Authors

Christopher D Whelan, Royal College of Surgeons in IrelandFollow
Andre Altmann, University College London
Juan A. Botía, UCL Institute of Neurology
Neda Jahanshad, University of Southern California
Derrek P. Hibar, University of Southern California
Julie Absil, Universite Libre de Bruxelles
Saud Alhusaini, Royal College of Surgeons in IrelandFollow
Marina KM Alvim, Universityof Campinas
Pia Auvinen, Kuopio University
Emanuele Bartolini, Meyer-University of Florence
Felipe PG Bergo, University of Campinas
Tauana Bernardes, University of Campinas
Karen Blackmon, New York University School of Medicine
Barbara Braga, University of Campinas
Maria Eugenia Caligiuri, IBFM-CNR Catanzaro, Italy
Anna Calvo, IDIBAPS Barcelona, Spain
Sarah J. Carr, King's College London
Shuai Chen, Xiamen University
Andrea Cherubini, IBFM-CNR Catanzaro, Italy
Philippe David, Universite Libre de Bruxelles
Martin Domin, University Medicine Greifswald
Sonya Foley, Cardiff University Brain Research Imaging Centre
Wendy França, University of Campinas
Gerrit Haaker, University Hospital, Freiburg
Dmitry Isaev, University of Southern California
Simon S. Keller, University of Liverpool
Raviteja Kotikalapudi, University of Tubingen
Magdalena A. Kowalczyk, Austin Campus, Melbourne
Ruben Kuzniecky, New York University School of Medicine
Soenke Langner, University Medicine Greifswald
Matteo Lenge, Meyer-University of Florence
Kelly M. Leyden, University of California San Diego
Min Liu, McGill University
Richard Q. Loi, University of California San Diego
Pascal Martin, University of Tubingen
Mario Mascalchi, University of Florence
Marcia E. Morita, University of Campinas
Jose C. Pariente, IDIBAPS Barcelona, Spain
Raul Rodríguez-Cruces, Universidad Nacional Autonoma de Mexico
Christian Rummel, University of Bern
Taavi Saavalainen, University of Eastern Finland
Mira K. Semmelroch, Austin Campus, Melbourne
Mariasavina Severino, Instituto Giannina Gaslini
Rhys H. Thomas, University Hospital of Wales
Manuela Tondelli, University of Modena and Reggio Emilia
Domenico Tortora, Instituto Giannina Gaslini
Anna Elisabetta Vaudano, University of Modena and Reggio Emilia
Lucy Vivash, University of Melbourne
Felix von Podewils, University Medicine Greifswald
Jan Wagner, University Hospital Bonn
Bernd Weber, University Hospital Bonn
Yi Yao, Xiamen Universityt, China
Clarissa L. Yasuda, University of Campinas
Guohao Zhang, University of Maryland
Nuria Bargalló, IDIBAPS Barcelona, Spain
Benjamin Bender, University of Tubingen
Neda Bernasconi, McGill University
Andrea Bernasconi, McGill University
Boris C. Bernhardt, McGill University
Ingmar Blümcke, University Hospital Erlangen
Chad Carlson, New York University School of Medicine
Gianpiero L. Cavalleri, Royal College of Surgeons in IrelandFollow
Fernando Cendes, University of Campinas
Luis Concha, Universidad Nacional Autonoma de Mexico
Norman Delanty, Royal College of Surgeons in IrelandFollow
Chantal Depondt, Universite Libre de Bruxelles
Orrin Devinsky, New York University School of Medicine
Colin P. Doherty, Royal College of Surgeons in Ireland
Niels K. Focke, University of Tubingen
Antonio Gambardella, IBFM-CNR Catanzaro, Italy
Renzo Guerrini, Meyer-University of Florence
Khalid Hamandi, University Hospital of Wales
Graeme D. Jackson, Austin Campus, Melbourne
Reetta Kälviäinen, Kuopio University
Peter Kochunov, University of Maryland School of Medicine
Patrick Kwan, Royal Melbourne Hospital
Angelo Labate, IBFM-CNR Catanzaro, Italy
Carrie R. McDonald, University of California San Diego
Stefano Meletti, University of Modena and Reggio Emilia
Terence J. O'Brien, University of Melbourne
Sebastien Ourselin, University College London
Mark P. Richardson, King's College London
Pasquale Striano, Universityt of Genoa
Thomas Thesen, New York University School of Medicine
Roland Wiest, University of Bern
Junsong Zhang, Xiamen University
Annamaria Vezzani, Mario Negri Institute of Neurology
Mina Ryten, King's College London
Paul M. Thompson, University of Southern California
Sanjay M. Sisodiya, UCL Institute of Neurology, London

