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

for the ENIGMA-Epilepsy Working Group, Seymour M. Lopez, Leon M. Aksman, Neil P. Oxtoby, Sjoerd B. Vos, Jun Rao, Erik Kaestner, Saud Alhusaini, Marina Alvim, Benjamin Bender, Andrea Bernasconi, Neda Bernasconi, Boris Bernhardt, Leonardo Bonilha, Lorenzo Caciagli, Benoit Caldairou, Maria Eugenia Caligiuri, Angels Calvet, Fernando Cendes, Luis ConchaEstefania Conde-Blanco, Esmaeil Davoodi-Bojd, Christophe de Bézenac, Norman Delanty, Patricia M. Desmond, Orrin Devinsky, Martin Domin, 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 Malpas, Pascal Martin, Mario Mascalchi, Mark Richardson

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2081-2095
Number of pages15
Issue number8
Early online date25 Jun 2022
Publication statusPublished - 10 Aug 2022


  • disease progression
  • duration of illness
  • event-based model
  • MTLE
  • patient staging


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