Author: "Maria-Del-Mar Amador" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Maria-Del-Mar Amador"' showing total 47 results

Start Over Author "Maria-Del-Mar Amador"

47 results on '"Maria-Del-Mar Amador"'

1. Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles

Author: Laura Le Gall, William J. Duddy, Cecile Martinat, Virginie Mariot, Owen Connolly, Vanessa Milla, Ekene Anakor, Zamalou G. Ouandaogo, Stephanie Millecamps, Jeanne Lainé, Udaya Geetha Vijayakumar, Susan Knoblach, Cedric Raoul, Olivier Lucas, Jean Philippe Loeffler, Peter Bede, Anthony Behin, Helene Blasco, Gaelle Bruneteau, Maria Del Mar Amador, David Devos, Alexandre Henriques, Adele Hesters, Lucette Lacomblez, Pascal Laforet, Timothee Langlet, Pascal Leblanc, Nadine Le Forestier, Thierry Maisonobe, Vincent Meininger, Laura Robelin, Francois Salachas, Tanya Stojkovic, Giorgia Querin, Julie Dumonceaux, Gillian Butler Browne, Jose‐Luis González De Aguilar, Stephanie Duguez, and Pierre Francois Pradat
Subjects: Secreted vesicles, Cell–cell communication, MND, sporadic ALS, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract: Abstract Background The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle‐secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology. Methods Sporadic ALS patients were confirmed to be ALS according to El Escorial criteria and were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS‐R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n = 27) or deltoids of aged‐matched healthy subjects (n = 30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RT‐qPCR, and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human‐derived iPSC MNs and on healthy human myotubes, with untreated cells used as controls. Results An accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy‐derived denervation‐naïve differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome‐like vesicles and disruption of RNA‐processing. Compared with vesicles from healthy control myotubes, when administered to healthy MNs the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA‐processing proteins. The RNA‐processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient MNs was abolished by anti‐CD63 immuno‐blocking of vesicle uptake. Conclusions ALS muscle vesicles are shown to be toxic to MNs, which establishes the skeletal muscle as a potential source of vesicle‐mediated toxicity in ALS.
Published: 2022
Full Text: View/download PDF

2. Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study

Author: Rabab Debs, Jean-Yves Hogrel, Gaëlle Bruneteau, Nadine Le Forestier, Peter Bede, Pascal Laforêt, Sophie Blancho, Anthony Behin, Timothée Lenglet, Véronique Marchand-Pauvert, François Salachas, Giorgia Querin, Pierre-François Pradat, Tanya Stojkovic, Maria del Mar Amador, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Etudes sur les sciences et les techniques (EST), Université Paris-Saclay, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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)-Centre National de la Recherche Scientifique (CNRS), H&R BLOCK, HRB: EIA-2017-019 Association Française contre les Myopathies, AFM Health Research Board, HRB Iris O'Brien Foundation Irish Institute of Clinical Neuroscience, IICN AFM-Téléthon: NCT0288587, This study was sponsored by the Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen., We are grateful for the generosity of all SMA patients who have kindly participated in this study. This study was supported by the Association Française contre les Myopathies (AFM-Téléthon). We also thank the Institut pour la Recherche sur la Moelle Épinière et l’Encephale (IRME) for their support of this the study. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. The rest of the authors have no specific sponsors to declare., Supported by the Association Française contre les Myopathies (AFM-Téléthon, NCT0288587)., Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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), and Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen.
Subjects: Adult, medicine.medical_specialty, Longitudinal study, Neurology, [SDV]Life Sciences [q-bio], Deltoid curve, Spinal Muscular Atrophies of Childhood, Outcome measures, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Outcome Assessment, Health Care, Humans, Medicine, Longitudinal Studies, Muscle Strength, 030212 general & internal medicine, Muscle, Skeletal, Neuroradiology, Longitudinal progression, business.industry, SMA, Spinal cord, 3. Good health, Clinical trial, medicine.anatomical_structure, Sample size determination, Adult SMA, Neurology (clinical), business, 030217 neurology & neurosurgery, MUNIX
Abstract: International audience; Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials. Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later. Longitudinal comparisons were conducted using the Wilcoxon-test for matched data. Responsiveness was estimated using standardized response means (SRM) and a composite score was generated based on the three most significant variables. Results: Significant functional decline was observed based on SMAFRS (p = 0.019), pinch and knee flexion strength (p = 0.030 and 0.027), MUNIX and MUSIX value in the ADM (p = 0.0006 and 0.043) and in TA muscle (p = 0.025). No significant differences were observed based on cervical MRI measures. A significant reduction was detected in the composite score (p = 0.0005, SRM = −1.52), which was the most responsive variable and required a smaller number of patients than single variables in the estimation of sample size for clinical trials. Conclusions: Quantitative strength testing, SMAFRS and MUNIX readily capture disease progression in adult SMA patients. Composite multimodal scores increase predictive value and may reduce sample size requirements in clinical trials.
Published: 2021

3. Cursive Eye-Writing With Smooth-Pursuit Eye-Movement Is Possible in Subjects With Amyotrophic Lateral Sclerosis

Author: Timothée Lenglet, Jonathan Mirault, Marie Veyrat-Masson, Aurélie Funkiewiez, Maria del Mar Amador, Gaelle Bruneteau, Nadine Le Forestier, Pierre-Francois Pradat, Francois Salachas, Yannick Vacher, Lucette Lacomblez, and Jean Lorenceau
Subjects: amyotrophic lateral sclerosis, assisted communication devices, smooth-pursuit eye movements, pilot clinical study, motor learning, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing a progressive motor weakness of all voluntary muscles, whose progression challenges communication modalities such as handwriting or speech. The current study investigated whether ALS subjects can use Eye-On-Line (EOL), a novel eye-operated communication device allowing, after training, to voluntarily control smooth-pursuit eye-movements (SPEM) so as to eye-write in cursive. To that aim, ALS participants (n = 12) with preserved eye-movements but impaired handwriting were trained during six on-site visits. The primary outcome of the study was the recognition of eye-written digits (0–9) from ALS and healthy control subjects by naïve “readers.” Changes in oculomotor performance and the safety of EOL were also evaluated. At the end of the program, 69.4% of the eye-written digits from 11 ALS subjects were recognized by naïve readers, similar to the 67.3% found for eye-written digits from controls participants, with however, large inter-individual differences in both groups of “writers.” Training with EOL was associated with a transient fatigue leading one ALS subject to drop out the study at the fifth visit. Otherwise, itching eyes was the most common adverse event (3 subjects). This study shows that, despite the impact of ALS on the motor system, most ALS participants could improve their mastering of eye-movements, so as to produce recognizable eye-written digits, although the eye-traces sometimes needed smoothing to ease digit legibility from both ALS subjects and control participants. The capability to endogenously and voluntarily generate eye-traces using EOL brings a novel way to communicate for disabled individuals, allowing creative personal and emotional expression.
Published: 2019
Full Text: View/download PDF

4. The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study

Author: Giorgia Querin, Mohamed-Mounir El Mendili, Timothée Lenglet, Anthony Behin, Tanya Stojkovic, François Salachas, David Devos, Nadine Le Forestier, Maria del Mar Amador, Rabab Debs, Lucette Lacomblez, Vincent Meninger, Gaëlle Bruneteau, Julien Cohen-Adad, Stéphane Lehéricy, Pascal Laforêt, Sophie Blancho, Habib Benali, Martin Catala, Menghan Li, Véronique Marchand-Pauvert, Jean-Yves Hogrel, Peter Bede, and Pierre-François Pradat
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging. Methods: Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations. Results: In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level. Conclusions: Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation. Keywords: Spinal muscular atrophy, SMA, Multimodal MRI, Spinal cord MRI, Grey matter and white matter degeneration
Published: 2019
Full Text: View/download PDF

5. Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

Author: Claudia Morelli, Federico Verde, Philip Van Damme, Maria del Mar Amador, Foudil Lamari, Susanne Petri, Koen Poesen, Jochen H. Weishaupt, Jens Kuhle, Markus Otto, Julian Grosskreutz, Elizabeth Gray, Steffen Halbgebauer, Mykyta Kachanov, François Salachas, Petra Steinacker, Vincenzo Silani, Aleksandra Maceski, Nayana Gaur, Martin R Turner, Alexander E Volk, Benjamin Mayer, Albert C. Ludolph, Claude Jardel, Patrick Weydt, Joost Raaphorst, Emily Feneberg, Simon Witzel, Marcel M. Verbeek, Patrick Oeckl, Neurology, ANS - Neurodegeneration, ANS - Neuroinfection & -inflammation, and EURO-NMD
Subjects: medicine.medical_specialty, Neurofilament, Gastroenterology, neurofilaments, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, chitotriosidase, Polymorphism (computer science), Neurofilament Proteins, Internal medicine, Gene duplication, Genotype, medicine, Humans, Amyotrophic lateral sclerosis, Stage (cooking), prognostic biomarker, business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Prognosis, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hexosaminidases, Neurology, Disease Progression, Biomarker (medicine), Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Objective: Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. Methods: Overall, 275 patients from 8 European neurological centers were examined. We included ALS with 6 months from symptom onset, other motoneuron diseases (oMND), ALS mimics (DCon) and non-neurodegenerative controls (Con). CSF CHIT1 levels were analyzed for diagnostic power and association with progression and survival in comparison to the benchmark neurofilament. The 24-bp duplication polymorphism of CHIT1 was analyzed in a subset of patients (N=65). Results: Homozygous CHIT1 duplication mutation carriers (9%) invariably had undetectable CSF CHIT1 levels, while heterozygous carriers had similar levels as patients with wildtype CHIT1 (p=0.414). In both early and late symptomatic ALS CHIT1 levels was increased, did not correlate with patients’ progression rates, and was higher in patients diagnosed with higher diagnostic certainty. Neurofilament levels correlated with CHIT1 levels and prevailed over CHIT1 regarding diagnostic performance. Both CHIT1 and neurofilaments were identified as independent predictors of survival in late but not early symptomatic ALS. Evidence is provided that CHIT1 predicts progression in El Escorial diagnostic category in the group of ALS cases with a short duration. Conclusions: CSF CHIT1 level may have additional value in the prognostication of ALS patients with a short history of symptoms classified in diagnostic categories of lower clinical certainty. To fully interpret apparently low CHIT1 levels knowledge of CHIT1 genotype is needed.
Published: 2021

6. Predictive genetic testing for Motor neuron disease: time for a guideline?

Author: Alisdair, McNeill, Maria-Del-Mar, Amador, Hilary, Bekker, Angus, Clarke, Ashley, Crook, Cathy, Cummings, Alison, McEwen, Christopher, McDermott, Oliver, Quarrell, Alessandra, Renieri, Jennifer, Roggenbuck, Kristiana, Salmon, Alexander, Volk, and Jochen, Weishaupt
Subjects: Amyotrophic Lateral Sclerosis, Humans, Genetic Testing, Motor Neuron Disease
Published: 2022

7. Pearlsamp; Oy-sters: Spinal Cord Candidiasis Linked to CARD9 Deficiency Masquerading as a Longitudinally Extensive Transverse Myelitis

Author: Lina Jeantin, Isabelle Plu, Maria del Mar Amador, Elisabeth Maillart, Fanny Lanternier, Valérie Pourcher, Vincent Davy, Institut Mutualiste de Montsouris (IMM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)
Subjects: Adult, Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Candidiasis, Chronic Mucocutaneous, Candidiasis, Middle Aged, Myelitis, Transverse, CARD Signaling Adaptor Proteins, Spinal Cord, Adrenal Cortex Hormones, Humans, Neurology (clinical), Glucans
Abstract: Candida spp. myelopathies are very rare. We report a case of subacute longitudinally extensive transverse myelitis in an apparently immunocompetent 55-year-old man. After a negative infectious workup, corticosteroids and plasma exchange were initiated. Although there was a transient initial improvement, symptoms then worsened, and the lumbar puncture was repeated. Candida albicans was isolated in the CSF, and a diagnosis of spinal cord candidiasis was made. Gene panel sequencing for inborn immune deficiencies identified a homozygous disease-causing CARD9 variant. Despite antifungal treatment, necrotic myelitis, meningoencephalitis, and cerebral vasculitis developed. Fungal spinal cord infections can mimic inflammatory myelitis, and beta-D-glucan testing of both serum and CSF may help narrow down the diagnosis. In cases of severe or unexpected invasive Candida spp. infection, even adults and apparently immunocompetent patients should be screened for inborn immune deficiencies and CARD9 deficiency in particular.
Published: 2022

