin scale) were assessed before surgery and 1 year after. Results: Before surgery, whereas cognitive and motor assessments were similar between groups, dopamine agonist (but not levodopa) dosages were higher in creative patients (p = 0.01). The Ardouin scale revealed also a specific psycho-behavioral profile of creative patients which had higher scores for mania (p

Published
2014
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10. Subthalamic stimulation in Parkinson's disease: restoring the balance of motivated behaviours

Author

Magaly Aya Kombo, Valérie Fraix, Eugénie Lhommée, Eric Seigneuret, Stephan Chabardes, Sebastien Carnicella, Jean-Louis Quesada, Stéphane Thobois, Paul Krack, Jean-Luc Bosson, Patrick Mertens, Alim-Louis Benabid, Emmanuelle Schmitt, Hélène Klinger, Jing Xie, Andrea Kistner, Amélie Bichon, Claire Ardouin, Emmanuel Broussolle, Gustavo Polo, and Pierre Pollak

Subjects
Male, medicine.medical_specialty, Levodopa, Dyskinesia, Drug-Induced, Parkinson's disease, Deep Brain Stimulation, Impulse Control Disorders/etiology/therapy, Neuropsychological Tests, Severity of Illness Index, Statistics, Nonparametric, Antiparkinson Agents, Cohort Studies, Physical medicine and rehabilitation, Dopamine, Subthalamic Nucleus, Punding, Deep Brain Stimulation/methods, medicine, Humans, Apathy, Psychiatry, Dopamine dysregulation syndrome, Aged, Psychiatric Status Rating Scales, Motivation, Dopaminergic, Parkinson Disease, Parkinson Disease/complications/therapy, Middle Aged, medicine.disease, ddc:616.8, Disruptive, Impulse Control, and Conduct Disorders, Motivation/drug effects/physiology, Subthalamic Nucleus/physiology, Dyskinesia, Dyskinesia, Drug-Induced/etiology/therapy, Levodopa/adverse effects/therapeutic use, Female, Neurology (clinical), Antiparkinson Agents/adverse effects, medicine.symptom, Psychology, medicine.drug
Abstract

Addictions to dopaminergic drugs or to pleasant behaviours are frequent and potentially devastating neuropsychiatric disorders observed in Parkinson's disease. They encompass impulse control disorders, punding and dopamine dysregulation syndrome. A relationship with dopaminergic treatment is strongly suggested. Subthalamic stimulation improves motor complications and allows for drastic reductions in medication. This treatment might, therefore, be considered for patients with behavioural addictions, when attempts to reduce dopaminergic medication have failed. However, conflicting data have reported suppression, alleviation, worsening or new onset of behavioural addictions after subthalamic stimulation. Non-motor fluctuations are also a disabling feature of the disease. We prospectively investigated behaviour in a cohort of 63 patients with Parkinson's disease, before and 1 year after subthalamic stimulation using the Ardouin scale, with systematic evaluation of functioning in overall appetitive or apathetic modes, non-motor fluctuations, dopaminergic dysregulation syndrome, as well as behavioural addictions (including impulse control disorders and punding) and compulsive use of dopaminergic medication. Defined drug management included immediate postoperative discontinuation of dopamine agonists and reduction in levodopa. Motor and cognitive statuses were controlled (Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, frontal score). After surgery, the OFF medication motor score improved (-45.2%), allowing for a 73% reduction in dopaminergic treatment, while overall cognitive evaluation was unchanged. Preoperative dopamine dysregulation syndrome had disappeared in 4/4, behavioural addictions in 17/17 and compulsive dopaminergic medication use in 9/9 patients. New onset of levodopa abuse occurred in one patient with surgical failure. Non-motor fluctuations were significantly reduced with improvements in off-dysphoria (P ≤ 0.001) and reduction in on-euphoria (P ≤ 0.001). There was an inversion in the number of patients functioning in an overall appetitive mode (29 before versus 2 after surgery, P ≤ 0.0001) to an overall apathetic mode (3 before versus 13 after surgery, P

