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

Journal article


Whelan, Christopher D., Altmann, Andre, Botía, Juan A., Jahanshad, Neda, Hibar, Derrek P., Absil, Julie, Alhusaini, Saud, Alvim, Marina K. M., Auvinen, Pia, Bartolini, Emanuele, Bergo, Felipe P. G., Bernardes, Tauana, Blackmon, Karen, Braga, Barbara, Caligiuri, Maria Eugenia, Calvo, Anna, Carr, Sarah J., Chen, Jian, Chen, Shuai, ... Sisodiya, Sanjay M.. (2018). Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain: a journal of neurology. 141(2), pp. 391-408. https://doi.org/10.1093/brain/awx341
AuthorsWhelan, Christopher D., Altmann, Andre, Botía, Juan A., Jahanshad, Neda, Hibar, Derrek P., Absil, Julie, Alhusaini, Saud, Alvim, Marina K. M., Auvinen, Pia, Bartolini, Emanuele, Bergo, Felipe P. G., Bernardes, Tauana, Blackmon, Karen, Braga, Barbara, Caligiuri, Maria Eugenia, Calvo, Anna, Carr, Sarah J., Chen, Jian, Chen, Shuai, Cherubini, Andrea, David, Philippe, Domin, Martin, Foley, Sonya, França, Wendy, Haaker, Gerrit, Isaev, Dmitry, Keller, Simon S., Kotikalapudi, Raviteja, Kowalczyk, Magdalena A., Kuzniecky, Ruben, Langner, Soenke, Lenge, Matteo, Leyden, Kelly M., Liu, Min, Loi, Richard Q., Martin, Pascal, Mascalchi, Mario, Morita, Marcia E., Pariente, Jose C., Rodríguez-Cruces, Raul, Rummel, Christian, Saavalainen, Taavi, Semmelroch, Mira K., Severino, Mariasavina, Thomas, Rhys H., Tondelli, Manuela, Tortora, Domenico, Vaudano, Anna Elisabetta, Vivash, Lucy, von Podewils, Felix, Wagner, Jan, Weber, Bernd, Yao, Yi, Yasuda, Clarissa L., Zhang, Guohao, Bargalló, Nuria, Bender, Benjamin, Bernasconi, Neda, Bernasconi, Andrea, Bernhardt, Boris C., Blümcke, Ingmar, Carlson, Chad, Cavalleri, Gianpiero L., Cendes, Fernando, Concha, Luis, Delanty, Norman, Depondt, Chantal, Devinsky, Orrin, Doherty, Colin P., Focke, Niels K., Gambardella, Antonio, Guerrini, Renzo, Hamandi, Khalid, Jackson, Graeme D., Kälviäinen, Reetta, Kochunov, Peter, Kwan, Patrick, Labate, Angelo, McDonald, Carrie R., Meletti, Stefano, O'Brien, Terence J., Ourselin, Sebastien, Richardson, Mark P., Striano, Pasquale, Thesen, Thomas, Wiest, Roland, Zhang, Junsong, Vezzani, Annamaria, Ryten, Mina, Thompson, Paul M. and Sisodiya, Sanjay M.
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.

Keywordsepilepsy; MRI; thalamus; precentral gyrus
Year2018
JournalBrain: a journal of neurology
Journal citation141 (2), pp. 391-408
PublisherOxford University Press
ISSN1460-2156
Digital Object Identifier (DOI)https://doi.org/10.1093/brain/awx341
Scopus EID2-s2.0-85041689668
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range391-408
FunderNational Health and Medical Research Council (NHMRC)
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online30 Jan 2018
Publication process dates
Accepted24 Oct 2017
Deposited06 Sep 2021
Grant IDNHMRC/628952
NHMRC/1060312
Permalink -

https://acuresearchbank.acu.edu.au/item/8wv63/structural-brain-abnormalities-in-the-common-epilepsies-assessed-in-a-worldwide-enigma-study

