Author: "Didier Hannequin" - Searchworks@Jio Institute Digital Library Search Results

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335 results on '"Didier Hannequin"'

101. Dissections artérielles cervicales multiples chez deux frères : dysplasie fibro-musculaire ou maladie du tissu conjonctif ?

Author: P. Verdure, Didier Hannequin, J. Perdu, Lucie Guyant-Maréchal, Annie Laquerrière, Emmanuel Gerardin, and Aude Triquenot-Bagan
Subjects: Pathology, medicine.medical_specialty, medicine.diagnostic_test, Arterial dissection, business.industry, Magnetic resonance imaging, 030204 cardiovascular system & hematology, medicine.disease, Connective tissue disease, 03 medical and health sciences, 0302 clinical medicine, Text mining, Neurology, Dysplasia, Severity of illness, Angiography, medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2008

102. Infarctus cérébral et iridodonésis révélant une homocystinurie par mutation hétérozygote composite de la cystathionine bêta-synthase

Author: Romain Lefaucheur, M. Quillard, Aude Triquenot-Bagan, Didier Hannequin, and O. Genevois
Subjects: Mutation, medicine.medical_specialty, biology, business.industry, Cerebral infarction, Homocystinuria, medicine.disease_cause, medicine.disease, Compound heterozygosity, Cystathionine beta synthase, Endocrinology, Neurology, Polymorphism (computer science), Internal medicine, biology.protein, Medicine, Neurology (clinical), business, Ectopia lentis, Stroke
Abstract: Iridodonesis or tremulous iris is a clinical sign of ectopia lentis which is frequently associated with homocystinuria. We present a forty-two-year-old woman victim of a left middle cerebral artery ischemic stroke. The clinical examination found bilateral iridodonesis and laboratory tests showed an increased level of serum homocysteine and homocystinuria. Homocystinuria was caused by a compound heterozygous I278T and D444N mutation of cystathionine beta-synthase (CBS) gene and also a C667T heterozygous polymorphism of methylene-tetrahydrofolate-reductase gene. This case was atypical because of the incomplete phenotype, development of complications in adulthood and the association of a rare compound heterozygous mutation of the CBS gene.
Published: 2008

103. Microsubthalamotomy: An immediate predictor of long-term subthalamic stimulation efficacy in Parkinson disease

Author: Bertrand Debono, Emmanuel Gerardin, David Maltête, Pierre Fréger, Didier Hannequin, Jean François Menard, Nathalie Chastan, Bruno Mihout, and Stéphane Derrey
Subjects: 0303 health sciences, medicine.medical_specialty, Deep brain stimulation, medicine.medical_treatment, Dopaminergic, Stimulation, medicine.disease, nervous system diseases, Central nervous system disease, 03 medical and health sciences, Subthalamic nucleus, 0302 clinical medicine, Degenerative disease, Neurology, Rating scale, Internal medicine, medicine, Physical therapy, Cardiology, Neurology (clinical), Psychology, 030217 neurology & neurosurgery, 030304 developmental biology, Morning
Abstract: A microsubthalamotomy (mSTN) effect is commonly described after implantation that improves Parkinson's motor disability and is considered to be an obvious sign of good placement of the definitive electrode within the subthalamic nucleus (STN). There has been no formal study, however, demonstrating whether this mSTN effect can predict the long-term efficacy of STN stimulation in Parkinson Disease. The mSTN effect was defined by the percentage improvement of unified parkinson's disease rating scale (UPDRS III) baseline score assessed the third day morning following STN implantation, after at least a 12 hour withdrawal of dopaminergic treatment and before the programmable pulse generator was switched on. It was assessed in 30 consecutive patients with PD submitted for STN stimulation. Multiple stepwise regression analysis showed that mSTN effect (P = 0.005) and global mean intensity of stimulation (P = 0.004) were accurate independent predictors of the 6-month postoperative UPDRS III motor score improvement in the off-drug/on-stimulation condition.
Published: 2008

104. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study

Author: Valérie Hahn-Barma, Bruno Dubois, Jean-Charles Lambert, Dominique Campion, Serge Bakchine, Agnès Camuzat, Christine Van Broeckhoven, Serge Belliard, Michèle Puel, Patrice Verpillat, Eric Guedj, Alexis Brice, Fabienne Clot, Marie-Odile Habert, Isabelle Le Ber, Jacqueline Mikol, Pascal Lejeune, Ftd-Mnd, Julie van der Zee, Mustapha Ghanim, Didier Hannequin, Vincent Deramecourt, Christian Meyrignac, Martine Vercelletto, Anne Rovelet-Lecrux, Florence Pasquier, Lucette Lacomblez, Vincent de La Sayette, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Department of Genetics, University Hospital, Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre des Maladies Cognitives et Comportementales [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerpen, Université de Reims Champagne-Ardenne (URCA), Neurologie générale et maladies inflammatoires du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Service d′Anatomie et de Cytologie Pathologiques [Lariboisiere], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Intercommunal, Centre Hospitalier Départemental, Laboratoire de Neuropsychologie, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Clinique neurologique, Hôpital Laennec, Service de neurologie, 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, Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine nucléaire [CHU Pitié-Salpétrière], 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 du Langage et de Neuropsychologie, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-06-MRAR-005-01, ANR, Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université de Rennes (UR), French research Network on FTD/FTD-MND, and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Pathology, Neuropsychological Tests, MESH: Epidemiologic Methods, MESH: Aphasia, Primary Progressive, Apraxia, MESH: Magnetic Resonance Imaging, Primary progressive aphasia, Progranulins, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Motor Neuron Disease, Corticobasal degeneration, Age of Onset, MESH: Brain Mapping, MESH: Heterozygote, Aged, 80 and over, MESH: Aged, Brain Mapping, 0303 health sciences, MESH: Middle Aged, Parkinsonism, Brain, MESH: Neuropsychological Tests, Middle Aged, Magnetic Resonance Imaging, MESH: Dementia, 3. Good health, Phenotype, Disease Progression, Intercellular Signaling Peptides and Proteins, Female, MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Haploinsufficiency, Frontotemporal dementia, Adult, Heterozygote, medicine.medical_specialty, MESH: Mutation, MESH: Age of Onset, MESH: Phenotype, MESH: Brain, 03 medical and health sciences, medicine, Humans, Dementia, Motor Neuron Disease, MESH: Intercellular Signaling Peptides and Proteins, Aged, 030304 developmental biology, MESH: Humans, Lewy body, MESH: Adult, medicine.disease, MESH: Male, MESH: Cognition Disorders, Aphasia, Primary Progressive, Mutation, Neurology (clinical), Cognition Disorders, Epidemiologic Methods, MESH: Female, 030217 neurology & neurosurgery
Abstract: Frontotemporal dementia (FTD), characterized by behavioural and language disorders, is a clinically, genetically and pathologically heterogeneous group of diseases. The most recently identified of the four known genes is GRN, associated with 17q-linked FTD with ubiquitin-immunoreactive inclusions. GRN was analysed in 502 probands with frontal variant FTD (fvFTD), FTD with motoneuron disease (FTD-MND), primary progressive aphasia (PPA) and corticobasal degeneration syndrome (CBDS). We studied the clinical, neuropsychological and brain perfusion characteristics of mutation carriers. Eighteen mutations, seven novel were found in 24 families including 32 symptomatic mutation carriers. No copy number variation was found. The phenotypes associated with GRN mutations vary greatly: 20/32 (63%) carriers had fvFTD, the other (12/32, 37%) had clinical diagnoses of PPA, CBDS, Lewy body dementia or Alzheimer's disease. Parkinsonism developed in 13/32 (41%), visual hallucinations in 8/32 (25%) and motor apraxia in 5/21 (24%). Constructional disorders were present in 10/21 (48%). Episodic memory disorders were frequent (16/18, 89%), consistent with hippocampal amnestic syndrome in 5/18 (28%). Hypoperfusion was observed in the hippocampus, parietal lobe and posterior cingulate gyrus, as well as the frontotemporal cortices. The frequency of mutations according to phenotype was 5.7% (20/352) in fvFTD, 17.9% (19/106) in familial forms, 4.4% in PPA (3/68), 3.3% in CBDS (1/30). Hallucinations, apraxia and amnestic syndrome may help differentiate GRN mutation carriers from others FTD patients. Variable phenotypes and neuropsychological profiles, as well as brain perfusion profiles associated with GRN mutations may reflect different patterns of neurodegeneration. Since all the mutations cause a progranulin haploinsufficiency, additional factors probably explain the variable clinical presentation of the disease.
Published: 2008

105. Suivi à deux ans de la cohorte de malades Alzheimer jeunes (COMAJ) à Lille

Author: Maureille, Aurélien, primary, Adeline, Rollin-Sillaire, additional, Chen, Yaohua, additional, Dubois, Bruno, additional, Didier, Hannequin, additional, and Pasquier, Florence, additional
Published: 2017
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106. ABCA7 rare variants and Alzheimer disease risk

Author: Kilan, Le Guennec, Gaël, Nicolas, Olivier, Quenez, Camille, Charbonnier, David, Wallon, Céline, Bellenguez, Benjamin, Grenier-Boley, Stéphane, Rousseau, Anne-Claire, Richard, Anne, Rovelet-Lecrux, Delphine, Bacq, Jean-Guillaume, Garnier, Robert, Olaso, Anne, Boland, Vincent, Meyer, Jean-François, Deleuze, Philippe, Amouyel, Hans Markus, Munter, Guillaume, Bourque, Mark, Lathrop, Thierry, Frebourg, Richard, Redon, Luc, Letenneur, Jean-François, Dartigues, Florence, Pasquier, Adeline, Rollin-Sillaire, Emmanuelle, Génin, Jean-Charles, Lambert, Didier, Hannequin, Dominique, Campion, Karl, Mondon, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, 03 medical and health sciences, 0302 clinical medicine, Belgium, Gene Frequency, Alzheimer Disease, Internal medicine, Missense mutation, Medicine, Humans, Exome, Genetic Predisposition to Disease, Allele frequency, Genetic Association Studies, Aged, business.industry, Case-control study, Odds ratio, Confidence interval, Minor allele frequency, 030104 developmental biology, Meta-analysis, Case-Control Studies, Mutation, ATP-Binding Cassette Transporters, Neurology (clinical), France, business, 030217 neurology & neurosurgery
Abstract: Objective:To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.Methods:We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.Results:After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68–7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89–4.20, p = 3.60 × 10−7).Conclusions:These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.
Published: 2015

107. De l’identification des bases moléculaires des calcifications cérébrales primaires aux mécanismes physiopathologiques : de nouvelles étapes

Author: Donatella Giovannini, Didier Hannequin, Marc Sitbon, Jean-Luc Battini, Gaël Nicolas, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biology, 03 medical and health sciences, 0302 clinical medicine, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Abstract: International audience
Published: 2015

108. Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Author: Paola, Caroppo, Marie-Odile, Habert, Stanley, Durrleman, Aurélie, Funkiewiez, Vincent, Perlbarg, Valérie, Hahn, Hugo, Bertin, Malo, Gaubert, Alexandre, Routier, Didier, Hannequin, Vincent, Deramecourt, Florence, Pasquier, Sophie, Rivaud-Pechoux, Martine, Vercelletto, Geoffrey, Edouart, Romain, Valabregue, Pascal, Lejeune, Mira, Didic, Jean-Christophe, Corvol, Habib, Benali, Stephane, Lehericy, Bruno, Dubois, Olivier, Colliot, Alexis, Brice, Isabelle, Le Ber, Arthur, Tenenhaus, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Laboratoire d'Imagerie Biomédicale (LIB), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-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)-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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Transferts, écoulements, fluides, énergétique (TREFLE), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique et d'Ingénierie de Bordeaux (I2M), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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 de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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)-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), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, CNRS, Inserm, Université de Lille, Lille Neurosciences & Cognition (LilNCog) - U 1172, Troubles cognitifs dégénératifs et vasculaires - U1171, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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], École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Colliot, Olivier, 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 [APHP]-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 [APHP], HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Polytechnique de Bordeaux-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, 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 [APHP], and CHU Pitié-Salpêtrière [APHP]
Subjects: Adult, Male, longitudinal, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, frontotemporal dementia, Cortical thickness, Progranulins, Fluorodeoxyglucose F18, preclinical study, progranulin, Humans, Longitudinal Studies, frontotemporal lobar degeneration, GRN, PET, dementia, presymptomatic, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organ Size, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Positron-Emission Tomography, Asymptomatic Diseases, Mutation, Disease Progression, Intercellular Signaling Peptides and Proteins, Female, Radiopharmaceuticals, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Research Article
Abstract: International audience; The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.
Published: 2015

109. TBK1 mutation frequencies in French frontotemporal dementia and amyotrophic lateral sclerosis cohorts

Author: Isabelle Le Ber, Anne De Septenville, Stéphanie Millecamps, Agnès Camuzat, Paola Caroppo, Philippe Couratier, Frédéric Blanc, Lucette Lacomblez, François Sellal, Marie-Céline Fleury, Vincent Meininger, Cécile Cazeneuve, Fabienne Clot, Olivier Flabeau, Eric LeGuern, Alexis Brice, Sophie Auriacombe, Mira Didic, Bruno Dubois, Véronique Golfier, Didier Hannequin, Richard Levy, Bernard-François Michel, Florence Pasquier, Catherine Thomas-Anterion, Michèle Puel, François Salachas, and Martine Vercelletto
Subjects: Aging, Mutation rate, Protein Serine-Threonine Kinases, medicine.disease_cause, Cohort Studies, Mutation Rate, C9orf72, mental disorders, medicine, Missense mutation, Humans, Amyotrophic lateral sclerosis, Loss function, Genetic Association Studies, Optineurin, Genetics, Mutation, business.industry, General Neuroscience, Amyotrophic Lateral Sclerosis, nutritional and metabolic diseases, medicine.disease, nervous system diseases, Frontotemporal Dementia, Neurology (clinical), France, Geriatrics and Gerontology, business, Developmental Biology, Frontotemporal dementia
Abstract: TANK1-binding kinase 1 (TBK1) has been recently identified as a new amyotrophic lateral sclerosis (ALS) gene. Loss-of-function (LoF) mutations in TBK1 could be responsible for 0.4%-4% of ALS. Considering the strong genetic overlap existing between frontotemporal dementia (FTD) and ALS, we have evaluated the frequencies of TBK1 mutations in a cohort of French FTD and of ALS patients. We identified 5 LoF mutations, in 4 FTD-ALS and 1 ALS patients. We also identified 5 heterozygous missense variants, predicted to be deleterious, in 1 isolated FTD, 1 FTD-ALS, and 3 ALS cases. Our results demonstrate that TBK1 loss-of-function mutations are more frequent in patients with FTD-ALS (10.8%) than in isolated ALS. TBK1 should thus also be sequenced, after exclusion of C9orf72 mutation, in patients presenting FTD, particularly in cases secondarily associated with ALS.
Published: 2015

110. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

Author: Donatella Giovannini, Anne Claire Richard, Michele Yang, François Boller, Pasquale Striano, Brent L. Fogel, Didier Hannequin, Uriel López-Sánchez, Marc Sitbon, Olivier Vanakker, Cyril Goizet, Marja W. Wessels, Gaël Nicolas, João Ricardo Mendes de Oliveira, Suppachok Wetchaphanphesat, María Jesús Sobrido, Jérémie Pariente, Sheila A Simpson, Cristina Castro-Fernández, Eliana Marisa Ramos, Witoon Mitarnun, Giovanni Coppola, Suppachok Kirdlarp, Elizabeth Spiteri, Vivek K. Unni, Henry L. Paulson, Beatriz Quintáns, Daniel H. Geschwind, François Tison, Dominique Campion, Anthony E. Lang, Zosia Miedzybrodzka, Martin Paucar, Per Svenningsson, Jean-Luc Battini, Joanna C. Jen, Andrea Legati, Stéphanie Cubizolle, Renee L. Sears, Angel Carracedo, Naomi Salins, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Bordeaux Segalen - Bordeaux 2, Fédération des Centres Mémoire de Ressource et de Recherche du Sud de la France [CHU Toulouse] (F-CMRR-SF), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratory of Molecular and Cellular Neuroscience, Rockefeller University [New York], Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Clinical Genetics, Centre hospitalier universitaire de Toulouse - CHU Toulouse-Hôpital La Grave-Casselardit [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]
Subjects: Male, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, DNA Mutational Analysis, Medical and Health Sciences, Receptors, G-Protein-Coupled, chemistry.chemical_compound, 0302 clinical medicine, Basal ganglia, Receptors, 2.1 Biological and endogenous factors, Aetiology, Receptor, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Brain Diseases, PDGFB, Calcinosis, Neurodegenerative Diseases, Biological Sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, 3. Good health, Virus, Pedigree, Neurological, Receptors, Virus, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.medical_specialty, Mutation, Missense, chemistry.chemical_element, Brain Diseases, Metabolic, Inborn, Genetic Association Studies, Genetic Predisposition to Disease, HEK293 Cells, Humans, Lod Score, Genetics, PDGFRB, Biology, Calcium, 03 medical and health sciences, G-Protein-Coupled, Rare Diseases, Internal medicine, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Neurosciences, Phosphate, medicine.disease, Endocrinology, Inborn, chemistry, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Metabolic, Missense, Xenotropic and Polytropic Retrovirus Receptor, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Calcification, Developmental Biology
Abstract: Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC. Lung GO Sequencing Project Lung GO Sequencing Project Women's Health Initiative (WHI) Sequencing Project Broad GO Sequencing Project Seattle GO Sequencing Project Heart GO Sequencing Project United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) Association Francaise contre les Myopathies Ligue Nationale contre le Cancer (Comite de l'Herault) Fondation pour la Recherche Medicale FEDER European Union Languedoc-Roussillon grant National Institute of Neurological Disorders and Stroke Informatics Center for Neurogenetics and Neurogenomics Fondation pour la Recherche Medicale Institut National du Cancer (INCA) France Labex GR-Ex Labex EpiGenMed French National Research Agency (ANR) Institut National de la Sante et de la Recherche Medicale (Inserm) European Commission Instituto de Salud Carlos III (ISCIII) INNOPHARMA project MINECO-USC Servizo Galego de Saúde (SERGAS) National Council for Scientific and Technological Development (CNPq) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) University Hospital of Rouen French CNR-MAJ United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS)
Published: 2015

111. Mutation in the 3’untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy

Author: Gaël Nicolas, Florence Riant, Thierry Frebourg, Dominique Campion, Pierre-Marie Preux, Claudia Goupil, Cyril Pottier, Bébène Ndamba-Bandzouzi, Pascal M'Belesso, Jean-Charles Lambert, Didier Hannequin, David Wallon, Elisabeth Tournier-Lasserve, Mariana Sarov-Rivière, Véronique Dorval, Dominique Hervé, Sébastien S. Hébert, Philippe Amouyel, Anne Rovelet-Lecrux, Maëlenn Guerchet, Anne Claire Richard, Jean-François Dartigues, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), 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), Département Imagerie et Simulation pour le Contrôle (DISC), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (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)-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 Paris-Saclay, Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), CentraleSupélec-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)
Subjects: Adult, Male, 0301 basic medicine, Untranslated region, [SDV]Life Sciences [q-bio], Molecular Sequence Data, medicine.disease_cause, Article, Amyloid beta-Protein Precursor, 03 medical and health sciences, 0302 clinical medicine, Gene duplication, mental disorders, Genetics, medicine, Amyloid precursor protein, Humans, Age of Onset, 3' Untranslated Regions, Genetics (clinical), Sequence Deletion, Regulation of gene expression, Mutation, Messenger RNA, Binding Sites, Base Sequence, biology, Three prime untranslated region, Computational Biology, Sequence Analysis, DNA, Middle Aged, medicine.disease, Cerebral Amyloid Angiopathy, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, biology.protein, Nucleic Acid Conformation, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cerebral amyloid angiopathy, 030217 neurology & neurosurgery
Abstract: International audience; Aβ-related cerebral amyloid angiopathy (CAA) is a major cause of primary non-traumatic brain hemorrhage. In families with an early onset of the disease, CAA can be due to amyloid precursor protein (APP) pathogenic variants or duplications. APP duplications lead to a ~1.5-fold increased APP expression, resulting in Aβ overproduction and deposition in the walls of leptomeningeal vessels. We hypothesized that rare variants in the 3’untranslated region (UTR) of APP might lead to APP overexpression in patients with CAA and no APP pathogenic variant or duplication. We performed direct sequencing of the whole APP 3’UTR in 90 patients with CAA and explored the functional consequences of one previously unreported variant. We identified three sequence variants in four patients, of which a two-base pair deletion (c.*331_*332del) was previously unannotated and absent from 175 controls of same ethnicity. This latter variant was associated with increased APP expression in vivo and in vitro. Bioinformatics and functional assays showed that the APP c.*331_*332del variant affected APP messenger RNA (mRNA) structure and binding of two microRNAs (miR-582-3p and miR-892b), providing a mechanism for the observed effects on APP expression. These results identify APP 3’UTR sequence variants as genetic determinants of Aβ-CAA.
Published: 2015

112. De novo deleterious genetic variations target a biological network centered on Aβ peptide in early-onset Alzheimer disease

Author: Didier Hannequin, A-C Richard, Dominique Campion, Anne Boland, Sophia Y. Breusegem, J.F. Deleuze, K Le Guennec, Anne Rovelet-Lecrux, Stéphane Rousseau, Aamir S. Mukadam, Olivier Quenez, David Wallon, Premendu P. Mathur, Pranitha Jenardhanan, Gaël Nicolas, Thierry Frebourg, Matthew N.J. Seaman, Cyril Pottier, Camille Charbonnier, and Sophie Coutant
Subjects: Male, DNA Copy Number Variations, Amyloid beta, Cellular and Molecular Neuroscience, Amyloid beta-Protein Precursor, Alzheimer Disease, Amyloid precursor protein, PSEN1, medicine, Presenilin-1, Missense mutation, Humans, Exome, Gene Regulatory Networks, Copy-number variation, Molecular Biology, Genetics, Comparative Genomic Hybridization, Amyloid beta-Peptides, biology, Genetic heterogeneity, Middle Aged, medicine.disease, Pedigree, Psychiatry and Mental health, biology.protein, Female, Alzheimer's disease, Multiplex Polymerase Chain Reaction
Abstract: We hypothesized that de novo variants (DNV) might participate in the genetic determinism of sporadic early-onset Alzheimer disease (EOAD, onset before 65 years). We investigated 14 sporadic EOAD trios first by array-comparative genomic hybridization. Two patients carried a de novo copy number variation (CNV). We then performed whole-exome sequencing in the 12 remaining trios and identified 12 non-synonymous DNVs in six patients. The two de novo CNVs (an amyloid precursor protein (APP) duplication and a BACE2 intronic deletion) and 3/12 non-synonymous DNVs (in PSEN1, VPS35 and MARK4) targeted genes from a biological network centered on the Amyloid beta (Aβ) peptide. We showed that this a priori-defined genetic network was significantly enriched in amino acid-altering DNV, compared with the rest of the exome. The causality of the APP de novo duplication (which is the first reported one) was obvious. In addition, we provided evidence of the functional impact of the following three non-synonymous DNVs targeting this network: the novel PSEN1 variant resulted in exon 9 skipping in patient's RNA, leading to a pathogenic missense at exons 8-10 junction; the VPS35 missense variant led to partial loss of retromer function, which may impact neuronal APP trafficking and Aβ secretion; and the MARK4 multiple nucleotide variant resulted into increased Tau phosphorylation, which may trigger enhanced Aβ-induced toxicity. Despite the difficulty to recruit Alzheimer disease (AD) trios owing to age structures of the pedigrees and the genetic heterogeneity of the disease, this strategy allowed us to highlight the role of de novo pathogenic events, the putative involvement of new genes in AD genetics and the key role of Aβ network alteration in AD.
Published: 2015

