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

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Details zur Publikation

Autor(en): 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
Zeitschrift: Brain
Jahr der Veröffentlichung: 2018
Band: 141
Heftnummer: 2
Seitenbereich: 391-408
ISSN: 0006-8950


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.

FAU-Autoren / FAU-Herausgeber

Blümcke, Ingmar Prof. Dr.
Lehrstuhl für Neuropathologie

Autor(en) der externen Einrichtung(en)
Azienda Ospedaliera Universitaria Meyer
Cardiff University
Consiglio Nazionale delle Ricerche (CNR)
Eberhard Karls Universität Tübingen
IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer
Istituto Giannina Gaslini
King’s College London
Mario Negri Institute for Pharmacological Research (IRCCS) / Istituto di Ricerche Farmacologiche Mario Negri
McGill University
National Autonomous University of Mexico / Universidad Nacional Autónoma de México (UNAM)
New York University (NYU)
Ohio State University
Philipps-Universität Marburg
Royal College of Surgeons in Ireland (RCSI)
Royal Melbourne Hospital (RMH)
The Florey Institute of Neuroscience and Mental Health
The University of Liverpool
The University of Melbourne
Universidade Estadual de Campinas (UNICAMP) / University of Campinas
Università degli Studi di Modena e Reggio Emilia (UNIMORE)
Universität Bern
Universitätsklinikum Freiburg
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
Université libre de Bruxelles (ULB)
University College London (UCL) (University of London)
University of California, San Diego
University of Eastern Finland
University of Genova / Università degli Studi di Genova
University of Maryland
University of Southern California (USC)
Xiamen University


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.

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


Zuletzt aktualisiert 2018-15-11 um 18:08