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Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data

Lopez, Seymour M., Aksman, Leon M., Oxtoby, Neil P., Vos, Sjoerd B., Rao, Jun, Kaestner, Erik, Alhusaini, Saud, Alvim, Marina, Bender, Benjamin, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Bonilha, Leonardo, Caciagli, Lorenzo, Caldairou, Benoit, Caligiuri, Maria Eugenia, Calvet, Angels, Cendes, Fernando, Concha, Luis, Conde‐Blanco, Estefania, Davoodi‐Bojd, Esmaeil, de Bézenac, Christophe, Delanty, Norman, Desmond, Patricia M., Devinsky, Orrin, Domin, Martin, Duncan, John S., Focke, Niels K., Foley, Sonya ORCID:, Fortunato, Francesco, Galovic, Marian, Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ives‐Deliperi, Victoria, Jackson, Graeme D., Jahanshad, Neda, Keller, Simon S., Kochunov, Peter, Kotikalapudi, Raviteja, Kreilkamp, Barbara A. K., Labate, Angelo, Larivière, Sara, Lenge, Matteo, Lui, Elaine, Malpas, Charles, Martin, Pascal, Mascalchi, Mario, Medland, Sarah E., Meletti, Stefano, Morita‐Sherman, Marcia E., Owen, Thomas W., Richardson, Mark, Riva, Antonella, Rüber, Theodor, Sinclair, Ben, Soltanian‐Zadeh, Hamid, Stein, Dan J., Striano, Pasquale, Taylor, Peter N., Thomopoulos, Sophia I., Thompson, Paul M., Tondelli, Manuela, Vaudano, Anna Elisabetta, Vivash, Lucy, Wang, Yujiang, Weber, Bernd, Whelan, Christopher D., Wiest, Roland, Winston, Gavin P., Yasuda, Clarissa Lin, McDonald, Carrie R., Alexander, Daniel C., Sisodiya, Sanjay M., Altmann, Andre and for the ENIGMA‐Epilepsy Working Group 2022. Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data. Epilepsia 63 (8) , pp. 2081-2095. 10.1111/epi.17316

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Objective: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross‐sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE‐HS) correlate with clinical features. Methods: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1‐weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA‐Epilepsy consortium, comprising 804 people with MTLE‐HS and 1625 healthy controls from 25 centers. Features with a moderate case–control effect size (Cohen d ≥ .5) were used to train an event‐based model (EBM), which estimates a sequence of disease‐specific biomarker changes from cross‐sectional data and assigns a biomarker‐based fine‐grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. Results: In MTLE‐HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10−16), age at onset (ρ = −.18, p = 9.82 × 10−7), and ASM resistance (area under the curve = .59, p = .043, Mann–Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE‐HS with mild or nondetectable abnormality on T1W MRI. Significance: From cross‐sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE‐HS subjects in other cohorts and help establish connections between imaging‐based progression staging and clinical features.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Wiley
ISSN: 0013-9580
Date of First Compliant Deposit: 27 June 2022
Date of Acceptance: 1 June 2022
Last Modified: 10 Nov 2022 11:30

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