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1. Neurostimulation for Parkinson's Disease with Early Motor Complications

Author: Schuepbach, W.M., Rau, J., Knudsen, K., Volkmann, J., Krack, P., Timmermann, L., Halbig, T.D., Hesekamp, H., Navarro, S.M., Meier, N., Falk, D., Mehdorn, M., Paschen, S., Maarouf, M., Barbe, M.T., Fink, G.R., Kupsch, A., Gruber, D., Schneider, G.H., Seigneuret, E., Kistner, A., Chaynes, P., Ory-Magne, F., Brefel Courbon, C., Vesper, J., Schnitzler, A., Wojtecki, L., Houeto, J.L., Bataille, B., Maltete, D., Damier, P., Raoul, S., Sixel-Doering, F., Hellwig, D., Gharabaghi, A., Kruger, R., Pinsker, M.O., Amtage, F., Regis, J.M., Witjas, T., Thobois, S., Mertens, P., Kloss, M., Hartmann, A., Oertel, W.H., Post, B., Speelman, H., Agid, Y., Schade-Brittinger, C., Deuschl, G., Neurology, Krack, Paul, and Diener, Hans Christoph (Beitragende*r)
Subjects: Adult, Male, medicine.medical_specialty, Parkinson's disease, DCN MP - Plasticity and memory, medicine.medical_treatment, Medizin, Electric Stimulation Therapy, 610 Medicine & health, Implantable Neurostimulators/adverse effects, law.invention, Antiparkinson Agents, Randomized controlled trial, Quality of life, Subthalamic Nucleus, law, Surveys and Questionnaires, Internal medicine, Activities of Daily Living, Dopamine Agonists/adverse effects/therapeutic use, Clinical endpoint, Humans, Medicine, Adverse effect, Neurostimulation, Electric Stimulation Therapy/adverse effects, Dyskinesias, Quality of Life, Intention-to-treat analysis, business.industry, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, Intention to Treat Analysis, Implantable Neurostimulators, Parkinson Disease/drug therapy/physiopathology/*therapy, Treatment Outcome, Dyskinesia, Dopamine Agonists, Antiparkinson Agents/adverse effects/therapeutic use, Physical therapy, Female, medicine.symptom, business, Dyskinesias/etiology
Abstract: Item does not contain fulltext BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P
Published: 2013
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2. The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism

Author: Klebe, Stephan, Golmard, Jean-Louis, Charfi, Rim, Edkins, Sarah, Evans, Jonathan R, Foltynie, Thomas, Freeman, Colin, Gao, Jianjun, Gardner, Michelle, Gibbs, Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Klein, Christine, Gústafsson, Omar, Harris, Clare, Hellenthal, Garrett, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hagenah, Johann, Hudson, Gavin, Hunt, Sarah E, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Gasser, Thomas, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Morris, Huw, Morrison, Karen E, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Pearson, Richard, Perlmutter, Joel S, Wurster, Isabel, Pétursson, Hjörvar, Pirinen, Matti, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Lesage, Suzanne, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, de Silva, Rohan, Smith, Colin, Spencer, Chris Ca, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Su, Zhan, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Deuschl, Günther, Traynor, Bryan J, Uitterlinden, G., Vandrovcova, Jana, Velseboer, Daan, Vidailhet, Marie, Vukcevic, Damjan, Walker, Robert, van de Warrenburg, Bart, Weale, Michael E, Wickremaratchi, Mirdhu, Durif, Franck, Williams, Nigel, Williams-Gray, Caroline H, Winder-Rhodes, Sophie, Martinez, Maria, Donnelly, Peter, Hardy, John, Heutink, Peter, Brice, Alexis, Wood, Nicholas W, Singleton, Andrew B, Nalls, Michael A, Damier, Philippe, Durr, Alexandra, Amouyel, Philippe, Lambert, Jean-Charles, Tzourio, Christophe, Maubaret, Cécilia, Charbonnier-Beaupel, Fanny, Tahiri, Khadija, Saad, Mohamad, Corvol, Jean-Christophe, Group, French Parkinson's Disease Genetics Study, Consortium, International Parkinson's Disease Genomics, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J-C, Damier, Ph, Destée, A., Durr, A., Durif, F., Klebe, S., Lohmann, E., Martinez, M., Penet, C., Bras, Jose M, Pollak, P., Krack, P., Rascol, O., Tison, F., Tranchant, C., Vérin, M., Viallet, F., Plagnol, Vincent, Hernandez, Dena G, Sharma, Manu, Sheerin, Una-Marie, Simón-Sánchez, Javier, Schulte, Claudia, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Band, Gavin, Simon-Sanchez, Javier, Barker, Roger A, Bellinguez, Céline, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob Ma, Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Chong, Sean, Clarke, Carl E, Cookson, Mark R, Kuhlenbäumer, Gregor, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Dartigues, Jean-François, Deloukas, Panos, Dexter, David T, van Dijk, Karin D, Dillman, Allissa, Durif, Frank, INSERM UMR_S9745, 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)-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), Département de Biostatistiques [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UCL Institute of neurology, UCL Institute of Neurology, Department of Clinical Genetics, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institute of Experimental Medicine, Christian-Albrechts-University, Department of Neurology, University of Lübeck, 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Christian-Albrechts-Universität zu Kiel (CAU), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-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), Departamento de Geologia CICESE, Centro de Investigacion Cientifica y de Education Superior de Ensenada [Mexico] (CICESE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Human genetics, NCA - Brain mechanisms in health and disease, NCA - neurodegeneration, Child and Adolescent Psychiatry / Psychology, ANS - Amsterdam Neuroscience, Neurology, Graduate School, 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), 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) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Département de Neurologie [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP]
Subjects: Male, medicine.medical_specialty, Genotype, DCN MP - Plasticity and memory, [SDV]Life Sciences [q-bio], genetics [Catechol O-Methyltransferase], Neurogenetics, Catechol O-Methyltransferase/genetics, Catechol O-Methyltransferase, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], 03 medical and health sciences, Sex Factors, 0302 clinical medicine, genetics [Parkinson Disease], Internal medicine, medicine, Humans, ddc:610, Parkinson Disease/genetics, Age of Onset, Allele, Aged, 030304 developmental biology, Genetics, 0303 health sciences, Movement Disorders, Parkinson's Disease, Catechol-O-methyl transferase, Parkinson Disease, Middle Aged, Polymorphism, Single Nucleotide/genetics, ddc:616.8, Sexual dimorphism, Psychiatry and Mental health, Human Movement & Fatigue [DCN MP - Plasticity and memory NCEBP 10], Endocrinology, Cohort, genetics [Polymorphism, Single Nucleotide], Surgery, Neurology (clinical), Age of onset, Psychology, 030217 neurology & neurosurgery, rs4680
Abstract: Item does not contain fulltext The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1+/-13.9, p=0.03) than the Val/Met (57.4+/-13.9) and the Met/Met genotypes (58.3+/-13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.
Published: 2013
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3. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

