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