113. Impaired functional differentiation for categories of objects in the ventral visual stream: A case of developmental visual impairment

Author: Franck Ramus, Emmanuel Gerardin, Lucie Hertz-Pannier, Laurent D. Cohen, Alice Goldenberg, Ghislaine Dehaene-Lambertz, Irene Altarelli, Didier Hannequin, Dorothée Pouliquen, Olivier Martinaud, and Dominique Parain
Subjects: medicine.medical_specialty, Visual perception, genetic structures, Adolescent, Cognitive Neuroscience, Developmental Disabilities, Visual impairment, Vision Disorders, Experimental and Cognitive Psychology, Grey matter, Audiology, Visual system, Brain mapping, Behavioral Neuroscience, medicine, Humans, Child, Brain Mapping, Epilepsy, Dyslexia, Brain, Electroencephalography, Voxel-based morphometry, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Agnosia, Visual Perception, Female, medicine.symptom, Psychology, Cognitive psychology
Abstract: We report the case of a 14-year-old girl suffering from severe developmental visual impairment along with delayed language and cognitive development, and featuring a clear-cut dissociation between spared dorsal and impaired ventral visual pathways. Visual recognition of objects, including faces and printed words, was affected. In contrast, movement perception and visually guided motor control were preserved. Structural MRI was normal on inspection, but Voxel Based Morphometry (VBM) revealed reduced grey matter density in the mesial occipital and ventral occipito-temporal cortex. Functional MRI during the perception of line drawings uncovered impaired differentiation which is normally observed at even younger ages: no local category preferences could be identified within the occipito-temporal cortex for faces, houses, words or tools. In contrast, movement-related activations appeared to be normal. Finally, those abnormalities evolved on the background of chronic bilateral occipital epileptic activity, including continuous spike-wave discharges during sleep, which may be considered as the primary cause of non-specific intellectual disability and visual impairment.
Published: 2015

114. Angiopathie amyloïde cérébrale sporadique

Author: Didier Hannequin, Ph. Chassagne, L. Cabrejo, Jean Doucet, Annie Laquerrière, and N. Puech
Subjects: Gynecology, medicine.medical_specialty, Neurology, business.industry, medicine, Neurology (clinical), Cerebral amyloid angiopathy, medicine.disease, business, Amyloid angiopathy
Abstract: Resume Introduction L’angiopathie amyloide cerebrale (AAC) sporadique est une microangiopathie, retrouvee a l’examen neuropathologique chez plus de 30 p. 100 des sujets de plus de 85 ans. Etat des connaissances. Les criteres diagnostiques de Boston differencient : « AAC certaine avec preuve neuropathologique », « AAC probable avec preuve biopsique », « AAC probable », « AAC possible ». L’expression clinique associe des hematomes lobaires ou cerebelleux et un syndrome dementiel d’aggravation progressive. Le syndrome dementiel, correspondant aux criteres de maladie d’Alzheimer, de demence vasculaire ou mixte, peut preceder les hemorragies dans 25 a 40 p. 100 des cas. L’IRM cerebrale est l’examen de reference objectivant des microhemorragies ou « microbleeds ». Perspectives. Cette revue confronte la prevalence de l’AAC, des hemorragies cerebrales et de leurs facteurs de risque chez la personne âgee. Une demarche diagnostique et preventive est proposee. Il parait necessaire d’identifier les patients atteints d’une AAC au sein de la population des personnes âgees dementes sous anticoagulant pour une fibrillation auriculaire. Conclusion. L’angiopathie amyloide cerebrale est suspectee en cas d’hematomes cerebraux lobaires ou cerebelleux, d’autant plus s’ils compliquent une demence. Chez le patient âge dement, des arguments d’imagerie sont a promouvoir pour depister une AAC et prevenir les risques hemorragiques notamment lors d’un traitement anticoagulant.
Published: 2006

115. Valosin-containing protein gene mutations: Clinical and neuropathologic features

Author: Annie Laquerrière, Charles Duyckaerts, Jacqueline Bou, F. Dugny, Thierry Frebourg, Didier Hannequin, Lucie Guyant-Maréchal, I. Le Ber, Dominique Campion, and Cécile Dumanchin
Subjects: Male, Heterozygote, Multiple Organ Failure, Valosin-containing protein, DNA Mutational Analysis, Cell Cycle Proteins, Chromosome Disorders, Biology, medicine.disease_cause, Risk Assessment, Myositis, Inclusion Body, Risk Factors, Valosin Containing Protein, Prevalence, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, Gene, Retrospective Studies, Adenosine Triphosphatases, Genetics, Mutation, Hereditary inclusion body myopathy, Incidence, Heterozygote advantage, Syndrome, Middle Aged, Osteitis Deformans, medicine.disease, Pedigree, Multisystem proteinopathy, biology.protein, Dementia, Female, France, Neurology (clinical), Frontotemporal dementia
Abstract: Background: Hereditary inclusion body myopathy (IBMPFD) with Paget disease of bone (PDB) and frontotemporal dementia (FTD) is a rare multisystem disorder with autosomal dominant inheritance. Recently, missense mutations in the gene encoding valosin-containing protein (VCP) have been found in individuals with IBMPFD. VCP/P97, which exerts a variety of cellular functions, plays a key role in the ubiquitin-proteasome dependent degradation of cytosolic proteins and in the retrotranslocation of misfolded proteins from the endoplasmic reticulum into the cytoplasm. Methods: The authors describe the clinical features of two kindreds in which VCP R93C and R155C missense mutations segregate and perform a histopathologic examination of brain, muscle, bone, and liver of three subjects harboring the R155C mutation. Results: Frontotemporal dementia was present in 100% of affected subjects in Family F1 and 70% in Family F2, as compared with an average of 30% in previously described IBMPFD families. In contrast, PDB was a more inconstant clinical feature. Biochemical and histopathologic data are consistent with the hypothesis that VCP R155C mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. Conclusions: VCP mutations are present in two families in which FTD is the most prominent symptom. The histopathologic study performed in patients harboring the R155C mutation supports the hypothesis that this mutation disrupts normal VCP function, leading to diffuse accumulation of ubiquitinated proteins within the cells. IBMPFD belongs to a class of genetic diseases associated with an alteration of the ubiquitin-proteasome system.
Published: 2006

116. Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients

Author: Gilles Edan, Nicolas Collongues, Frédéric Blanc, Eloi Magnin, Marc Bataillard, Mickael Cohen, Thierry Levade, David Brassat, Jean-Philippe Neau, Patrizia Amati-Bonneau, Xavier Ayrignac, Maurice Giroud, Patrick Vermersch, Eric Berger, Cyril Goizet, Celine Bellesme, Clarisse Carra-Dalliere, Jean Louis Devoize, Christophe Verny, Anne Marie Guennoc, Pierre Labauge, Marc Debouverie, Pierre Clavelou, Thibault Moreau, Jean Pelletier, Laurent Magy, Bruno Brochet, Christian Denier, Jean-Philippe Camdessanché, Sandrine Wiertlewski, Nicolas Menjot de Champfleur, Jean-Christophe Ouallet, Gilles Defer, Frédérique Taithe, Elsa Kaphan, Nathalie Derache, Françoise Durand-Dubief, Michel Clanet, Sandra Vukusic, Christine Lebrun-Frenay, Stéphane Mathis, Olivier Outteryck, Bertrand Audoin, Lucie Guyant-Maréchal, Odile Boespflug Tanguy, Elisabeth Tournier-Lasserve, Didier Hannequin, Hélène Zéphir, Jean-Baptiste Chanson, Emmanuelle Le Page, Patrick Aubourg, Sophie Pittion, Jérôme De Seze, Imen Dorboz, Véronique Deburghgraeve, Giovanni Castelnovo, Dominique Bonneau, Julien Masliah-Planchon, David-Axel Laplaud, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Neuroradiology, Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Marseille, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Strasbourg], CHU Strasbourg, Laboratoire d'imagerie et de neurosciences cognitives (Strasbourg), Laboratoire d'Imagerie et de Neurosciences Cognitives (LINC), Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Etienne, Centre Hospitalier Universitaire de Nice (CHU Nice), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gérontologie (BICETRE - Géronto), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Neurologie [CHU Limoges], CHU Limoges, Centre Hospitalier d'Angoulême (CH Angoulême), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université Montpellier 1 ( UM1 ), Université Paris-Sud - Paris 11 ( UP11 ) -Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Imagerie et de Neurosciences Cognitives ( LINC ), Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique ( CNRS ) -Université Louis Pasteur - Strasbourg I-IFR37-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Nice, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Laboratoire d'Immunologie ( EA 2686 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA-D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National des Sciences Appliquées ( INSA ) -Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Service de Neurologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gérontologie ( BICETRE - Géronto ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Biologie Neurovasculaire et Mitochondriale Intégrée, Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurologie [Caen], CHU Caen-Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHRU Tours, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier d'Angoulême, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Promoting Research Oriented Towards Early Cns Therapies ( PROTECT ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Sorbonne Paris Cité ( USPC ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Pathology, leukodystrophy, Adolescent, [SDV]Life Sciences [q-bio], White matter, Leukoencephalopathy, Young Adult, metabolic, Leukoencephalopathies, medicine, Humans, Age of Onset, 10. No inequality, CADASIL, Aged, Retrospective Studies, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, business.industry, Leukodystrophy, Retrospective cohort study, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, White Matter, 3. Good health, Cerebrovascular Disorders, medicine.anatomical_structure, Cohort, Female, Neurology (clinical), France, Age of onset, genetic, business, MRI
Abstract: International audience; Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.
Published: 2014

117. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

Author: Francis Eustache, B Dupuy, Béatrice Desgranges, Fausto Viader, Florence Mézenge, Alice Pélerin, Gaël Chételat, Vincent de la Sayette, Jean-Claude Baron, and Didier Hannequin
Subjects: Male, medicine.medical_specialty, Time Factors, Neuropsychological Tests, Audiology, Developmental psychology, Arts and Humanities (miscellaneous), Fluorodeoxyglucose F18, Memory, Predictive Value of Tests, medicine, Humans, Semantic memory, Dementia, Cognitive decline, Episodic memory, Brain Concussion, Aged, Aged, 80 and over, Analysis of Variance, Brain Mapping, Recall, Neuropsychology, Reproducibility of Results, Middle Aged, Stepwise regression, medicine.disease, Regression, Psychology, Functional imaging, Positron-Emission Tomography, Female, Neurology (clinical), Cognition Disorders, Mental Status Schedule, Psychology, Follow-Up Studies
Abstract: The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.
Published: 2005

118. La dystrophie musculaire des ceintures autosomique dominante associée à des troubles de la conduction cardiaque (LGMD1B). Description de 8 nouvelles familles avec mutations du gène LMNA