Author: Healy, Daniel G., Mario, Falchi, O'Sullivan, Sean S., Bonifati, Vincenzo, Alexandra, Durr, Susan, Bressman, Alexis, Brice, Jan, Aasly, Zabetian, Cyrus P., Stefano, Goldwurm, Ferreira, Joaquim J., Eduardo, Tolosa, Kay, Denise M., Christine, Klein, Williams, David R., Connie, Marras, Lang, Anthony E., Wszolek, Zbigniew K., Jose, Berciano, Schapira, Anthony H. V., Timothy, Lynch, Bhatia, Kailash P., Thomas, Gasser, Lees, Andrew J., Wood, Nicholas W., International Lrrk Consortium, Collaborators, Tazir, M., Ysmail Dahlouk, F., Belarbi, S., Hecham, N., Barbosa, E., Chien, H. F., Rieder, C. R., Jardim, L. B., Rogaeva, E., Lesage, S., Lohmann, E., Vidailhet, M., Bonnet, A. M., Agid, Y., Pollak, P., Tison, F., Durif, F., Broussolle, E., Berg, D., Hagenah, J., Gosal, D., Gibson, M., Vanacore, Nicola, Berardelli, Alfredo, Fabbrini, Giovanni, Fabrizio, E., Meco, Giuseppe, Stocchi, F., Dalla Libera, A., De Mari, M., Lamberti, P., Cossu, G., Pezzoli, G., Zini, M., Tesei, S., Zecchinelli, A., Sironi, F., Antonini, A., Mariani, C., Sacilotto, G., Meucci, N., Canesi, M., Di Fonzo, A., Oostra, B., Correia Guedes, L., Rosa, Mm, Coelho, M., Sampaio, C., Gaig, C., C. S., Lu, Wu Chou, Y. H., Quinn, N. P., Abou Sleiman, P. M., Muqit, M. M., Khan, N. L., Gandhi, S., Vaughan, J., Payami, H., Nutt, J. J., Factor, S. A., Higgins, D. S., Farrer, M. J., Hulihan, M., Brown, L., Mata, I. F., Samii, A., Yearout, D., Griffith, A., Leis, B. C., Roberts, J. W., Clinical Genetics, Department of Clinical Neurosciences, University College of London [London] (UCL)-Institute of Neurology, Genomic Medicine, Imperial College London-Kings College, Reta Lila Weston Institute for Neurological Studies, Queen Mary University of London (QMUL), Department of Clinical Genetics (DCG), Erasmus University Medical Centre, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Department of Neurology, Beth Israel Medical Centre- Albert Einstein College of Medicine [New York], St. Olav's Hospital, University of Washington [Seattle], Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Parkinson Institute, Istituti Clinici di Perfezionamento, Neurological Clinic Research Unit, Institute of Molecular Medicine-Lisbon School of Medicine, Neurology Service, Institut Clinic Maltias del Sistema Nervios-Hospital Clinic Universitari-University of Barcelona, Division of Genetic Disorders, New York State Department of Health [Albany], University of Luebeck, Faculty of Medicine (Neurosciences), Monash University [Clayton], University of Toronto, Mayo Clinic Jacksonville, Service of Neurology, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC)-Instituto de Salud Carlos III [Madrid] (ISC), Mater Misericordiae University Hospital (The Mater Hospital), Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Department of Neurodegenerative Diseases, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen-Hertie-Institut for Clinical Brain Research, Department of Molecular Pathogenesis, UK Medical Research Council, UK Parkinson's Disease Society, UK Brain Research Trust, Internationaal Parkinson Fonds, Volkswagen Foundation, National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging, Udall Parkinson's Disease Centre of Excellence, Pacific Alzheimer Research Foundation Centre, Italian Telethon Foundation, Fondazione Grigioni per il Morbo di Parkinson, Michael J Fox Foundation for Parkinson's Research, Safra Global Genetics Consortium, US Department of Veterans Affairs, French Agence Nationale de la Recherche., ANR-05-NEUR-0019,LRRK2 in PD,Pathologie moléculaire et modèles murins du gène LRRK2, impliqué dans la maladie de Parkinson(2005), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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), Beth Israel Medical Centre- Albert Einstein College of Medicine, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Mater Misericordiae University Hospital, Eberhard Karls Universität Tübingen-Hertie-Institut for Clinical Brain Research, ANR-05-NEURO-019,ANR-05-NEURO-019, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Gerontology, Male, Risk, Pediatrics, medicine.medical_specialty, Parkinson's disease, Genotype, International Cooperation, DNA Mutational Analysis, Glycine, Clinical Neurology, Penetrance, Disease, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, medicine, Serine, Humans, Genetic Predisposition to Disease, Genetic Testing, Age of Onset, 030304 developmental biology, Genetic testing, Family Health, 0303 health sciences, medicine.diagnostic_test, business.industry, Case-control study, Age Factors, Parkinson Disease, medicine.disease, LRRK2, 3. Good health, nervous system diseases, Dyskinesia, Case-Control Studies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neurology (clinical), genetics, parkinson, Age of onset, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Summary Background Mutations in LRRK2 , the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2 -associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2 ? Methods Researchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2 -associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD. Findings Six mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2 -associated PD were more benign than those of idiopathic PD. Interpretation Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients. Funding UK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research Trust; Internationaal Parkinson Fonds; Volkswagen Foundation; National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging; Udall Parkinson's Disease Centre of Excellence; Pacific Alzheimer Research Foundation Centre; Italian Telethon Foundation; Fondazione Grigioni per il Morbo di Parkinson; Michael J Fox Foundation for Parkinson's Research; Safra Global Genetics Consortium; US Department of Veterans Affairs; French Agence Nationale de la Recherche.
Published: 2008
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4. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa

Author: IBANEZ P, LESAGE S, LOHMANN E, THOBOIS S, BORG M, AGID Y, DURR, A, BRICE A, FRENCH PARKINSON'S DISEASE GENETICS STUDY G.R.O.U.P., DE MICHELE, GIUSEPPE, Ibanez, P, Lesage, S, Lohmann, E, Thobois, S, DE MICHELE, Giuseppe, Borg, M, Agid, Y, Durr, A, Brice, A, and FRENCH PARKINSON'S DISEASE GENETICS STUDY, G. R. O. U. P.
Published: 2006

5. Parkin mutations are frequent in patients with isolated early-onset parkinsonism

Author: Periquet, M, Latouche, M, Lohmann, E, Rawal, N, De Michele, G, Ricard, S, Teive, H, Fraix, V, Vidailhet, M, Nicholl, D, Barone, Paolo, Wood, Nw, Raskin, S, Deleuze, Jf, Agid, Y, Dürr, A, Brice, A, French Parkinson's Disease Genetics Study Group, European Consortium on Genetic Susceptibility in Parkinson's Disease, Periquet, M, Latouche, M, Lohmann, E, Rawal, N, DE MICHELE, Giuseppe, Ricard, S, Teive, H, Fraix, V, Vidailhet, M, Nicholl, D, Barone, P, Wood, Nw, Raskin, S, Deleuze, Jf, Agid, Y, Durr, A, Brice, A, FRENCH PARKINSON'S DISEASE GENETICS STUDY, Group, and EUROPEAN CONSORTIUM ON GENETIC SUSCEPTIBILITY IN PARKINSON'S, Disease
Published: 2003

6. Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism

Author: IBANEZ P, BONIFATI V, LOHMANN E, THOBOIS S, POLLAK P, AGID Y, HEUTINK P, DURR A, BRICE A, FRENCH PARKINSON'S DISEASE GENETICS STUDY GROUP, DE MICHELE, GIUSEPPE, Ibanez, P, DE MICHELE, Giuseppe, Bonifati, V, Lohmann, E, Thobois, S, Pollak, P, Agid, Y, Heutink, P, Durr, A, Brice, A, and FRENCH PARKINSON'S DISEASE GENETICS STUDY, Group
Published: 2003