Published
2012

11. Subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease

Author

Napoleon Torres, Paul Krack, Thierry Bougerol, Olivier David, Pierre Pollak, Laurent Goetz, Stephan Chabardes, Mircea Polosan, Valérie Fraix, Albert J. Fenoy, Brigitte Piallat, Alim L. Benabid, Jean-Louis Quesada, Eric Seigneuret, INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service de Psychiatrie, CHU Grenoble-CHU Grenoble, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de neuroradiologie, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CIC - Grenoble, INSERM U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de neurochirurgie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Service de Psychiatrie, CHU Grenoble, and David, Olivier

Subjects
Male, Action Potentials/physiology, Obsessive-Compulsive Disorder, medicine.medical_treatment, MESH: Neurons, Action Potentials, Functional Laterality, Functional Laterality/physiology, Magnetic Resonance Imaging/methods, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Degenerative disease, Basal ganglia, Premovement neuronal activity, MESH: Action Potentials, Neurons, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, Subthalamic nucleus, medicine.anatomical_structure, Imaging, Three-Dimensional/methods, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Anxiety disorder, Adult, Deep brain stimulation, Parkinson Disease/pathology, MESH: Imaging, Three-Dimensional, Central nervous system disease, 03 medical and health sciences, Imaging, Three-Dimensional, Subthalamic Nucleus, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Functional Laterality, Obsessive-Compulsive Disorder/pathology, 030304 developmental biology, Aged, MESH: Subthalamic Nucleus, MESH: Obsessive-Compulsive Disorder, MESH: Humans, MESH: Adult, Subthalamic Nucleus/pathology, medicine.disease, MESH: Male, ddc:616.8, Neurology (clinical), Neuron, Neurons/physiology, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract

International audience; OBJECTIVE: Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high-frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive-compulsive disorder. METHODS: We compared the neuronal activity of the subthalamic nucleus recorded in 9 patients with obsessive-compulsive disorder with that of 11 patients with Parkinson disease measured during intraoperative exploration for deep brain stimulation. RESULTS: The mean subthalamic neuron discharge rate was statistically lower in patients with obsessive-compulsive disorder than in patients with Parkinson disease (20.5 ± 11.0 Hz, n = 100 and 30.8 ± 15.6 Hz, n = 93, respectively, p < 0.001). The relative proportion of burst neurons did not differ significantly between the 2 diseases (75% vs 73%). Interestingly, burst neurons were predominantly left-sided in obsessive-compulsive disorder. INTERPRETATION: The recording of burst neurons within the nonmotor subthalamic nucleus in patients with obsessive-compulsive disorder is a novel finding that suggests the existence of deregulation of the nonmotor basal ganglia loop, possibly left-sided. Potentially, burst activity might interfere with normal processes occurring within nonmotor loops.

Published
2011
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12. Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation

Author

Jean-Louis Quesada, Pierre Pollak, Alim-Louis Benabid, Emmanuel Broussolle, Jean-Luc Bosson, Hélène Klinger, Rachid Hassani, Paul Krack, Anthonin Reilhac, Gustavo Polo, Jing Xie, Andrea Kistner, Marc Savasta, Maria Clara Coelho Braga, Didier Lebars, Eric Seigneuret, Claire Ardouin, Nicolas Costes, Stéphane Thobois, Patrick Mertens, Alexandra Juphard, Léon Tremblay, Stephan Chabardes, Valérie Fraix, Christelle Lagrange, Eugénie Lhommée, Savasta, Marc, Service de neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité de Désordres du Mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Unité de Désordres du Mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Neurologie A, Hôpital des Spécialités, INSERM U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de neurochirurgie, ANTE-INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Université de Lyon, Service de Neurochirurgie [Hopital Pierre Wertheimer - HCL], Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Programme Hospitalier de Recherche Clinique Interregional and Eutherapie Pharmaceutical Company, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Parkinson's disease, Deep Brain Stimulation, Postoperative Complications, 0302 clinical medicine, Depression/etiology/psychology, MESH: Postoperative Complications, Limbic System, Apathy, MESH: Double-Blind Method, Prospective Studies, MESH: Dopamine Agonists, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Depression, Methylphenidate, Dopamine Agonists/adverse effects, Dopaminergic, Parkinson Disease, Denervation/psychology, MESH: Follow-Up Studies, Middle Aged, Denervation, MESH: Predictive Value of Tests, Substance Withdrawal Syndrome, 3. Good health, MESH: Limbic System, Substance Withdrawal Syndrome/etiology/psychology, Dopamine Agonists, Postoperative Complications/chemically induced/etiology/psychology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, medicine.drug, Adult, medicine.medical_specialty, Levodopa, MESH: Depression, MESH: Substance Withdrawal Syndrome, Deep Brain Stimulation/adverse effects, Dopamine agonist, Parkinson Disease/drug therapy/psychology/surgery, 03 medical and health sciences, Double-Blind Method, Predictive Value of Tests, Dopamine receptor D3, Dopamine, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Denervation, Aged, 030304 developmental biology, MESH: Humans, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, ddc:616.8, Surgery, Limbic System/surgery, Neurology (clinical), MESH: Deep Brain Stimulation, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease, Follow-Up Studies
Abstract

International audience; Apathy has been reported to occur after subthalamic nucleus stimulation, a treatment of motor complications in advanced Parkinson's disease. We carried out a prospective study of the occurrence of apathy and associated symptoms, predictors and mechanisms in the year following subthalamic stimulation. Dopamine agonist drugs were discontinued immediately after surgery and levodopa was markedly reduced within 2 weeks. Apathy and depression were assessed monthly, using the Starkstein apathy scale and the Beck Depression Inventory. Dopamine agonists were re-introduced if patients developed apathy or depression. Preoperative non-motor fluctuations were evaluated using the Ardouin Scale. Depression, apathy and anxiety were evaluated both on and off levodopa. Analysis of predictors of apathy was performed using a Cox proportional hazard model. Twelve patients who developed apathy and a control group of 13 patients who did not underwent [11C]-raclopride positron emission tomography scanning before and after oral intake of methylphenidate. In 63 patients with Parkinson's disease treated with subthalamic stimulation, dopaminergic treatment was decreased by 82% after surgery. Apathy occurred after a mean of 4.7 (3.3-8.2) months in 34 patients and was reversible in half of these by the 12-month follow-up. Seventeen patients developed transient depression after 5.7 (4.7-9.3) months and these fell into the apathy group with one single exception. At baseline, fluctuations in depression, apathy and anxiety scores were greater in the group with apathy. Fluctuations in apathy, depression and anxiety ratings during a baseline levodopa challenge were also significant predictors of postoperative apathy in univariate analysis, but not motor and cognitive states or the level of reduction of dopaminergic medication. The multivariate model identified non-motor fluctuations in everyday life and anxiety score during the baseline levodopa challenge as two independent significant predictors of postoperative apathy. Without methylphenidate, [11C]-raclopride binding potential values were greater in apathetic patients bilaterally in the orbitofrontal, dorsolateral prefrontal, posterior cingulate and temporal cortices, left striatum and right amygdala, reflecting greater dopamine D2/D3 receptor density and/or reduced synaptic dopamine level in these areas. The variations of [11C]-raclopride binding potential values induced by methylphenidate were greater in non-apathetic patients in the left orbitofrontal cortex, dorsolateral prefrontal cortex, thalamus and internal globus pallidus and bilaterally in the anterior and posterior cingulate cortices, consistent with a more important capacity to release dopamine. Non-motor fluctuations are related to mesolimbic dopaminergic denervation. Apathy, depression and anxiety can occur after surgery as a delayed dopamine withdrawal syndrome. A varying extent of mesolimbic dopaminergic denervation and differences in dopaminergic treatment largely determine mood, anxiety and motivation in patients with Parkinson's disease, contributing to different non-motor phenotypes.