Author: P.-A. Bohu, P. Laforêt, Bruno Eymard, Isabelle Pénisson-Besnier, Philippe Petiot, V. Drouin-Garraud, R. Ben Yaou, L. Demay, Didier Hannequin, Xavier Ferrer, Annick Toutain, H.M. Bécane, Nathalie Streichenberger, P. Richard, J.-M. Mussini, E. Ollagnon, and Gisèle Bonne
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine.disease, Sudden death, LMNA, Neurology, Skeletal pathology, X ray computed, medicine, Neurology (clinical), Muscular dystrophy, business, Limb-girdle muscular dystrophy
Abstract: Resume Introduction La dystrophie musculaire des ceintures de type 1B (LGMD1B), due a des mutations du gene LMNA , associe une faiblesse musculaire des ceintures a une atteinte cardiaque caracterisee par des troubles de la conduction auriculo-ventriculaire et une cardiomyopathie dilatee. Elle reste une forme peu connue de dystrophie des ceintures, et seulement 7 mutations du gene LMNA ont ete decrites comme etant responsables d’une LGMD1B. Le diagnostic clinique et genetique de cette myopathie est essentiel pour assurer la prise en charge de l’atteinte cardiaque et le conseil genetique. Patients et methodes Nous decrivons l’atteinte musculaire et cardiaque de 14 patients appartenant a 8 familles chez qui ont ete identifiees 6 mutations differentes, dont 4 nouvelles, du gene LMNA . Resultats Onze patients avaient une LGMD1B avec une atteinte scapulo-humerale et pelvi-femorale. Treize patients avaient une atteinte cardiaque. Des troubles de la conduction etaient presents chez 12 patients, et des troubles du rythme chez 9 patients. Sept patients ont beneficie de l’implantation d’un pacemaker ou d’un defibrillateur. Une transplantation cardiaque fut pratiquee dans 2 cas. Conclusion Cette etude permet de preciser les principales caracteristiques cliniques de cette affection musculaire ainsi que les premieres relations phenotype/genotype resultant de ces nouvelles observations.
Published: 2005

119. Cardiac conduction alterations in a French family with amyloidosis of the finnish type with the p.Asp187Tyr mutation in theGSN gene

Author: Stéphanie Baert-Desurmont, Annick Cabot, Pascale Saugier-Veber, Didier Hannequin, Geneviève Dérumeaux, Nathalie Chastan, and Thierry Frebourg
Subjects: Male, Pathology, medicine.medical_specialty, Physiology, Mutant, Biology, Cellular and Molecular Neuroscience, Tongue, Heart Conduction System, Physiology (medical), Cardiac conduction, medicine, Humans, Point Mutation, Hereditary gelsolin amyloidosis, Gelsolin, Aged, Aspartic Acid, Amyloidosis, Facies, Dystrophy, Arrhythmias, Cardiac, Middle Aged, medicine.disease, Pedigree, Surgery, Peripheral neuropathy, Tyrosine, Lattice corneal dystrophy, France, Neurology (clinical), Amyloidosis, Familial
Abstract: Familial amyloidosis of the Finnish type (FAF) is a rare autosomal-dominant disorder caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin, an actin-modulating protein. The main symptoms include corneal lattice dystrophy, progressive cranial and peripheral neuropathy, and skin changes. To date, only two mutations in the GSN gene have been described: the p.Asp187Asn mutation in most patients and the p.Asp187Tyr mutation in a Danish and Czech family. We report on the third family with the p.Asp187Tyr mutation and the first French FAF family. Severe cardiac conduction alterations in three patients were mainly caused by cardiac sympathetic denervation. These findings demonstrate the cardiological involvement of the FAF phenotype and suggest that cardiological follow-up is required in FAF patients.
Published: 2005

120. Ophtalmoplégie, blépharospasme et palilalie associés à des anticorps anti-Ri

Author: L. Iasci, Miret N, Mihout B, Evelyne Guegan-Massardier, Olivier Martinaud, and Didier Hannequin
Subjects: Gynecology, medicine.medical_specialty, Neurology, business.industry, medicine, Neurology (clinical), business
Abstract: Resume Introduction Les plus frequents des anticorps anti-neuronaux rapportes sont les anti-Hu et les anti-Yo. Les anti-Ri, plus rares, se manifestent le plus souvent par un opsoclonus-myoclonus et sont en general associes a un cancer du sein. Observation Nous rapportons le cas d’une femme de 54 ans presentant un syndrome paraneoplasique a anticorps anti-Ri positifs s’exprimant par une symptomatologie inhabituelle comportant une ophtalmoplegie, un blepharospasme, une palilalie et une ataxie, ayant permis de reveler un adenocarcinome du sein. Apres chimiotherapie, radiotherapie et cures d’immunoglobulines, aucune amelioration n’a ete constatee a dix mois de la tumorectomie. Conclusion Une semiologie evolutive rapide du tronc cerebral doit faire evoquer un syndrome paraneoplasique avec anticorps anti-Ri et rechercher un cancer du sein ou du poumon.
Published: 2005

121. A Diagnosis of Idiopathic Basal Ganglia Calcification in an 82-Year-Old Man

Author: Gaël Nicolas, Adeline Dreano, Dominique Campion, David Wallon, Brigitte Salle, Olivier Martinaud, Alaina Borden, and Didier Hannequin
Subjects: Pathology, medicine.medical_specialty, business.industry, Medicine, Basal ganglia calcification, Anatomy, Geriatrics and Gerontology, business
Published: 2013

122. Démences : nouveaux concepts, nouveaux enjeux

Author: Florence Pasquier, Pour le comité d’organisation, Didier Hannequin, Olivier Godefroy, Hélène Amieva, and Bruno Dubois
Subjects: Gerontology, Neurology, medicine, Dementia, Neurology (clinical), Psychology, medicine.disease
Published: 2013

123. A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24

Author: Annie Laquerrière, Nicolas Sergeant, Charles Duyckaerts, Thierry Frebourg, Maria Martinez, Guillaume Bassez, Patrick Magnier, Didier Hannequin, Bruno Eymard, Pascale Saugier-Veber, Thierry Maisonobe, G Raux, Isabelle Le Ber, Christine Bétard, André Delacourte, Dominique Campion, and Carol Girard
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Genetic Linkage, Myotonic Disorder, Tau protein, tau Proteins, Biology, Myotonic dystrophy, Proximal myotonic myopathy, Atrophy, medicine, Humans, Dementia, Sex Ratio, Age of Onset, Muscle, Skeletal, Aged, Chromosomes, Human, Pair 15, Muscle Weakness, Myosin Heavy Chains, Chromosome Mapping, RNA-Binding Proteins, Middle Aged, medicine.disease, Myotonia, Magnetic Resonance Imaging, Pedigree, Phenotype, biology.protein, Female, Neurology (clinical), Myotonic Disorders, Frontotemporal dementia
Abstract: The majority of proximal myotonic myopathy syndromes reported so far have been related to the myotonic dystrophy (DM) type 2 (DM2) mutation, an expanded (CCTG)n repeat in the ZNF9 gene. Here, we describe the phenotype and the histological features in muscle and brain of the first large pedigree with a non-myotonic dystrophy type 1 (DM1) non-DM2 multisystem myotonic disorder associated with severe frontotemporal dementia. Thirty individuals from three generations underwent detailed neurological, neuropsychological, electrophysiological, brain imaging and molecular analyses. Ten of them had proximal muscle weakness at onset, clinical/electrical myotonia and DM-type cataracts. The mean age at onset was 46.7 +/- 12.6 years (range: 32-69). Dementia was observed later in the course of the disease. On muscle biopsies, rare nuclear clumps, rimmed vacuoles and small angulated type 1 and type 2 fibres were seen early in the disease. They were replaced by fibrous adipose tissue at later stages. Immunohistochemical analysis of myosin heavy chain isoforms showed no selective fibre type atrophy-both type 1 and type 2 fibres being affected. Cortical atrophy without white matter lesions was seen on brain MRI. A brain single photon emission computed tomography (SPECT) study revealed marked frontotemporal hypoperfusion. Post-mortem examination of the brains of two patients showing prominent frontotemporal spongiosis, neuronal loss and rare neuronal and glial tau inclusions suggested frontotemporal dementia. Western blot analyses of the tau protein showed a triplet of isoforms (60, 64 and 69 kDa) in neocortical areas, and a doublet (64 and 69 kDa) in subcortical areas that distinguish our myotonic disorder from other's myotonic dystrophies. Molecular analyses failed to detect a repeat expansion in the DMPK and ZNF9 genes excluding both DM1 and DM2, whereas a genome-wide linkage analysis strongly suggested a linkage to chromosome 15q21-24. This previously unreported multisystem myotonic disorder including findings resembling DM1, DM2 and frontotemporal dementia provides further evidence of the clinical and genetic heterogeneity of the myotonic dystrophies. We propose to designate this disease myotonic dystrophy type 3, DM3.
Published: 2004

124. Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment

Author: C. Lalevée, Fausto Viader, Francis Eustache, Béatrice Desgranges, François Le Doze, Vincent de La Sayette, Brigitte Landeau, Karim Berkouk, Jean-Claude Baron, B Dupuy, Gaël Chételat, and Didier Hannequin
Subjects: Male, Statistics as Topic, Hippocampal formation, Grey matter, Statistical parametric mapping, Hippocampus, Atrophy, Fluorodeoxyglucose F18, Memory, medicine, Humans, Memory impairment, Prospective Studies, Episodic memory, Aged, Memory Disorders, Resting state fMRI, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Posterior cingulate, Female, Neurology (clinical), Radiopharmaceuticals, Cognition Disorders, Psychology, Neuroscience, Tomography, Emission-Computed
Abstract: The present study aims to unravel, in the same study, both morphological and functional specific substrates of encoding versus retrieval deficits in patients with amnestic mild cognitive impairment (MCI). For this purpose, 21 highly screened MCI patients with isolated memory impairment, who attended a memory clinic and fulfilled operational criteria for MCI, underwent (i) two episodic memory subtests designed to assess preferentially either incidental encoding or retrieval capacity; (ii) a high-resolution T1-weighted volume MRI scan; and (iii) a resting state [18F]fluoro-2-deoxy-D-glucose PET study. Using statistical parametric mapping, positive correlations between memory scores on one hand, and grey matter density and normalized partial volume effect-corrected brain glucose utilization (ncCMRglc) on the other hand, were computed. Deficits in both encoding and retrieval were correlated with declines in hippocampal region grey matter density. The encoding subtest also correlated with hippocampal ncCMRglc, whereas the retrieval subtest correlated with the posterior cingulate area ncCMRglc only. The present findings highlight a distinction in the neural substrates of encoding and retrieval deficits in MCI. Furthermore, they unravel a partial dissociation between metabolic and structural correlates, suggesting distinct interpretations. Hippocampal atrophy was related to both encoding and retrieval deficits, possibly reflecting a direct effect on hippocampal functioning, as well as an indirect effect, through remote functional disruption, on posterior cingulate region synaptic function, respectively.
Published: 2003