7. How much phenotypic variation can be attributed to parkin genotype?

Author: LOHMANN E, PERIQUET M, BONIFATI V, WOOD NW, BONNET AM, FRAIX V, BROUSSOLLE E, HORSTINK MW, VIDAILHET M, VERPILLAT P, GASSER T, NICHOLL D, TEIVE H, RASKIN S, RASCOL O, DESTEE A, RUBERG M, GASPARINI F, MECO G, AGID Y, DURR A, BRICE A, FRENCH PARKINSON'S DISEASE GENETICS STUDY GROUP, EUROPEAN CONSORTIUM ON GENETIC SUSCEPTIBILITY IN PARKINSON'S DISEASE, DE MICHELE, GIUSEPPE, Lohmann, E, Periquet, M, Bonifati, V, Wood, Nw, DE MICHELE, Giuseppe, Bonnet, Am, Fraix, V, Broussolle, E, Horstink, Mw, Vidailhet, M, Verpillat, P, Gasser, T, Nicholl, D, Teive, H, Raskin, S, Rascol, O, Destee, A, Ruberg, M, Gasparini, F, Meco, G, Agid, Y, Durr, A, Brice, A, FRENCH PARKINSON'S DISEASE GENETICS STUDY, Group, and EUROPEAN CONSORTIUM ON GENETIC SUSCEPTIBILITY IN PARKINSON'S, Disease
Published: 2003

8. Association between early-onset Parkinson's disease and parkin gene mutations

Author: LÜCKING CB, DÜRR A, BONIFATI V, VAUGHAN J, GASSER T, HARHANGI BS, MECO G, DENèFLE P, WOOD NW, AGID Y, BRICE A., DE MICHELE, GIUSEPPE, Lücking, Cb, Dürr, A, Bonifati, V, Vaughan, J, DE MICHELE, Giuseppe, Gasser, T, Harhangi, B, Meco, G, Denèfle, P, Wood, Nw, Agid, Y, and Brice, A.
Published: 2000

9. Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study

Author: Ross, Owen A, Soto-Ortolaza, Alexandra I, Brighina, Laura, Riess, Olaf, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, van de Loo, Simone, Abahuni, Nadine, Gispert-Sánchez, Suzana, Hilker, Rüdiger, Auburger, Georg, Van Broeckhoven, Christine, Xiromerisiou, Georgia, Tsimourtou, Vaia, Ralli, Styliani, Kountra, Persa, Markou, Katerina, Patramani, Gianna, Vogiatzi, Christina, Lynch, Tim, Gibson, J Mark, Craig, Dr David, Carr, Jonathan, Valente, Enza Maria, Ferraris, Alessandro, Bentivoglio, Anna Rita, Ialongo, Tamara, Guidubaldi, Arianna, Piano, Carla, Ferrarese, Carlo, Tarantino, Patrizia, Annesi, Ferdinanda, Chartier-Harlin, Marie-Christine, Annesi, Grazia, Quattrone, Aldo, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Satake, Wataru, Dardiotis, Efthimios, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Boczarska-Jedynak, Magdalena, Tan, Eng King, Bardien, Soraya, Jeon, Beom Seok, Park, Sung Sup, Kim, Yun Joong, Dickson, Dennis W, Sohn, Young Ho, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Pedersen, Nancy L, Wirdefeldt, Karin, Nilsson, Christer, Puschmann, Andreas, Diehl, Nancy N, Wu, Ruey-Meei, Maraganore, Demetrius M, Ahlskog, Eric, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Farrer, M., Elbaz, Alexis, Heckman, Michael G, Fiske, Brian, Gibson, Rachel, Hadjigeorgiou, Georgios M, Ioannidis, John P A, Jeon, Beom S, Aasly, Jan O, Kruger, Rejko, Kyratzi, Elli, Lesage, Suzanne, Lin, Chin-Hsien, Lynch, Timothy, Mellick, George D, Mutez, Eugénie, Sharma, Manu, Silburn, Peter A, Stefanis, Leonidas, Tadic, Vera, Theuns, Jessie, Uitti, Ryan J, Vassilatis, Demetrios K, Vilariño-Güell, Carles, White, Linda R, Wszolek, Zbigniew K, Farrer, Matthew J, Bacon, Justin A, Disease, Genetic Epidemiology Of Parkinson's, Sutherland, G. T., Siebert, G. A., Nuytemans, Karen, Meeus, Bram, Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, De Deyn, Peter P, Cras, Patrick, Rogaeve, Ekaterina, Destée, A., Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Bozi, Maria, Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Brice, Alexis, Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Gasser, Thomas, Krüger, Rejko, Berg, Daniela, Schulte, Claudia, Ross, O, Soto Ortolaza, A, Heckman, M, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Van Broeckhoven, C, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Ferraris, A, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Farrer, M, Engelborghs, Sebastiaan, De Deyn, Peter Paul, Cras, Patrick, Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium, Pathologic Biochemistry and Physiology, and Pollak, Pierre
Subjects: Male, Polymorphism, Single Nucleotide/*genetics, International Cooperation, Ethnic Groups/genetics, Ethnic Group, Genome-wide association study, Protein-Serine-Threonine Kinase, methods [Genome-Wide Association Study], genetics [Ethnic Groups], 0302 clinical medicine, Gene Frequency, genetics [Parkinson Disease], Risk Factors, Exons/genetics, Ethnicity, Parkinson Disease/genetics, Medicine(all), Genetics, Aged, 80 and over, 0303 health sciences, Parkinson Disease, Exons, genetics [Exons], Middle Aged, Polymorphism, Single Nucleotide/genetics, Protein-Serine-Threonine Kinases, LRRK2, 3. Good health, genetics [Polymorphism, Single Nucleotide], Genome-Wide Association Study/methods, Female, Case-Control Studie, Human, Adult, Parkinson Disease/*genetics, Genotype, Adolescent, Protein-Serine-Threonine Kinases/*genetics, Protein-Serine-Threonine Kinases/genetics, Exon, Protein Serine-Threonine Kinases, Biology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, genetics [Protein-Serine-Threonine Kinases], Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Humans, Genetic Predisposition to Disease, ddc:610, LRRK2 protein, human, Risk factor, Allele frequency, 030304 developmental biology, Aged, Risk Factor, Case-control study, Exons/*genetics, Odds ratio, nervous system diseases, ddc:616.8, Minor allele frequency, Genetic epidemiology, Case-Control Studies, Neurology (clinical), Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. METHODS: LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. FINDINGS: 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 1.33-15.09; p=0.012). INTERPRETATION: The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. FUNDING: Michael J Fox Foundation and National Institutes of Health. Lancet Neurol
Published: 2011
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10. Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Author: Redgrave, P. (Peter), Rodriguez-Diaz, M. (Manuel), Smith, Y. (Yoland), Rodriguez-Oroz, M.C. (María Cruz), Lehericy, S. (Stephane), Bergman, H. (Hagai), Agid, Y. (Yves), DeLong, M.R. (Mahlon R.), and Obeso, J.A. (José A.)
Subjects: Nerve Net/pathology, Neural Pathways/pathology, Models, Neurological, Parkinson Disease/physiopathology
Abstract: Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved.
Published: 2010

11. Sequencing of the a-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations

Author: VAUGHAN JR, FARRER MJ, WSZOLEK ZK, GASSER T, DüRR A, AGID Y, BONIFATI V, VOLPE G, LINCOLN S, BRETELER M, MECO M, BRICE A, MARSDEN CD, HARDY J, WOOD NW, DE MICHELE, GIUSEPPE, Vaughan, Jr, Farrer, Mj, Wszolek, Zk, Gasser, T, Dürr, A, Agid, Y, Bonifati, V, DE MICHELE, Giuseppe, Volpe, G, Lincoln, S, Breteler, M, Meco, M, Brice, A, Marsden, Cd, Hardy, J, and Wood, Nw
Published: 1998

12. Treatment of end-of-dose wearing-off in Parkinson's disease:Stalevo® (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess®/Comtan® (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment

Author: Brooks, D. J., Agid, Y., Eggert, K., Widner, H., Østergaard, K., and Holopainen, A.
Subjects: Levodopa, Catechol-O-methyltransferase inhibition, Parkinson's disease, Stalevo®, Dopadecarboxylase inhibitor, Wearing-off, nervous system diseases
Abstract: The aim of this study was to evaluate the efficacy of the new optimised levodopa, Stalevo® (levodopa, carbidopa and entacapone) in patients with Parkinson's disease experiencing end-of-dose wearing-off. Treatment with Stalevo was compared to treatment with traditional immediate-release levodopa and dopa-decarboxylase inhibitor (DDCI) formulations along with adjunct entacapone (Comtess®/Comtan®). A European, open, parallel-group, active treatment-controlled phase IIIb study evaluating 176 patients randomised to switch from their current regimen of levodopa/DDCI to either an equivalent dose of Stalevo or levodopa/DDCI plus entacapone. After 6 weeks, treatments were assessed using the Clinical Global Impression of Change, the Unified Parkinson's Disease Rating Scale and a Motor Fluctuations Questionnaire. Over 70% of patients in both the Stalevo and adjunct entacapone arms felt that they were clinically improved and over 80% experienced a reduction in fluctuations. Although there was no significant difference between Stalevo and levodopa/DDCI plus entacapone with regard to motor improvement and side effects, 81% of patients stated that they preferred treatment with Stalevo compared with taking two separate tablets (i.e. levodopa/DDCI and entacapone). Stalevo was well tolerated and safe when substituted for levodopa DDCI preparations.
Published: 2005
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13. Tourett's syndrome and deep brain stimulation

Author: Jl, Houeto, Karachi, C., Mallet, L., Pillon, B., Yelnik, J., Mesnage, V., Ml, Welter, Navarro, S., Pelissolo, A., Damier, P., Pidoux, B., Dormont, Didier, Cornu, P., Agid, Y., and Mingot, Agnès
Published: 2005

14. Treatment of end-of-dose wearing-off in Parkinson′s disease: stalevo (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess/Comtan (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment:TC-INIT Study Group

Author: Brooks, DJ, Agid, Y, Eggert, K, Widner, H, Østergaard, Karen, and Holopainen, A
Published: 2005

15. Tourette's sybdrome and deep brain stimulation

Author: Jl, Houeto, Karachi, C., Mallet, L., Pillon, B., Yelnik, J., Mesnage, V., Ml, Welter, Navarro, S., Pelissolo, A., Damier, P., Pidoux, B., Dormont, Didier, Cornu, P., Agid, Y., and Mingot, Agnès
Published: 2005

16. How much phenotypic variation can be attributed to parkin genotype?

Author: Lohmann, E., Periquet, M., Bonifati, V., Wood, N.W., Michele, G. de, Bonnet, A.M., Fraix, V., Brousolle, E., Horstink, M.W.I.M., Vidailhet, M., Verpillat, P., Gasser, T., Nicholl, D., Teive, H., Raskin, S., Rascol, O., Destee, A., Ruberg, M., Gasparini, F., Meco, G., Agid, Y., Durr, A., and Brice, A.
Subjects: Adult, Aged, 80 and over, Male, Heterozygote, Adolescent, Genotype, Ubiquitin-Protein Ligases, Mutation, Missense, Genetic Variation, Parkinson Disease, Exons, Middle Aged, nervous system diseases, Antiparkinson Agents, Levodopa, Phenotype, Cognitive neurosciences [UMCN 3.2], Mutation, Disease Progression, Humans, Female, Age of Onset, Aged
Abstract: Item does not contain fulltext To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations.
Published: 2003

17. [Parkinson disease: mechanisms of cell death]

Author: Pp, Michel, Etienne Hirsch, and Agid Y
Subjects: Neurons, Cell Death, Mutation, Cytokines, Humans, Parkinson Disease, Nitric Oxide, Neuroglia, Receptors, Dopamine
Abstract: Parkinson disease is a neurodegenerative disorder of aging characterized by a selective and progressive loss of dopaminergic neurons within the substantia nigra. The diagnosis of the disease is made when neuronal cell loss exceeds 50 p. 100 indicating that the degenerative process started well before the onset of the first clinical symptoms. Three populations of dopaminergic neurons seem to coexist in the substantia nigra of parkinsonian patients; (1) senescent neurons that are still spared by the pathological process; (2) sick neurons exhibiting generally a preserved morphology but showing evidence of biochemical and metabolic abnormalities; (3) neurons which have entered into a final state of agony and exhibit the hallmarks of apoptosis, a controlled form of cell death that requires the activation of a particular type of proteases, caspases. In the inherited forms of the disease that are caused by mutations of genes encoding the Parkin, alpha-synuclein and UCHL-1 proteins, the degenerative process results from the dysfunction of an enzymatic complex of proteolysis, the proteasome. This probably leads to the intracellular accumulation of abnormal proteins that become deleterious for dopaminergic neurons. In the sporadic forms of the disease that are the most frequent, causes of the cell demise remain still unknown but neurodegeneration might also result from a decreased activity of the proteasome. A defect in the detoxification of reactive oxygen species or an energy failure caused by inhibition of the mitochondrial respiratory chain, at the complex I level, are other hypothesis that are frequently mentioned. Finally, activated glial cells (astrocytes and microglia) located around the degenerating dopaminergic neurons might also intervene in the mechanism of degeneration by perpetuating or even amplifying the primary neuronal insult. Proinflammatory cytokines acting on cell death membrane receptors and diffusable messengers such as nitric oxide could be part of this process.
Published: 2003

18. French Parkinson's Disease Genetics Study Group. Screening for DJ-1 mutations in early onset autosomal recessive Parkinsonism

Author: Ibanez, P, de Michele, G, Bonifati, Vincenzo, Lohmann, E, Thobois, S, Pollak, P, Agid, Y, Heutink, P, Dürr, A, Brice, A, and Clinical Genetics
Published: 2003

19. Concurrent excitatory and inhibitory effects of high frequency stimulation: an oculomotor study

Author: Bejjani, B, Arnulf, I, Houeto, J, Milea, D, Demeret, S, Pidoux, B, Damier, P, Cornu, P, Dormont, D, and Agid, Y
Subjects: Paper, Male, integumentary system, Eye Movements, Electric Stimulation Therapy, Parkinson Disease, Syndrome, Middle Aged, nervous system, Oculomotor Nerve, Mesencephalon, Subthalamic Nucleus, Humans, Electrodes
Abstract: To describe a reversible neurological condition resembling a crossed midbrain syndrome resulting from high frequency stimulation (HFS) in the midbrain.Postoperative evaluation of quadripolar electrodes implanted in the area of the subthalamic nucleus of 25 patients with Parkinson's disease (PD) successfully treated by HFS.Four of the 25 patients experienced reversible acute diplopia, with dystonic posture and tremor in the contralateral upper limb when the white matter between the red nucleus and the substantia nigra was stimulated. The motor signs resembled those caused by lesions of the red nucleus. The ipsilateral resting eye position was "in and down" (three patients) or "in" (one patient). Enophthalmos was seen. Abduction was impaired and vertical eye movements were limited, but adduction was spared. The movements of the controlateral eye were normal. The ocular signs could be best explained by sustained hyperactivity of the extrinsic oculomotor nerve. Simultaneous tonic contraction of the superior rectus, the inferior rectus, and inferior oblique may cause the enophthalmos and partial limitation of upward and downward eye movements. Antagonist tonic contraction of the ipsilateral medial rectus severely impairs abduction.This crossed midbrain syndrome, possibly resulting from simultaneous activation of oculomotor nerve and lesion-like inhibition of the red nucleus suggests that high frequency stimulation has opposite effects on grey and white matter.
Published: 2002

20. The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease

Author: Bonifati, Vincenzo, de Michele, G, Lucking, CB, Durr, A, Fabrizio, E, Ambrosio, G, Vanacore, N, de Mari, M, Marconi, R, Capus, L, Breteler, Monique, Gasser, T, Oostra, Ben, Wood, NW, Agid, Y, Filla, A, Meco, G, Brice, A, Clinical Genetics, and Epidemiology
Published: 2001

