A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Journal: bioRxiv : the preprint server for biology

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Affiliated Institutions:  Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. Neuroscience Research Center, University Magna Græcia, Catanzaro, CZ, Italy. Institute of Neurobiology, Universidad Nacional Autónoma de México, Querétaro, México. Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom. Department of Neurology, University of Campinas--UNICAMP, Campinas, São Paulo, Brazil. Department of Neurology, Emory University, Atlanta, GA, USA. Department of Neurology, University of Medicine Göttingen, Göttingen, Germany. Institute of Diagnostic Radiology and Neuroradiology, Functional Imaging Unit, University Medicine Greifswald, Greifswald, Germany. Department of Neurology, University Medicine Greifswald, Epilepsy Center, Greifswald, Germany. Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany. Support Center for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Germany. Department of Neuroscience, Central Clinical School, Alfred Hospital, Monash University, Melbourne, Victoria, Australia. Departments of Medicine and Radiology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia. Scientific Institute IRCCS E.Medea, Epilepsy Unit, Conegliano (TV), Italy. Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, Modena, Italy. Neurology Unit, OCB Hospital, Azienda Ospedaliera-Universitaria, Modena, Italy. Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland. Department of Neurology, St James' Hospital, Dublin, Ireland. Epilepsy Center, Neuro Center, Kuopio University Hospital, Member of the European Reference Network for Rare and Complex Epilepsies EpiCARE, Kuopio, Finland. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne VIC , Australia. Neuroradiology Research Program, Meyer Children Hospital of Florence, University of Florence, Florence, Italy. Transitional and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. Contol and Intelligent Processing Center of Excellence (CIPCE), School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran. Department of Neurology, Henry Ford Health System, Detroit, MI, USA. Cognitive Science Department, Xiamen University, Xiamen, China. Child Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital IRCCS, Florence, Italy. IRCCS Stella Maris Foundation, Pisa, Italy. Cardiff University Brain Research Imaging Centre (CUBRIC), College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK. Department of Neuroradiology, University Hospital Bonn, Bonn, Germany. Institute of Experimental Epileptology and Cognition Research, University Hospital Bonn, Bonn, Germany. Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. Department of Neurology, Hôpital Erasme, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium. Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. School of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. Department of Neurology, NYU Grossman School of Medicine, New York, NY, United States. IRCCS Istituto Giannina Gaslini, Genova, Italy. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. Department of Radiation Medicine and Applied Sciences; Department of Psychiatry, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, United States. Department of Neurosciences, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, United States. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK. Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zürich, Zürich, Switzerland. Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. Neurophysiopathology and Movement Disorders Clinic, Regional Epilepsy Center, University of Messina, Italy. BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

Abstract summary 

Temporal 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.We 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.In 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.This 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.

Authors & Co-authors:  Chen Ngo Rodríguez-Cruces Royer Caligiuri Gambardella Concha Keller Cendes Yasuda Alvim Bonilha Gleichgerrcht Focke Kreilkamp Domin von Podewils Langner Rummel Wiest Martin Kotikalapudi Bender O'Brien Sinclair Vivash Kwan Desmond Lui Duma Bonanni Ballerini Vaudano Meletti Tondelli Alhusaini Doherty Cavalleri Delanty Kälviäinen Jackson Kowalczyk Mascalchi Semmelroch Thomas Soltanian-Zadeh Davoodi-Bojd Zhang Lenge Guerrini Bartolini Hamandi Foley Rüber Bauer Weber Caldairou Depondt Absil Carr Abela Richardson Devinsky Pardoe Severino Striano Tortora Kaestner Hatton Arienzo Vos Ryten Taylor Duncan Whelan Galovic Winston Thomopoulos Thompson Sisodiya Labate McDonald Caciagli Bernasconi Bernasconi Larivière Schrader Bernhardt

Study Outcome 

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Statistics
Citations :  Feigin VL, Nichols E, Alam T, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459–480.
Authors :  88
Identifiers
Doi : 2024.03.02.583073
SSN : 
Study Population
Male,Female
Mesh Terms
Other Terms
Epilepsy;aging;atrophy;lifespan;multimodal;temporal lobe epilepsy
Study Design
Study Approach
Country of Study
Publication Country
United States