Download files


Publisher's version
  • 63
    total views
  • 45
    total downloads
  • 1
    views this month
  • 0
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence
Lorenzetti, Valentina, Gaillard, Alexandra, Beyer, Emillie, Kowalczyk, Magdalena, Kamboj, Sunjeev K., Manning, Victoria and Gleeson, John Francis Martin. (2023). Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence. BMC Psychiatry. 23(1), p. Article 407. https://doi.org/10.1186/s12888-023-04789-7
Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
Larivière, Sara, Royer, Jessica, Rodríguez-Cruces, Raúl, Paquola, Casey, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S., Cendes, Fernando, Yasuda, Clarissa L., Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K., Domin, Martin, von Podewills, Felix, Langner, Soenke, Rummel, Christian, Wiest, Roland, Martin, Pascal, ... Bernhardt, Boris C.. (2022). Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression. Nature Communications. 13(1), p. Article 4320. https://doi.org/10.1038/s41467-022-31730-5
Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy
Park, Bo-yong, Larivière, Sara, Rodríguez-Cruces, Raul, Royer, Jessica, Tavakol, Shahin, Wang, Yezhou, Caciagli, Lorenzo, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S, Cendes, Fernando, Alvim, Marina K M, Yasuda, Clarissa, Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K, Kreilkamp, Barbara A K, Domin, Martin, ... Bernhardt, Boris C. (2022). Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy. Brain. 145(4), pp. 1285-1298. https://doi.org/10.1093/brain/awab417
Brain anatomical alterations in young cannabis users : Is it all hype? A meta-analysis of structural neuroimaging studies
Lorenzetti, Valentina, Kowalczyk, Magdalena, Duehlmeyer, Leonie, Greenwood, Lisa-Marie, Chye, Yann, Yücel, Murat, Whittle, Sarah and Roberts, Carl A.. (2022). Brain anatomical alterations in young cannabis users : Is it all hype? A meta-analysis of structural neuroimaging studies. Cannabis and Cannabinoid Research. 8(1), pp. 184-196. https://doi.org/10.1089/can.2021.0099
A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies
Altmann, Andre, Ryten, Mina, Di Nunzio, Martina, Ravizza, Teresa, Tolomeo, Daniele, Reynolds, Regina H., Somani, Alyma, Bacigaluppi, Marco, Iori, Valentina, Micotti, Edoardo, Di Sapia, Rossella, Cerovic, Milica, Palma, Eleonora, Ruffolo, Gabriele, Botía, Juan A., Absil, Julie, Alhusaini, Saud, Alvim, Marina K. M., Auvinen, Pia, ... Sisodiya, Sanjay M.. (2022). A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies. Neuropathology and Applied Neurobiology. 48(1), p. Article e12758. https://doi.org/10.1111/nan.12758
Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users : A systematic review of fMRI studies
Sehl, Hannah, Terrett, Gill, Greenwood, Lisa-Marie, Kowalczyk, Magdalena, Thomson, Hannah, Poudel, Govinda, Manning, Victoria and Lorenzetti, Valentina. (2021). Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users : A systematic review of fMRI studies. Psychopharmacology. 238(10), pp. 2709-2728. https://doi.org/10.1007/s00213-021-05973-x
Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study
Roberts, Carl A., Lorenzetti, Valentina, Albein-Urios, Natalia, Kowalczyk, Magdalena A., Martinez-Gonzalez, Jose M. and Verdejo-Garcia, Antonio. (2021). Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study. Progress in Neuropsychopharmacology and Biological Psychiatry. 110, p. 110298. https://doi.org/10.1016/j.pnpbp.2021.110298
Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study
Larivière, Sara, Rodríguez-Cruces, Raúl, Royer, Jessica, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S., Cendes, Fernando, Yasuda, Clarissa, Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K., Domin, Martin, von Podewills, Felix, Langner, Soenke, Rummel, Christian, Wiest, Roland, Martin, Pascal, Kotikalapudi, Raviteja, ... Bernhardt, Boris C.. (2020). Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study. Science Advances. 6(47), p. eabc6457. https://doi.org/10.1126/sciadv.abc6457
Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin
Kowalczyk, Magdalena A., Omidvarnia, Amir, Dhollander, Thijs and Jackson, Graeme D.. (2020). Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin. Epilepsia. 61(11), pp. 2558-2571. https://doi.org/10.1111/epi.16695
Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection
Omidvarnia, Amir, Kowalczyk, Magdalena A., Pedersen, Mangor and Jackson, Graeme D.. (2019). Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection. Clinical Neurophysiology. 130(3), pp. 368-378. https://doi.org/10.1016/j.clinph.2018.11.024
Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients
Alhusaini, Saud, Kowalczyk, Magdalena A., Yasuda, Clarissa L., Semmelroch, Mira K., Katsurayama, Marilise, Zabin, Matheus, Zanão, Tamires, Nogueira, Mateus H., Alvim, Marina K. M., Ferraz, Victória R., Tsai, Meng-Han, Fitzsimons, Mary, Lopes-Cendes, Iscia, Doherty, Colin P., Cavalleri, Gianpiero L., Cendes, Fernando, Jackson, Graeme D. and Delanty, Norman. (2019). Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients. Neurology. 92(4), pp. e351-e358. https://doi.org/10.1212/WNL.0000000000006834
Human GABRG2 generalized epilepsy : Increased somatosensory and striato-thalamic connectivity
Pedersen, Mangor, Kowalczyk, Magdalena, Omidvarnia, Amir, Perucca, Piero, Gooley, Samuel, Petrou, Steven, Scheffer, Ingrid E., Berkovic, Samuel F. and Jackson, Graeme D.. (2019). Human GABRG2 generalized epilepsy : Increased somatosensory and striato-thalamic connectivity. Neurology Genetics. 5(4), p. e340. https://doi.org/10.1212/NXG.0000000000000340
Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy : A single-institution retrospective review.
Kowalczyk, Magdalena A., Omidvarnia, Amir, Abbott, David F., Tailby, Chris, Vaughan, David N. and Jackson, Graeme D.. (2019). Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy : A single-institution retrospective review. Epilepsia. 61(1), pp. 49-60. https://doi.org/10.1111/epi.16399
Cognitive impairment in epilepsy : The role of reduced network flexibility
Tailby, Chris, Kowalczyk, Magdalena A. and Jackson, Graeme D.. (2018). Cognitive impairment in epilepsy : The role of reduced network flexibility. Annals of Clinical and Translational Neurology. 5(1), pp. 29-40. https://doi.org/10.1002/acn3.503
Mapping the verbal semantic memory network before anterior temporal lobectomy using a combination of rTMS and fMRI
Sethi, M., Carney, P., Kowalczyk, M., Pedersen, M., Tailby, C. and Jackosn, G.. (2001). Mapping the verbal semantic memory network before anterior temporal lobectomy using a combination of rTMS and fMRI. Epilepsia. 58(Suppl. 5), p. S182. https://doi.org/10.1111/epi.13944