Published
2010
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13. Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson's disease

Author

M.U. Ferraye, Eric Seigneuret, Alim-Louis Benabid, Pierre Pollak, Laurent Goetz, J.F. Le Bas, Brigitte Piallat, Valérie Fraix, Bettina Debû, Stephan Chabardes, Paul Krack, Jérôme Yelnik, C. Henry-Lagrange, Claire Ardouin, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U836, équipe 7, Nanomédecine et cerveau, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France Michael J. Fox Foundation CHU de Grenoble, Savasta, Marc, and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Male, Parkinson's disease, Deep Brain Stimulation, 0302 clinical medicine, Gait (human), Pedunculopontine Tegmental Nucleus, MESH: Double-Blind Method, Pedunculopontine nucleus, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, Cross-Over Studies, MESH: Middle Aged, Parkinson Disease, MESH: Follow-Up Studies, Middle Aged, Pedunculopontine Tegmental Nucleus/physiology, 3. Good health, Subthalamic nucleus, Treatment Outcome, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, medicine.drug, medicine.medical_specialty, Levodopa, MESH: Pedunculopontine Tegmental Nucleus, MESH: Cross-Over Studies, 03 medical and health sciences, Physical medicine and rehabilitation, Oscillopsia, Parkinson Disease/complications/physiopathology/therapy, Double-Blind Method, Deep Brain Stimulation/methods, medicine, Humans, MESH: Gait Disorders, Neurologic, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gait Disorders, Neurologic, 030304 developmental biology, Aged, MESH: Humans, Gait Disturbance, Gait Disorders, Neurologic/etiology/physiopathology/therapy, medicine.disease, MESH: Male, ddc:616.8, Physical therapy, Neurology (clinical), MESH: Deep Brain Stimulation, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease, Follow-Up Studies
Abstract

International audience; Gait disturbances are frequent and disabling in advanced Parkinson's disease. These symptoms respond poorly to usual medical and surgical treatments but were reported to be improved by stimulation of the pedunculopontine nucleus. We studied the effects of stimulating the pedunculopontine nucleus area in six patients with severe freezing of gait, unresponsive to levodopa and subthalamic nucleus stimulation. Electrodes were implanted bilaterally in the pedunculopontine nucleus area. Electrode placement was checked by postoperative magnetic resonance imaging. The primary outcome measures were a composite gait score, freezing of gait questionnaire score and duration of freezing episodes occurring during a walking protocol at baseline and one-year follow-up. A double-blind cross-over study was carried out from months 4 to 6 after surgery with or without pedunculopontine nucleus area stimulation. At one-year follow-up, the duration of freezing episodes under off-drug condition improved, as well as falls related to freezing. The other primary outcome measures did not significantly change, nor did the results during the double-blind evaluation. Individual results showed major improvement of all gait measures in one patient, moderate improvement of some tests in four patients and global worsening in one patient. Stimulation frequency ranged between 15 and 25 Hz. Oscillopsia and limb myoclonus could hinder voltage increase. No serious adverse events occurred. Although freezing of gait can be improved by low-frequency electrical stimulation of the pedunculopontine nucleus area in some patients with Parkinson's disease our overall results are disappointing compared to the high levels of expectation raised by previous open label studies. Further controlled studies are needed to determine whether optimization of patient selection, targeting and setting of stimulation parameters might improve the outcome to a point that could transform this experimental approach to a treatment with a reasonable risk-benefit ratio.

