A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan
Authors: Chen Judy , Ngo Alexander , Rodríguez-Cruces Raúl , Royer Jessica , Caligiuri Maria Eugenia , Gambardella Antonio , Concha Luis , Keller Simon S. , Cendes Fernando , Yasuda Clarissa L. , Alvim Marina K. M. , Bonilha Leonardo , Gleichgerrcht Ezequiel , Focke Niels K. , Kreilkamp Barbara , Domin Martin , von Podewils Felix , Langner Soenke , Rummel Christian , Wiest Roland , Martin Pascal , Kotikalapudi Raviteja , Bender Benjamin , O’Brien Terence J. , Sinclair Benjamin , Vivash Lucy , Kwan Patrick , Desmond Patricia M. , Lui Elaine , Duma Gian Marco , Bonanni Paolo , Ballerini Alice , Vaudano Anna Elisabetta , Meletti Stefano , Tondelli Manuela , Alhusaini Saud , Doherty Colin P. , Cavalleri Gianpiero L. , Delanty Norman , Kälviäinen Reetta , Jackson Graeme D. , Kowalczyk Magdalena , Mascalchi Mario , Semmelroch Mira , Thomas Rhys H. , Soltanian-Zadeh Hamid , Davoodi-Bojd Esmaeil , Zhang Junsong , Lenge Matteo , Guerrini Renzo , Bartolini Emanuele , Hamandi Khalid , Foley Sonya , Rüber Theodor , Bauer Tobias , Weber Bernd , Caldairou Benoit , Depondt Chantal , Absil Julie , Carr Sarah J. A. , Abela Eugenio , Richardson Mark P. , Devinsky Orrin , Pardoe Heath , Severino Mariasavina , Striano Pasquale , Tortora Domenico , Kaestner Erik , Hatton Sean N. , Arienzo Donatello , Vos Sjoerd B. , Ryten Mina , Taylor Peter N. , Duncan John S. , Whelan Christopher D. , Galovic Marian , Winston Gavin P. , Thomopoulos Sophia I. , Thompson Paul M. , Sisodiya Sanjay M. , Labate Angelo , McDonald Carrie R. , Caciagli Lorenzo , Bernasconi Neda , Bernasconi Andrea , Larivière Sara , Schrader Dewi , Bernhardt Boris C. 
Published: March 2024

ABSTRACTObjectivesTemporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments.MethodsWe studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves.ResultsIn TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions.ConclusionsThis study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.