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

• Type of Material: Article
• Authors: Seymour M Lopez, University College London; Leon M Aksman, University College London; Neil P Oxtoby, University College London; Sjoerd B Vos, University College London; Jun Rao, University of California San Diego; Erik Kaestner, University of California San Diego; Saud Alhusaini, Brown University; Marina Alvim, University of Campinas; Benjamin Bender, University Hospital Tübingen; Andrea Bernasconi, McGill University; Neda Bernasconi, McGill University; Boris Bernhardt, McGill University; Leonardo Bonilha, Emory University; Lorenzo Caciagli, McGill University; Benoit Caldairou, McGill University; Maria Eugenia Caligiuri, Magna Graecia University of Catanzaro; Angels Calvet, University of Barcelona; Fernando Cendes, University of Campinas; Luis Concha, National Autonomous University of Mexico; Estefania Conde-Blanco, Hospital Clinic of Barcelona; Esmaeil Davoodi-Bojd, Henry Ford Health System; Christophe de Bezenac, University of Liverpool; Norman Delanty, Royal College of Surgeons in Ireland; Patricia M Desmond, University of Melbourne; Orrin Devinsky, New York University; Martin Domin, Greifswald University Medicine; John S Duncan, Emory University; Niels K Focke, University Medical Center; Sonya Foley, Cardiff University; Francesco Fortunato, Magna Graecia University of Catanzaro; Marian Galovic, University College London; Antonio Gambardella, Magna Graecia University of Catanzaro; Ezequiel Gleichgerrcht, Medical University of South Carolina; Renzo Guerrini, University of Florence; Khalid Hamandi, Cardiff University; Victoria Ives-Deliperi, University of Cape Town; Graeme D Jackson, Florey Institute of Neuroscience and Mental Health; Neda Jahanshad, University of Southern California; Simon S Keller, University of Liverpool; Peter Kochunov, University of Maryland Baltimore; Raviteja Kotikalapudi, University Hospital Tübingen; Barbara AK Kreilkamp, University of Liverpool; Angelo Labate, Magna Graecia University of Catanzaro; Sara Larivière, McGill University; Matteo Lenge, University of Florence; Elaine Lui, University of Melbourne; Charles Malpas, Royal Melbourne Hospital; Pascal Martin, University of Maryland; Mario Mascalchi, University of Florence; Sarah E Medland, QIMR Berghofer Medical Research Institute; Stefano Meletti, University of Modena and Reggio Emilia; Marica E Morita-Sherman, University of Campinas; Thomas W Owen, Newcastle University; Mark Richardson, Kings College London; Antonella Riva, Giannina Gaslini Institute; Theodor Rüber, University Hospital Bonn; Ben Sinclair, Monash University; Hamid Soltanian-Zadeh, Henry Ford Health System; Dan J Stein, University of Cape Town; Pasquale Striano, Giannina Gaslini Institute; Peter N Taylor, University College London; Sophia I Thomopoulos, University of Southern California; Paul M Thompson, University of Southern California; Manuela Tondelli, University of Modena and Reggio Emilia; Anna Elisabetta Vaudano, University of Modena and Reggio Emilia; Lucy Vivash, Monash University; Yujiang Wang, University College London; Bernd Weber, University of Bonn; Christopher D Whelan, Royal College of Surgeons in Ireland; Roland Wiest, University of Bern; Gavin P Winston, University College London; Clarissa Lin Yasuda, University of Campinas; Carrie R McDonald, University of California San Diego; Daniel C Alexander, University College London; Sanjay M Sisodiya, University College London; Andre Altmann, University College London
• Language: English
• Date: 2022-06-25
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/epi.17316
• Title of Journal or Parent Work: EPILEPSIA
• Volume: 63
• Issue: 8
• Start Page: 2081
• End Page: 2095
• Keywords: MTLE; Life Sciences & Biomedicine; Neurosciences & Neurology; Science & Technology; event-based model; duration of illness; HIPPOCAMPAL SCLEROSIS; Clinical Neurology; NETWORK; GRAY-MATTER ATROPHY; WHITE-MATTER; DISEASE PROGRESSION; VOLUME; BIOMARKER; patient staging; DAMAGE; disease progression
• Research Categories: Health Sciences, Radiology; Engineering, Biomedical

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.