Giorgia Querin1,2, Peter Bede1,2,3, Mohamed Mounir El Mendili2,4, Menghan Li2, Mélanie Pélégrini-Issac2, Daisy Rinaldi5,6, Martin Catala7, Dario Saracino5, François Salachas1, Agnes Camuzat5, Véronique Marchand-Pauvert2, Julien Cohen-Adad8,9, Olivier Colliot5,10,11, Isabelle Le Ber5,6,12, Pierre-François Pradat1,2,13. 1. Department of Neurology, SLA Reference Center, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France. 2. Laboratory of Biomedical Imaging, National Center for Scientific Research, National Institute of Health and Medical Research, Sorbonne University, Paris, France. 3. Computational Neuroimaging Group, Academic Unit of Neurology, Trinity College Dublin, Dublin, Ireland. 4. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY. 5. Brain and Spinal Cord Institute, Sorbonne University, National Institute of Health and Medical Research U1127, National Center for Scientific Research Mixed Unit of Research 7225, Pitié-Salpêtrière Hospital, Paris, France. 6. Reference Center for Rare or Early Dementia, Pitié-Salpêtrière Hospital, Paris, France. 7. Department of Neurology, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Sorbonne University, National Center for Scientific Research Mixed Unit of Research 7622, National Institute of Health and Medical Research Accademic Research Unit 1156, Biology Institute Paris-Seine, Paris, France. 8. NeuroPoly Laboratory, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, Quebec, Canada. 9. Functional Neuroimaging Unit, Research Center of the University Institute of Geriatrics of Montreal, University of Montreal, Montreal, Quebec, Canada. 10. Aramis Project Team, Inria Research Center of Paris, Paris, France. 11. Center for Image Acquisition and Processing, Brain and Spinal Cord Institute, Paris, France. 12. Institute of Memory and Alzheimer's Disease, Center of Excellence of Neurodegenerative Disease, Department of Neurology, SLA Reference Center, Pitié-Salpêtrière Hospital, Public Hospital Network of Paris, Paris, France. 13. Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Clinical-Translational Research and Innovation Center, Altnagelvin Hospital, Londonderry, United Kingdom.
Abstract
OBJECTIVE: C9orf72 hexanucleotide repeats expansions account for almost half of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases. Recent imaging studies in asymptomatic C9orf72 carriers have demonstrated cerebral white (WM) and gray matter (GM) degeneration before the age of 40 years. The objective of this study was to characterize cervical spinal cord (SC) changes in asymptomatic C9orf72 hexanucleotide carriers. METHODS: Seventy-two asymptomatic individuals were enrolled in a prospective study of first-degree relatives of ALS and FTD patients carrying the c9orf72 hexanucleotide expansion. Forty of them carried the pathogenic mutation (C9+ ). Each subject underwent quantitative cervical cord imaging. Structural GM and WM metrics and diffusivity parameters were evaluated at baseline and 18 months later. Data were analyzed in C9+ and C9- subgroups, and C9+ subjects were further stratified by age. RESULTS: At baseline, significant WM atrophy was detected at each cervical vertebral level in C9+ subjects older than 40 years without associated changes in GM and diffusion tensor imaging parameters. At 18-month follow-up, WM atrophy was accompanied by significant corticospinal tract (CST) fractional anisotropy (FA) reductions. Intriguingly, asymptomatic C9+ subjects older than 40 years with family history of ALS (as opposed to FTD) also exhibited significant CST FA reduction at baseline. INTERPRETATION: Cervical SC imaging detects WM atrophy exclusively in C9+ subjects older than 40 years, and progressive CST FA reductions can be identified on 18-month follow-up. Cervical SC magnetic resonance imaging readily captures presymptomatic pathological changes and disease propagation in c9orf72-associated conditions. ANN NEUROL 2019;86:158-167.
