ArticlebioRxiv : the preprint server for biology2023
Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.
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65 authors at 20 institutions in 10 countries.
Rebecca KerestesDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0003-1298-9904
Andrew PerryMonash Bioinformatics Platform, Monash University, Melbourne, VIC, Australia.
Lucy VivashDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0002-1182-0907
Terence J O'BrienDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0002-7198-8621
Marina K M AlvimDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.ORCID 0000-0002-6780-0761
Donatello ArienzoDepartment of Psychiatry, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
Ítalo K AventuratoDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.
Alice BalleriniDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.ORCID 0000-0002-0544-1599
Gabriel F BaltazarDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.
Núria BargallóMagnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Benjamin BenderDepartment of Radiology, Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany.
Ricardo BrioschiDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.
Eva BürkleDepartment of Radiology, Diagnostic and Interventional Neuroradiology, University Hospital Tübingen, Tübingen, Germany.
Maria Eugenia CaligiuriNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.ORCID 0000-0002-2030-5552
Fernando CendesDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.ORCID 0000-0001-9336-9568
Jane de TisiDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
John S DuncanDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-1373-0681
Jerome P EngelDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Sonya FoleyCardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.
Francesco FortunatoInstitute of Neurology, Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.ORCID 0000-0001-8395-7809
Antonio GambardellaNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.ORCID 0000-0001-7384-3074
Thea GiacominiDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.ORCID 0000-0002-7802-8789
Renzo GuerriniFunctional and Epilepsy Neurosurgery Unit, Neurosurgery Department, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Gerard HallSchool of Computing, Newcastle University, Newcastle upon Tyne, United Kingdom.ORCID 0000-0002-5212-7850
Khalid HamandiCardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.
Victoria Ives-DeliperiNeuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID 0000-0003-2640-249X
Rafael B JoãoDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.
Simon S KellerInstitute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Benedict KleiserDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Angelo LabateNeurophysiopatology and Movement Disorders Clinic, University of Messina, Messina, Italy.
Matteo LengeFunctional and Epilepsy Neurosurgery Unit, Neurosurgery Department, Children's Hospital A. Meyer-University of Florence, Florence, Italy.ORCID 0000-0003-2848-621X
Cassandra MarottaDepartment of Neurology, Alfred Health, Melbourne, VIC, Australia.
Pascal MartinDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Mario Mascalchi'Mario Serio' Department of Clinical and Experimental Medical Sciences, University of Florence, Florence, Italy.ORCID 0000-0002-5537-2982
Stefano MelettiDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.ORCID 0000-0003-0334-539X
Conor Owens-WaltonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID 0000-0003-0589-638X
Costanza B ParodiIRCCS Istituto 'Giannina Gaslini', Genova, Italy.
Saül Pascual-DiazMagnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
David PowellMonash Bioinformatics Platform, Monash University, Melbourne, VIC, Australia.
Jun RaoDepartment of Psychiatry, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.
Michael RebsamenSupport Center for Advanced Neuroimaging, University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Johannes ReiterDepartment of Epileptology, University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-4235-8209
Antonella RivaIRCCS Istituto 'Giannina Gaslini', Genova, Italy.ORCID 0000-0001-9152-5571
Theodor RüberDepartment of Epileptology, University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-6180-7671
Christian RummelSupport Center for Advanced Neuroimaging, University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID 0000-0003-2345-7938
Freda SchefflerNeuroscience Institute, University of Cape Town, Cape Town, South Africa.
Mariasavina SeverinoIRCCS Istituto 'Giannina Gaslini', Genova, Italy.ORCID 0000-0003-4730-5322
Lucas S SilvaDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.ORCID 0000-0002-0645-8456
Richard J StabaDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Dan J SteinDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0001-7218-7810
Pasquale StrianoDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.ORCID 0000-0002-6065-1476
Peter N TaylorDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0001-9407-7188
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID 0000-0002-0046-4070
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID 0000-0002-4720-8867
Domenico TortoraIRCCS Istituto 'Giannina Gaslini', Genova, Italy.
Anna Elisabetta VaudanoDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.ORCID 0000-0002-6280-7526
Bernd WeberInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany.
Roland WiestSupport Center for Advanced Neuroimaging, University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Gavin P WinstonDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0001-9395-1478
Clarissa L YasudaDepartment of Neurology, University of Campinas - UNICAMP, Campinas, Brazil.
Hong ZhengImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Carrie R McDonaldDepartment of Psychiatry, Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-0721-5640
Sanjay M SisodiyaDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0002-1511-5893
Ian H HardingDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.ORCID 0000-0002-6843-9592
ENIGMA-Epilepsy Working Group
Universidade Estadual de Campinas (UNICAMP) · BRIstituto Giannina Gaslini · ITMonash University · AUNational Hospital for Neurology and Neurosurgery · GBUniversity of Southern California · USMagna Graecia University · ITUniversity of Bern · CHUniversity of California San Diego · USUniversity of Modena and Reggio Emilia · ITHertie Institute for Clinical Brain Research · DEMeyer Children's Hospital · ITUniversity Hospital Bonn · DEUniversity of California, Los Angeles · USUniversity of Cape Town · ZAUniversity of Messina · ITAlfred Health · AUCardiff University · GBCentro de Investigación Biomédica en Red de Salud Mental · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESNewcastle University · GB
Funding
TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAN HORN, JOHN DARRELL · 2012 to 2022
$14.1MTranslational Platform for Epilepsy Therapy and Biomarker DiscoveryR01NS127524 · NINDS · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Denes V. Agoston, LISA D COLES · 2022 to 2026
$11.0MIN VIVO STUDIES OF THE EPILEPTIC HIPPOCAMPUSR01NS033310 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JEROME NONE ENGEL, Richard Staba · 1994 to 2026
$7.5MBRain Aging and Cognition in Epilepsy (BRACE): A longitudinal investigationof vascular, genetic, and biomarker risk profiles in elderly patients with epilepsyR01NS120976 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARRIE R MCDONALD · 2021 to 2026
$4.1MLifespan Epilepsy Network Signatures (LENS): Leveraging ENIGMA-Epilepsy to Predict Cognitive Aging and Surgical OutcomesR01NS122827 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARRIE R MCDONALD · 2021 to 2026
$3.8MDefining the Epileptogenic Network and Identifying Which Components Generate SeizuresR01NS106957 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Richard Staba · 2018 to 2026
$3.4MMultimodal imaging of memory in epilepsy from whole brain networks to local neuronal responses: Implications for surgical decision-makingR01NS124585 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MCDONALD, CARRIE R · 2022 to 2025
$3.3MENIGMA World Aging CenterR01AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2021 to 2025
$3.3MENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMAR01MH116147 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2021
$2.5MMedical Research Council MR/S00355X/1NIA NIH HHS R01 AG058854NIBIB NIH HHS P41 EB015922NIMH NIH HHS R01 MH116147NINDS NIH HHS R01 NS033310NINDS NIH HHS R01 NS106957NINDS NIH HHS R01 NS120976NINDS NIH HHS R01 NS122827NINDS NIH HHS R01 NS124585NINDS NIH HHS R01 NS127524
Abstract
Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed ( Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.
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anterior lobecerebellumepilepsyMRIposterior lobe
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