Published
2010
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14. Pedunculopontine nucleus stimulation induces monocular oscillopsia

Author

Peggy Gerardin, Muriel Ferraye, Bettina Debû, Pierre Pollak, Stephan Chabardes, Eric Seigneuret, Jean-Francois LeBas, Alim-Louis Benabid, Valérie Fraix, C. Tilikete, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Espace et action, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France Michael J Fox Foundation, and Savasta, Marc

Subjects
Eye Movements, genetic structures, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Antiparkinson Agents, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Stimulation, Antiparkinson Agents, Levodopa, Pedunculopontine Tegmental Nucleus/*physiology, Vision, Monocular/*physiology, 0302 clinical medicine, Gait (human), MESH: Eye Movements, Mesencephalon, Pedunculopontine Tegmental Nucleus, Parkinson Disease/*complications/*drug therapy, Pedunculopontine nucleus, MESH: Aged, MESH: Levodopa, 0303 health sciences, Mesencephalon/*physiology, MESH: Electric Stimulation, Parkinson Disease, Electrodes, Implanted, Levodopa/*therapeutic use, Psychiatry and Mental health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Psychology, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Pedunculopontine Tegmental Nucleus, Midbrain, 03 medical and health sciences, Oscillopsia, Vision, Monocular, medicine, Oculomotor Nerve Diseases, Humans, MESH: Gait Disorders, Neurologic, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Oculomotor Nerve Diseases, Gait Disorders, Neurologic, 030304 developmental biology, Aged, Monocular, MESH: Humans, MESH: Vision, Monocular, Oculomotor Nerve Diseases/*etiology/*physiopathology, Eye movement, Eye Movements/*physiology, MESH: Mesencephalon, Electric Stimulation, Electric Stimulation/adverse effects, ddc:616.8, Gait Disorders, Neurologic/*drug therapy/*etiology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, MESH: Electrodes, Implanted, Neurology (clinical), Neuroscience, Antiparkinson Agents/*therapeutic use, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract

International audience; Two patients with Parkinson's disease with pedunculopontine nucleus (PPN) stimulation for gait impairments reported "trembling vision" during the setting of the electrical parameters, although there was no clinically observable abnormal eye movement. Oculomotor recordings revealed frequency locked voltage dependent vertical or oblique movements of the eye ipsilateral to the active contact, suggesting current spreading to the mesencephalic oculomotor fibres. These results emphasise the difficulty of stimulating this mesencephalic region.

Published
2009
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15. Gait is associated with an increase in tonic firing of the sub-cuneiform nucleus neurons

Author

Muriel Ferraye, Alim-Louis Benabid, Eric Bardinet, Pierre Pollak, S. Chabardes, Brigitte Piallat, Jérôme Yelnik, Napoleon Torres, Laurent Goetz, Eric Seigneuret, Bettina Debû, Valérie Fraix, Paul Krack, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle tête, cou et chirurgie réparatrice [Grenoble], CHU Grenoble, Neurosciences cognitives et imagerie cérébrale (NCIC), Centre National de la Recherche Scientifique (CNRS), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Michael J. Fox Foundation Fondation de France Medtronic, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Issartel, Jean-Paul, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Neuro-Imagerie de Recherche (CENIR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
medicine.medical_treatment, MESH: Neurons, Action Potentials, Gait Disorders, Neurologic/etiology/*pathology, Stereotaxic Techniques, 0302 clinical medicine, Gait (human), Parkinson Disease/complications/surgery, Tegmentum Mesencephali/*pathology, MESH: Action Potentials, Pedunculopontine nucleus, Neurons, 0303 health sciences, General Neuroscience, Parkinson Disease, Electrodes, Implanted, medicine.anatomical_structure, Imaging, Three-Dimensional/methods, Locomotion/physiology, MESH: Tegmentum Mesencephali, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brainstem, Locomotion, Deep brain stimulation, Tegmentum Mesencephali, Central nervous system, MESH: Locomotion, MESH: Stereotaxic Techniques, MESH: Imaging, Three-Dimensional, Biology, Action Potentials/*physiology, Midbrain, Cuneiform nucleus, 03 medical and health sciences, Imaging, Three-Dimensional, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Gait Disorders, Neurologic, Wakefulness, Gait Disorders, Neurologic, 030304 developmental biology, MESH: Humans, ddc:616.8, MESH: Wakefulness, nervous system, MESH: Electrodes, Implanted, Neuron, Neuroscience, Neurons/*physiology, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract

International audience; In animals, the pedunculopontine (PPN) and the sub-cuneiform (SCU) nuclei located in the upper brainstem are involved during the processing of gait. Similar functional nuclei are suspected in humans but their role in gait is unclear. Here we show that, using extra-cellular recordings of the PPN/SCU region obtained in two parkinsonian patients, the SCU neurons increased their firing rate without modifying their firing pattern during mimicked steps. We conclude that SCU neurons are activated during gait processes.

Published
2009
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16. Early stimulation of DYT1 primary generalized dystonia prevents from its secondary irreversible complications

Author

Pierre Pollak, Eric Seigneuret, Paul Krack, Alim-Louis Benabid, Marie Vidailhet, Mathieu Anheim, Laurent Vercueil, Stephan Chabardes, Valérie Fraix, Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurochirurgie, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Collaboration, Savasta, Marc, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
medicine.medical_specialty, Deep Brain Stimulation/*methods, MESH: Mutation, Adolescent, MESH: Dystonia, Mutation/*genetics, Stimulation, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Generalized dystonia, medicine, Humans, ComputingMilieux_MISCELLANEOUS, MESH: Adolescent, MESH: Humans, MESH: Middle Aged, Dystonia/genetics/*prevention & control, business.industry, Middle Aged, 3. Good health, Surgery, ddc:616.8, Molecular Chaperones/*genetics, Neurology, Neurology (clinical), MESH: Deep Brain Stimulation, MESH: Molecular Chaperones, business, 030217 neurology & neurosurgery
Abstract

International audience

Published
2008
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17. Phase I Study of Topotecan in Combination with Concurrent Radiotherapy in Adults with Glioblastoma.

Author

Thierry Lesimple, Mohammed B. Hassel, Daniel Gédouin, and Eric Seigneuret

Abstract

A phase I study was performed to determine the maximum tolerated dose and the recommended dose of continuous intravenous infusion of topotecan in combination with radiotherapy (RT) in patients with previously untreated glioblastoma multiforme (GBM). Twenty patients with histologically proven GBM and 1 with rhabdoid tumor were enrolled. After surgery or stereotactic biopsy, patients received cranial RT (60 Gy/30 fractions/40 days) and 3 cycles of topotecan as continuous infusion (CIV) from day 1 to 5 on weeks 1, 3, and 5 during RT. The dose of topotecan was escalated from 0.6 to 1.0 mg/m2/day. Four dose levels were tested. One grade 4 thrombocytopenia was seen at level 1 (topotecan dose 0.6 mg/m2/day; 6 patients). No dose-limiting toxicity was seen at level 2 (0.8 mg/m2/day; 3 patients) or an intermediate level of 2 bis (0.9 mg/m2/day; 6 patients). Six patients were included at level 3 (1.0 mg/m2/day), 4 of whom experienced dose-limiting toxicities, including 3 episodes of grade 4 thrombocytopenia, 1 platelet transfusion, 1 febrile neutropenia, and 1 grade 4 neutropenia of more than 7 days. Eighty percent of patients with GBM were alive at 12 months. The dose-limiting toxicity of topotecan administered as CIV for 5 days every 2 weeks is hematological. The maximum tolerated dose is 1.0 mg/m2/day and the recommended dose is 0.9 mg/m2/day. A phase II trial using the recommended dose of topotecan is ongoing. [ABSTRACT FROM AUTHOR]

Published
2003

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