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Publication Detail
Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Lopez SM, Aksman LM, Oxtoby NP, Vos SB, Rao J, Kaestner E, Alhusaini S, Alvim M, Bender B, Bernasconi A, Bernasconi N, Bernhardt B, Caciagli L, Caldairou B, Caligiuri ME, Calvet A, Cendes F, Concha L, Conde-Blanco E, Davoodi-Bojd E, de Bézenac C, Delanty N, Desmond PM, Devinsky O, Domin M, Duncan JS, Focke NK, Foley S, Fortunato F, Galovic M, Gambardella A, Gleichgerrcht E, Guerrini R, Hamandi K, Ives-Deliperi V, Jackson GD, Jahanshad N, Keller SS, Kochunov P, Kotikalapudi R, Kreilkamp BAK, Labate A, Larivière S, Lenge M, Lui E, Malpas C, Martin P, Mascalchi M, Medland SE, Meletti S, Morita-Sherman ME, Owen TW, Richardson M, Riva A, Rüber T, Sinclair B, Soltanian-Zadeh H, Stein DJ, Striano P, Taylor PN, Thomopoulos SI, Thompson PM, Tondelli M, Vaudano AE, Vivash L, Wang Y, Weber B, Whelan CD, Wiest R, Winston GP, Yasuda CL, McDonald CR, Alexander DC, Sisodiya SM, Altmann A, ENIGMA-Epilepsy Working Group
  • Publisher:
    Wiley
  • Publication date:
    25/06/2022
  • Journal:
    Epilepsia
  • Medium:
    Print-Electronic
  • Status:
    Published
  • Country:
    United States
  • Print ISSN:
    0013-9580
  • Language:
    English
  • Keywords:
    MTLE, event-based model, disease progression, patient staging, duration of illness, Key Points, Word Count: 3, 979
  • Notes:
    This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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 multi-centre 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) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) 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 of onset and anti-seizure 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 to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable 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.
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Dept of Computer Science
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Dept of Med Phys & Biomedical Eng
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Clinical & Experimental Epilepsy
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Dept of Computer Science
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Clinical & Experimental Epilepsy
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UCL Queen Square Institute of Neurology
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