125. A risk for early-onset Alzheimer's disease associated with the APBB1 gene (FE65) intron 13 polymorphism

Author: Laurent Pradier, Emmanuelle Génin, Jesus Benavides, Emmanuelle Cousin, Dominique Campion, Luc Mercken, Thierry Frebourg, Didier Hannequin, Alexis Brice, Sylvain Ricard, Bruno Dubois, Jean-Francois Deleuze, C. Chansac, and Sandrine Mace
Subjects: Male, Oncology, medicine.medical_specialty, Genotype, Nerve Tissue Proteins, Disease, Biology, Central nervous system disease, Sex Factors, Alzheimer Disease, Risk Factors, Internal medicine, medicine, Humans, Dementia, Early-onset Alzheimer's disease, Age of Onset, Allele, Alleles, Aged, Aged, 80 and over, Genetics, Polymorphism, Genetic, General Neuroscience, Age Factors, Nuclear Proteins, Odds ratio, Middle Aged, medicine.disease, Introns, Genotype frequency, Case-Control Studies, Female, Alzheimer's disease
Abstract: Alzheimer's disease (AD) is a genetically complex neurodegenerative disorder and the leading cause of dementia of the elderly. Recently, Hu et al. suggested that a trinucleotide deletion in intron 13 of the APBB1 gene was a factor protecting against late-onset AD. We report here the results of a case/control study aimed at replicating this association. Our study included 461 AD patients and 397 matched controls. We compared the allele and genotype frequencies of the polymorphism between the two groups but did not find any statistically significant difference ( P =0.08 and P =0.09, respectively). By contrast, adjusting for age and sex, we found a slight risk associated with the deletion (odds ratio=1.47, 95% confidence interval=1.05–2.04). Stratification by age showed that the risk effect associated with the deletion concerned subjects aged less than 65 years.
Published: 2003

126. Severe myoclonus-dystonia syndrome associated with a novel epsilon-sarcoglycan gene truncating mutation

Author: Dominique Campion, Emmanuelle Deslandre, G Raux, Guillaume Lefebvre, Lucie Maréchal, Dominique Parain, Thierry Frebourg, Carole Girard, Cécile Dumanchin, and Didier Hannequin
Subjects: Dystonia, Genetics, congenital, hereditary, and neonatal diseases and abnormalities, Mutation, medicine.medical_specialty, Neurological disorder, Biology, medicine.disease_cause, medicine.disease, Phenotype, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Exon, Endocrinology, SGCE, hemic and lymphatic diseases, Internal medicine, medicine, medicine.symptom, Myoclonus, Genetics (clinical), Dystonic disorder
Abstract: Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions, associated with psychiatric manifestations. MDS is usually considered as a benign disease. In most of the families, MDS is linked to chromosome 7q21 and mutations within epsilon-sarcoglycan (SGCE) gene have been recently described. We report a MDS family with a severe and heterogeneous phenotype, including myoclonus with important functional impact and several psychiatric features, characterized by obsessive-compulsive disorder, depression, and anxiety. This phenotype was shown to be associated with a novel truncating mutation located within exon 4 of SGCE.
Published: 2003

127. Recurrent diplopia over a 30-year period: natural history of a Lewis and Sumner syndrome

Author: Jean Paul Bouwyn, David Wallon, Didier Hannequin, Anne-Laure Bedat-Millet, Guillaume Perot, Romain Lefaucheur, Patrick Ahtoy, and David Maltête
Subjects: medicine.medical_specialty, Weakness, Neurology, Neural Conduction, Polyradiculoneuropathy, Neurological examination, Diplopia, Humans, Medicine, Longitudinal Studies, Abducens nerve, Ulnar Nerve, Neuroradiology, medicine.diagnostic_test, business.industry, General Medicine, Middle Aged, Evoked Potentials, Motor, Magnetic Resonance Imaging, Surgery, Natural history, medicine.anatomical_structure, Upper limb, Female, Neurology (clinical), medicine.symptom, business
Abstract: We described the case of a patient with recurrent episodes of isolated diplopia over the last 30 years. On her last event, neurological examination revealed not only a right third and sixth cranial nerves involvement, but also a right peripheral facial palsy and a motor weakness on the left ulnar territory. Electrophysiological nerves motor conduction study revealed a conduction block on the left ulnar nerve and a less severe on the right ulnar nerve. Asymmetrical upper limb sensorimotor weakness combined with conduction block and cranial nerves palsy led to a diagnosis of Lewis and Sumner syndrome (LSS). This case is unusual by the presentation of the disease and is, to our knowledge the longer natural disease course of LSS reported. Moreover, it suggests that the recurrent diplopia variant may represent a separate entity with a good prognosis even in absence of invasive treatment.
Published: 2012

128. Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis

Author: Agnès Camuzat, Patrice Verpillat, Michèle Puel, Alexis Brice, Didier Hannequin, Olivier Moreaud, Françoise Clerget-Darpoux, Dominique Campion, Lucette Lacomblez, Bruno Dubois, Mira Didic, Véronique Golfier, Serge Belliard, and Catherine Thomas-Antérion
Subjects: Adult, Male, Apolipoprotein E, Oncology, medicine.medical_specialty, White People, Apolipoproteins E, Internal medicine, mental disorders, Genotype, Genetics, medicine, Humans, Allele, Risk factor, Allele frequency, Genetics (clinical), Aged, business.industry, Case-control study, Odds ratio, Middle Aged, medicine.disease, Case-Control Studies, Dementia, Female, France, business, Frontotemporal dementia
Abstract: No definite genetic risk factor of non-monogenic frontotemporal dementia (FTD) has yet been identified. Several groups have examined the potential association of FTD with the apolipoprotein E (APOE) gene, but the results are inconsistent. Our objective was to determine whether APOE is a risk factor of FTD, using the largest series of patients with FTD and controls analysed so far (94 unrelated patients and 392 age and sex-matched controls), and a meta-analysis. Homozygosity for the E2E2 genotype was significantly associated with FTD (odds ratio (OR)=11.3; P=0.033, exact test). After stratification on familial history (FH) for FTD, the OR for E2E2 was still found significant when analysing only patients with a positive FH (OR=23.8; P=0.019). The meta-analysis, using 10 case-control studies with available genotype or allele information, comprising a total of 364 FTD patients and 2671 controls, including the patients of the present study, did not reach statistical significance even if the E2E2 genotype was more frequent in patients than in controls (0.018 vs 0.006, respectively). Because of studies heterogeneity (Mantel-Haenszel statistics: P=0.004), we analysed on one hand the neuropathologically-confirmed studies, and on the other hand the clinical-based studies. In the neuropathologically-confirmed studies (Mantel-Haenszel statistics: P=ns), we found a significant increase of the E2 allele frequency in FTD patients (OR[E2 vs E3]=2.01; 95% CI=1.02-3.98; P=0.04). The same result was found in the clinical-based studies, but studies heterogeneity remained. No result was significant with the E4 allele. The E2 allele seems so to be a risk factor of FTD whereas this allele is associated with the lowest risk in Alzheimer's disease. If this finding was confirmed, it could provide new insights into the mechanisms of differential risk related to APOE in neurodegenerative diseases.
Published: 2002

129. Impact de la TEP au Florbetaben sur le diagnostic et la prise en charge de patients éligibles à une analyse du LCR pour une suspicion de maladie d’Alzheimer

Author: Mathieu Ceccaldi, Claire Houzard, Franck Semah, Rossella Gismondi, P. Krolak Salmon, Mathieu Chastan, Audrey Perrotin, Eric Guedj, Santiago Bullich, Trevor Shields, Olivier Godefroy, Antoine Verger, Nicola Raffa, Andrew W. Stephens, M.-O. Habert, Bruno Dubois, Thérèse Rivasseau Jonveaux, Aleksandar Jovalekic, Florence Pasquier, and Didier Hannequin
Subjects: Radiological and Ultrasound Technology, Biophysics, Radiology, Nuclear Medicine and imaging
Abstract: Introduction La maladie d’Alzheimer (MA) est de diagnostic difficile, en particulier dans ses formes precoces et atypiques, ou cas de comorbidites. Dans ce contexte, l’analyse des biomarqueurs du Liquide Cephalo-Rachidien (LCR) est recommandee, mais reste non realisable ou non-conclusive chez certains patients. Cette etude s’est interessee a l’impact de la TEP amyloide au 18F-Florbetaben sur le diagnostic et la prise en charge de ce groupe particulier de patients. Materiels & methodes Cette etude multicentrique (ClinicalTrials.gov : NCT02681172 ) a ete realisee au sein de 19 CMRR (Centre Memoire de Ressources et de Recherche), et services de Medecine Nucleaire associes. Elle incluait les patients eligibles pour une analyse des biomarqueurs du LCR en reference aux recommandations formulees par la Haute Autorite de sante (HAS), mais pour lesquels la ponction lombaire (PL) etait non realisable (contre-indication ; refus) ou pour lesquels les resultats etaient consideres comme ambigus. La TEP amyloide au 18F-Florbetaben etait realisee localement aupres de medecins nucleaires formes a l’interpretation de ces images. Apres diffusion du compte-rendu, le diagnostic retenu et la prise en charge etaient compares a l’evaluation initiale realisee avant la TEP. Resultats Cette etude incluait au final 205 patients (103 hommes ; 70,9 ans ± 9,7) avec un examen TEP realise et interpretable. Parmi eux, 118 n’avaient pas eu de PL, avec un refus pour 75 de ces cas. Au total, 132 des 205 examens (64,4 %) etaient positifs (amyloide + ). Apres diffusion des resultats des examens, 137/205 des diagnostics initiaux (66,8 %) etaient modifies, plus particulierement encore en cas de resultats negatifs (83,6 % vs. 57,6 % en cas d’amyloide + ; p p Conclusion L’interpretation visuelle de la TEP amyloide au 18F-Florbetaben conduite localement par des medecins nucleaires formes a ces examens influence les decisions d’expertise clinique chez les patients pour qui la PL n’est pas realisable ou pour qui les resultats du LCR restent ambigus. Ces resultats encouragent l’integration de la TEP amyloide au schema d’expertise de prise en charge diagnostique de la MA. Financement : Piramal Imaging.
Published: 2017

130. Microangiopathy in primary familial brain calcification: Evidence from skin biopsies

Author: Annie Laquerrière, Didier Hannequin, Gaël Nicolas, Florent Marguet, and João Ricardo Mendes de Oliveira
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Primary (chemistry), business.industry, Microangiopathy, MEDLINE, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Text mining, Medicine, Neurology (clinical), business, Clinical/Scientific Notes, 030217 neurology & neurosurgery, Genetics (clinical), Calcification
Published: 2017

131. NEUROMYELITIS OPTICA WITH VERY LATE ONSET

Author: Didier Hannequin, Ozlem Ozkul, Romain Lefaucheur, Bertrand Bourre, Patrick Ahtoy, David Maltête, and E. Tollard
Subjects: medicine.medical_specialty, Pediatrics, Neuromyelitis optica, business.industry, Follow up studies, Late onset, medicine.disease, Surgery, medicine, Geriatrics and Gerontology, Age of onset, business, Neuromielitis optica, Spinal cord pathology
Published: 2011

132. Multimodal neuroimaging study in presymptomatic GRN mutations carriers

Author: Paola Caroppo, Marie-Odile Habert, Stanley Durrleman, Hugo Bertin, Alexandre Routier, Vincent Perlbarg, Didier Hannequin, Basile Pinsart, Romain Valabrègue, Vincent Deramecourt, Florence Pasquier, Sophie Rivaud-Pechoux, Martine Vercelletto, Ali Bouyahia, Geoffrey Edouart, Guignebert, A., Habib Benali, Stéphane Lehericy, Olivier Colliot, Alexis Brice, Isabelle Le Ber, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-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), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Neurofonctionnelle, Université Pierre et Marie Curie - Paris 6 (UPMC), Troubles cognitifs vasculaires et dégénératifs - EA 2691 (TCDV), Université de Lille, Droit et Santé, Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut d'imagerie neurofonctionnelle (IIN), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-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), 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), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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], Service de Neurologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), 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), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], INSERM UMR_S975, 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)-Centre de référence sur les démences rares et maladie de Pick, 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 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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)-Centre de référence sur les démences rares et maladie de Pick, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-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), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Colliot, Olivier
Subjects: [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience
Published: 2014

133. Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin

Author: Isabelle Le Ber, Foudil Lamari, Didier Hannequin, Lionel Naccache, Fabienne Clot, Anne de Septenville, Alexis Brice, Anne Bertrand, Serge Belliard, Olivier Colliot, Paola Caroppo, Agnès Camuzat, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service de Neurophysiologie Clinique [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière], GRC Neurométabolisme, Université Pierre et Marie Curie - Paris 6 (UPMC), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Service de Neurophysiologie [CHU Pitié-Salpêtrière], 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)-Sorbonne Université (SU)-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)-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)-Inria de Paris, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], 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], 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)-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)-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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and 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)-Inria de Paris
Subjects: Male, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Cerebrum, MESH: Atrophy, White matter, Atrophy, Progranulins, mental disorders, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Dementia, Humans, MESH: Intercellular Signaling Peptides and Proteins, Cerebrum, Aged, Cerebral atrophy, MESH: Aged, MESH: Humans, MESH: Middle Aged, business.industry, Parietal lobe, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Frontotemporal lobar degeneration, Middle Aged, medicine.disease, White Matter, Hyperintensity, MESH: Male, medicine.anatomical_structure, MESH: White Matter, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Intercellular Signaling Peptides and Proteins, Neurology (clinical), MESH: Frontotemporal Lobar Degeneration, Frontotemporal Lobar Degeneration, Haploinsufficiency, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Mutations in the progranulin (GRN) gene are responsible for 20% of familial cases of frontotemporal dementias. All cause haploinsufficiency of progranulin, a protein involved in inflammation, tissue repair, and cancer. Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes. We describe 4 GRN mutation carriers with remarkable widespread white matter lesions (WML) associated with lobar atrophy shown on magnetic resonance imaging.; Four GRN mutation carriers (age at onset, 56-65 years) presenting with severe WML were selected from 31 GRN mutation carriers who were followed up in our dementia centers. The WML were predominantly in the frontal and parietal lobes and were mostly confluent, affecting the periventricular subcortical white matter and U-fibers. In all patients, common vascular, metabolic, inflammatory, dysimmune, and mitochondrial disorders were excluded and none had severe vascular risk factors.; Our data suggest that white matter involvement may be linked to progranulin pathological processes in a subset of GRN mutation carriers. The plasma progranulin measurement, which is predictive of GRN mutations, and GRN sequencing should thus be included in investigations of patients with frontotemporal lobar degenerations who show unusual white matter hyperintensities and atrophy on magnetic resonance imaging.
Published: 2014

134. P4‐085: MEMENTO: A NATIONAL COHORT ON DETERMINANTS AND BIOMARKERS OF ALZHEIMER'S DISEASE AND ASSOCIATED DISORDERS

Author: Frédéric Blanc, Olivier Godefroy, Marc Paccalin, Mathieu Ceccaldi, Caroline Hommet, Catherine Belin, Olivier Hanon, Armelle Gentric, Pierre Krolak-Salmon, Jérémie Pariente, Olivier Rouaud, Florence Pasquier, Olivier Marcy, François Sellal, Olivier Moreaud, Olivier Beauchet, Sandrine Harston, Geneviève Chêne, Jean-François Dartigues, Jacques Hugon, Bruno Dubois, Renaud David, Isabelle Jalenques, Pierre-Jean Ousset, Pierre Vandel, Marie-Odile Barrellon, Carole Dufouil, Didier Hannequin, Martine Vercelletto, Audrey Gabelle, and Athanase Benetos
Subjects: Epidemiology, business.industry, Visual analogue scale, Health Policy, Trail Making Test, Disease, National cohort, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Paired associate, Medicine, Psychological testing, Neurology (clinical), Geriatrics and Gerontology, Prevention trials, business, Self report, Clinical psychology
Abstract: sequence (n1⁄423), were evaluated on the Saykin scale modified for severity (Saykin-mod-sev), (Saykin, Reisberg modification, 2013), and an Emotional Severity Scale (ESS), (Guillo BenArous, 2013). We compared the scales with respect to scores on a battery of psychological tests and demographic variables, specifically, age, gender, and education. Results: We found a significant relationship between the Saykin ADNI Self Report Index and the Trail Making Test B (P1⁄40.009) (see figure). We also found a significant relationship between the Visual Analogue Scale and the Paired Associates Delayed Recall measure (p1⁄40.028). For the demographic variables a significant relationship was found with selected tests (see Figure). Conclusions: These findings could be of relevance for future prevention trials. Ultimately, we need to determine the sensitivity of temporally based scales in comparison with severity based scales and identify optimal predictors of eventual MCI and AD.
Published: 2014

135. O1‐09‐01: IMPACT OF CEREBROSPINAL FLUID BIOMARKERS OF ALZHEIMER'S DISEASE IN CLINICAL PRACTICE: A MULTICENTRIC STUDY

Author: Claire Paquet, Florence Pasquier, Didier Hannequin, Eloi Magnin, Julien Dumurgier, Philippe Robert, Bernard Croisile, Emmanuelle Duron, Anne-Cécile Troussière, David Wallon, Nathalie Philippi, Jacques Hugon, Vincent de La Sayette, François Mouton-Liger, and Audrey Gabelle
Subjects: medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Disease, Clinical Practice, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Cerebrospinal fluid, Developmental Neuroscience, medicine, Neurology (clinical), Geriatrics and Gerontology, Intensive care medicine, business
Published: 2014

136. P1‐249: ASSOCIATION BETWEEN MULTIPLE NEUROIMAGING MARKERS AND COGNITIVE PROFILES IN THE MEMENTO COHORT

Author: Martine Vercelletto, Bruno Vellas, Philippe Robert, François Sellal, Marie-Odile Habert, Pierre Krolak-Salmon, Didier Hannequin, Marie-Odile Barrellon, Stéphane Lehéricy, Mathieu Ceccaldi, Marie Chupin, Bruno Dubois, Jacques Hugon, Olivier Rouaud, Sandrine Harston, Olivier Hanon, Vincent Bouteloup, Olivier Moreaud, Frédéric Blanc, Olivier Beauchet, Geneviève Chêne, Olivier Godefroy, Catherine Belin, Marc Paccalin, Carole Dufouil, Caroline Hommet, Audrey Gabelle, Athanase Benetos, Jean-François Mangin, Florence Pasquier, and Jean-François Dartigues
Subjects: Epidemiology, business.industry, Health Policy, Cognition, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Cohort, Medicine, Neurology (clinical), Geriatrics and Gerontology, Association (psychology), business, Clinical psychology
Published: 2014

137. P1‐129: CSF AD BIOMARKERS IN MEMORY CLINIC PATIENTS: THE EP.L.M.FR STUDY

Author: Luc Buée, Claire Paquet, Olivier Bousiges, Didier Hannequin, Jacques Touchon, Audrey Gabelle, Olivier Vercruysse, Sylvain Lehmann, Constance Delaby, Jacques Hugon, Frédéric Blanc, Eloi Magnin, David Wallon, Julien Dumurgier, Muriel Quillard, Jean-Louis Laplanche, Katell Peoc'h, Florence Pasquier, Stéphanie Bombois, Susanna Schraen, and Christophe Hirtz
Subjects: Oncology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Memory clinic, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Internal medicine, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2014

138. hnRNPA2B1 and hnRNPA1 mutations are rare in patients with 'multisystem proteinopathy' and frontotemporal lobar degeneration phenotypes

Author: Edor Kabashi, Gaël Nicolas, Alexis Brice, Agnès Camuzat, Isabelle Le Ber, Serena Lattante, Didier Hannequin, Ludmila Jornea, Inge Van Bortel, Morwena Latouche, Kawtar Bouya-Ahmed, David Wallon, Anne de Septenville, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), 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), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], 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: Aging, Pathology, medicine.medical_specialty, hnRNPA1, MESH: Mutation, Heterogeneous Nuclear Ribonucleoprotein A1, MESH: Osteitis Deformans, Settore MED/03 - GENETICA MEDICA, medicine.disease_cause, Myositis, Inclusion Body, Cohort Studies, Pathogenesis, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, parasitic diseases, mental disorders, medicine, Amyotrophic lateral sclerosis, Gene, MESH: Cohort Studies, Exome sequencing, MESH: Amyotrophic Lateral Sclerosis, Mutation, business.industry, General Neuroscience, Amyotrophic Lateral Sclerosis, nutritional and metabolic diseases, Frontotemporal lobar degeneration, MESH: Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Osteitis Deformans, hnrRNPA2B1, medicine.disease, MESH: Myositis, Inclusion Body, Phenotype, Multisystem proteinopathy, nervous system diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), MESH: Frontotemporal Lobar Degeneration, ALS, Frontotemporal Lobar Degeneration, Geriatrics and Gerontology, FTLD, business, Developmental Biology
Abstract: International audience; hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed.
Published: 2014

139. Overall mutational spectrum of SLC20A2, PDGFB and PDGFRB in idiopathic basal ganglia calcification

Author: Christine Tranchant, Dominique Campion, Cyril Pottier, Didier Hannequin, Emmanuel Roze, Christophe Verny, Franck Durif, Mathieu Anheim, Pascal Favrole, Gaël Nicolas, Anne-Claire Richard, Thierry Frebourg, Gabrielle Rudolf, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), 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 [APHP]-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Département de Neurologie, CHU Strasbourg-Hopital Civil, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Université Paris Diderot - Paris 7 (UPD7)-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)-CHU Pitié-Salpêtrière [AP-HP], 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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, PDGFRB, Basal ganglia calcification, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Basal Ganglia Diseases, Genetics, medicine, Humans, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, PDGFB, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Sodium-Phosphate Cotransporter Proteins, Type III, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Calcinosis, Neurodegenerative Diseases, Molecular medicine, Human genetics, Mutation, Female, business, 030217 neurology & neurosurgery
Abstract: Familial idiopathic basal ganglia calcification (IBGC) or Fahr’s disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient’s disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.
Published: 2014

140. A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia

Author: Olivier Rouaud, David Wallon, Didier Hannequin, Christian Duvillard, Yannick Béjot, Agnès Jacquin, Christel Thauvin-Robinet, Dominique Campion, Anne Rovelet-Lecrux, Marie-Hélène Aubriot-Lorton, Cyril Pottier, Maurice Giroud, Gaël Nicolas, Stéphane Rousseau, and Thierry Frebourg
Subjects: Proband, Pathology, medicine.medical_specialty, Nonsense mutation, Short Report, Basal ganglia calcification, PDGFRB, Biology, Polymorphism, Single Nucleotide, Basal Ganglia, Laryngeal Diseases, Young Adult, Basal Ganglia Diseases, Genetics, medicine, Humans, Basal ganglia disease, Genetics (clinical), Dystonia, Brain Diseases, PDGFB, Brain, Exons, Proto-Oncogene Proteins c-sis, Ribonucleoprotein, U2 Small Nuclear, medicine.disease, Pedigree, DNA Topoisomerases, Type I, Codon, Nonsense, Female, RNA Splicing Factors, Tomography, X-Ray Computed, Calcification
Abstract: Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.
Published: 2014

