Year: 2021
Type: article
Study design: Observational Study
Abstract: C9orf72 repeat expansions are rarely associated with primary progressive aphasias (PPA). In-depth characterization of the linguistic deficits, and the underlying patterns of grey-matter atrophy in PPA associated with the C9orf72 expansions (PPA-C9orf72) are currently lacking. In this study, we comprehensively analyzed a unique series of 16 patients affected by PPA-C9orf72. Eleven patients were issued from two independent French and Finnish cohorts, and five were identified by means of literature review. Voxel-based morphometry (VBM) studies were performed on three of them. This study depicts the spectrum of C9orf72-related aphasic phenotypes, and illustrates their linguistic presentation. The non-fluent/agrammatic variant was the most frequent phenotype in our series (9/16 patients, 56%), with apraxia of speech being the main defining feature. Left frontal lobe atrophy was present in these subjects, peaking in inferior frontal gyrus. Three patients (19%) showed the semantic variant, with progression of atrophy in temporo-polar regions, later involving orbitofrontal cortex. Anterior temporal lobe dysfunction was also particularly relevant in two patients (12.5%) with mixed forms of PPA. Lastly, two patients (12.5%) had unclassifiable PPA with predominating word-finding difficulties. No PPA-C9orf72 patients in our series fulfilled the criteria of the logopenic variant. Importantly, this study underlines the role of C9orf72 mutation in the disruption of the most anterior parts of the language network, including prefrontal and temporo-polar areas. It provides guidelines for C9orf72 testing in PPA patients, with important clinical impact as gene-specific therapies are upcoming.
Source: Cortex
Authors: Dario Saracino, Amandine Géraudie, Anne M. Remes, Sophie Ferrieux, Marie Noguès-Lassiaille, Simona Bottani, Lorenzo Cipriano, Marion Houot, Aurélie Funkiewiez, Agnès Camuzat, Daisy Rinaldi, Marc Teichmann, Jérémie Pariente, Philippe Couratier, Claire Boutoleau-Bretonnière, Sophie Auriacombe, Frédérique Etcharry-Bouyx, Richard Levy, Raffaella Migliaccio, Eino Solje, Isabelle Le Ber, Sophie Auriacombe, Serge Belliard, Frédéric Blanc, Eve Benchetrit, Hugo Bertin, Claire Boutoleau-Bretonnière, Anne Bertrand, Anne Bissery, Stéphanie Bombois, Marie-Paule Boncoeur, Alexis Brice, Mathieu Ceccaldi, Mathieu Chastan, Yaohua Chen, Marie Chupin, Olivier Colliot, Philippe Couratier, Xavier Delbeuck, Christine Delmaire, Vincent Deramecourt, Mira Didic, Charles Duyckaerts, Frédérique Etcharry-Bouyx, Maïté Formaglio, Emmanuel Gerardin, Véronique Golfier, Marie-Odile Habert, idier Hannequin, Lucette Lacomblez, Julien Lagarde, Géraldine Lautrette, Isabelle Le Ber, Benjamin Le Toullec, Marie-Anne Mackowiak, Olivier Martinaud, Bernard-François Michel, Jacques Monteil, Assi-Hervé Oya, Jérémie Pariente, Florence Pasquier, Grégory Petyt, Daisy Rinaldi, Adeline Rollin-Sillaire, Carole Roué-Jagot, Sabrina Sayah, Marie Sarazin, Christel Thauvin-Robinet, Catherine Thomas-Anterion, François Sellal, Martine Vercelletto, David Wallon
Institutions: Centre National de la Recherche Scientifique, Institut national de recherche en sciences et technologies du numérique, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Institut du Cerveau, ARAMIS: Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain sain et pathologique, Université Toulouse III - Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse, Toulouse NeuroImaging Center, Oulu University Hospital, University of Oulu, University of Campania "Luigi Vanvitelli", École Pratique des Hautes Études, Université Paris Sciences et Lettres, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier Universitaire de Nantes, Centre d'Investigation Clinique de Nantes, Centre Hospitalier Universitaire de Bordeaux, Institut des Maladies Neurodégénératives, Hôpital Pellegrin, Centre Hospitalier Universitaire d'Angers, University of Eastern Finland, Kuopio University Hospital, Centre Hospitalier Universitaire de Rennes, Hôpital Civil, Strasbourg, Hôpital Roger Salengro, Hôpital de la Timone, Hôpital Charles-Nicolle, Laboratoire d’Imagerie Biomédicale, Centre Hospitalier Sainte-Anne, Hôpital Sainte-Marguerite, CHU Dijon Bourgogne
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,150
OpenAlex ID: W3202448503