Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data
Authors: 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 , 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 ,   for the ENIGMA‐Epilepsy Working Group
Published: June 2022

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.