141. PDGFB partial deletion: a new, rare mechanism causing brain calcification with leukoencephalopathy

Author: Louis Vernier, Anne Rovelet-Lecrux, Dominique Campion, David Wallon, Thierry Frebourg, Gaël Nicolas, Cyril Pottier, Françoise Chapon, Gérard Landemore, Didier Hannequin, Olivier Martinaud, Elisabeth Tournier-Lasserve, and Carol Prieto-Morin
Subjects: Genetics, Heterozygote, PDGFB, Sodium-Phosphate Cotransporter Proteins, Type III, Point mutation, Autosomal dominant trait, Calcinosis, PDGFRB, Locus (genetics), Neurodegenerative Diseases, General Medicine, Exons, Proto-Oncogene Proteins c-sis, Biology, Cellular and Molecular Neuroscience, Basal Ganglia Diseases, Leukoencephalopathies, Cancer research, Humans, Female, Copy-number variation, Allele, Cognitive decline, Gene Deletion, Aged
Abstract: Idiopathic basal ganglia calcification (IBGC) is a progressive cerebral disorder with diverse motor, cognitive, and psychiatric expression. It is inherited as an autosomal dominant trait. Three IBGC-causing genes have been identified in the past 2 years: SLC20A2, PDGFRB, and PDGFB. Biological and genetic evidence showed that loss of function of either SLC20A2 or the PDGFB/PDGFRB pathway was the mechanism underlying calcification in patients with a mutation. Recently, in a study focusing on SLC20A2, a large deletion at this locus was reported. No study has systematically searched for copy number variants (CNV) involving these three genes. We designed a quantitative PCR assay of multiple short fluorescent fragments (QMPSF) to detect CNVs involving one of these three genes in a single assay. Among the 27 unrelated patients from our IBGC case series with no mutation in SLC20A2, PDGFRB, and PDGFB, we identified in one patient a heterozygous partial deletion involving exons 2 to 5 of PDGFB. This patient exhibited both strio-pallido-dentate calcification and white matter hyperintensity of presumed vascular origin, associated with mood disorder, subtle cognitive decline, and gait disorder. We confirmed by RT-PCR experiments that the allele carrying the deletion was transcribed. The resulting cDNA lacks sequence for several critical functional domains of the protein. Intragenic deletion of PDGFB is a new and rare mechanism causing IBGC. CNVs involving the three IBGC-causing genes should be investigated in patients with no point mutation.
Published: 2014

142. Frontotemporal dementia and its subtypes: A genome-wide association study

Author: Yolande A.L. Pijnenburg, Wei Gu, Harro Seelaar, Robert Perneczky, Alfredo Postiglione, Ronald C. Petersen, Timothy D. Griffiths, Pau Pastor, Marc Cruts, Elise G.P. Dopper, Sabrina Pichler, Chiara Fenoglio, Patrizia Rizzu, Adeline Rollin, Maria Serpente, Peter Heutink, Sandro Sorbi, Lauren Bartley, Maria Landqvist Waldö, Luigi Ferrucci, William S. Brooks, Luisa Benussi, William W. Seeley, Maria Anfossi, Atik Baborie, Innocenzo Rainero, Rosa Capozzo, Alessandro Padovani, Stefano F. Cappa, Glenda M. Halliday, Jørgen E. Nielsen, Sara Ortega-Cubero, Vivianna M. Van Deerlin, Ekaterina Rogaeva, Mike A. Nalls, Giacomina Rossi, Alberto Lleó, Edward D. Huey, Jordi Clarimón, Simon Mead, Janine Diehl-Schmid, John Q. Trojanowski, Adaikalavan Ramasamy, Matthias Riemenschneider, John Hardy, Annibale Alessandro Puca, Cristina Razquin, Mercè Boada, Martine Vercelletto, Isabelle Le Ber, Graziella Milan, Johannes Attems, Francesca Frangipane, Jason D. Warren, Lena E. Hjermind, John R. Hodges, Gianluigi Forloni, Dennis W. Dickson, Daniela Galimberti, Elisa Rubino, Karin Nilsson, Raffaele Maletta, Christine Van Broeckhoven, Valeria Novelli, Anna Richardson, Anna Karydas, David S. Knopman, Nick C. Fox, Stuart Pickering-Brown, Carlos Cruchaga, Isabel Hernández, Livia Bernardi, Philip Scheltens, Martin N. Rossor, Julie S. Snowden, Massimo Franceschi, Rosa Rademakers, Bruce L. Miller, Alan J. Thomas, Florence Lebert, Matthew C. Baker, Jonathan D. Rohrer, Keith A. Josephs, Tim Van Langenhove, Fabrizio Tagliavini, Carol Dobson-Stone, Elizabeth Thompson, Silvia Bagnoli, Barbara Borroni, Sara Rollinson, Irene Piaceri, David M. A. Mann, Bernd Ibach, Ian G. McKeith, Agustín Ruiz, Huw R. Morris, Giancarlo Logroscino, Maura Gallo, Elena Alonso, Alexis Brice, Adrian Danek, Paolo Sorrentino, Nicoletta Smirne, Raffaele Ferrari, Panagiotis Alexopoulos, Johannes C. M. Schlachetzki, Alexander Gerhard, Manuel Mayhaus, Alexander Kurz, Amalia C. Bruni, Michael Tierney, Didier Hannequin, William Deschamps, Florence Pasquier, Joseph E. Parisi, Rafael Blesa, Elio Scarpini, Ian R. A. Mackenzie, Peter R. Schofield, Giuliano Binetti, Evelyn Jaros, Julie van der Zee, John Collinge, Maria Elena Conidi, Howard J. Rosen, Caroline Graff, Christer Nilsson, Huei-Hsin Chiang, Nigel J. Cairns, Jordan Grafman, Eric M. Wassermann, Parastoo Momeni, Maria Grazia Spillantini, Ging-Yuek Robin Hsiung, Andrew B. Singleton, Chiara Cupidi, James Uphill, Dimitrios Kapogiannis, Bradley F. Boeve, Christopher Morris, Vincent Deramecourt, Giorgio Giaccone, James B. Rowe, Murray Grossman, Benedetta Nacmias, Roberta Ghidoni, Véronique Golfier, Dena G. Hernandez, Lorenzo Pinessi, Neill R. Graff-Radford, John C. van Swieten, Pietro Pietrini, Gilles Gasparoni, Peter St George-Hyslop, Mark Kristiansen, Eric Haan, Olivier Piguet, John B.J. Kwok, Human genetics, Neurology, NCA - neurodegeneration, Surgery, Clinical Genetics, Erasmus MC other, Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jb, Dobson Stone, C, Brooks, W, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hern?ndez, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarim?n, J, Lle?, A, Blesa, R, Wald?, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ir, Hsiung, Gy, Mann, Dm, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega Cubero, S, Alonso, E, Perneczky, R, Diehl Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jc, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossman, M, Trojanowski, Jq, van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, Sf, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Eg, Seelaar, H, Pijnenburg, Ya, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, Alfredo, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebert, F, Kapogiannis, D, Ferrucci, L, Pickering Brown, S, Singleton, Ab, Hardy, J, and Momeni, P.
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Genotype, Semantic dementia, Genome-wide association study, Locus (genetics), classification [Frontotemporal Dementia], methods [Genome-Wide Association Study], diagnosis [Frontotemporal Dementia], C9orf72, mental disorders, medicine, Dementia, Humans, ddc:610, genetics [Frontotemporal Dementia], Aged, Genetics, Aged, 80 and over, Genetic heterogeneity, Middle Aged, medicine.disease, Frontotemporal Dementia, Female, Human medicine, Neurology (clinical), Alzheimer's disease, Psychology, Frontotemporal dementia, Genome-Wide Association Study
Abstract: Summary Background Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes— MAPT , GRN , and C9orf72 —have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p −8 ) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p −8 ). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10 −8 ; odds ratio=1·204 [95% CI 1·11–1·30]), rs9268856 (p=5·51 × 10 −9 ; 0·809 [0·76–0·86]) and rs1980493 (p value=1·57 × 10 −8 , 0·775 [0·69–0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38 / CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10 −7 ; 0·814 [0·71–0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis . Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center.
Published: 2014

143. PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum

Author: Tobias B. Haack, Didier Hannequin, Amjad Farooq, Michael A. Gonzalez, Tim M. Strom, Adriana P. Rebelo, Alexandra Durr, Wilson Marques, Christoph Kernstock, Charles Marques Lourenço, Stephan Züchner, Ludger Schöls, Holger Prokisch, Rebecca Schüle, Giovanni Stevanin, Matthis Synofzik, Marcos M. Lima-Martínez, and Marie Coutelier
Subjects: Male, Models, Molecular, physiopathology [Spinocerebellar Ataxias], medicine.disease_cause, Gonadotropin-Releasing Hormone, physiopathology [Heredodegenerative Disorders, Nervous System], genetics [Exome], Exome, genetics [Spinocerebellar Ataxias], Exome sequencing, Genetics, Mutation, etiology [Ataxia], genetics [Cerebellar Ataxia], genetics [Ataxia], Middle Aged, genetics [Retinal Dystrophies], ddc, physiology [Mutation], Phospholipases, Spinocerebellar ataxia, Heredodegenerative Disorders, Nervous System, Female, medicine.symptom, physiopathology [Cerebellar Ataxia], ataxia, early onset ataxia, genetics, hereditary spastic paraplegia, hypogonadism, recessive ataxia, retinal degeneration, spastic ataxia, spasticity, Adult, Ataxia, genetics [Heredodegenerative Disorders, Nervous System], Cerebellar Ataxia, genetics [Phospholipases], Hereditary spastic paraplegia, genetics [Hypogonadism], genetics [Mutation], Biology, PNPLA6 protein, human, physiopathology [Hypogonadism], physiopathology [Retinal Dystrophies], genetics [Spastic Paraplegia, Hereditary], Retinal Dystrophies, genetics [Gonadotropin-Releasing Hormone], medicine, Spinocerebellar Ataxias, Humans, Family, ddc:610, Boucher Neuhäuser syndrome, genetics [DNA], Cerebellar ataxia, Spastic Paraplegia, Hereditary, Hypogonadism, Original Articles, DNA, deficiency [Gonadotropin-Releasing Hormone], medicine.disease, Neurology (clinical)
Abstract: Boucher-Neuhäuser and Gordon Holmes syndromes are clinical syndromes defined by early-onset ataxia and hypogonadism plus chorioretinal dystrophy (Boucher-Neuhäuser syndrome) or brisk reflexes (Gordon Holmes syndrome). Here we uncover the genetic basis of these two syndromes, demonstrating that both clinically distinct entities are allelic for recessive mutations in the gene PNPLA6. In five of seven Boucher-Neuhäuser syndrome/Gordon Holmes syndrome families, we identified nine rare conserved and damaging mutations by applying whole exome sequencing. Further, by dissecting the complex clinical presentation of Boucher-Neuhäuser syndrome and Gordon Holmes syndrome into its neurological system components, we set out to analyse an additional 538 exomes from families with ataxia (with and without hypogonadism), pure and complex hereditary spastic paraplegia, and Charcot-Marie-Tooth disease type 2. We identified four additional PNPLA6 mutations in spastic ataxia and hereditary spastic paraplegia families, revealing that Boucher-Neuhäuser and Gordon Holmes syndromes in fact represent phenotypic clusters on a spectrum of neurodegenerative diseases caused by mutations in PNPLA6. Structural analysis indicates that the majority of mutations falls in the C-terminal phospholipid esterase domain and likely inhibits the catalytic activity of PNPLA6, which provides the precursor for biosynthesis of the neurotransmitter acetylcholine. Our findings show that PNPLA6 influences a manifold of neuronal systems, from the retina to the cerebellum, upper and lower motor neurons and the neuroendocrine system, with damage of this protein causing an extraordinarily broad continuous spectrum of associated neurodegenerative disease.
Published: 2014