21. Dual-release formulation, a novel principle in L-dopa treatment of Parkinson's disease

Author: Descombes, S., Muriel Bonnet, Gasser, U. E., Thalamas, C., Dingemanse, J., Arnulf, I., Bareille, M. P., Agid, Y., Rascol, O., and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], THERAPEUTICS, NERVOUS SYSTEM, PARKINSON'S DISEASE
Published: 2001

22. Dyskinesias assessment in Phase II studies

Author: Damier P, Jaillon C, Clavier I, Isabelle Arnulf, Am, Bonnet, Bp, Bejjani, and Agid Y
Subjects: Levodopa, Dyskinesia, Drug-Induced, Clinical Protocols, Dose-Response Relationship, Drug, Dopamine, Dopamine Agonists, Brain, Humans, Biological Transport, Sensitivity and Specificity
Published: 1999

23. Glial cell participation in the degeneration of dopaminergic neurons in Parkinson's disease

Author: Ec, Hirsch, Hunot S, Damier P, Brugg B, Ba, Faucheux, Patrick Pierre Michel, Ruberg M, Mp, Muriel, Mouatt-Prigent A, and Agid Y
Subjects: Neurons, Dopamine, Nerve Degeneration, Humans, Parkinson Disease, Neuroglia
Published: 1999

24. [Study of cortical atrophy with magnetic resonance imaging in corticobasal degeneration]

Author: Ballan G, Tison F, VINCENT DOUSSET, Vidailhet M, Agid Y, and Henry P
Subjects: Cerebral Cortex, Male, Tomography, Emission-Computed, Single-Photon, Nerve Degeneration, Humans, Female, Neurodegenerative Diseases, Age of Onset, Middle Aged, Magnetic Resonance Imaging, Aged, Retrospective Studies, Tomography, Emission-Computed
Abstract: Corticobasal degeneration (C.B.D.) is a neurodegenerative disorder characterized mainly by an asymmetrical a kineto-rigid syndrome associated with fronto-parietal cortical signs, particularly apraxia. Conventional imaging even magnetic resonance imaging (M.R.I.) has often been considered as poorly contributive for the diagnosis of C.B.D. We retrospectively studied routinely performed M.R.I. scans of 15 patients presenting a clinical and metabolic (P.E.T/S.P.E.C.T.) syndrome characteristic of probable C.B.D. M.R.I. scans were assessed by 3 investigators, not aware of the clinically most affected side, taking into account M.R.I. technical parameters. We quantified, on each side, the cortical atrophy (frontal, parietal and temporal) and the white matter changes, by using the semi-quantified method of Victoroff et al. (1994). Abnormalities were considered if observed by at least 2 of the 3 investigators. Abnormalities were then correlated with the side initially and most severely affected. The most contributive findings were the asymmetric parietal atrophy (clinically correlated in 93 p. 100 of cases), asymmetric frontal atrophy (clinically correlated in 60 p. 100) and asymmetric dilatation of the lateral ventricles (clinically correlated in 60 p. 100). 80 p. 100 of affected subjects displayed at least 2 of these M.R.I. abnormalities. These results are in accordance with the metabolic and pathologic features of C.B.D. This study demonstrates that M.R.I. evaluation of the cortical atrophy asymmetry may contribute to the diagnosis of C.B.D.
Published: 1998

25. Somatotopical organization of striatal activation during finger and toe movement: a 3-T functional magnetic resonance imaging study

Author: Lehéricy, Stéphane, van de Moortele, P. F., Lobel, E., Paradis, A. L., Vidailhet, M., Frouin, V., Neveu, P., Agid, Y., Marsault, C., Le Bihan, D., IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-anatomie fonctionnelle du comportement et de ses troubles, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Laboratoire de Physiologie de la Perception et de l'Action (LPPA), Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de neurologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CEA : DSV/iRCM/SCSR/LEFG (LEFG), Laboratoire d'Exploration Fonctionnelle des Génomes (LEFG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service NEUROSPIN (NEUROSPIN), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de physiologie de la perception et de l'action (LPPA), Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Montréal (UQAM), Service de neurologie 1 [CHU Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Brain Mapping, MESH: Humans, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Movement, MESH: Adult, MESH: Psychomotor Performance, MESH: Movement, Toes, Magnetic Resonance Imaging, Basal Ganglia, Corpus Striatum, MESH: Male, MESH: Toes, MESH: Corpus Striatum, MESH: Magnetic Resonance Imaging, Fingers, MESH: Basal Ganglia, MESH: Fingers, Humans, Female, MESH: Female, Psychomotor Performance, MESH: Brain Mapping
Abstract: International audience; The present study aimed at determining the distribution and somatotopical organization of striatal activation during performance of simple motor tasks. Ten right-handed healthy volunteers were studied by using a 3-T whole-body magnetic resonance unit and echo planar imaging. The tasks consisted of self-paced flexion/extension of the right fingers or toes. Motor activation was found mainly in the putamen posterior to the anterior commissure (10 of 10 subjects) and the globus pallidus (6 subjects), whereas the caudate nucleus was activated in only 3 subjects, and in a smaller area. Thus, performance of a simple motor task activated the sensorimotor territory of the basal ganglia. Within the putamen, there was a somatotopical organization of the foot and hand areas similar to that observed in nonhuman primates. These data suggest that functional magnetic resonance imaging can be used to study normal function of the basal ganglia and should therefore also allow investigation of patients with movement disorders.
Published: 1998
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26. Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations

Author: Vaughan, JR, Farrer, MJ, Wszolek, ZK, Gasser, T, Durr, A, Agid, Y, Bonifati, V, de Michele, G, Volpe, G, Lincoln, S, Breteler, Monique, Meco, G, Brice, A, Marsden, CD, Hardy, J, Wood, NW, and Epidemiology
Published: 1998

27. The alpha-synuclein Ala53Thr mutation is not a common cause of familial Parkinson's disease: a study of 230 European cases

Author: Vaughan, J, Durr, A, Tassin, J, Bereznai, B, Gasser, T, Bonifati, V, de Michele, G, Fabrizio, E, Volpe, G, Bandmann, O, Johnson, WG, Golbe, LI, Breteler, Monique, Meco, G, Agid, Y, Brice, A, Marsden, CD, Wood, NW, and Epidemiology
Published: 1998

28. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease

Author: Agid, Y., Etienne Hirsch, Ruberg, M., Mouattprigent, A., Marquez, J., Michel, Pp, Herrero, Mt, Javoyagid, F., Vyas, S., and Anglade, P.
Subjects: Aged, 80 and over, Neurons, Substantia Nigra, Microscopy, Electron, nervous system, Parkinson's disease, Dopamine, Autophagy, Humans, Apoptosis, Parkinson Disease, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología::616.8 - Neurología. Neuropatología. Sistema nervioso [CDU], Aged
Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss confined mostly to dopaminergic neurons of the substantia nigra. Several factors, including oxidative stress, and decreased activity of complex 1 mitochondrial respiratory chain, are involved in the degenerative process. Yet, the underlying mechanisms leading to dopaminergic cell loss remain elusive. Morphological assessrnent for different modes of cell death: apoptosis, necrosis or autophagic degeneration, can contribute significantly to the understanding of this neurona1 loss. Ultrastructural examination revealed characteristics of apoptosis and autophagic degeneration in melanized neurons of the substantia nigra in PD patients. The results suggest that even at the final stage of the disease, the dopaminergic neurons are undergoing active process of cell death.
Published: 1997

29. Recombination hot spot in a 3.2-kb region of the Charcot-Marie-Tooth type 1A repeat sequences: new tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A. French CMT Collaborative Research Group