8. Clinical trials in pediatric ALS: a TRICALS feasibility study

Author: Tessa Kliest, Ruben P.A. Van Eijk, Ammar Al-Chalabi, Alberto Albanese, Peter M. Andersen, Maria Del Mar Amador, Geir BrÅthen, Veronique Brunaud-Danel, Lev Brylev, William Camu, Mamede De Carvalho, Cristina Cereda, Hakan Cetin, Delia Chaverri, Adriano Chiò, Philippe Corcia, Philippe Couratier, Fabiola De Marchi, Claude Desnuelle, Michael A. Van Es, JesÚs Esteban, Massimiliano Filosto, Alberto GarcÍa Redondo, Julian Grosskreutz, Clemens O. Hanemann, Trygve HolmØy, Helle HØyer, Caroline Ingre, Blaz Koritnik, Magdalena Kuzma-Kozakiewicz, Thomas Lambert, Peter N. Leigh, Christian Lunetta, Jessica Mandrioli, Christopher J. Mcdermott, Thomas Meyer, Jesus S. Mora, Susanne Petri, MÓnica Povedano, Evy Reviers, Nilo Riva, Kit C.B. Roes, Miguel Á. Rubio, FranÇois Salachas, Stayko Sarafov, Gianni SorarÙ, Zorica Stevic, Kirsten Svenstrup, Anette Torvin MØller, Martin R. Turner, Philip Van Damme, Lucie A.G. Van Leeuwen, Luis Varona, Juan F. VÁzquez Costa, Markus Weber, Orla Hardiman, Leonard H. Van Den Berg, Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, King's College Hospital (KCH), Department Neurological Sciences, Milan University, IRCCS Humanitas Clinical Institute, Rozzano, M, Umeå University, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille, Ministry of Healthcare of Russian Federation, Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital, Montpellier, Université de Lisbonne, Medizinische Universität Wien = Medical University of Vienna, Hospital Universitario La Paz, Università degli studi di Torino = University of Turin (UNITO), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Neurologie [CHU Limoges], CHU Limoges, Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges] (SLA CHU Limoges), Neurology Clinic, University Hospital 'Maggiore della Carità', Novara, Hôpital Pasteur [Nice] (CHU), Centro de Diagnóstico de Enfermedades Moleculares, Dpto. Biol. Mol. Centro de Biología Molecular-SO UAM-CSIC. Universidad Autónoma Madrid, Campus Cantoblanco, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Car, University of Brescia, Lubeck University Hospital, Peninsula Schools of Medicine and Dentistry, Plymouth University, University of Oslo (UiO), Akershus University Hospital [Lørenskog], Telemark Hospital Trust [Skien, Norway], Karolinska Institutet, Department of Neurology, Karolinska University Hospital [Stockholm], University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Departement de Neurology (MEDICAL UNIVERSITY OF WARSAW), Medical University of Warsaw - Poland, University Hospitals of North Midlands NHS Trust, Royal Stoke Hospital, Stoke-on-Trent, United Kingdom., University of Sussex, University of Modena and Reggio Emilia, Department of Biomedical Sciences, Department of Neuroscience, Academic Neurology Unit, University of Sheffield, Sant Rafael Hospital, Department of Neurology, Hannover Medical School, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, University of Barcelona, Leuven University Hospitals, Division of Neuroscience, San Raffaele Scientific Institute, San Raffaele Scientific Institute, Milan, Italy, Radboud University Medical Center [Nijmegen], IMIM-Hospital del Mar, Generalitat de Catalunya, Medical University of Sofia [Bulgarie], Université de Padoue, Institute of Neurology, Clinical Center of Serbia, University of Belgrade, Belgrade, University of Belgrade [Belgrade], University of Copenhagen = Københavns Universitet (UCPH), Aarhus University Hospital, University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, UK, University Hospitals Leuven [Leuven], Servicio de Neurología, Hospital de Cruces, Barakaldo, Vizcaya, Neurology Service, Hospital Universitario La Fe, Valencia, Cantonal Hospital St Gallen (KSSG), and Department of Neurology, The Adelaide and Meath Hospital, Trinity College Dublin
Subjects: Adult, Databases, Factual, Neurologi, GENETICS, Clinical Neurology, AMYOTROPHIC-LATERAL-SCLEROSIS, Pediatric amyotrophic lateral sclerosis, pediatric investigation plan, Databases, Prevalence, Humans, clinical trial, clinical trials, ethics, therapy, Child, Feasibility Studies, Europe, Amyotrophic Lateral Sclerosis, Factual, Science & Technology, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Neurology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Neurosciences & Neurology, Life Sciences & Biomedicine
Abstract: Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (
Published: 2022

9. Traitement de la sialorrhée dans la sclérose latérale amyotrophique et la maladie de Parkinson par radiothérapie des glandes salivaires : analyse de 281 cas

Author: Avi Assouline, Antoine Schernberg, Maria Del Mar Amador, Nadine Le Forestier, Gaëlle Bruneteau, François Salachas, and Pierre-François Pradat
Subjects: Neurology, Neurology (clinical)
Published: 2022

10. Impact of a frequent nearsplice SOD1 variant in Amyotrophic Lateral Sclerosis: optimizing SOD1 genetic screening for gene therapy opportunities

Author: Stéphanie Millecamps, Aude-Marie Grapperon, Serge Lumbroso, François Salachas, Patrick Vourc'h, Aude Chiot, Delphine Bohl, Cécile Cazeneuve, Emilien Bernard, Anne-Laure Fauret-Amsellem, Kevin Mouzat, William Camu, Maria del Mar Amador, Christian S Lobsiger, Philippe Corcia, Beata Gyorgy, Séverine Boillée, Jean-Christophe Antoine, Shahram Attarian, Elisa Teyssou, Annie Verschueren, Yannick Marie, Claire Guissart, Jean-Philippe Camdessanché, Danielle Seilhean, Eric Leguern, François Muratet, Vincent Meininger, Justine Guegan, 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], 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), Hôpital privé des Peupliers (Paris), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité fonctionnelle de neurogénétique moléculaire et cellulaire, 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 Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Gestionnaire, HAL Sorbonne Université 5, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)
Subjects: MESH: Mutation, MESH: Pedigree, Genetic enhancement, animal diseases, [SDV]Life Sciences [q-bio], SOD1, Disease, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, medicine.disease_cause, MESH: Phenotype, 03 medical and health sciences, 0302 clinical medicine, MESH: Aged, 80 and over, medicine, Missense mutation, MESH: Superroxide Dismutase-1, Amyotrophic lateral sclerosis, Gene, MESH: Amyotrophic Lateral Sclerosis, 030304 developmental biology, Genetics, MESH: Aged, MESH: Genetic Therapy, 0303 health sciences, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Middle Aged, MESH: Genetic Testing, nutritional and metabolic diseases, MESH: Adult, medicine.disease, Phenotype, MESH: Male, 3. Good health, nervous system diseases, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, nervous system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Surgery, Neurology (clinical), MESH: Female, 030217 neurology & neurosurgery
Abstract: ObjectiveMutations in superoxide dismutase 1 gene (SOD1), encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the production of these aberrant and deleterious SOD1 species, antisense oligonucleotide approaches have recently emerged and showed promising effects in clinical trials. To offer the possibility to any patient with SOD1-ALS to benefit of such a gene therapy, it is necessary to ascertain whether any variant of unknown significance (VUS), detected for example in SOD1 non-coding sequences, is pathogenic.MethodsWe analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.ResultsWe identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358–10T>G nearsplice SOD1 variant was corroborated based on its high frequency (as the second most frequent SOD1 variant) in French fALS, the segregation analysis confirmed in eight affected members of a large pedigree, the typical SOD1-related phenotype observed (with lower limb onset and prominent lower motor neuron involvement), and findings on postmortem tissues showing SOD1 misaccumulation.ConclusionsOur results highlighted nearsplice/intronic mutations in SOD1 are responsible for a significant portion of French fALS and suggested the systematic analysis of the SOD1 mRNA sequence could become the method of choice for SOD1 screening, not to miss these specific cases.
Published: 2021

11. New advances in Amyotrophic Lateral Sclerosis genetics: towards gene therapy opportunities for familial and young cases

Author: Stéphanie Millecamps, Elisa Teyssou, Maria-Del-Mar Amador, François Muratet, Séverine Boillée, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], 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), Gestionnaire, HAL Sorbonne Université 5, 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Motor neuron diseases, Genetic counseling, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Disease, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, pathogenic mutation, TARDBP, frontotemporal dementia, 03 medical and health sciences, 0302 clinical medicine, inclusion body myopathy, C9orf72, Medicine, Humans, 030212 general & internal medicine, Genetic Testing, Amyotrophic lateral sclerosis, Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Amyotrophic Lateral Sclerosis, Oligogenic Inheritance, Genetic Therapy, medicine.disease, Penetrance, 3. Good health, [SDV] Life Sciences [q-bio], Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Neurology (clinical), Paget's disease of bone, business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: International audience; Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.
Published: 2021

12. Candidose médullaire due à une mutation Card9 mimant une myélite aiguë transverse inflammatoire : à propos d’un cas et revue de la littérature

Author: Lina Jeantin, Maria Del Mar Amador, Isabelle Plu, Valérie Pourcher, Elisabeth Maillart, and Davy Vincent
Subjects: Neurology, Neurology (clinical)
Published: 2022

13. Genetic screening of ANXA11 revealed novel mutations linked to Amyotrophic Lateral Sclerosis

Author: Selma Machat, Elisa Teyssou, Vincent Meininger, Yannick Marie, Géraldine Lautrette, Beata Gyorgy, Stéphanie Millecamps, Philippe Couratier, Séverine Boillée, Mélanie Ferrien, Danielle Seilhean, Cécile Cazeneuve, François Muratet, Thierry Larmonier, Justine Guegan, François Salachas, Pascal Cintas, Safaa Saker, Nadine Le Forestier, Maria-Del-Mar Amador, William Camu, Eric LeGuern, 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), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], 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), Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges] (SLA CHU Limoges), CHU Limoges, Généthon, Unité fonctionnelle de neurogénétique moléculaire et cellulaire, 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 Sclérose Latérale amyotrophique [CHU Toulouse], Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital privé des Peupliers (Paris), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neuropathologie [CHU Pitié Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Sclérose Latérale Amyotrophique et maladies, Unité de neurophysiologie clinique [CHU Toulouse], and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Male, Aging, Pathology, medicine.medical_specialty, Annexins, Datasets as Topic, ANXA11, frontotemporal dementia, 03 medical and health sciences, 0302 clinical medicine, Databases, Genetic, medicine, Humans, Exome, Motor neuron disease, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cognitive decline, Amyotrophic lateral sclerosis, Genetic Association Studies, neuropathology, business.industry, General Neuroscience, Neurodegeneration, Amyotrophic Lateral Sclerosis, FTD, Frontotemporal lobar degeneration, Motor neuron, Spinal cord, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Mutation, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), France, Geriatrics and Gerontology, Frontotemporal Lobar Degeneration, ALS, Annexin A11, business, 030217 neurology & neurosurgery, Developmental Biology, Frontotemporal dementia
Abstract: ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.
Published: 2021

14. Questioning the causality of HTT CAG-repeat expansions in FTD/ALS

Author: Maria del Mar Amador, Giulia Coarelli, Quentin Thomas, Alexandra Durr, Anna Heinzmann, and Isabelle Le Ber
Subjects: 0303 health sciences, Huntingtin Protein, DNA Repeat Expansion, General Neuroscience, Amyotrophic Lateral Sclerosis, MEDLINE, Computational biology, Causality, 03 medical and health sciences, 0302 clinical medicine, Frontotemporal Dementia, Humans, Psychology, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2021

