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

Christopher D Whelan; 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; Renzo Guerrini; Sebastien Ourselin; Mark P Richardson

doi:10.1093/brain/awx341

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

Christopher D Whelan, 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 CherubiniPhilippe 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, Renzo Guerrini, Sebastien Ourselin, Mark P Richardson

Research output: Contribution to journal › Article › peer-review

318 Citations (Scopus)

97 Downloads (Pure)

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.

Original language	English
Pages (from-to)	391-408
Journal	Brain
Volume	141
Issue number	2
Early online date	30 Jan 2018
DOIs	https://doi.org/10.1093/brain/awx341
Publication status	Published - 30 Jan 2018

Access to Document

10.1093/brain/awx341Licence: CC BY

Structural brain abnormalities in the common_CARR_Publisheodnline30January2018_GOLD VoR (CC BY)Final published version, 871 KBLicence: CC BY

Cite this

Whelan, C. D., Altmann, A., Botía, J. A., Jahanshad, N., Hibar, D. P., Absil, J., Alhusaini, S., Alvim, M. K. M., Auvinen, P., Bartolini, E., Bergo, F. P. G., Bernardes, T., Blackmon, K., Braga, B., Caligiuri, M. E., Calvo, A., Carr, S. J., Chen, J., Chen, S., ... Richardson, M. P. (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

@article{5c6b5465465e401cbfc04da26973d021,

title = "Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study",

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{\textquoteright}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.",

author = "Whelan, {Christopher D} and Andre Altmann and Bot{\'i}a, {Juan A} and Neda Jahanshad and Hibar, {Derrek P} and Julie Absil and Saud Alhusaini and Alvim, {Marina K M} and Pia Auvinen and Emanuele Bartolini and Bergo, {Felipe P G} and Tauana Bernardes and Karen Blackmon and Barbara Braga and Caligiuri, {Maria Eugenia} and Anna Calvo and Carr, {Sarah J} and Jian Chen and Shuai Chen and Andrea Cherubini and Philippe David and Martin Domin and Sonya Foley and Wendy Fran{\c c}a and Gerrit Haaker and Dmitry Isaev and Keller, {Simon S} and Raviteja Kotikalapudi and Kowalczyk, {Magdalena A} and Ruben Kuzniecky and Soenke Langner and Matteo Lenge and Leyden, {Kelly M} and Min Liu and Loi, {Richard Q} and Pascal Martin and Mario Mascalchi and Morita, {Marcia E} and Pariente, {Jose C} and Raul Rodr{\'i}guez-cruces and Christian Rummel and Taavi Saavalainen and Semmelroch, {Mira K} and Mariasavina Severino and Thomas, {Rhys H} and Manuela Tondelli and Domenico Tortora and Renzo Guerrini and Sebastien Ourselin and Richardson, {Mark P}",

year = "2018",

month = jan,

day = "30",

doi = "10.1093/brain/awx341",

language = "English",

volume = "141",

pages = "391--408",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "2",

}

Whelan, CD, Altmann, A, Botía, 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, França, 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, Rodríguez-cruces, R, Rummel, C, Saavalainen, T, Semmelroch, MK, Severino, M, Thomas, RH, Tondelli, M, Tortora, D, Guerrini, R , Ourselin, S & Richardson, MP 2018, 'Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study', Brain, vol. 141, no. 2, pp. 391-408. https://doi.org/10.1093/brain/awx341

TY - JOUR

T1 - Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

AU - Whelan, Christopher D

AU - Altmann, Andre

AU - Botía, Juan A

AU - Jahanshad, Neda

AU - Hibar, Derrek P

AU - Absil, Julie

AU - Alhusaini, Saud

AU - Alvim, Marina K M

AU - Auvinen, Pia

AU - Bartolini, Emanuele

AU - Bergo, Felipe P G

AU - Bernardes, Tauana

AU - Blackmon, Karen

AU - Braga, Barbara

AU - Caligiuri, Maria Eugenia

AU - Calvo, Anna

AU - Carr, Sarah J

AU - Chen, Jian

AU - Chen, Shuai

AU - Cherubini, Andrea

AU - David, Philippe

AU - Domin, Martin

AU - Foley, Sonya

AU - França, Wendy

AU - Haaker, Gerrit

AU - Isaev, Dmitry

AU - Keller, Simon S

AU - Kotikalapudi, Raviteja

AU - Kowalczyk, Magdalena A

AU - Kuzniecky, Ruben

AU - Langner, Soenke

AU - Lenge, Matteo

AU - Leyden, Kelly M

AU - Liu, Min

AU - Loi, Richard Q

AU - Martin, Pascal

AU - Mascalchi, Mario

AU - Morita, Marcia E

AU - Pariente, Jose C

AU - Rodríguez-cruces, Raul

AU - Rummel, Christian

AU - Saavalainen, Taavi

AU - Semmelroch, Mira K

AU - Severino, Mariasavina

AU - Thomas, Rhys H

AU - Tondelli, Manuela

AU - Tortora, Domenico

AU - Guerrini, Renzo

AU - Ourselin, Sebastien

AU - Richardson, Mark P

PY - 2018/1/30

Y1 - 2018/1/30

N2 - 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.

AB - 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.

U2 - 10.1093/brain/awx341

DO - 10.1093/brain/awx341

M3 - Article

SN - 0006-8950

VL - 141

SP - 391

EP - 408

JO - Brain

JF - Brain

IS - 2

ER -

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

Abstract

Access to Document

Fingerprint

Cite this