Author: Lopes J, LeGuern E, Gouider R, Tardieu S, Abbas N, Birouk N, Gugenheim M, Bouche P, Agid Y, and Alexis Brice
Subjects: Recombination, Genetic, congenital, hereditary, and neonatal diseases and abnormalities, Genomic Library, Polymorphism, Genetic, Genotype, Restriction Mapping, Chromosome Mapping, Charcot-Marie-Tooth Disease, Humans, Crossing Over, Genetic, Cloning, Molecular, Hereditary Sensory and Motor Neuropathy, Chromosomes, Artificial, Yeast, Chromosomes, Human, Pair 17, Repetitive Sequences, Nucleic Acid, Research Article
Abstract: Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who where unrelated. A hot spot of crossover breakpoints, located in a 3.2-kb region, accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots.
Published: 1996

30. High frequency of mutations in codon 98 of the peripheral myelin protein P0 gene in 20 French CMT1 patients

Author: Rouger H, LeGuern E, Gouider R, Tardieu S, Birouk N, Gugenheim M, Bouche P, Agid Y, and Alexis Brice
Subjects: Male, Letter, Base Sequence, Charcot-Marie-Tooth Disease, DNA Mutational Analysis, Molecular Sequence Data, Humans, Female, Codon, Myelin P0 Protein, Pedigree
Published: 1996

31. Is dopaminergic cell death accompanied by concomitant nerve plasticity?

Author: Etienne Hirsch, Agid, Y., Javoyagid, F., Strada, O., Kastner, A., Mouattprigent, A., Obeso, Ja, Herrero, Mt, Faucheux, Ba, Raismanvozari, R., Blanchard, V., and Anglade, P.
Subjects: Neuronal Plasticity, Cell Death, Dopamine, Nerve Degeneration, Animals, Humans, Parkinson Disease, Nervous System Diseases, Parkinson Disease, Secondary
Published: 1996

32. [Phenotype of familial forms of early-onset Alzheimer's disease linked to chromosome 14. Clinical and neuropsychological characteristics of a large group]

Author: Hannequin D, Campion D, Tardieu S, Auzou P, Martinez M, Dubois B, Clerget-Darpoux F, Agid Y, and Alexis Brice
Subjects: Adult, Chromosomes, Human, Pair 14, Male, Phenotype, Alzheimer Disease, Genetic Linkage, Mutation, Humans, Female, Middle Aged, Pedigree
Abstract: We report the clinical features and neuropsychological data of chromosome-14 linked early-onset Alzheimer's disease in a large family (FAD-RO1). Information available in the literature from eight additional chromosome 14-linked Alzheimer's disease kindreds was compared with the data obtained from six kindreds with amyloid precursor protein gene mutations (APP). In the chromosome 14-linked families the disease has an earlier onset and a shorter duration than in families with APP mutations, with an age at death lower than sixty years of age. Seizures, myoclonus and extra pyramidal signs were frequently present in the cases of FAD-RO1 as in six chromosome 14-linked kindreds, but these features were absent in two other ones. The high frequency of seizures (80%) in FAD-RO1 and two other chromosome 14-linked kindreds is remarkable. Seizures and myoclonus were encountered at a lower prevalence in APP kindreds. This review suggests that some clinical features are more prevalent in chromosome 14-linked than in APP kindreds but a phenotypic heterogeneity does exist within and between families. The profile of deterioration of the neuropsychological performances, as illustrated by the FAD-RO1 members, shows that chromosome 14-linked kindreds do not demonstrate a specific expression in comparison to APP kindreds. Memory was first impaired. Deficits in visuo-spatial and visuopractic abilities were then noted. Finally the verbal performance deteriorated.
Published: 1995

33. Are dopaminergic neurons selectively vulnerable to Parkinson's disease?

Author: Agid Y, Ruberg M, Javoy-Agid F, Etienne Hirsch, Raisman-Vozari R, Vyas S, Faucheux B, Michel P, Kastner A, and Blanchard V
Subjects: Cell Death, Risk Factors, Dopamine, Nerve Degeneration, Brain, Humans, Cell Count, Parkinson Disease, Environmental Exposure, Receptors, Dopamine
Published: 1993

34. The efficacy of levodopa treatment declines in the course of Parkinson's disease: do nondopaminergic lesions play a role?

Author: Agid Y, Am, Graybiel, Ruberg M, Etienne Hirsch, Blin J, Dubois B, and Javoy-Agid F
Subjects: Levodopa, Substantia Nigra, Brain Mapping, Neurotransmitter Agents, Neural Pathways, Brain, Humans, Parkinson Disease, Long-Term Care, Corpus Striatum, Receptors, Dopamine, Receptors, Neurotransmitter
Published: 1990

35. The nigrostriatal system in Parkinson's disease

Author: Am, Graybiel, Etienne Hirsch, and Agid Y
Subjects: Substantia Nigra, Brain Mapping, Neurotransmitter Agents, Nerve Degeneration, Animals, Humans, Parkinson Disease, Corpus Striatum, Receptors, Dopamine, Receptors, Neurotransmitter
Abstract: Patterns of dopaminergic cell loss in the midbrain and patterns of mesostriatal fiber loss in the caudate nucleus and putamen are described for cases of idiopathic Parkinson's disease. Neither cell loss nor fiber loss is homogeneous. In the midbrain, quantitative analysis points to a selective vulnerability of neurons in the most heavily pigmented dopaminergic cell groups. In the striatum, a dorsolateral-to-ventromedial gradient of loss appears to characterize both the caudate nucleus and the putamen. These patterns of loss and sparing have implications both for analysis of the clinical symptoms of Parkinson's disease and for study of the etiology of this disease.
Published: 1990

36. [3H]spiperone binding in the nigrostriatal system in human brain

Author: F Javoy-Agid, Bokobza B, M Ruberg, Agid Y, and Montfort Jc
Subjects: Male, Spiperone, medicine.medical_specialty, Time Factors, Apomorphine, Nigrostriatal pathway, Substantia nigra, Striatum, In Vitro Techniques, Biology, Binding, Competitive, Internal medicine, Basal ganglia, medicine, Humans, Phentolamine, Butaclamol, Aged, Nerve Endings, Pharmacology, Pars compacta, Cinanserin, Putamen, Butyrophenones, Corpus Striatum, Domperidone, Substantia Nigra, Kinetics, medicine.anatomical_structure, Endocrinology, nervous system, Postmortem Changes, Haloperidol, Female, Caudate Nucleus, Sulpiride, Pars reticulata, Neuroscience, medicine.drug
Abstract: The characteristics of [ 3 H]spiperone binding in human brain were compared in three areas of the nigrostriatal pathway: areas containing the nerve terminals (caudate nucleus, putamen and pallidum); the area containing the cell bodies (substantia nigra pars compacta); the area containing the dendrites (pars reticulata). The affinity constants were calculated from saturation binding curves and from the kinetics of association and dissociation. The pharmacological profile of the receptors was also established by displacement studies. The affinity constants and pharmacological profiles were similar in the striatum and the substantia nigra, although the latter contained a much smaller number of sites. In the substantia nigra, however, curved Scatchard plots were obtained, indicating that a second lower affinity site binding [ 3 H]spiperone was also present. A considerable proportion (50%) of [ 3 H]spiperone binding to nigral membranes could be displaced by the serotonin antagonist cinanserine, compared to the striatum (20%). The effect of post-mortem conditions on binding levels was studied in the rat. A loss of 20% occurred during the first hours after death, but was stable by 6 h until at least 24 h.
Published: 1984
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37. Glycine receptors in the human brain: characterization of 3H-strychnine binding and status in pathological conditions