144. Just do it! How performing an action enhances remembering in transient global amnesia

Author: Mathieu Hainselin, Aurelija Juskenaite, Didier Hannequin, Francis Eustache, Olivier Martinaud, Béatrice Desgranges, Peggy Quinette, Vincent de La Sayette, Fausto Viader, Eustache, Francis, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This work was supported by Caen University Hospital, as part of a clinical research project. INSERM managed the PhD funding of Mathieu Hainselin, provided by Lower Normandy Regional Council and the Vicq d'Azyr association.
Subjects: Male, MESH: Mental Recall, Enactment effect, MESH: Movement, Anxiety, Neuropsychological Tests, MESH: Stroop Test, 0302 clinical medicine, Amnesia, Transient Global, Retrospective memory, Explicit memory, MESH: Memory, Episodic memory, MESH: Aged, MESH: Middle Aged, Long-term memory, 05 social sciences, MESH: Affect, MESH: Neuropsychological Tests, Middle Aged, Memory, Short-Term, Neuropsychology and Physiological Psychology, MESH: Memory, Episodic, Data Interpretation, Statistical, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cues, medicine.symptom, Psychology, Cognitive psychology, Memory, Episodic, Movement, Cognitive Neuroscience, Amnesia, Experimental and Cognitive Psychology, 050105 experimental psychology, MESH: Memory, Short-Term, 03 medical and health sciences, Memory, Source amnesia, MESH: Trail Making Test, MESH: Analysis of Variance, MESH: Amnesia, Transient Global, medicine, Humans, Transient global amnesia, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Memory for action, Analysis of Variance, Trail Making Test, MESH: Humans, Recall, Self-performed task, MESH: Anxiety, Autobiographical memory, Binding, MESH: Male, Affect, Mental Recall, Stroop Test, MESH: Data Interpretation, Statistical, MESH: Female, 030217 neurology & neurosurgery, MESH: Cues
Abstract: International audience; Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of a massive episodic memory deficit that spares other cognitive functions. As such, it provides a unique human amnesia model for testing the enactment effect (i.e., better memory for performed actions than for verbally encoded sentences). Our main aim was to test whether the enactment effect is preserved in TGA patients, both to have a better understanding and to test the robustness of this effect in a massive amnesia. Object-action pairs were encoded under four conditions: verbal, experimenter-performed, and two enacted conditions (self-performed and self-performed with choice). We tested object-action pair retrieval using cued recall (CR) and recognition tasks, and source memory using a free recall task. We also assessed binding, executive functions, short-term memory, episodic memory, anxiety and mood. We run correlations to control for their putative effects on memory for action. Data were collected from 24 patients, 16 of whom were examined during the acute phase and eight the day-after, as well as from 18 healthy controls. The memory performances of the patients in the acute phase improved for both (i) the CR score, between the verbal, experimenter-performed and self-performed with choice conditions, and (ii) the total recognition score, between the verbal condition and the two enacted conditions. Correlations were found between self-performed task (SPT) enhancement and both the binding and anxiety. In spite of their severely impaired episodic memory, patients with TGA benefit from the enactment effect. These results are discussed in relation to the role of motor components and episodic integration in memory for actions. We suggest that enactment effect can be used in clinical practice and rehabilitation, possible even for patients with a massive memory impairment.
Published: 2014

145. Use of haplotype information to test involvement of the LRP gene in Alzheimer's disease in the French population

Author: Dominique Campion, Catherine Thomas-Antérion, Michèle Puel, Bruno Dubois, Didier Hannequin, Yves Agid, Patrice Verpillat, Françoise Clerget-Darpoux, Serge Belliard, Sandrine Bouley, and Alexis Brice
Subjects: Adult, Male, Genotype, Population, Disease, Biology, Linkage Disequilibrium, Sex Factors, Gene Frequency, Alzheimer Disease, Genetics, Humans, Receptors, Immunologic, education, Gene, Alleles, Genetics (clinical), Aged, Aged, 80 and over, education.field_of_study, Polymorphism, Genetic, Haplotype, Age Factors, Exons, Middle Aged, Test (assessment), Haplotypes, Female, lipids (amino acids, peptides, and proteins), France, Low Density Lipoprotein Receptor-Related Protein-1
Abstract: The low density lipoprotein receptor-related protein gene (LRP) is a good candidate gene for Alzheimer's Disease (AD). Its protein is involved in the physiopathology of AD and has been found in senile plaques; on the other hand, LRP is located in 12q, a region in which genetic linkage to AD was reported. Two common polymorphisms, a tetranucleotide repeat in the 5' untranslated region and a single nucleotide polymorphism at position 766 in exon 3, were found to be associated with AD, but contradictory results were obtained in subsequent association studies. In the absence of clear hypotheses concerning the association of these polymorphisms with AD and their functional role, our objective was to test the association between AD and the two LRP polymorphisms in a large French case-control sample (274 Caucasian AD patients and 290 matched controls) using haplotype analysis. First, the separate study of each polymorphism showed no significant difference in genotype and allele frequencies between AD cases and controls. Second, strong linkage disequilibrium was found between alleles of the two polymorphisms in controls and in cases and the linkage disequilibrium between the 91 bp and C alleles were opposite in cases and in controls. Third, we found that the frequency of the 91-C haplotype was higher in cases than in controls, but the type I error was 0.061, slightly higher than the conventional one of 5%. The haplotype frequencies did not vary significantly as a function of age and APOE epsilon4 status. One interest in this study is the use of the haplotype analysis, which can be used to combine information from several polymorphisms, taking into account their dependence.
Published: 2001

146. Dysarthria and orofacial apraxia in corticobasal degeneration

Author: Canan Ozsancak, Pascal Auzou, and Didier Hannequin
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Apraxias, Neurological disorder, Neuropsychological Tests, Audiology, Severity of Illness Index, Apraxia, Central nervous system disease, Dysarthria, Degenerative disease, Basal Ganglia Diseases, Parkinsonian Disorders, Tongue, medicine, Humans, Corticobasal degeneration, Language disorder, Aged, Cerebral Cortex, Psychiatric Status Rating Scales, Speech Intelligibility, Neurodegenerative Diseases, medicine.disease, nervous system diseases, medicine.anatomical_structure, Neurology, Female, France, Neurology (clinical), medicine.symptom, Psychology
Abstract: The authors evaluated dysarthria and orofacial apraxia (OFA) in 10 patients with a clinical diagnosis of corticobasal degeneration (CBD). Nine patients were slightly dysarthric according to the French version of the Frenchay Dysarthria Assessment, which evaluates the motricity of the components of the vocal tract. The severity of dysarthria assessed by an intelligibility score was correlated to the global severity of the disease, but not to the duration of the disease. Voluntary movements of the tongue and the lips were impaired in all patients. OFA, evaluated with simple and sequential gestures, was present in nine patients. Sequential gestures were more frequently impaired. The score of OFA was not correlated to the severity of dysarthria, suggesting independent underlying mechanisms. Thus, when specifically assessed, dysarthria and OFA are more frequent in CBD than usually reported. We propose that the underlying pathophysiology is the result of a deficit in programming and execution of repetitive movements.
Published: 2000

147. Voice onset time in aphasia, apraxia of speech and dysarthria: a review

Author: Pascal Auzou, Francis Eustache, Canan Ozsancak, Richard J. Morris, Didier Hannequin, and Mary Jan
Subjects: Linguistics and Language, medicine.medical_specialty, Neurogenic Communication Disorders, Voice-onset time, Phonology, Audiology, medicine.disease, Apraxia, Language and Linguistics, Linguistics, Speech and Hearing, Dysarthria, Aphasia, medicine, Speech disorder, Language disorder, medicine.symptom, Psychology
Abstract: Voice onset time (VOT) is an objective temporal acoustic parameter defined as the time between the release of the oral constriction for plosive production and the onset of vocal fold vibrations. Many researchers consider VOT to be the most reliable acoustic cue for the distinction between voiced and voiceless stops. Previous studies have explored the physiological and linguistic factors underlying VOT production in normal speakers across several languages. A major clinical goal of acoustic analysis in speech disorder is to establish a correlation between the acoustic abnormalities and the phonetic perturbations. VOT could thus be used as an acoustic parameter that indicates the phonetic contrast between voiced and voiceless stops. This paper includes a critical review of the measurement of VOT, factors of VOT variability and the effect of neurogenic communication disorders on VOT. We review the VOT data from subjects who exhibit aphasia, apraxia of speech and dysarthria. These studies reveal that VOT pert...
Published: 2000

148. Usefulness of Transcranial Color-Coded Sonography in the Diagnosis of Cerebral Vasospasm

Author: Didier Hannequin, J. Thiébot, F. Callonec, Pierre Fréger, J. P. Lestrat, E. Clavier, and François Proust
Subjects: Adult, Male, medicine.medical_specialty, Ultrasonography, Doppler, Transcranial, Arterial Occlusive Diseases, Sensitivity and Specificity, Cerebral vasospasm, Aneurysm, medicine.artery, medicine, Anterior cerebral artery, Humans, Prospective Studies, cardiovascular diseases, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, Intracranial Aneurysm, Vasospasm, Cerebral Arteries, Middle Aged, medicine.disease, Cerebral Angiography, Transcranial Doppler, Cerebrovascular Circulation, Angiography, Middle cerebral artery, cardiovascular system, Female, Neurology (clinical), Radiology, Internal carotid artery, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity, Carotid Artery, Internal
Abstract: Background and Purpose —The noninvasive diagnosis of cerebral vasospasm with the use of conventional transcranial Doppler ultrasonography (TCD) is based on a velocity study of the middle cerebral artery (MCA). The authors report a prospective comparative study between transcranial color-coded sonography (TCCS), conventional transcranial Doppler (TCD), and angiography in the diagnosis of cerebral vasospasm after surgical treatment for aneurysm. Methods —Thirty consecutive patients underwent routine angiography after surgical treatment for intracranial aneurysm. The distribution of vasospasm was determined after a prospective calculation of the angiographic diameter of the MCA, internal carotid artery (ICA), and anterior cerebral artery (ACA). The blood flow velocities (systolic and maximum) of the MCA, ICA, and ACA were evaluated by TCCS and TCD. Results —The correlation between mean maximum velocity and angiographic diameter was significant for the MCA ( r =−0.637, P r =−0.676, P r =−0.425, P Conclusions —The authors suggest that TCCS is useful for accurate monitoring of cerebral vasospasm in the MCA and ICA. In the ACA, TCCS monitors the hemodynamic state of the anterior part of the circle of Willis, which could expose the patient to a delayed ischemic deficit.
Published: 1999

149. Syndrome parkinsonien chronique chez un homme exposé pendant dix ans à des pulvérisations d’insecticides

Author: P.A. Bohu, Didier Hannequin, L. Aubeneau, and David Maltête
Subjects: Neurology, Neurology (clinical)
Abstract: Resume Introduction Des syndromes parkinsoniens aigus et reversibles sont classiquement decrits lors d’intoxications massives par ingestion de substances organophosphorees. Les intoxications consecutives a des pulverisations aigues de pesticides sont, en revanche, beaucoup plus rares. Observation Nous rapportons un cas de syndrome parkinsonien atypique chronique persistant au decours de pulverisations repetees d’insecticides pendant dix ans. Conclusion Cette observation suggere que les pesticides agricoles ou domestiques pourraient etre impliques dans certains syndromes parkinsoniens chroniques.
Published: 2008

150. Démence et protéine Tau élevée : quels diagnostics craindre ?

Author: Grangeon, Lou, primary, Paquet, Claire, additional, Bombois, Stéphanie, additional, Maltete, David, additional, Didier, Hannequin, additional, and Wallon, David, additional
Published: 2016
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