15. Who and Why? Requests for Presymptomatic Genetic Testing for Amyotrophic Lateral Sclerosis/Frontotemporal Dementia vs Huntington Disease

Author: Ariane Herson, Stéphanie Staraci, François Salachas, Maria del Mar Amador, Cécile Cazeneuve, Marcela Gargiulo, Alexandra Durr, Christilla Boucher, Isabelle Le Ber, Fabienne Clot, 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), Service de Génétique Cytogénétique et Embryologie [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), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], 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), UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière], Unité fonctionnelle de neurogénétique moléculaire et cellulaire, Gestionnaire, HAL Sorbonne Université 5, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Service de Génétique médicale [CHU Pitié-Salpêtrière], Gargiulo, Marcela, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pediatrics, medicine.medical_specialty, Genetic counseling, Population, [SHS.PSY]Humanities and Social Sciences/Psychology, Neurogenetics, Article, [SHS.PSY] Humanities and Social Sciences/Psychology, 03 medical and health sciences, 0302 clinical medicine, Huntington's disease, mental disorders, Medicine, Presymptomatic Testing, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, education, Genetics (clinical), 030304 developmental biology, Genetic testing, 0303 health sciences, education.field_of_study, medicine.diagnostic_test, business.industry, medicine.disease, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: ObjectiveWe aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD).MethodsWe retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit.ResultsOf the 106 presymptomatic testing (PT) requests from subjects at risk of ALS/FTD, 65% were seen in the last 3 years. Over two-thirds of the subjects were at risk of carrying mutations responsible for ALS, FTD, or both. Sixty-two percent of the subjects came from families with a known hexanucleotide repeat expansion in C9ORF72. During the same period, we counseled 840 subjects at risk of HD. Subjects at risk of ALS/FTD had the presymptomatic test significantly sooner after being aware of their risk, but were older than those at risk of HD. The youngest subjects requesting the test had the highest disease load in the family (p < 0.05).ConclusionsDemands for PT for ALS/FTD have been increasingly growing, particularly since the discovery of the C9ORF72 gene. The major specificity of the genetic counseling for these diseases is the unpredictability of the clinical phenotype for most of the genes involved. Awareness of this added uncertainty does not prevent individuals from taking the test, as the dropout rate is not higher than that for HD.
Published: 2020

16. Impact of a frequent nearsplice

Author: François, Muratet, Elisa, Teyssou, Aude, Chiot, Séverine, Boillée, Christian S, Lobsiger, Delphine, Bohl, Beata, Gyorgy, Justine, Guegan, Yannick, Marie, Maria Del Mar, Amador, Francois, Salachas, Vincent, Meininger, Emilien, Bernard, Jean-Christophe, Antoine, Jean-Philippe, Camdessanché, William, Camu, Cécile, Cazeneuve, Anne-Laure, Fauret-Amsellem, Eric, Leguern, Kevin, Mouzat, Claire, Guissart, Serge, Lumbroso, Philippe, Corcia, Patrick, Vourc'h, Aude-Marie, Grapperon, Shahram, Attarian, Annie, Verschueren, Danielle, Seilhean, and Stéphanie, Millecamps
Subjects: Adult, Aged, 80 and over, Male, Amyotrophic Lateral Sclerosis, DNA Mutational Analysis, Genetic Therapy, Middle Aged, Pedigree, Phenotype, Superoxide Dismutase-1, Mutation, Humans, Female, Genetic Testing, Aged
Abstract: Mutations in superoxide dismutase 1 gene (We analysed SOD1 mutation distribution after SOD1 sequencing in a large cohort of 470 French familial ALS (fALS) index cases.We identified a total of 27 SOD1 variants in 38 families including two SOD1 variants located in nearsplice or intronic regions of the gene. The pathogenicity of the c.358-10TG nearspliceOur results highlighted nearsplice/intronic mutations in
Published: 2020

17. predictive factors for prognosis after gastrostomy placement in routine non-invasive ventilation users ALS patients

Author: Jésus Gonzalez-Bermejo, Pierre-François Pradat, Adèle Hesters, Gaëlle Bruneteau, Morgane Faure, Maria-Alejandra Galarza Jimenez, Nadine Le Forestier, Maria del Mar Amador, Timothée Lenglet, Capucine Morelot, François Salachas, Rabab Debs, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Recherche en Ethique, Université Paris-Sud - Paris 11 (UP11), Etudes sur les sciences et les techniques (EST), Université Paris-Saclay, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Ulster, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Neurophysiologie Respiratoire Expérimentale et Clinique, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Laboratoire d'Imagerie Biomédicale [Paris] (LIB)
Subjects: Adult, Male, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Vital Capacity, lcsh:Medicine, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Weight loss, Respiratory signs and symptoms, Medicine, Humans, Amyotrophic lateral sclerosis, lcsh:Science, Aged, Retrospective Studies, Aged, 80 and over, Gastrostomy, Multidisciplinary, Noninvasive Ventilation, business.industry, Proportional hazards model, Mortality rate, lcsh:R, Middle Aged, medicine.disease, Prognosis, 3. Good health, Parenteral nutrition, 030228 respiratory system, Anesthesia, Female, lcsh:Q, medicine.symptom, Airway, business, Body mass index, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Due to the expanding use of non-invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS), the question of enteral nutrition is increasingly raised in NIV users ALS patients. Here, we aimed to determine the prognostic factors for survival after gastrostomy placement in routine NIV users, taking into consideration ventilator dependence. Ninety-two routine NIV users ALS patients, who underwent gastrostomy insertion for severe dysphagia and/or weight loss, were included. We used a Cox proportional hazards model to identify factors affecting survival and compared time from gastrostomy to death and 30-day mortality rate between dependent (daily use ≥ 16 h) and non-dependent NIV users. The hazard of death after gastrostomy was significantly affected by 3 factors: age at onset (HR 1.047, p = 0.006), body mass index 2 at the time of gastrostomy placement (HR 2.012, p = 0.016) and recurrent accumulation of airway secretions (HR 2.614, p = 0.001). Mean time from gastrostomy to death was significantly shorter in the dependent than in the non-dependent NIV users group (133 vs. 250 days, p = 0.04). The 30-day mortality rate was significantly higher in dependent NIV users (21.4% vs. 2.8%, p = 0.03). Pre-operative ventilator dependence and airway secretion accumulation are associated with worse prognosis and should be key decision-making criteria when considering gastrostomy tube placement in NIV users ALS patients.
Published: 2020

18. A multi-center study of neurofilament assay reliability and inter-laboratory variability

Author: Andrea Malaspina, Philip Van Damme, Henrik Zetterberg, Maria del Mar Amador, Koen Poesen, Elizabeth Gray, Jens Kuhle, Charlotte E. Teunissen, Aleksandra Maceski, Patrick Oeckl, Kaj Blennow, Markus Otto, Petra Steinacker, François Salachas, Vittoria Lombardi, Maxim De Schaepdryver, Martin R Turner, Andreas Jeromin, Robert Bowser, Albert C. Ludolph, Ulf Andreasson, Foudil Lamari, Marleen J. A. Koel-Simmelink, Jiyan An, Amanda Heslegrave, Irina Nilsson, Laboratory Medicine, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Oncology, medicine.medical_specialty, Neurofilament, Coefficient of variation, Neurofilament light, Intermediate Filaments, 03 medical and health sciences, 0302 clinical medicine, Neurofilament Proteins, Internal medicine, medicine, Humans, Inter-laboratory, Amyotrophic lateral sclerosis, Neurofilament heavy chain, Reliability (statistics), business.industry, Amyotrophic Lateral Sclerosis, Reproducibility of Results, medicine.disease, Neurology, Multi center study, Neurology (clinical), business, Laboratories, 030217 neurology & neurosurgery, Biomarkers
Abstract: Objectives: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S. Methods: Serum, plasma and CSF samples from a group of five ALS and five neurological control patients were distributed across 10 international specialist neurochemical laboratories for analysis by a range of commercial and in-house neurofilament assays. The performance of all assays was evaluated for their ability to differentiate between the groups. The inter-assay coefficient of variation was calculated where appropriate from sample measurements performed across multiple laboratories using the same assay. Results: All assays could differentiate ALS patients from controls in CSF. Inter-assay coefficient of variation of analytical platforms performed across multiple laboratories varied between 6.5% and 41.9%. Conclusions: This study is encouraging for the growing momentum toward integration of neurofilament measurement into the specialized ALS clinic. It demonstrates the importance of 'round robin' studies necessary to ensure the analytical quality required for translation to the routine clinical setting. A standardized neurofilament probe is needed which can be used as international benchmark for analytical performance in ALS. ispartof: Amyotrophic Lateral Sclerosis And Frontotemporal Degeneration vol:21 issue:5-6 pages:452-458 ispartof: location:England status: published
Published: 2020

19. Homoplasmic deleterious MT-ATP6/8 mutations in adult patients

Author: Claude Jardel, Norma B. Romero, Sandrine Filaut, Isabelle Serre, Benoit Rucheton, Francis Haraux, Maria del Mar Amador, Anne Lombès, Sarah Leonard-Louis, T. Maisonobe, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Protéines et Systèmes Membranaires (LPSM), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Adult, Male, Mitochondrial DNA, Mitochondrial Diseases, Mitochondrial disease, [SDV]Life Sciences [q-bio], oxidative phosphorylation, Oxidative phosphorylation, Biology, Hybrid Cells, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Glycolysis, Muscle, Skeletal, Molecular Biology, Gene, Cells, Cultured, Homoplasmy, ATP synthase, homoplasmy, cybrids, High-Throughput Nucleotide Sequencing, Cell Biology, Sequence Analysis, DNA, Fibroblasts, Mitochondrial Proton-Translocating ATPases, medicine.disease, Molecular biology, mitochondrial disease, 030104 developmental biology, MT-ATP6, Mutation, biology.protein, Molecular Medicine, Female, 030217 neurology & neurosurgery
Abstract: To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis. It included oxidative phosphorylation spectrophotometric assays, western blots, structural analysis, ATP production, glycolysis and cell proliferation evaluation. We demonstrated the deleterious nature of three original mutations. Striking gradation in severity of the mutations consequences and differences between muscle, fibroblasts and cybrids implied a likely under-diagnosis of human complex V defects.
Published: 2020

20. Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS

Author: Jean-Philippe Camdessanché, Emilien Bernard, Jean-Christophe Antoine, Guillaume Banneau, Etienne Allart, Maria-Del-Mar Amador, François Muratet, Elisa Teyssou, Gabrielle Rudolf, Giovanni Stevanin, Christine Tranchant, Véronique Danel-Brunaud, Marie-Céline Fleury, Stéphanie Millecamps, Mathieu Anheim, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie et Pathologie du Mouvement, Hôpital Roger Salengro, Centre Hospitalier Universitaire (CHU) de Lille, CHU de Lille, Service de neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Neurologie [CHU Strasbourg], Hôpital de Hautepierre [Strasbourg]-Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer], Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), MILLECAMPS, Stéphanie, 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Hereditary spastic paraplegia, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, 03 medical and health sciences, 0302 clinical medicine, C9orf72, medicine, Spasticity, Amyotrophic lateral sclerosis, Exome, Tetraplegia, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Bulbar palsy, Genetics, 0303 health sciences, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurology (clinical), medicine.symptom, business, Trinucleotide repeat expansion, 030217 neurology & neurosurgery
Abstract: ObjectiveThe aim of this study was to evaluate whether mutations in ERLIN2, known to cause SPG18, a recessive hereditary spastic paraplegia (SP) responsible for the degeneration of the upper motor neurons leading to weakness and spasticity restricted to the lower limbs, could contribute to amyotrophic lateral sclerosis (ALS), a distinct and more severe motor neuron disease (MND), in which the lower motor neurons also profusely degenerates, leading to tetraplegia, bulbar palsy, respiratory insufficiency, and ultimately the death of the patients.MethodsWhole-exome sequencing was performed in a large cohort of 200 familial ALS and 60 sporadic ALS after a systematic screening for C9orf72 hexanucleotide repeat expansion. ERLIN2 variants identified by exome analysis were validated using Sanger analysis. Segregation of the identified variant with the disease was checked for all family members with available DNA.ResultsHere, we report the identification of ERLIN2 mutations in patients with a primarily SP evolving to rapid progressive ALS, leading to the death of the patients. These mutations segregated with the disease in a dominant (V168M) or recessive (D300V) manner in these families or were found in apparently sporadic cases (N125S).ConclusionsInheritance of ERLIN2 mutations appears to be, within the MND spectrum, more complex that previously reported. These results expand the clinical phenotype of ERLIN2 mutations to a severe outcome of MND and should be considered before delivering a genetic counseling to ERLIN2-linked families.
Published: 2019

21. Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes

Author: Maria del Mar Amador, F. Lamari, Rabab Debs, Marion Masingue, Bertrand Degos, Vincent Perlbarg, Emmanuel Roze, Fanny Mochel, Service de neurologie 1 [CHU Pitié-Salpétrière], 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 Biochimie Métabolique [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Diarrhea, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Xanthoma, Chenodeoxycholic Acid, Severity of Illness Index, Gastroenterology, Cerebrotendinous Xanthomatosis, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Intellectual Disability, Internal medicine, Chenodeoxycholic acid, Severity of illness, Genetics, medicine, Humans, Child, Genetics (clinical), Retrospective Studies, Neurologic Examination, Electromyography, business.industry, Brain, Neurodegenerative Diseases, Retrospective cohort study, Xanthomatosis, Cerebrotendinous, Middle Aged, Jaundice, medicine.disease, Magnetic Resonance Imaging, Pathophysiology, 3. Good health, Cholestanol, 030104 developmental biology, Peripheral neuropathy, chemistry, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disease related to sterols metabolism. It affects both central and peripheral nervous systems but treatment with chenodeoxycholic acid (CDCA) has been reported to stabilize clinical scores and improve nerve conduction parameters. Few quantitative brain structural studies have been conducted to assess the effect of CDCA in CTX.Methods and results: We collected retrospectively clinical, neurophysiological, and quantitative brain structural data in a cohort of 14 patients with CTX treated by CDCA over a mean period of 5 years. Plasma cholestanol levels normalized under treatment with CDCA within a few months. We observed a significant clinical improvement in patients up to 25 years old, whose treatment was initiated less than 15 years after the onset of neurological symptoms. Conversely, patients whose treatment was initiated more than 25 years after neurological disease onset continued their clinical deterioration. Eleven patients presented with a length-dependent peripheral neuropathy, whose electrophysiological parameters improved significantly under CDCA. Volumetric analyses in a subset of patients showed no overt volume loss under CDCA. Moreover, diffusion weighted imaging showed improved fiber integrity of the ponto-cerebellar and the internal capsule with CDCA. CDCA was well tolerated in all patients with CTX.Conclusion: CDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy.
Published: 2018

22. Cerebrospinal fluid metabolomics highlights dysregulation of energy metabolism in overt hepatic encephalopathy

Author: Marika Rudler, Nicolas Weiss, Dominique Thabut, Foucauld Isnard, Maria del Mar Amador, Foudil Lamari, Frédéric Sedel, Suleiman Attala, Christophe Junot, Pierre Barbier Saint Hilaire, Benoit Colsch, and Augustin Schaefer
Subjects: 0301 basic medicine, medicine.medical_specialty, Cirrhosis, Biology, Blood–brain barrier, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Cerebrospinal fluid, Metabolomics, Ammonia, Internal medicine, medicine, Humans, Amino Acids, Hepatic encephalopathy, Hepatology, medicine.disease, Pathophysiology, Metabolic pathway, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Hepatic Encephalopathy, 030211 gastroenterology & hepatology, Energy Metabolism
Abstract: Background & Aims Hepatic encephalopathy (HE) is a neurological complication observed in patients with liver disease and/or porto-systemic shunt. The proportion of cirrhotic patients developing overt HE is about 20%, and 60–80% of cirrhotic patients exhibit mild cognitive impairment potentially related to minimal HE. However, the pathophysiological mechanisms of HE remain poorly understood. In this context, metabolomics was used to highlight dysfunction of metabolic pathways in cerebrospinal fluid (CSF) samples of patients suffering from HE. Methods CSF samples were collected in 27 control patients without any proven neurological disease and 14 patients with symptoms of HE. Plasma samples were obtained from control patients, and from cirrhotic patients with and without HE. Metabolomic analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Results Concentrations of 73 CSF metabolites, including amino acids, acylcarnitines, bile acids and nucleosides, were altered in HE patients. Accumulation of acetylated compounds, which could be due to a defect of the Krebs cycle in HE patients, is reported for the first time. Furthermore, analysis of plasma samples showed that concentrations of metabolites involved in ammonia, amino-acid and energy metabolism are specifically and significantly increased in CSF samples of HE patients. Lastly, several drugs were detected in CSF samples and could partially explain worsening of neurological symptoms for some patients. Conclusion By enabling the simultaneous monitoring of a large set of metabolites in HE patients, CSF metabolomics highlighted alterations of metabolic pathways linked to energy metabolism that were not observed in plasma samples. Lay summary CSF metabolomics provides a global picture of altered metabolic pathways in CSF samples of HE patients and highlights alterations of metabolic pathways linked to energy metabolism that are not observed in plasma samples.
Published: 2016

23. The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study

Author: Rabab Debs, Jean-Yves Hogrel, Gaëlle Bruneteau, Tanya Stojkovic, Maria del Mar Amador, Julien Cohen-Adad, Lucette Lacomblez, David Devos, Nadine Le Forestier, Peter Bede, Timothée Lenglet, Menghan Li, Sophie Blancho, Pierre-François Pradat, Pascal Laforêt, Anthony Behin, François Salachas, Habib Benali, Martin Catala, Véronique Marchand-Pauvert, Mohamed-Mounir El Mendili, Stéphane Lehéricy, Vincent Meininger, Giorgia Querin, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centres de référence pour la sclérose latérale amyotrophique [CHU Pitié-Salpêtrière], 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), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Recherche en Ethique, Université Paris-Sud - Paris 11 (UP11), École Polytechnique de Montréal (EPM), Université de Montréal (UdeM), Unité de Neuroimagerie Fonctionnelle [Montréal] (UNF-CRIUGM), Université de Montréal (UdeM)-Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Neuro-Imagerie de Recherche (CENIR), Hôpital Raymond Poincaré [AP-HP], Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Concordia University [Montreal], Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Trinity College Dublin, University of Ulster, CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, Lille Neurosciences & Cognition (LilNCog) - U 1172, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), 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), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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], Gestionnaire, Hal Sorbonne Université, 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), Service de neurologie 1 [CHU Pitié-Salpétrière], 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pathology, UMN, Upper motor neuron, [SDV]Life Sciences [q-bio], LL, Lower limb, RD, Radial diffusivity, Spinal Muscular Atrophies of Childhood, lcsh:RC346-429, ALS, Amyotrophic lateral sclerosis, 0302 clinical medicine, Grey matter and white matter degeneration, Spinal cord MRI, Multimodal MRI, SMA, Spinal muscular atrophy, Medicine, FA, Fractional anisotropy, Gray Matter, SMA, Spinal muscular atrophy, GM, Grey matter, UL, Upper limb, HC, Healthy control, 05 social sciences, Brain, Middle Aged, Magnetic Resonance Imaging, White Matter, FWE, Familywise error, TR, repetition time, [SDV] Life Sciences [q-bio], Diffusion Tensor Imaging, medicine.anatomical_structure, Spinal Cord, Neurology, FOV, Field-of-view, WM, White matter, lcsh:R858-859.7, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], EPI, Echo-planar imaging, Motor cortex, Adult, CST, Corticospinal tract, medicine.medical_specialty, CSA, cross-sectional area, Grey matter, Adolescent, ROI, Region-of-interest, MNI, Montreal Neurological Institute, Cognitive Neuroscience, LMN, Lower motor neuron, SC, Spinal cord, lcsh:Computer applications to medicine. Medical informatics, Lower motor neuron, Article, 050105 experimental psychology, MND, Motor neuron disease, Muscular Atrophy, Spinal, White matter, Young Adult, 03 medical and health sciences, AD, Axial diffusivity, Neuroimaging, TE, Echo time, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurology. Diseases of the nervous system, Aged, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MD, mean diffusivity, SMAFRS, SMA functional rating scale, business.industry, VBM, Voxel-based morphometry, SMN1, Survival-motor-neuron 1 gene, MRC, Medical Research Council, TFCE, Threshold-free cluster enhancement, medicine.disease, Spinal cord, white matter degeneration, FDR, False discovery rate, DTI, diffusion tensor imaging, Neurology (clinical), 6MWT, Six-minute walk test, business, TBSS, Tract-based spatial statistics, 030217 neurology & neurosurgery
Abstract: Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging. Methods Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations. Results In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level. Conclusions Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation., Highlights • (SMA) type 3 and 4 is a lower motor neuron syndrome. Nevertheless, wider involvement of the nervous system might be possible. • 25 adults type 3 and 4 SMA patients were studied using brain and cervical spinal cord neuroimaging techniques. • Grey matter atrophy was observed in the spinal cord. No white matter degeneration was present at brain and spinal level. • Increased grey matter density was detected in cerebral motor regions and explained as compensatory mechanism.
Published: 2019

24. The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy

Author: Vincent Meininger, Pierre-François Pradat, Jean-Yves Hogrel, Gaëlle Bruneteau, Timothée Lenglet, Nadine Le Forestier, Tanya Stojkovic, François Salachas, Rabab Debs, Anthony Behin, Sophie Blancho, Giorgia Querin, Pascal Laforêt, Véronique Marchand-Pauvert, Lucette Lacomblez, Maria del Mar Amador, Peter Bede, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Département de Recherche en Ethique, Université Paris-Sud - Paris 11 (UP11), Hôpital privé des Peupliers (Paris), Hôpital Raymond Poincaré [AP-HP], Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la Recherche sur la Moelle Epinière et l'Encéphale (IRME), Trinity College Dublin, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Adult, Male, Recruitment, Neurophysiological, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Deltoid curve, Adult spinal muscular atrophy, Spinal Muscular Atrophies of Childhood, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Physical medicine and rehabilitation, Physiology (medical), medicine, Humans, Muscle Strength, Muscle, Skeletal, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MUSIX, business.industry, SMA type III, Motor unit number, Motor unit loss, Spinal muscular atrophy, Middle Aged, SMA, medicine.disease, Sensory Systems, Compound muscle action potential, SMA type IV, body regions, Motor unit, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Muscle strength, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MUNIX
Abstract: International audience; Objective : Objective of this study is the comprehensive characterisation of motor unit (MU) loss in type III and IV Spinal Muscular Atrophy (SMA) using motor unit number index (MUNIX), and evaluation of compensatory mechanisms based on MU size indices (MUSIX).Methods : Nineteen type III and IV SMA patients and 16 gender- and age-matched healthy controls were recruited. Neuromuscular performance was evaluated by muscle strength testing and functional scales. Compound motor action potential (CMAP), MUNIX and MUSIX were studied in the abductor pollicis brevis (APB), abductor digiti minimi (ADM), deltoid, tibialis anterior and trapezius muscles. A composite MUNIX score was also calculated.Results : SMA patients exhibited significantly reduced MUNIX values (p
Published: 2018

25. Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?

