Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

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, Blümcke 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 (2018)


Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 141

Pages Range: 391-408

Journal Issue: 2

DOI: 10.1093/brain/awx341

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.

Authors with CRIS profile

Involved external institutions

University College London (UCL) GB United Kingdom (GB) University of Southern California (USC) US United States (USA) (US) Universidade Estadual de Campinas (UNICAMP) / University of Campinas BR Brazil (BR) New York University (NYU) US United States (USA) (US) Universitätsklinikum Freiburg DE Germany (DE) The University of Liverpool GB United Kingdom (GB) Eberhard Karls Universität Tübingen DE Germany (DE) The Florey Institute of Neuroscience and Mental Health AU Australia (AU) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald DE Germany (DE) University of California, San Diego US United States (USA) (US) Université libre de Bruxelles (ULB) / Free University of Brussels BE Belgium (BE) Azienda Ospedaliera Universitaria Meyer IT Italy (IT) University of Eastern Finland FI Finland (FI) Cardiff University GB United Kingdom (GB) McGill University CA Canada (CA) Royal College of Surgeons in Ireland (RCSI) IE Ireland (IE) Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy IT Italy (IT) Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) ES Spain (ES) King’s College London GB United Kingdom (GB) Ohio State University US United States (USA) (US) Xiamen University CN China (CN) Universität Bern CH Switzerland (CH) Istituto Giannina Gaslini IT Italy (IT) Università degli Studi di Modena e Reggio Emilia (UNIMORE) IT Italy (IT) The University of Melbourne AU Australia (AU) Philipps-Universität Marburg DE Germany (DE) University of Maryland US United States (USA) (US) Royal Melbourne Hospital (RMH) AU Australia (AU) National Autonomous University of Mexico / Universidad Nacional Autónoma de México (UNAM) MX Mexico (MX) University of Genova / Università degli Studi di Genova IT Italy (IT) Mario Negri Institute for Pharmacological Research (IRCCS) / Istituto di Ricerche Farmacologiche Mario Negri IT Italy (IT)

How to cite

APA:

Whelan, C.D., Altmann, A., Botia, J.A., Jahanshad, N., Hibar, D.P., Absil, J.,... Sisodiya, S.M. (2018). Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain, 141(2), 391-408. https://doi.org/10.1093/brain/awx341

MLA:

Whelan, Christopher D., et al. "Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study." Brain 141.2 (2018): 391-408.

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