Author: Lloyd, K. G., Maria Graziella DE MONTIS, Javoy-Agid, F., Beaumont, K., Lowenthal, A., Constantinidis, J., and Agid, Y.
Subjects: Kinetics, Huntington Disease, Membranes, Receptors, Glycine, Species Specificity, Spinal Cord, Brain, Humans, Parkinson Disease, Receptors, Cell Surface, Strychnine
Published: 1983

38. [3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy

Author: Agid Y, Bernard Scatton, M Ruberg, Bokobza B, and F Javoy-Agid
Subjects: medicine.medical_specialty, Spiperone, Dopamine, Caudate nucleus, Substantia nigra, Striatum, Nucleus Accumbens, Receptors, Dopamine, Levodopa, Internal medicine, medicine, Humans, Paralysis, Aged, Phenylacetates, Pharmacology, Chemistry, Pars compacta, Putamen, Brain, Homovanillic Acid, Parkinson Disease, Butyrophenones, Substantia Nigra, Endocrinology, nervous system, Caudate Nucleus, Pars reticulata, medicine.drug
Abstract: The density of D2-type dopamine receptors, measured by the binding of [3H]spiperone was normal in the substantia nigra, caudate nucleus and nucleus accumbens of Parkinsonian subjects and above control levels in the putamen, in spite of massive lesions of the dopaminergic neurons. Dopamine levels were reduced in the putamen, caudate nucleus, and nucleus accumbens by 97, 85 and 68%, respectively and by 78 and 93% in the pars compacta and pars reticulata of the substantia nigra. HVA levels were much less affected suggesting that increased activity of the remaining dopaminergic neurons compensated to some extent for the lesions. Neuroleptic treatment and the presence of dementia in the Parkinsonian subjects affected [3H]spiperone binding and dopamine concentrations. Dopamine and HVA levels in the striatum of subjects with supranuclear palsy indicate that the nigrostriatal system was lesioned to the same degree in this disease as in idiopathic Parkinsonism, but spiperone binding was reduced by half in all the structures studies.
Published: 1984

39. Frequency and spectrum of mutations in the protein kinase Cy gene associated with spinocerebellar ataxia type 14 (SCA14)

Author: Brice, A., Klebe, S., Hahn-Barma, V., Bouslam, N., Jedinak, P., Forlani, S., Agid, Y., Durr, A., and Giovanni Stevanin

40. Effect of dopaminergic denervation and levodopa therapy on tyrosine hydroxylase mRNA expression in the monkey substantia nigra

Author: Herrero, M. -T, Vyas, S., Levy, R., Faucon, N., Guillen, J., Luquin, M. R., Jorge Guridi, Javoy-Agid, F., Agid, Y., Hirsch, E. C., and Obeso, J. A.

41. Chronic thalamic stimulation with three-dimensional MR stereotactic guidance

Author: Dormont D, Cornu P, Pidoux B, Am, Bonnet, Alessandra Biondi, Oppenheim C, Hasboun D, Damier P, Cuchet E, Philippon J, Agid Y, and Marsault C
Subjects: Male, Neurologic Examination, Brain Mapping, Electric Stimulation Therapy, Parkinson Disease, Equipment Design, Middle Aged, Magnetic Resonance Imaging, Electrodes, Implanted, Stereotaxic Techniques, Treatment Outcome, Thalamic Nuclei, Tremor, Image Processing, Computer-Assisted, Journal Article, Humans, Female
Abstract: PURPOSE: To report a method of electrode implantation in the ventralis intermedius nucleus of the thalamus for the treatment of tremor using a 3-D stereotactic MR imaging technique. METHODS: Five patients (three men and two women; mean age, 59 years) with medically refractory tremor had intrathalamic implantation of a stimulating electrode. Stereotactic MR imaging was performed on a 1.5-T unit equipped with an MR-compatible Leksell G stereotactic frame fixed to the patient's head. Calculation of the coordinates of the theoretical target was based on the coordinates of the anterior commissure, the posterior commissure, and the midline sagittal plane as determined via stereotactic MR imaging. During the surgical procedure, the best position for the stimulating electrode was determined by electrophysiological and clinical studies. Postoperative MR control studies were done in all cases to verify the position of the electrode. RESULTS: Stereotactic MR imaging allowed precise implantation of the stimulating electrode in all patients. Electrode stimulation produced a 90% reduction of the tremor in two patients, an 80% and 70% reduction in one patient each, and a persistent microthalamotomy-like effect in the fifth patient. Examination of the MR control studies showed that mean error in the positioning of the electrodes was 0.77 +/- 0.6 mm (mean +/- SD) in the x direction and 0.80 +/- 1.02 mm in the y direction. CONCLUSION: Although our series is relatively small, the precision achieved with stereotactic MR imaging proves that it can be used with confidence for precise functional neurosurgical procedures.

42. Large-scale replication and heterogeneity in Parkinson disease genetic loci

Author: Sharma, Manu, Ioannidis, John P A, Facheris, Maurizio, Klein, Christine, Djarmati, Ana, Hagenah, Johann, Lohmann, Katja, Auburger, Georg, Hilker, Rüdiger, van de Loo, Simone, Dardiotis, Efthimios, Tsimourtou, Vaia, Ralli, Styliani, Farrer, Matthew, Kountra, Persa, Patramani, Gianna, Vogiatzi, Cristina, Hattori, Nobutaka, Tomiyama, Hiroyuki, Funayama, Manabu, Yoshino, Hiroyo, Li, Yuanzhe, Imamichi, Yoko, Toda, Tatsushi, Garraux, Gaetan, Satake, Wataru, Lynch, Tim, Gibson, J Mark, Valente, Enza Maria, Ferraris, Alessandro, Dallapiccola, Bruno, Ialongo, Tamara, Brighina, Laura, Corradi, Barbara, Piolti, Roberto, Gispert, Suzana, Tarantino, Patrizia, Annesi, Ferdinanda, Jeon, Beom S, Park, Sung-Sup, Aasly, J., Opala, Grzegorz, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Boczarska-Jedynak, Magdalena, Tan, Eng King, Belin, Andrea Carmine, Olson, Lars, Galter, Dagmar, Westerlund, Marie, Sydow, Olof, Nilsson, Christer, Puschmann, Andreas, Lin, J. J., Maraganore, Demetrius M, Ahlskog, J Eric, Vilariño-Güell, Carles, de Andrade, Mariza, Lesnick, Timothy G, Rocca, Walter A, Checkoway, Harvey, Ross, Owen A, Wszolek, Zbigniew K, Uitti, Ryan J, Hadjigeorgiou, Georgios M, Hicks, Andrew A, Jeon, Beom, Aasly, Jan O, Lesage, Suzanne, Lill, Christina M, Lin, Juei-Jueng, Lynch, Timothy, Lichtner, Peter, Lang, Anthony E, Mok, Vincent, Mellick, George D, Morrison, Karen E, Annesi, Grazia, Pramstaller, Peter P, Pichler, Irene, Park, Sung Sup, Quattrone, Aldo, Rogaeva, Ekaterina, Stefanis, Leonidas, Stockton, Joanne D, Brice, Alexis, Silburn, Peter A, Theuns, Jessie, Tan, Eng-King, Wirdefeldt, Karin, Wszolek, Zbigniew, Xiromerisiou, Georgia, Yueh, Kuo-Chu, Van Broeckhoven, Christine, Zhao, Yi, Gasser, Thomas, Maraganore, Demetrius, Krüger, Rejko, Consortium, GEO-PD, Boyle, R. S., Sellbach, A., O'Sullivan, J. D., Sutherland, G. T., Siebert, G. A., Bertram, Lars, Dissanayaka, N. N. W., Crosiers, David, Pickut, Barbara, Engelborghs, Sebastiaan, Meeus, Bram, De Deyn, Peter P, Cras, Patrick, Bozi, Maria, Agid, Y., Anheim, M., Bonnet, A-M, Borg, M., Brice, A., Broussolle, E., Corvol, J. C., Damier, P., Destée, A., Dürr, A., Durif, F., Lesage, S., Lohmann, E., Pollak, P., Rascol, O., Tison, F., Tranchant, C., Viallet, F., Vidailhet, M., Clarke, Carl, Tzourio, Christophe, Amouyel, Philippe, Loriot, Marie-Anne, Mutez, Eugénie, Duflot, Aurélie, Legendre, Jean-Philippe, Waucquier, Nawal, Riess, Olaf, Berg, Daniela, Schulte, Claudia, Pathologic Biochemistry and Physiology, Pollak, Pierre, De Deyn, Peter Paul, and GEO-PD Consortium
Subjects: Male, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Case-control studies, Biology, Polymorphism, Single Nucleotide, Gene Frequency, genetics [Parkinson Disease], Humans, Genetic Predisposition to Disease, ddc:610, Allele, Parkinson Disease/genetics, Allele frequency, Alleles, Genetic association, Aged, Genetics, Medicine(all), Case-control study, Parkinson Disease, Odds ratio, Middle Aged, ddc:616.8, Genetic epidemiology, Genetic Loci, Case-Control Studies, Female, Neurology (clinical), Human medicine, Genome-Wide Association Study
Abstract: Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson9s Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 ( LAMP3 , BST1 , and MAPT ) and susceptibility per-allele odds ratios of 1.14–1.43 ( STK39 , GAK , SNCA , LRRK2 , SYT11 , and HIP1R ). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes ( I 2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA , LRRK2 , LAMP3 , HIP1R , and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology ® 2012;79:659–667
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43. Consequences of nigrostriatal denervation on the functioning of the basal ganglia in human and nonhuman primates: An in situ hybridization study of cytochrome oxidase subunit I mRNA

