TY - JOUR
T1 - Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy
AU - Casella, Chiara
AU - Vecchiato, Katy
AU - Cromb, Daniel
AU - Guo, Yourong
AU - Winkler, Anderson M
AU - Hughes, Emer
AU - Dillon, Louise
AU - Green, Elaine
AU - Colford, Kathleen
AU - Egloff, Alexia
AU - Siddiqui, Ata
AU - Price, Anthony
AU - Grande, Lucilio Cordero
AU - Wood, Tobias C
AU - Malik, Shaihan
AU - Teixeira, Rui Pedro A G
AU - Carmichael, David W
AU - O'Muircheartaigh, Jonathan
N1 - Funding Information:
The study was funded by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (206675/Z/17/Z). This research was also supported by GOSHCC Sparks Grant V4419 and King's Health Partners, in part by the Medical Research Council (UK; grants MR/K006355/1 and MR/LO11530/1) and Medical Research Council Center for Neurodevelopmental Disorders, King's College London (MR/N026063/1), and by core funding from the Wellcome Engineering and Physical Sciences Research Council Centre for Medical Engineering at King's College London (WT203148/Z/16/Z). Infrastructure support was provided by the National Institute for Health Research Mental Health Biomedical Research Centre at South London, Maudsley NHS Foundation Trust, King's College London and the National Institute for Health Research Mental Health Biomedical Research Centre at Guy's and St Thomas' Hospitals NHS Foundation Trust.
Publisher Copyright:
© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2023/12/13
Y1 - 2023/12/13
N2 - OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity.METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative).RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients.SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.
AB - OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity.METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative).RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients.SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.
UR - http://www.scopus.com/inward/record.url?scp=85180850065&partnerID=8YFLogxK
U2 - 10.1111/epi.17861
DO - 10.1111/epi.17861
M3 - Article
C2 - 38088235
SN - 0013-9580
JO - Epilepsia
JF - Epilepsia
ER -