Peer Reviewed

1

Document Type

Article

Publication Date

22-1-2018

Keywords

MRI, Epilepsy, Precentral Gyrus, Thalamus

Funder/Sponsor

This study was supported in part by a Center grant (U54 EB020403) from the National Institutes of Health as part of the 2014 Big Data to Knowledge (BD2K) Initiative. The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner. The UNICAMP research centre was funded by FAPESP (Sa˜o Paulo Research Foundation); Contract grant number: 2013/07559-3. The BRI at the Florey Institute of Neuroscience and Mental Health acknowledges funding from the National Health and Medical Research Council of Australia (NHMRC Project Grant 628952, Practitioner Fellowship 1060312). The UCSD research centre acknowledges support from the U.S. National Institute of Neurological Disorders and Stroke (NIH/NINDS, grant no. R01NS065838). The UNAM centre was funded by grants UNAM-DGAPA IB201712 and Conacyt 181508 RRC Graduate Fellowship Conacyt 329866. UNIMORE acknowledges funding from the Carismo Foundation (grant number: A.010@FCRMO RINT@MELFONINFO) and the Italian Ministry of Health, Emilia-Romagna Region (N. PRUA1GR-2013-00000120). Work conducted at Kuopio University Hospital was funded by Government Grant 5772810. Work at the University of Eastern Finland was funded by Vaajasalo Foundation and Saastamoinen Foundation. Funding sources for the King’s College London research centre include: National Institute for Health Research Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust; Medical Research Council (grants G0701310 and MR/K013998/ 1); Epilepsy Research UK. Work conducted at the University of Liverpool was funded by the UK Medical Research Council (grant MR/K023152/1). The Cardiff University centre acknowledges funding from Cardiff University Brain Research Imaging Centre, Cardiff and Vale University Health Board, Epilepsy Research UK and Health and Care Research Wales, Wales Government. Montreal Neurological Institute funding sources include the Canadian Institutes of Health Research (CIHR MOP57840 and CIHR MOP-123520). Dr. Bernhardt acknowledges funding through NSERC Discovery, CIHR Foundation, SickKids New Investigator, and FRQS Junior 1. NYU funding includes: Finding a Cure for Epilepsy and Seizures (FACES); The Morris and Alma Schapiro Fund; Epilepsy Foundation. The Royal Melbourne Hospital group received funding from The Royal Melbourne Hospital Neurosciences Foundation. The Bern research centre was funded by Swiss National Science Foundation, grants no. 124089, 140332 and 320030-163398. The NYU School of Medicine site acknowledges support from Finding A Cure for Epilepsy and Seizures (FACES). Dr. Chen at the Ohio State University was partially sponsored by the National Science Foundation IIS-1302755, DBI1260795, DBI-1062057, and CNS-1531491. At the Florence research centre, Dr. Blu¨ mcke and Dr. Haaker received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no: Health-Fs-602531-2013 (see DESIRE, http://epilepsydesireproject.eu/, for more information). The Xiamen University group was partly supported by the National Nature Science Foundation of China (No. 61772440), and the Open Project Program of the State Key Lab of CAD&CG (No. A1706). Dr Altmann holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship. This work was partly supported by the Medical Research Council [grant number MR/L016311/ 1], and supported by the MRC through the MRC Sudden Death Brain Bank (C.S.) and by a Project Grant (G0901254 to J.H. and M.W.) and Training Fellowship (G0802462 to M.R.).

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.

Disciplines

Life Sciences

Citation

Whelan CD, Altmann A, Botia JA, Jahanshad N, Hibar DP, Absil J, et al. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain. 2018 [Epub ahead of print]

PubMed ID

29365066

DOI Link

10.1093/brain/awx341

Creative Commons License

Creative Commons License
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