Author: Vila, M., Levy, R., MARIA TRINIDAD HERRERO, Ruberg, M., Faucheux, B., Obeso, J. A., Agid, Y., and Hirsch, E. C.

44. Distinct frontal regions for processing sentence syntax and story grammar

Author: Sirigu, A., laurent cohen, Zalla, T., Pradat-Diehl, P., Eeckhout, P., Grafman, J., and Agid, Y.

45. [In vivo study of central serotoninergic receptors in man using positron tomography]

Author: Jc, Baron, yves samson, Comar D, Crouzel C, Deniker P, and Agid Y
Subjects: Kinetics, Piperidines, Chlorpromazine, Cerebellum, Receptors, Serotonin, Brain, Humans, Ketanserin, Frontal Lobe, Tomography, Emission-Computed
Abstract: In an attempt to characterize in vivo the central serotonergic (5-HT2) receptors in humans with positron emission tomography (PET), we have used 11C-labeled-ketanserin, a seratonergic antagonist that has high affinity and selectivity for the 5-HT2 receptors in vitro. Earlier in vivo studies in rats had demonstrated a preferential accumulation of 3H-ketanserin in the frontal cortex relative to cerebellum, in accordance with known differences in density of 5-HT2 receptor in these two brain structures (5-HT2 receptors are dense in frontal cortex and sparse or absent in cerebellum). In rats, tracer accumulation in frontal cortex represented specific binding of 3H-ketanserin to 5-HT2 receptors in vivo as demonstrated by inhibition, saturation, and displacement studies. In 5 control subjects, we found a statistically significant retention of 11C-ketanserin in frontal cortex relative to cerebellum after intravenous injection of a tracer dose of the radioligand, suggesting specific in vivo binding of 11C-ketanserin to frontal cortex. To substantiate this hypothesis, we studied 4 subjects administered unlabeled chlorpromazine (CPZ) intramuscularly in therapeutic amounts (75 mg) two hours before the PET study. Pretreatment with CPZ decreased significantly the retention of 11C-ketanserin by the frontal cortex, indicating that almost total occupation of the ketanserin receptors by CPZ had been achieved prior to the injection of the radioligand. Despite these positive results, both the duration and the magnitude of tracer retention by frontal cortex in control subjects were much smaller than was reported in rats, presumably indicating lower specific binding, higher nonspecific binding, and faster drug metabolism in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

46. A second family linked to spinocerebellar ataxia 5

Author: Herman, A., Giovanni Stevanin, Cancel, G., Didierjean, O., Lebre, As, Agid, Y., Brice, A., and Durr, A.

47. Somatotopical organization of striatal activation during hand and toes movements: A 3T fMRI study

Author: Lehéricy, S., Pierre-Francois Van de Moortele, Lobel, E., Paradis, A. -L, Vidailhet, M., Agid, Y., Marsault, C., and Le Bihan, D.

48. Huntington's disease in French families: CAG repeat expansion and linkage disequilibrium analysis

Author: Dodé C, Dürr A, Pêcheux C, Jf, Mouret, Belal S, Bachner L, Agid Y, Jc, Kaplan, Alexis Brice, and Feingold J
Subjects: Huntington Disease, Haplotypes, Gene Amplification, Humans, France, Polymerase Chain Reaction, Linkage Disequilibrium
Abstract: The molecular defect causing Huntington's disease (HD) has been found as an expansion of CAG triplets in the 5' coding region of IT15 gene. In the 29 French families reported, the HD disease is due to the expansion of the CAG triplets region above 38 copies. The complete sequencing of 10 HD alleles PCR products allowed us to confirm that expansion is restricted to the CAG repeat region and does not extend to the adjacent CCG repeat region which is also present in the PCR product. Then, we analysed linkage disequilibrium between the molecular defect and 6 DNA markers mapping to the 4p16.3 region. The most striking finding in this study is the presence of a strong linkage disequilibrium between HD and D4S127 (PvuII), D4S95 (AccI, MboI, TaqI) located in a region of 130 kb distal to IT15 gene. Two major haplotypes, comprising D4S127 (PvuII) and D4S95 (MboI, AccI) polymorphic sites, were found in the normal population as only one was found associated with HD alleles. This result can be interpreted either as an evidence for a rather recent founder effect or as several independent mutations occuring in chromosomes bearing the same haplotype.

49. Linkage disequilibrium at the Machado-Joseph disease/spinal cerebellar ataxia 3 locus: evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation

Author: Stevanin G, Cancel G, Didierjean O, Dürr A, Abbas N, Cassa E, Feingold J, Agid Y, and Alexis Brice
Subjects: Chromosomes, Human, Pair 14, Letter, Haplotypes, Portugal, Mutation, Humans, France, Machado-Joseph Disease, Brazil, Linkage Disequilibrium, Spinocerebellar Degenerations

50. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease

Author: Obeso, Ja, Guridi, J., Rodriguez-Oroz, Mc, Agid, Y., Bejjani, P., Bonnet, Am, Lang, Ae, Lozano, Am, Kumar, R., Benabid, A., Pollack, P., Krack, P., Rehncrona, S., Ekberg, R., Grabowski, M., Albanese, A., Scerrati, M., Moro, E., Koller, W., Wilkinson, Sb, Pahwa, R., Volkmann, J., Allert, N., Freund, Hj, Kulisevsky, J., Gironell, A., Molet, J., Tronnier, V., Fogel, W., Krause, M., Funk, T., Kern, C., Kestenbach, U., Iansek, R., Rosenfeld, J., Churchyard, A., O Sullivan, D., Pell, M., Markus, R., Bayes, A., Blesa, R., Oliver, B., Olanow, Cw, isabelle germano, Brin, M., Jankovic, J., Grossman, Rg, Ondo, Wg, Vitek, Jl, Bakay, Rae, DeLong, MR, Tolosa, E., Rumia, J., Valldeoriola, F., Lang, Am, Lozano, A., Koller, Wc, Vitek, J., Wilkinson, S., and Deep-Brain Stimulation Parkinsons

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