Author: Vincent Meininger, Pascal Cintas, Nadia Vandenberghe, Jean-Philippe Camdessanché, Sophie Demeret, François Salachas, Sophie Pittion, Emilien Delmont, Maria del Mar Amador, Sarah Louis, Timothée Lenglet, Claude Desnuelle, Gaëlle Bruneteau, Nawel Berhoune, Sophie Gronier, Pierre-François Pradat, Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), 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'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de neurologie [CHU de Saint-Étienne], Centre de Référence Maladies Neuromusculaires et SLA, hôpital Archet 1, Centre Sclérose Latérale amyotrophique [CHU Toulouse], Département Neurologie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Sclérose Latérale Amyotrophique et maladies [CHRU Nancy], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Laboratoire d'Imagerie Biomédicale (LIB), 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), 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), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service de Neurologie [CHU de Saint-Étienne], Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], 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), Centre Sclérose Latérale Amyotrophique et maladies, Unité de neurophysiologie clinique [CHU Toulouse], CHU Toulouse [Toulouse], 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Neuromuscular transmission, Disease, immunology, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Receptors, Cholinergic, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, Genetics (clinical), Aged, Autoantibodies, Retrospective Studies, Aged, 80 and over, myasthenia gravis, neuromuscular transmission, business.industry, Autoantibody, Retrospective cohort study, medicine.disease, Myasthenia gravis, nervous system diseases, 3. Good health, Riluzole, 030104 developmental biology, Neurology, Concomitant, Pediatrics, Perinatology and Child Health, Immunology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve years period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity.
Published: 2016

26. Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study

Author: Eya Mseddi, Vincent Meininger, Eric Bardinet, Pierre-François Pradat, Gaëlle Bruneteau, Daniel Delgadillo, Marie-Laure Welter, Maryse Feron, Nadine Le Forestier, Malek Abidi, Maria del Mar Amador, Annabelle Couillandre, Rabab Debs, Nicolas Termoz, Lucette Lacomblez, Giovanni de Marco, Peter Bede, François Salachas, Giorgia Querin, Mélanie Pélégrini-Issac, Timothée Lenglet, Centre de Recherche sur le Sport et le Mouvement (CeRSM), Université Paris Nanterre (UPN), Centre de Neuro-Imagerie de Recherche (CENIR), 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 neurologie 2 [CHU Pitié-Salpêtrière], Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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], 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 neurologie 1 [CHU Pitié-Salpétrière], Fédération des Maladies du Système Nerveux, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d'imagerie neurofonctionnelle (IIN), 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), 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), Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), 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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], 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), 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)-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), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Laboratoire d'Imagerie Biomédicale [Paris] (LIB)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Neurology, Context (language use), Neuroimaging, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Magnetic resonance imaging, Basal ganglia, medicine, Cerebellar Degeneration, Humans, Prospective Studies, Amyotrophic lateral sclerosis, Gray Matter, myotrophic lateral sclerosis, Postural Balance, Postural instability, Gait Disorders, Neurologic, Gait impairment, Aged, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Gait, Biomechanical Phenomena, 030104 developmental biology, Gait analysis, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Introduction Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribu-tion to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.Objective The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.Methods Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings.Results ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, “unsteady” ALS patients have reduced caudate and brain stem volumes compared to “steady” ALS patients.Interpretation Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability
Published: 2018

27. Targeted versus untargeted omics — the CAFSA story

Author: Emmanuel Roze, Frédéric Sedel, Christel Depienne, Ron A. Wevers, Christophe Junot, Agnès Rastetter, Clément Frainay, Claude Jardel, Farid Ichou, F. Lamari, Maria del Mar Amador, Benoit Colsch, Fabien Jourdan, Fanny Mochel, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], 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), MedDay Pharmaceuticals, Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Radboud University Medical Center [Nijmegen], Les Hôpitaux Universitaires de Strasbourg (HUS), French Ministry of Health (PHRC SPECTMET-II) [RCB 2010-A01395-34], Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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), 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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Male, Folate, DNA Mutational Analysis, 01 natural sciences, Mass Spectrometry, chemistry.chemical_compound, Exome, Genetics (clinical), Exome sequencing, Tetrahydrofolates, Cerebellar ataxia, Genomics, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, DNA Polymerase gamma, Cerebrospinal fluid, Female, medicine.symptom, medicine.drug, Adult, Mitochondrial disease, DNA, Mitochondrial, 03 medical and health sciences, Metabolomics, All institutes and research themes of the Radboud University Medical Center, Exome Sequencing, Genetics, medicine, Humans, Carnitine, business.industry, Siblings, 010401 analytical chemistry, medicine.disease, N-Acetylneuraminic Acid, Sialic acid, 0104 chemical sciences, 030104 developmental biology, Targeted mass spectrometry, chemistry, Case-Control Studies, Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background In 2009, untargeted metabolomics led to the delineation of a new clinico-biological entity called cerebellar ataxia with elevated cerebrospinal free sialic acid, or CAFSA. In order to elucidate CAFSA, we applied sequentially targeted and untargeted omic approaches. Methods and results First, we studied five of the six CAFSA patients initially described. Besides increased CSF free sialic acid concentrations, three patients presented with markedly decreased 5-methyltetrahydrofolate (5-MTHF) CSF concentrations. Exome sequencing identified a homozygous POLG mutation in two affected sisters, but failed to identify a causative gene in the three sporadic patients with high sialic acid but low 5-MTHF. Using targeted mass spectrometry, we confirmed that free sialic acid was increased in the CSF of a third known POLG-mutated patient. We then pursued pathophysiological analyses of CAFSA using mass spectrometry-based metabolomics on CSF from two sporadic CAFSA patients as well as 95 patients with an unexplained encephalopathy and 39 controls. This led to the identification of a common metabotype between the two initial CAFSA patients and three additional patients, including one patient with Kearns-Sayre syndrome. Metabolites of the CSF metabotype were positioned in a reconstruction of the human metabolic network, which highlighted the proximity of the metabotype with acetyl-CoA and carnitine, two key metabolites regulating mitochondrial energy homeostasis. Conclusion Our genetic and metabolomics analyses suggest that CAFSA is a heterogeneous entity related to mitochondrial DNA alterations either through POLG mutations or a mechanism similar to what is observed in Kearns-Sayre syndrome.
Published: 2018

28. Pure cerebellar ataxia linked to large C9orf72 repeat expansion

Author: Paul H. Gordon, Maria del Mar Amador, Philippe Corcia, Patrick Vourc'h, Philippe Couratier, Vincent Meininger, Anne-Marie Guennoc, Christian R. Andres, and Hélène Blasco
Subjects: Adult, Male, 0301 basic medicine, Cerebellar Ataxia, Biology, 03 medical and health sciences, 0302 clinical medicine, C9orf72, medicine, Humans, Genetic Testing, Amyotrophic lateral sclerosis, Genetic testing, Family Health, Genetics, DNA Repeat Expansion, C9orf72 Protein, Cerebellar ataxia, medicine.diagnostic_test, C9orf72 Gene, Intron, Proteins, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Neurology, Female, Neurology (clinical), medicine.symptom, Trinucleotide repeat expansion, 030217 neurology & neurosurgery
Abstract: Excessive repeats of the hexaplet GGGGCC in intron 1 of the C9orf72 gene are the most frequent genetic mutations so far identified that are linked to amyotrophic lateral sclerosis (ALS) and frontot...
Published: 2015

29. Multicenter evaluation of neurofilaments in early symptomatic amyotrophic lateral sclerosis

Author: Marcel M. Verbeek, Claude Jardel, Maria del Mar Amador, Susanne Petri, Koen Poesen, Philip Van Damme, Christian Barro, Markus Otto, Beatrice Stubendorff, Sonja Koerner, Julian Grosskreutz, Jens Kuhle, Benjamin Mayer, Foudil Lamari, François Salachas, Petra Steinacker, Joost Raaphorst, Patrick Weydt, Albert C. Ludolph, Martin R Turner, Elizabeth Gray, Emily Feneberg, Jochen H. Weishaupt, Claudia Morelli, Petra Muckova, Vincenzo Silani, Federico Verde, Patrick Oeckl, and Neurology
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Neurofilament, Diagnostic accuracy, Disease, Gastroenterology, Sensitivity and Specificity, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neurofilament Proteins, Internal medicine, medicine, Humans, In patient, Symptom onset, Amyotrophic lateral sclerosis, Phosphorylation, Aged, Aged, 80 and over, Heavy chain, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 030104 developmental biology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Follow-Up Studies
Abstract: ObjectiveTo examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS).MethodsWe measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures.ResultsNfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%) and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not vary between clinical diagnostic categories of ALS in the early symptomatic phase group. Baseline NfL and pNfH levels were not significantly different in patients with ALS with clinical progression to definite or probable ALS at follow-up.ConclusionThe measurement of Nf has potential to enhance diagnostic accuracy of ALS in those presenting soon after symptom onset, and is measurable across multiple centers.Classification of evidenceThis study provides Class II evidence that CSF and serum Nf concentrations discriminate ALS with early symptom onset from other neurologic diseases.
Published: 2017

30. Outcome of gastrostomy in parkinsonism: A retrospective study

Author: Christine Payan, Lucette Lacomblez, Maria del Mar Amador, Clémence Marois, Jean-Christophe Corvol, Anne-Marie Bonnet, Valérie Mesnage, David Grabli, Nadine Le Forestier, Bertrand Degos, Marie Vidailhet, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Dpt Recherche en Ethiques (ES3), Université Paris-Sud - Paris 11 (UP11), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-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), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], CHU Saint-Antoine [AP-HP], and HAL UPMC, Gestionnaire
Subjects: Male, Aspiration pneumonia, Pediatrics, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Survival, medicine.medical_treatment, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Parkinsonian syndrome, 03 medical and health sciences, 0302 clinical medicine, Parkinsonian Disorders, Humans, Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, Prospective cohort study, Aged, Proportional Hazards Models, Retrospective Studies, Outcome, Gastrostomy, business.industry, Proportional hazards model, Adverse effects, Gastrostomy tube insertion, Parkinsonism, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Neurology, Female, 030211 gastroenterology & hepatology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Long Term Adverse Effects, Geriatrics and Gerontology, Deglutition Disorders, business, 030217 neurology & neurosurgery
Abstract: International audience; Objective : To investigate the indications and the outcomes of gastrostomy tube insertion in patients with parkinsonian syndromes.Methods : Consecutive patients with Parkinson's disease or atypical parkinsonism, seen in two French tertiary referral movement disorders centers, that received gastrostomy tube insertion (GTI) for feeding between 2008 and 2014 were included in this retrospective study. Data regarding clinical status, indications and outcomes were retrieved from medical files. The main outcome measure was survival duration following gastrostomy insertion according to Kaplan-Meier estimate. Cox analysis was also performed to identify factors associated with survival. Finally, we described short term and long term adverse effects occurring during the follow-up period.Results : We identified 33 patients with Parkinsonism that received GTI during the study period. One patient was excluded from the analysis because of missing data. Among 32 patients, 7 (22%) had Parkinson's disease and 25 (78%) had atypical parkinsonism. The median survival following the procedure was 186 days (CI 95% [62–309]). In Cox model analysis, total dependency was the only factor negatively associated with survival (HR 0.1; 95% CI [0.02–0.4], p = 0.001). Pneumonia was the most frequent adverse event.Conclusion : In this sample of patients with parkinsonian syndromes, survival after GTI was short particularly in totally dependent subjects. Aspiration pneumonia was not prevented by GTI. A larger prospective study is warranted to assess the potential benefits of gastrostomy, in order to identify the most appropriate indications and timing for the procedure.
Published: 2017

31. Reversal learning reveals cognitive deficits and altered prediction error encoding in the ventral striatum in Huntington's disease

Author: Florian Schlagenhauf, Lorenz Deserno, Patricia Panneck, Konstantin Prass, Josef Priller, Katharina Nickchen, Thomas D. Hälbig, Andreas Heinz, Maria del Mar Amador, Joachim Behr, Katharina Dehnicke, and Rebecca Boehme
Subjects: 0301 basic medicine, physiopathology [Huntington Disease], Male, Huntingtin, physiopathology [Cognitive Dysfunction], diagnostic imaging [Cognitive Dysfunction], physiopathology [Ventral Striatum], physiopathology [Gray Matter], Striatum, Neuropsychological Tests, Functional Laterality, Cohort Studies, genetics [Huntington Disease], Behavioral Neuroscience, 0302 clinical medicine, ddc:150, Gray Matter, diagnostic imaging [Huntington Disease], Brain Mapping, medicine.diagnostic_test, Neuropsychology, Cognition, Middle Aged, Magnetic Resonance Imaging, diagnostic imaging [Ventral Striatum], Psychiatry and Mental health, Huntington Disease, medicine.anatomical_structure, Neurology, Disease Progression, Female, Psychology, Algorithms, Adult, Cognitive Neuroscience, Central nervous system, Reversal Learning, physiology [Reversal Learning], 03 medical and health sciences, Cellular and Molecular Neuroscience, Huntington's disease, medicine, Humans, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, Computer Simulation, Ventral striatum, diagnostic imaging [Gray Matter], medicine.disease, 030104 developmental biology, Ventral Striatum, psychology [Huntington Disease], Neurology (clinical), Probability Learning, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by a triad of movement disorder, neuropsychiatric symptoms and cognitive deficits. The striatum is particularly vulnerable to the effects of mutant huntingtin, and cell loss can already be found in presymptomatic stages. Since the striatum is well known for its role in reinforcement learning, we hypothesized to find altered behavioral and neural responses in HD patients in a probabilistic reinforcement learning task performed during functional magnetic resonance imaging. We studied 24 HD patients without central nervous system (CNS)-active medication and 25 healthy controls. Twenty HD patients and 24 healthy controls were able to complete the task. Computational modeling was used to calculate prediction error values and estimate individual parameters. We observed that gray matter density and prediction error signals during the learning task were related to disease stage. HD patients in advanced disease stages appear to use a less complex strategy in the reversal learning task. In contrast, HD patients in early disease stages show intact encoding of learning signals in the degenerating left ventral striatum. This effect appears to be lost with disease progression.
Published: 2017

32. Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism

Author: Natalia Shor, Didier Dormont, Maria del Mar Amador, Catherine Lubetzki, Anne Bertrand, HAL-UPMC, Gestionnaire, Service de Neuroradiologie [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), 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), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], 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), 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), and 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]
Subjects: Adult, Pathology, medicine.medical_specialty, peripheral neuropathy, Central nervous system, 030218 nuclear medicine & medical imaging, Multiple sclerosis, 03 medical and health sciences, Myelin, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Paralysis, Humans, Medicine, Trigeminal Nerve, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Myelin Sheath, cranial nerve, medicine.diagnostic_test, business.industry, Cranial nerves, Peripheral Nervous System Diseases, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Peripheral neuropathy, Neurology, Physical therapy, cisternal enhancement, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, Subarachnoid space, business, 030217 neurology & neurosurgery
Abstract: International audience; Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.
Published: 2017

33. Radiotherapy treatment of sialorrhea in patients with amyotrophic lateral sclerosis requiring non-invasive ventilation

Author: Maria del Mar Amador, Jésus Gonzalez-Bermejo, Pierre-François Pradat, and Avi Assouline
Subjects: Adult, Male, medicine.medical_specialty, Orthopnea, medicine.medical_treatment, Pilot Projects, Aspiration pneumonia, Drooling, Clinical Protocols, medicine, Humans, Amyotrophic lateral sclerosis, Nose, Aged, Mechanical ventilation, Noninvasive Ventilation, Sialorrhea, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Neurology, Anesthesia, Physical therapy, Breathing, Female, Neurology (clinical), medicine.symptom, business
Abstract: In amyotrophic lateral sclerosis (ALS), bulbar dysfunction may lead to sialorrhea [1], which affects up to 25 % of patients [2], and is a significant purveyor of distress trough a permanent drooling mouth, an increased risk of saliva aspiration pneumonia and a limited tolerance of non-invasive ventilation (NIV). We recently demonstrated that radiotherapy (RT) of the salivary glands was efficient and safe in the treatment of refractory sialorrhea in ALS [3]. Nevertheless, when orthopnoea occurs, decubitus position necessary to RT requires NIV. Performing RT in patients undergoing mechanical ventilation is technically challenging. The objective of this pilot study was to evaluate the efficacy and tolerance of a new protocol of RT specifically designed for ALS patients requiring mechanical ventilation for decubitus position. Five ALS patients, with established ALS according to revised El Escorial criteria [4], respiratory insufficiency and profuse sialorrhea resistant to classical pharmacological treatments (atropine drops, hyoscine patches and amitriptyline) were included. For patient characteristics see Table 1. All patients had severe orthopnea and were treated, at least over night, with non-invasive positive pressure ventilation without oxygen, using a facial mask. Irradiation was performed at the Clinique de la Porte de Saint-Cloud (Boulogne, France). Treatment was delivered through a conventional linear accelerator with 6 MV photons in both submandibular glands and two thirds of both parotid glands. Patients lied during sessions in 30 decubitus position for a maximum period of 10 min. The thermoplastic mask for radiotherapy was specifically designed to fit the facial mask of NIV, incorporating a large opening over the mouth and nose (Fig. 1). RT efficacy was assessed with the Sialorrhea Scoring Scale (SSS) that we previously validated in ALS patients [5]. The scale allows a semiquantification of sialorrhea in 9 grades ranging from 1 (dry mouth) to 9 (profuse sialorrhea). Approval for the study was obtained from the Regional Committee for Medical Research Ethics. Irradiation was completed in all 5 cases without any perprocedure complication. Assessment at the end of RT showed improvement in all patients with complete response (CR: SSS 1–3) in 4 cases and partial response (PR: SSS 4–5) in one case. Further evaluation at 3 months revealed persistent significant reduction in salivary production with 3 patients maintaining a CR and 2 patients a PR. Mild pain (acute toxicity of RT grade 1–2) was observed in 1 patient, but resolved in the weeks following the end of treatment. & Pierre-Francois Pradat pierre-francois.pradat@psl.aphp.fr
Published: 2015

34. Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Author: Sanna-Kaisa Herukka, Julian Grosskreutz, Peter M. Andersen, Andreas Jeromin, François Salachas, Albert C. Ludolph, Maria del Mar Amador, Susanne Petri, Koen Poesen, André Huss, Erdem Tüzün, Claudia Morelli, Patrick Oeckl, Berrak Yetimler, Petra Muckova, Ana I. Rodríguez Mahillo, Magdalena Kuzma-Kozakiewicz, Wim Robberecht, Foudil Lamari, Claude Jardel, Janine Kirby, Robert Bowser, Jesus S. Mora, María Hernández-Barral, Anna Karin Rikardsson, Mamede de Carvalho, Philip Van Damme, Markus Otto, Vincenzo Silani, Petra Steinacker, Heidrun Rhode, Júlia Costa, Martin R Turner, Elizabeth Gray, and Pamela J. Shaw
Subjects: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, Neurofilament, Intermediate Filaments, Enzyme-Linked Immunosorbent Assay, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Neurochemical, medicine, Diagnostic biomarker, Humans, Amyotrophic lateral sclerosis, Phosphorylation, Aged, business.industry, Amyotrophic Lateral Sclerosis, Reproducibility of Results, Middle Aged, medicine.disease, United States, Clinical neurology, Europe, 030104 developmental biology, Neurology, Biomarker (medicine), Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract: OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a “reverse” round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n = 150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p 568.5 pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up. © 2016 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases
Published: 2016

35. Personality Changes After Encephalitis: When 'Organic Personality Disorder' Is Not Enough

Author: Thomas Mauras and Maria del Mar Amador
Subjects: Autoimmune encephalitis, Pediatrics, medicine.medical_specialty, business.industry, medicine.disease, Akathisia, Intensive care unit, law.invention, Personality changes, Cerebrospinal fluid, Swallowing, law, Medicine, medicine.symptom, business, Encephalitis, Altered level of consciousness
Abstract: F.C. is a previously healthy 21-year-old female presenting a challenging emotional and behavioral disorder starting at the age of 19. At that age, while attending university, she started complaining of concentration difficulties. Subsequent ophthalmoplegia with bilateral ptosis, abnormal jaw movements, and difficulties in swallowing prompted neurological evaluation. Brain magnetic resonance imaging (MRI) revealed large bilateral lesions in deep brain structures (Fig. 35.1). Cell count in cerebrospinal fluid (CSF) was 16 lymphocytes. One single CSF sample was positive for anti-GAD testing (Oxford Laboratory), but following tests remained negative for this or other antibodies, as well as an extensive inflammatory, infectious, and neoplastic workup. Autoimmune encephalitis was suspected. Initial treatment was administered in the intensive care unit because of altered level of consciousness. It involved high-dose corticoid therapy, plasma exchanges, and intravenous immune globulins. Clinical evolution was satisfactory with rapid improvement of neurological symptoms. The first behavioral changes occurred during the intensive care unit (ICU) stay in the form of stereotypic handwashing without intrusive thoughts, hyperphagia, and akathisia. Three weeks after admission, she was transferred to a neurological ward and discharged after 2 further weeks.
Published: 2016

36. Myoclonies d’action et protéinurie modérée isolée : penser SCARB2

Author: Anne Doé De Maindreville, Emmanuel Flamand-Roze, David Grabli, Anne Thiriaux, Marie-Laure Gross, Maria del Mar Amador, and M. Vidailhet
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Les epilepsies myocloniques progressives (EMP) sont des maladies hereditaires rares habituellement severes, alliant des myoclonies et des crises epileptiques. Nous rapportons un cas rare avec nephropathie. Observation Un homme de 30 ans, senegalais, aux antecedents de tremblements fins des extremites et de maladresse du membre superieur droit depuis environ 10 ans, est hospitalise pour des myoclonies multi-focales, asymetriques, asynchrones, essentiellement d’action mais egalement stimulo-sensibles isolees. Les fonctions superieures semblent conservees. Les explorations biologiques (metabolique, infectieuse et immunitaire) et morphologiques s’averent normales hormis une legere proteinurie a 235 mg par 24 heures. L’EEG est aspecifique ; l’EMG montre une legere neuropathie axonale. Les causes classiques d’EMP sont eliminees par la biologie moleculaire. La presence d’une proteinurie isolee va permettre d’orienter le diagnostic vers un syndrome action myoclonus with renal failure (AMRF), confirme genetiquement (codeletion du gene SCARB2). A 31 ans, le patient presente une ataxie, une dysarthrie et des crises tonico-cloniques generalisees. L’etat clinique du patient se degrade rapidement, responsable d’une grabatisation 6 ans plus tard. Le patient decede a l’âge de 39 ans suite a des etats de mal epileptiques myocloniques recidivants malgre un traitement antiepileptique et symptomatique adapte. Il ne presentera pas d’insuffisance renale au cours de son evolution. Discussion Devant un tableau d’EMP, la presence d’une proteinurie isolee, meme minime, permet d’evoquer le diagnostic d’AMRF. Maladie genetique autosomique recessive rare, elle implique le gene SCARB2 qui code pour une glycoproteine lysosomale membranaire, la LIMP-2 (role dans la regulation du transport lysosomal). Le traitement nephrologique n’a pas d’influence sur l’evolution neurologique. L’evolution est fatale en une dizaine d’annees. Conclusion Devant un tableau d’EMP, la presence d’une proteinurie isolee, meme minime, doit faire evoquer le diagnostic d’AMRF qui sera confirme genetiquement.
Published: 2018

37. Cat Bite: An Unusual Cause of Foot Drop

Author: Maria del Mar Amador, Bertrand Degos, and Gaëlle Bruneteau
Subjects: Foot drop, medicine.diagnostic_test, business.industry, 030231 tropical medicine, Magnetic resonance imaging, General Medicine, Peroneal neuropathy, Cat bite, 03 medical and health sciences, 0302 clinical medicine, Anesthesia, Medicine, Gait disorders, 030212 general & internal medicine, Antibiotic prophylaxis, medicine.symptom, business
Published: 2016

38. Gastrostomie dans les syndromes parkinsoniens : étude rétrospective sur les indications de sa mise en place et l’évolution des patients

