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Title: Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.
Austin Authors: Whelan, Christopher D;Altmann, Andre;Botía, Juan A;Jahanshad, Neda;Hibar, Derrek P;Absil, Julie;Alhusaini, Saud;Alvim, Marina K M;Auvinen, Pia;Bartolini, Emanuele;Bergo, Felipe P G;Bernardes, Tauana;Blackmon, Karen;Braga, Barbara;Caligiuri, Maria Eugenia;Calvo, Anna;Carr, Sarah J;Chen, Jian;Chen, Shuai;Cherubini, Andrea;David, Philippe;Domin, Martin;Foley, Sonya;França, Wendy;Haaker, Gerrit;Isaev, Dmitry;Keller, Simon S;Kotikalapudi, Raviteja;Kowalczyk, Magdalena A;Kuzniecky, Ruben;Langner, Soenke;Lenge, Matteo;Leyden, Kelly M;Liu, Min;Loi, Richard Q;Martin, Pascal;Mascalchi, Mario;Morita, Marcia E;Pariente, Jose C;Rodríguez-Cruces, Raul;Rummel, Christian;Saavalainen, Taavi;Semmelroch, Mira K;Severino, Mariasavina;Thomas, Rhys H;Tondelli, Manuela;Tortora, Domenico;Vaudano, Anna Elisabetta;Vivash, Lucy;von Podewils, Felix;Wagner, Jan;Weber, Bernd;Yao, Yi;Yasuda, Clarissa L;Zhang, Guohao;Bargalló, Nuria;Bender, Benjamin;Bernasconi, Neda;Bernasconi, Andrea;Bernhardt, Boris C;Blümcke, Ingmar;Carlson, Chad;Cavalleri, Gianpiero L;Cendes, Fernando;Concha, Luis;Delanty, Norman;Depondt, Chantal;Devinsky, Orrin;Doherty, Colin P;Focke, Niels K;Gambardella, Antonio;Guerrini, Renzo;Hamandi, Khalid;Jackson, Graeme D ;Kälviäinen, Reetta;Kochunov, Peter;Kwan, Patrick;Labate, Angelo;McDonald, Carrie R;Meletti, Stefano;O'Brien, Terence J;Ourselin, Sebastien;Richardson, Mark P;Striano, Pasquale;Thesen, Thomas;Wiest, Roland;Zhang, Junsong;Vezzani, Annamaria;Ryten, Mina;Thompson, Paul M;Sisodiya, Sanjay M
Affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA
Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
Translational Imaging Group, Centre for Medical Image Computing, University College London, London, UK
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK
Department of Radiology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Department of Neurology, University of Campinas, Campinas, Brazil
Epilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland
Pediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Italy
IRCCS Stella Maris Foundation, Pisa, Italy
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, USA
Department of Physiology, Neuroscience and Behavioral Science, St. George's University, Grenada, West Indies
Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK
Department of Computer Science and Engineering, The Ohio State University, USA
Cognitive Science Department, Xiamen University, Xiamen, China
Fujian Key Laboratory of the Brain-like Intelligent Systems, China
Functional Imaging Unit, Institute of Diagnostic Radiology Neuroradiology, University Medicine Greifswald, Greifswald, Germany
Cardiff University Brain Research Imaging Centre, School of Psychology, Wales, UK
Department of Neurosurgery, University Hospital, Freiburg, Germany
Department of Neuropathology, University Hospital Erlangen, Germany
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, UK
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Multimodal Imaging Laboratory, University of California San Diego, San Diego, California, USA
Department of Psychiatry, University of California San Diego, San Diego, California, USA
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, Mcgill University, Montreal, Quebec, Canada
Neuroradiology Unit, Children's Hospital A. Meyer, Florence, Italy
"Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy
Instituto de Neurobiología, Universidad Nacional Autónoma de México. Querétaro, Querétaro, México
Support Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
Central Finland Central Hospital, Medical Imaging Unit, Jyväskylä, Finland
Neuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genova, Italy
Institute of Psychological Medicine and Clinical Neurosciences, Hadyn Ellis Building, Maindy Road, Cardiff, UK
Department of Neurology, University Hospital of Wales, Cardiff, UK
Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy
Department of Medicine, University of Melbourne, Parkville, VIC, 3052, Australia
Department of Neurology, Royal Melbourne Hospital, Parkville, 3050, Australia
Department of Neurology, University Medicine Greifswald, Greifswald, Germany
Department of Epileptology, University Hospital Bonn, Bonn, Germany
Department of Neurology, Philips University of Marburg, Marburg Germany
Department of Neurocognition / Imaging, Life&Brain Research Centre, Bonn, Germany
The Affiliated Chenggong Hospital of Xiamen University, Xiamen, China
Multimodal Imaging and Connectome Analysis Lab, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
Medical College of Wisconsin, Department of Neurology, Milwaukee, WI, USA
FutureNeuro Research Centre, RCSI, Dublin, Ireland
Division of Neurology, Beaumont Hospital, Dublin 9, Ireland
Department of Neurology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium
Neurology Department, St. James's Hospital, Dublin 8, Ireland
Department of Clinical Neurophysiology, University Medicine Göttingen, Göttingen, Germany
Institute of Neurology, University "Magna Græcia", Catanzaro, Italy
Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Maryland, USA
Department of Neurology, King's College London, UK
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
Dept of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, 20156 Milano, Italy
Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK
Chalfont Centre for Epilepsy, Bucks, UK
Issue Date: 1-Feb-2018
Publication information: Brain : a journal of neurology 2018; 141(2): 391-408
Abstract: Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.
DOI: 10.1093/brain/awx341
PubMed URL: 29365066
Type: Journal Article
Subjects: MRI
precentral gyrus
Appears in Collections:Journal articles

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