Authors

Christopher D Whelan, Royal College of Surgeons in IrelandFollow
Andre Altmann
Juan A Botía
Neda Jahanshad
Derrek P Hibar
Julie Absil
Saud Alhusaini
Marina K M Alvim
Pia Auvinen
Emanuele Bartolini
Felipe P G Bergo
Tauana Bernardes
Karen Blackmon
Barbara Braga
Maria Eugenia Caligiuri
Anna Calvo
Sarah J Carr
Jian Chen
Shuai Chen
Andrea Cherubini
Philippe David
Martin Domin
Sonya Foley
Wendy França
Gerrit Haaker
Dmitry Isaev
Simon S Keller
Raviteja Kotikalapudi
Magdalena A Kowalczyk
Ruben Kuzniecky
Soenke Langner
Matteo Lenge
Kelly M Leyden
Min Liu
Richard Q Loi
Pascal Martin
Mario Mascalchi
Marcia E Morita
Jose C Pariente
Raul Rodríguez-Cruces
Christian Rummel
Taavi Saavalainen
Mira K Semmelroch
Mariasavina Severino
Rhys H Thomas
Manuela Tondelli
Domenico Tortora
Anna Elisabetta Vaudano
Lucy Vivash
Felix von Podewils
Jan Wagner
Bernd Weber
Yi Yao
Clarissa L Yasuda
Guohao Zhang
Nuria Bargalló
Benjamin Bender
Neda Bernasconi
Andrea Bernasconi
Boris C Bernhardt
Ingmar Blümcke
Chad Carlson
Gianpiero L. Cavalleri, Royal College of Surgeons in IrelandFollow
Fernando Cendes
Luis Concha
Norman Delanty, Royal College of Surgeons in IrelandFollow
Chantal Depondt
Orrin Devinsky
Colin P Doherty
Niels K Focke
Antonio Gambardella
Renzo Guerrini
Khalid Hamandi
Graeme D Jackson
Reetta Kälviäinen
Peter Kochunov
Patrick Kwan
Angelo Labate
Carrie R McDonald
Stefano Meletti
Terence J O'Brien
Sebastien Ourselin
Mark P Richardson
Pasquale Striano
Thomas Thesen
Roland Wiest
Junsong Zhang
Annamaria Vezzani
Mina Ryten
Paul M Thompson
Sanjay M Sisodiya

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, Alhusaini S, Alvim MKM, Auvinen P, Bartolini E, Bergo FPG, Bernardes T, Blackmon K, Braga B, Caligiuri ME Calvo A, Carr SJ, Chen J, Chen S, Cherubini A, David P, Domin M, Foley S, Franca W, Haaker G, Isaev D, Keller SS, Kotikalapudi R, Kowalczyk MA. Kuzniecky R, Langner S, Lenge M, Leyden KM, Liu M, Loi RQ, Martin P, Mascalchi M, Morita ME, Pariente JC, Rodriguez-Cruces, R, Rummel C, Saavalainen, T, Semmelroch MK, Severino M. Thomas RH, Tondelli M, Tortora D, Vaudano AE , Vivash L, von Podewils F, Wagner J, Weber B, Yao Y, Yasuda CL, Zhang G, Bargallo N, Bender B, Bernasconi N, Bernasconi A, Bernhardt BC, Blumcke I, Carlson C, Cavalleri GL, Cendes F, Concha L, Delanty N , Depondt C, Devinsky O, Doherty CP, Focke NK, Gambardella A, Guerrini R, Hamandi K, Jackson GD, Kalviainen R, Kochunov P, Kwan P, Labate A, McDonald CR, Meletti S, O'Brien TJ, Ourselin S, Richardson MP, Striano P, Thesen T, Wiest R, Zhang J, Vezzani A, Ryten M, Thompson PM, Sisodiya SM. 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

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