OBJECTIVE:C9orf72hexanucleotide repeats expansions account for almost half of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases. Recent imaging studies in asymptomatic C9orf72 carriers have demonstrated cerebral white (WM) and gray matter (GM) degeneration before the age of 40 years. The objective of this study was to characterize cervical spinal cord (SC) changes in asymptomatic C9orf72hexanucleotide carriers. METHODS: Seventy-two asymptomatic individuals were enrolled in a prospective study of first-degree relatives of ALS and FTDpatients carrying the c9orf72hexanucleotide expansion. Forty of them carried the pathogenic mutation (C9+ ). Each subject underwent quantitative cervical cord imaging. Structural GM and WM metrics and diffusivity parameters were evaluated at baseline and 18 months later. Data were analyzed in C9+ and C9- subgroups, and C9+ subjects were further stratified by age. RESULTS: At baseline, significant WM atrophy was detected at each cervical vertebral level in C9+ subjects older than 40 years without associated changes in GM and diffusion tensor imaging parameters. At 18-month follow-up, WM atrophy was accompanied by significant corticospinal tract (CST) fractional anisotropy (FA) reductions. Intriguingly, asymptomatic C9+ subjects older than 40 years with family history of ALS (as opposed to FTD) also exhibited significant CST FA reduction at baseline. INTERPRETATION: Cervical SC imaging detects WM atrophy exclusively in C9+ subjects older than 40 years, and progressive CST FA reductions can be identified on 18-month follow-up. Cervical SC magnetic resonance imaging readily captures presymptomatic pathological changes and disease propagation in c9orf72-associated conditions. ANN NEUROL 2019;86:158-167.
Authors: Julien Cohen-Adad; Eva Alonso-Ortiz; Mihael Abramovic; Carina Arneitz; Nicole Atcheson; Laura Barlow; Robert L Barry; Markus Barth; Marco Battiston; Christian Büchel; Matthew Budde; Virginie Callot; Anna J E Combes; Benjamin De Leener; Maxime Descoteaux; Paulo Loureiro de Sousa; Marek Dostál; Julien Doyon; Adam Dvorak; Falk Eippert; Karla R Epperson; Kevin S Epperson; Patrick Freund; Jürgen Finsterbusch; Alexandru Foias; Michela Fratini; Issei Fukunaga; Claudia A M Gandini Wheeler-Kingshott; Giancarlo Germani; Guillaume Gilbert; Federico Giove; Charley Gros; Francesco Grussu; Akifumi Hagiwara; Pierre-Gilles Henry; Tomáš Horák; Masaaki Hori; James Joers; Kouhei Kamiya; Haleh Karbasforoushan; Miloš Keřkovský; Ali Khatibi; Joo-Won Kim; Nawal Kinany; Hagen Kitzler; Shannon Kolind; Yazhuo Kong; Petr Kudlička; Paul Kuntke; Nyoman D Kurniawan; Slawomir Kusmia; René Labounek; Maria Marcella Laganà; Cornelia Laule; Christine S Law; Christophe Lenglet; Tobias Leutritz; Yaou Liu; Sara Llufriu; Sean Mackey; Eloy Martinez-Heras; Loan Mattera; Igor Nestrasil; Kristin P O'Grady; Nico Papinutto; Daniel Papp; Deborah Pareto; Todd B Parrish; Anna Pichiecchio; Ferran Prados; Àlex Rovira; Marc J Ruitenberg; Rebecca S Samson; Giovanni Savini; Maryam Seif; Alan C Seifert; Alex K Smith; Seth A Smith; Zachary A Smith; Elisabeth Solana; Yuichi Suzuki; George Tackley; Alexandra Tinnermann; Jan Valošek; Dimitri Van De Ville; Marios C Yiannakas; Kenneth A Weber; Nikolaus Weiskopf; Richard G Wise; Patrik O Wyss; Junqian Xu Journal: Nat Protoc Date: 2021-08-16 Impact factor: 17.021
Authors: Rangariroyashe H Chipika; We Fong Siah; Mary Clare McKenna; Stacey Li Hi Shing; Orla Hardiman; Peter Bede Journal: J Neurol Date: 2020-10-31 Impact factor: 6.682