Author: Christine Payan, Lucette Lacomblez, Valérie Mesnage, Clémence Marois, David Grabli, and Maria del Mar Amador
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Les troubles de deglutition se compliquent de denutrition, de pneumopathies d’inhalation, voire de deces dans les syndromes parkinsoniens. Une gastrostomie peut etre proposee mais sa pertinence n’a jamais ete evaluee. Objectifs Nos objectifs etaient de decrire les caracteristiques des patients parkinsoniens beneficiant d’une gastrostomie, d’evaluer leur devenir et de preciser la morbi-mortalite de cette procedure. Patients et methodes Nous avons inclus retrospectivement les patients suivis dans 2 centres parisiens, presentant un syndrome parkinsonien (SP) et ayant beneficie d’une pose de gastrostomie entre 2004 et 2014. Nous avons recueilli les donnees demographiques, l’histoire naturelle du SP, le statut nutritionnel, la cognition, l’autonomie, les capacites de communication des patients au moment de la gastrostomie, ainsi que la survenue de complications precoces et tardives, et du deces sur une periode de 2 ans apres la gastrostomie. Resultats Sur 32 patients inclus, 44 % avaient une atrophie multi-systematisee. Au moment de la gastrostomie, 72 % presentaient une denutrition, 91 % des troubles de la communication et 75 % etaient totalement dependants. Trois patients ont presente des complications immediates dont 2 ayant entraine le deces. La duree d’hospitalisation etait de 18 jours (± 31). La survie a 1 an etait de 41 %. A 2 ans, 44 % des patients avaient eu une pneumopathie d’inhalation et 69 % etaient decedes. Discussion La plupart des patients presentaient une maladie tres evoluee avec denutrition, degradation cognitive et troubles de la communication majeurs. Les complications immediates de la pose de gastrostomie semblent rares mais la procedure ne previent pas la survenue de pneumopathies d’inhalation. La mortalite reste tres importante avec plus de deux tiers des patients decedes a 2 ans. Conclusion La gastrostomie, proposee aux patients parkinsoniens les plus graves, n’elimine pas la survenue de pneumopathie d’inhalation et reste associee a une mortalite importante. Sa pertinence est donc discutable.
Published: 2016

39. La diplopie non paralytique d’origine cérébelleuse

Author: Alexandra Durr, Claire Ewenczyk, Maria del Mar Amador, Bertrand Gaymard, Dimitri Psimaras, and Silvia Fenu
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction En absence de paralysie oculomotrice, un dysfonctionnement du cervelet peut etre a l’origine d’une diplopie binoculaire de l’adulte, dite non paralytique (DNP). Cette diplopie est souvent variable et fluctuante. Objectifs Illustrer les differents aspects de la diplopie non paralytique de l’adulte d’origine cerebelleuse et caracteriser ses mecanismes. Patients et methodes Nous avons inclus dix-huit patients presentant divers types de DNP d’origine cerebelleuse. Les patients ont realise le bilan suivant : un examen oculomoteur et neurologique, un score SARA (Scale for the Assessment and Rating of Ataxia), un enregistrement des mouvements oculaires, une IRM cerebrale. Selon les caracteristiques de leur diplopie (de loin, de pres, en position laterale extreme), les patients ont ete rassembles en 3 groupes de 6 patients chacun. Resultats Tous nos patients avec DNP (vitesses des saccades identiques sur les deux yeux) presentent un syndrome cerebelleux oculomoteur (saccades dysmetriques, gaze-evoked/downbeat nystagmus) et somatique, et/ou une atrophie cerebelleuse a l’IRM. Dans le 1er groupe (diplopie de loin) les patients presentent une esotropie. Dans le 2e groupe (diplopie de pres) les patients presentent une exotropie. Dans le 3e groupe (diplopie en position laterale extreme) les patients montrent une skew-deviation alternante. Discussion Le cervelet controle la vergence. Son dysfonctionnement peut donc entrainer une diplopie liee a une esotropie ou a une exotropie. Le cervelet controle egalement la position de chaque œil, independamment de l’autre. Un defaut d’alignement des globes produira une diplopie, souvent dans les positions laterales extremes (patients du 3e groupe) ou la diplopie verticale est liee a une skew-deviation alternante. Conclusion La diplopie binoculaire non paralytique acquise de l’adulte est un symptome sensible et parfois anticipateur d’un dysfonctionnement cerebelleux. Elle doit donc faire rechercher un syndrome cerebelleux somatique.
Published: 2017

40. ATXN2 trinucleotide repeat length correlates with risk of ALS

Author: Pietro Fratta, Aleksey Shatunov, Isabelle Le Ber, Vincenzo La Bella, Owen A. Ross, Peter M. Andersen, Tim Van Langenhove, François Salachas, Monica Forzan, John Powell, Jan H. Veldink, Andrea Malaspina, Claire Troakes, Maria del Mar Amador, Christine Van Broeckhoven, Nancy M. Bonini, Stéphanie Millecamps, Daniel Stahl, Cinzia Gellera, Aaron D. Gitler, John Hardy, Vincent Meininger, Giovanni Stevanin, Katie Sidle, Serena Lattante, Gianni Sorarù, Ben Gaastra, Leonard H. van den Berg, Christopher Shaw, Philip Van Damme, Guy A. Rouleau, Safa Al-Sarraj, Bing-Wen Soong, Richard W. Orrell, Maryam Shoai, Yi-Chung Lee, Isabella Fogh, Hussein Daoud, Rosa Rademakers, Wim Robberecht, Ashley R. Jones, Wouter van Rheenen, Ammar Al-Chalabi, Bradley N. Smith, Francesca Luisa Conforti, Edor Kabashi, William Sproviero, Sproviero, W., Shatunov, A., Stahl, D., Shoai, M., van Rheenen, W., Jones, A., Al Sarraj, S., Andersen, P., Bonini, N., Conforti, F., Van Damme, P., Daoud, H., Del Mar Amador, M., Fogh, I., Forzan, M., Gaastra, B., Gellera, C., Gitler, A., Hardy, J., Fratta, P., LA BELLA, V., Le Ber, I., Van Langenhove, T., Lattante, S., Lee, Y., Malaspina, A., Meininger, V., Millecamps, S., Orrell, R., Rademakers, R., Robberecht, W., Rouleau, G., Ross, O., Salachas, F., Sidle, K., Smith, B., Soong, B., Sorarù, G., Stevanin, G., Kabashi, E., Troakes, C., van Broeckhoven, C., Veldink, J., van den Berg, L., Shaw, C., Powell, J., and Al Chalabi, A.
Subjects: Male, Expansion, 0301 basic medicine, Aging, ATXN2 gene, Settore MED/03 - GENETICA MEDICA, 0302 clinical medicine, Trinucleotide Repeats, Genetic Report Abstract, Amyotrophic lateral sclerosis, Ataxin-2, Genetics, CAG, General Neuroscience, ATXN2, Triplet, 3. Good health, Female, Psychology, Neurovetenskaper, Risk, Neuroscience(all), Age of onset, Clinical Neurology, 03 medical and health sciences, SCA2, Trinucleotide repeat, Journal Article, medicine, Humans, Allele, Alleles, Genetic Association Studies, Amyotrophic lateral sclerosi, Intermediate expansion, Neuroscience (all), Neurosciences, Exponential risk, Case-control study, medicine.disease, Clinical neurology, Ageing, 030104 developmental biology, Case-Control Studies, Human medicine, Neurology (clinical), ALS, Geriatrics and Gerontology, Trinucleotide Repeat Expansion, Trinucleotide repeat expansion, Neuroscience, 030217 neurology & neurosurgery, Meta-Analysis, Developmental Biology
Abstract: We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. publisher: Elsevier articletitle: ATXN2 trinucleotide repeat length correlates with risk of ALS journaltitle: Neurobiology of Aging articlelink: http://dx.doi.org/10.1016/j.neurobiolaging.2016.11.010 content_type: article copyright: © 2016 The Author(s). Published by Elsevier Inc. ispartof: Neurobiology of Aging vol:51 pages:178- ispartof: location:United States status: published
Published: 2017

41. Histoire naturelle de la xanthomatose cérébrotendineuse : une pathologie pédiatrique diagnostiquée à l’âge adulte

Author: Yann Nadjar, Fanny Mochel, Emmanuel Flamand-Roze, Foudil Lamari, Maria del Mar Amador, Philippe Couvert, and Bertrand Degos
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction La xanthomatose cerebrotendineuse (XCT) est une erreur innee du metabolisme traitable a expression principalement neurologique a l’âge adulte. L’elevation du cholestanol plasmatique est un biomarqueur specifique de la XCT. Objectifs Decrire l’histoire naturelle de la XCT dans notre population et identifier les marqueurs precoces de la maladie pour favoriser l’initiation du traitement avant la survenue d’un handicap neurologique irreversible. Methodes Il s’agit d’une etude clinique retrospective de 17 patients avec XCT vivant en France. Des donnees demographiques, cliniques, d’electrophysiologie et d’imagerie ont ete recueillies. Resultats Les modes d’entree neurologique (âge de debut 28 ans ; 15–50) etaient des difficultes de marche (61 %), des troubles cognitivo-comportementaux (25 % ; syndrome frontal, irritabilite, psychose), ou des troubles mixtes (14 %). Les troubles de la marche etaient lies a une atteinte cerebello-pyramidale (43 %), cerebelleuse isolee (28 %), pyramidale isolee (14 %), ou peripherique de type CMT (14 %). Soixante-quinze pour cent des patients avaient des antecedents de cataracte et/ou de diarrhee chronique dans l’enfance precedant l’atteinte neurologique. Discussion Selon les resultats de notre etude, 75 % des patients avec XCT presentaient des signes precurseurs identifiables dans l’enfance. Pourtant le diagnostic a ete porte en majorite a l’âge adulte. L’identification plus precoce de la XCT permettrait la mise en route du traitement par acide chenodesoxycholique (CDCA) avant la survenue de manifestations cliniques traduisant une neurodegenerescence. Conclusion L’identification d’une cataracte et/ou d’une diarrhee chronique et/ou de troubles psychiatriques atypiques depuis l’enfance ou l’adolescence doit faire rechercher une XCT grâce au dosage du cholestanol plasmatique.
Published: 2015

42. La sclérose latérale amyotrophique est un syndrome

Author: Maria del Mar Amador and François Salachas
Subjects: Neurology, Neurology (clinical)
Abstract: Dans le sillage de la description visionnaire que nous a legue Jean Martin Charcot a la grande epoque de la methode anatomo-clinique en 1865, la maladie eponyme a longtemps beneficie d’un statut a part au sein des affections qui ont fait l’objet de la grande vague descriptive qu’a connu notre specialite a la fin du XIX e siecle. La degenerescence exclusive des neurones de la voie motrice, l’absence de troubles cognitifs, la presence constante de crampes et de fasciculations ont confere a la SLA l’image d’une maladie si homogene dans sa presentation qu’elle devait l’etre aussi dans ses mecanismes. Cette conception uniciste est a l’origine d’une quete du Graal visant a decoder le mystere de l’apparition de ses manifestations et de la marche ineluctable de sa progression. Les descriptions neuropathologiques mettant a profit l’utilisation de nouveaux marqueurs tels que l’ubiquitine et les neurofilaments sont venues dans un premier temps etayer la vision archetypale initiee par Charcot. L’apport tres pragmatique des neurologues anglo-saxons est ensuite venu perturber ce bel ordonnancement nosologique digne d’un jardin a la francaise en introduisant le terme de « Motor Neuron Disease » ouvrant la porte a tous les amalgames specieux. Le suivi longitudinal de grandes cohortes de patients a permis de confirmer l’heterogeneite clinique de la SLA qu’il s’agisse de son mode de debut, de son rythme et de son mode de propagation, de la presence de troubles comportementaux et de la duree de survie. La mise en evidence de mutations responsables des formes familiales de la maladie a fait naitre l’espoir de disposer d’un modele clinique et physiopathologique universel permettant d’acceder rapidement a un traitement specifique. Il a cependant fallu admettre que la pleiotropie clinique des formes familiales liees au gene SOD1 et a ceux decouverts par la suite etaient une realite. La SLA illustre donc bien les phenomenes de convergence et de divergence clinique qui l’apparentent desormais a un syndrome. Sa segmentation fera plus que jamais appel a l’expertise clinique qui, seule, permettra de faire emerger des biomarqueurs pertinents.
Published: 2015

43. Hypersignaux de la substance blanche et microdélétion 6p25 : à propos d’un cas

Author: Maria del Mar Amador, Martin Catala, Marine Boudot De La Motte, Savine Vicart, Dominique Bourgeois, and Catherine Lubetzki
Subjects: Neurology, Neurology (clinical)
Abstract: Introduction Les microdeletions 6p25 sont a l’origine de phenotypes variables : atteinte ophtalmologique, surdite, retard mental, malformations cranio-faciales… Des anomalies de la substance blanche sont plus rarement decrites. Observation Nous rapportons le cas d’une patiente de 24 ans, issue d’une union consanguine, suivie depuis la petite enfance pour un glaucome congenital bilateral (syndrome d’Axenfeld Rieger clinique) et une surdite bilaterale. Elle presente egalement des migraines avec aura depuis l’adolescence. A l’occasion d’un bilan d’hirsutisme, une IRM cerebrale est realisee, retrouvant de nombreux hypersignaux de la substance blanche peri-ventriculaire et sous corticaux ne prenant pas le contraste. La patiente est hospitalisee pour suspicion de sclerose en plaques. L’examen clinique retrouve des reflexes osteotendineux vifs, la surdite et une dysmorphie faciale. Le bilan biologique standard, immunologique, infectieux, metabolique et carentiel est normal ainsi que le bilan neuropsychologique. L’IRM cerebrale a 6 mois est inchangee et l’IRM medullaire ne retrouve pas d’anomalie. L’analyse du LCR n’a pas pu etre realisee. Une surdite et/ou des anomalies du parenchyme cerebral n’etant pas habituellement associees au syndrome d’Axenfeld Rieger, l’hypothese d’un syndrome des genes contigus a ete soulevee. Une deletion en 6p25.3 emportant le gene FOXC1 , responsable quand il est mute du syndrome d’Axenfeld Rieger, a ete mise en evidence par CGH Array. Discussion Un certain nombre d’anomalies cerebrales ont ete decrites associees aux microdeletions 6p25 : malformation de Dandy-Walker, hypoplasie du corps calleux, hydrocephalie, dilatation des espaces perivasculaires. Des hypersignaux de la substance blanche ont ete rapportes de facon plus recente dans environ 20 % des cas, conduisant chez certains, comme chez notre patiente a un diagnostic errone de sclerose en plaques. Conclusion Des hypersignaux de la substance blanche peuvent faire evoquer a tort une maladie inflammatoire du systeme nerveux central. Associes a un syndrome malformatif, ils doivent faire rechercher une cause genetique.
Published: 2016

44. Response to the Letter to the Editor: 'Radiotherapy of salivary glands as treatment of sialorrhea in patients with amyotrophic lateral sclerosis requiring non-invasive ventilation: what are we doing?'

Author: Avi Assouline, Jésus Gonzalez-Bermejo, Pierre-François Pradat, and Maria del Mar Amador
Subjects: Male, medicine.medical_specialty, Letter to the editor, Neurology, medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, In patient, Amyotrophic lateral sclerosis, Mechanical ventilation, Noninvasive Ventilation, Sialorrhea, business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Surgery, Radiation therapy, 030220 oncology & carcinogenesis, Female, Noninvasive ventilation, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2016

45. Natural history of cerebrotendinous xanthomatosis: a paediatric disease diagnosed in adulthood

Author: Yann Nadjar, Bertrand Degos, Foudil Lamari, Frédéric Sedel, Fanny Mochel, Philippe Couvert, Emmanuel Roze, Maria del Mar Amador, Service des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], 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 Biochimie Métabolique [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), UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière], GRC Neurométabolisme, 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), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière] (Pôle MSN), HAL UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Adult, Male, Diarrhea, Pediatrics, medicine.medical_specialty, Adolescent, Disease, Kaplan-Meier Estimate, Cerebrotendinous Xanthomatosis, Cataract, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognitive dysfunction, Psychiatric symptoms, medicine, Humans, Genetics(clinical), Pharmacology (medical), Young adult, Child, Letter to the Editor, Genetics (clinical), Cerebellar ataxia, Medicine(all), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Cholestanol, Cerebrotendinous xanthomatosis, General Medicine, Xanthomatosis, Cerebrotendinous, Middle Aged, 3. Good health, Natural history, 030104 developmental biology, Child, Preschool, medicine.symptom, Differential diagnosis, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Cerebrotendinous xanthomatosis (CTX) is among the few inherited neurometabolic disorders amenable to specific treatment. It is easily diagnosed using plasma cholestanol. We wished to delineate the natural history of the most common neurological and non-neurological symptoms in thirteen patients with CTX. Diarrhea almost always developed within the first year of life. Cataract and school difficulties usually occurred between 5 and 15 years of age preceding by years the onset of motor or psychiatric symptoms. The median age at diagnosis was 24.5 years old. It appears critical to raise awareness about CTX among paediatricians in order to initiate treatment before irreversible damage occurs. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0419-x) contains supplementary material, which is available to authorized users.
Full Text: View/download PDF

46. Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19

Author: Virginie, Lambrecq, Aurélie, Hanin, Esteban, Munoz-Musat, Lydia, Chougar, Salimata, Gassama, Cécile, Delorme, Louis, Cousyn, Alaina, Borden, Maria, Damiano, Valerio, Frazzini, Gilles, Huberfeld, Frank, Landgraf, Vi-Huong, Nguyen-Michel, Phintip, Pichit, Aude, Sangare, Mario, Chavez, Capucine, Morélot-Panzini, Elise, Morawiec, Mathieu, Raux, Charles-Edouard, Luyt, Pierre, Rufat, Damien, Galanaud, Jean-Christophe, Corvol, Catherine, Lubetzki, Benjamin, Rohaut, Sophie, Demeret, Nadya, Pyatigorskaya, Lionel, Naccache, Vincent, Navarro, Safia, Said, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Cardiologie [CHU Pitié-Salpêtrière], Service de Département d'Information Médicale [CHU Pitié-Salpêtrière] (DIM), Unité fonctionnelle d'épilepsie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [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)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Département Médico-Universitaire réanimation anesthésie médecine péri-opératoire [Sorbonne Université] (DMU DREAM), CHU Tenon [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)-CHU Pitié-Salpêtrière [AP-HP], Groupe de recherche clinique en anesthésie réanimation médecine périopératoire [CHU Pitié-Salpétrière] (GRC ARPE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Centre de référence des épilepsies rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service de Neurologie [CHU Pitié-Salpêtrière], Cohort COVID-19 Neurosciences (CoCo Neurosciences) Study Group: Jean-Yves Delattre, Stephanie Carvalho, Sandrine Sagnes, Bruno Dubois, Celine Louapre, Tanya Stojkovic, Ahmed Idbaih, Charlotte Rosso, David Grabli, Ana Zenovia Gales, Bruno Millet, Eleonore Bayen, Sophie Dupont, Gaelle Bruneteau, Stephane Lehericy, Danielle Seilhean, Alexandra Durr, Aurelie Kas, Foudil Lamari, Marion Houot, Vanessa Batista Brochard, Pascale Pradat-Diehl, Khe Hoang-Xuan, Bertrand Fontaine, Philippe Fossati, Isabelle Arnulf, Alexandre Carpentier, Yved Edel, Anna Luisa Di Stefano, Gilberte Robain, Philippe Thoumie, Bertrand Degos, Tarek Sharshar, Sonia Alamowitch, Emmanuelle Apartis-Bourdieu, Charles-Siegried Peretti, Renata Ursu, Nathalie Dzierzynski, Kiyoka Kinugawa Bourron, Joel Belmin, Bruno Oquendo, Eric Pautas, Marc Verny, Yves Samson, Sara Leder, Anne Leger, Sandrine Deltour, Flore Baronnet, Stéphanie Bombois, Mehdi Touat, Caroline Dehais, Caroline Houillier, Florence Laigle-Donadey, Dimitri Psimaras, Agusti Alentorn, Nadia Younan, Nicolas Villain, Maria Del Mar Amador, Louise-Laure Mariani, Nicolas Mezouar, Graziella Mangone, Aurélie Meneret, Andreas Hartmann, Clément Tarrano, David Bendetowicz, Pierre-Francois Pradat, Michel Baulac, Sara Sambin, Florence Chochon, Adele Hesters, Bastien Herlin, An Hung Nguyen, Valérie Procher, Alexandre Demoule, Julien Mayaux, Morgane Faure, Claire Ewenczyk, Giulia Coarelli, Anna Heinzmann, Perrine Charles, Marion Masingue, Guillaume Bassez, Isabelle An, Yulia Worbe, Rabab Debs, Timothee Lenglet, Natalia Shor, Delphine Leclercq, Albert Cao, Clémence Marois, Nicolas Weiss, Loic Le Guennec, Vincent Degos, Alice Jacquens, Thomas Similowski, Jean-Yves Rotge, Bertrand Saudreau, Victor Pitron, Nassim Sarni, Nathalie Girault, Redwan Maatoug, Smaranda Leu, Lionel Thivart, Karima Mokhtari, Isabelle Plu, Bruno Goncalves, Laure Bottin, Marion Yger, Gaelle Ouvrard, Rebecca Haddad, Flora Ketz, Carmelo Lafuente, Christel Oasi, Bruno Megarbane, Dominique Herve, Haysam Salman, Armelle Rametti-Lacroux, Alize Chalancon, Anais Herve, Hugo Royer, Florence Beauzor, Valentine Maheo, Christelle Laganot, Camille Minelli, Aurélie Fekete, Abel Grine, Marie Biet, Rania Hilab, Aurore Besnard, Meriem Bouguerra, Gwen Goudard, Saida Houairi, Saba Al-Youssef, Christine Pires, Anissa Oukhedouma, Katarzyna Siuda-Krzywicka, Tal Seidel Malkinson, Hanane Agguini, Hassen Douzane Agguini, Safia Said, Raux, Mathieu, 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)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: Male, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Brain Diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Research, [SDV]Life Sciences [q-bio], COVID-19, Electroencephalography, Middle Aged, Magnetic Resonance Imaging, Cohort Studies, [SDV] Life Sciences [q-bio], Online Only, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Electronic Health Records, Humans, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Original Investigation
Abstract: Key Points Question Can electroencephalography (EEG), combined with clinical, biological, and magnetic resonance imaging (MRI) analyses, help to better characterize patients with neurologic coronavirus disease 2019 (COVID-19) and diagnose specific COVID-19–related encephalopathy? Findings Neurologic manifestations, biological findings, EEG findings, and brain MRI images were analyzed in a cohort study of 78 adult patients with COVID-19. Nine patients had no identified cause of brain injury, as revealed by biological and MRI findings; their injury was defined as COVID-19–related encephalopathy. Meaning This study suggests that, although neurologic manifestations, EEG findings, and MRI findings may appear heterogeneous and nonspecific, multimodal monitoring may better identify patients with COVID-19–related encephalopathy and guide treatment strategy., Importance There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19–related encephalopathy and guide clinical management. Objectives To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19–related encephalopathy. Design, Setting, and Participants This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020. Exposures Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription–polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest. Main Outcomes and Measures Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records. Results Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter–enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19–related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter–enhancing lesions. Conclusions and Relevance The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19–related encephalopathy and guide treatment strategy., This cohort study investigates clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with coronavirus disease 2019 (COVID-19) and refines the features of COVID-19–related encephalopathy.
Published: 2021

47. Who and Why? Requests for Presymptomatic Genetic Testing for Amyotrophic Lateral Sclerosis/Frontotemporal Dementia vs Huntington Disease.

Author: Amador MDM, Gargiulo M, Boucher C, Herson A, Staraci S, Salachas F, Clot F, Cazeneuve C, Le Ber I, and Durr A
Abstract: Objective: We aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD)., Methods: We retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit., Results: Of the 106 presymptomatic testing (PT) requests from subjects at risk of ALS/FTD, 65% were seen in the last 3 years. Over two-thirds of the subjects were at risk of carrying mutations responsible for ALS, FTD, or both. Sixty-two percent of the subjects came from families with a known hexanucleotide repeat expansion in C9ORF72 . During the same period, we counseled 840 subjects at risk of HD. Subjects at risk of ALS/FTD had the presymptomatic test significantly sooner after being aware of their risk, but were older than those at risk of HD. The youngest subjects requesting the test had the highest disease load in the family ( p < 0.05)., Conclusions: Demands for PT for ALS/FTD have been increasingly growing, particularly since the discovery of the C9ORF72 gene. The major specificity of the genetic counseling for these diseases is the unpredictability of the clinical phenotype for most of the genes involved. Awareness of this added uncertainty does not prevent individuals from taking the test, as the dropout rate is not higher than that for HD., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

47 results on '"Maria-Del-Mar Amador"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources