Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study
Por:
Whelan C.D., Altmann A., Botía J.A., Jahanshad N., Hibar D.P., Absil J., Alhusaini S., Alvim M.K.M., Auvinen P., Bartolini E., Bergo F.P.G., Bernardes T., Blackmon K., Braga B., Caligiuri M.E., Calvo A., Carr S.J., Chen J., Chen S., Cherubini A., David P., Domin M., Foley S., França W., Haaker G., Isaev D., Keller S.S., Kotikalapudi R., Kowalczyk M.A., Kuzniecky R., Langner S., Lenge M., Leyden K.M., Liu M., Loi R.Q., Martin P., Mascalchi M., Morita M.E., Pariente J.C., Rodríguez-Cruces R., Rummel C., Saavalainen T., Semmelroch M.K., Severino M., Thomas R.H., Tondelli M., Tortora D., Vaudano A.E., Vivash L., Von Podewils F., Wagner J., Weber B., Yao Y., Yasuda C.L., Zhang G., Bargalló N., Bender B., Bernasconi N., Bernasconi A., Bernhardt B.C., Blümcke I., Carlson C., Cavalleri G.L., Cendes F., Concha L., Delanty N., Depondt C., Devinsky O., Doherty C.P., Focke N.K., Gambardella A., Guerrini R., Hamandi K., Jackson G.D., Kälviäinen R., Kochunov P., Kwan P., Labate A., McDonald C.R., Meletti S., O'Brien T.J., Ourselin S., Richardson M.P., Striano P., Thesen T., Wiest R., Zhang J., Vezzani A., Ryten M., Thompson P.M., Sisodiya S.M.
Publicada:
1 feb 2018
Resumen:
Progressive functional decline in the epilepsies is largely unexplained.
We formed the ENIGMA-Epilepsy consortium to understand factors that
influence brain measures in epilepsy, pooling data from 24 research
centres in 14 countries across Europe, North and South America, Asia,
and Australia. Structural brain measures were extracted from MRI brain
scans across 2149 individuals with epilepsy, divided into four epilepsy
subgroups including idiopathic generalized epilepsies (n = 367), mesial
temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n =
415; right, n = 339), and all other epilepsies in aggregate (n = 1026),
and compared to 1727 matched healthy controls. We ranked brain
structures in order of greatest differences between patients and
controls, by meta-analysing effect sizes across 16 subcortical and 68
cortical brain regions. We also tested effects of duration of disease,
age at onset, and age-by-diagnosis interactions on structural measures.
We observed widespread patterns of altered subcortical volume and
reduced cortical grey matter thickness. Compared to controls, all
epilepsy groups showed lower volume in the right thalamus (Cohen's d =
-0.24 to -0.73; P51.49 x 10(-4)), and lower thickness in the precentral
gyri bilaterally (d = -0.34 to -0.52; P < 4.31 x 10(-6)). Both MTLE
subgroups showed profound volume reduction in the ipsilateral
hippocampus (d = -1.73 to -1.91, P < 1.4 x 10(-19)), and lower thickness
in extrahippocampal cortical regions, including the precentral and
paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 x
10(-4)). Thickness differences of the ipsilateral temporopolar,
parahippocampal, entorhinal, and fusiform gyri, contralateral pars
triangularis, and bilateral precuneus, superior frontal and caudal
middle frontal gyri were observed in left, but not right, MTLE (d =
-0.29 to -0.54; P < 1.49 x 10(-4)). Contrastingly, thickness differences
of the ipsilateral pars opercularis, and contralateral transverse
temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to
-0.51; P < 1.49 x 10(-4)). Lower subcortical volume and cortical
thickness associated with a longer duration of epilepsy in the
all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b <
-0.0018; P < 1.49 x 10(-4)). In the largest neuroimaging study of
epilepsy to date, we provide information on the common epilepsies that
could not be realistically acquired in any other way. Our study provides
a robust ranking of brain measures that can be further targeted for
study in genetic and neuropathological studies. This worldwide
initiative identifies patterns of shared grey matter reduction across
epilepsy syndromes, and distinctive abnormalities between epilepsy
syndromes, which inform our understanding of epilepsy as a network
disorder, and indicate that certain epilepsy syndromes involve more
widespread structural compromise than previously assumed.
Filiaciones:
Whelan C.D.:
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
Department of Molecular and Cellular Therapeutics, Royal College of Sur. in Ireland, Dublin, Ireland
Altmann A.:
Translational Imaging Group, Centre for Medical Image Computing, University College London, London, United Kingdom
Botía J.A.:
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Jahanshad N.:
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
Hibar D.P.:
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
Absil J.:
Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Alhusaini S.:
Department of Molecular and Cellular Therapeutics, Royal College of Sur. in Ireland, Dublin, Ireland
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
Alvim M.K.M.:
Department of Neurology, University of Campinas, Campinas, Brazil
Auvinen P.:
Epilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland
Institute of Clinical Medicine Neurology, University of Eastern Finland, Kuopio, Finland
Bartolini E.:
Pediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Italy
IRCCS Stella Maris Foundation, Pisa, Italy
Bergo F.P.G.:
Department of Neurology, University of Campinas, Campinas, Brazil
Bernardes T.:
Department of Neurology, University of Campinas, Campinas, Brazil
Blackmon K.:
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, United States
Department of Physiology, Neuroscience and Behavioral Science, St. George's University, Grenada, Grenada
Braga B.:
Department of Neurology, University of Campinas, Campinas, Brazil
Caligiuri M.E.:
Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy
Calvo A.:
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
Carr S.J.:
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
Chen J.:
Department of Computer Science and Engineering, Ohio State University, United States
Chen S.:
Cognitive Science Department, Xiamen University, Xiamen, China
Fujian Key Laboratory of the Brain-like Intelligent Systems, China
Cherubini A.:
Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy
David P.:
Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Domin M.:
Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
Foley S.:
Cardiff University Brain Research Imaging Centre, School of Psychology, United Kingdom
França W.:
Department of Neurology, University of Campinas, Campinas, Brazil
Haaker G.:
Department of Neurosurgery, University Hospital, Freiburg, Germany
Department of Neuropathology, University Hospital Erlangen, Germany
Isaev D.:
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
Keller S.S.:
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, United Kingdom
Kotikalapudi R.:
Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
Kowalczyk M.A.:
Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, VIC, Australia
Kuzniecky R.:
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, United States
Langner S.:
Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
Lenge M.:
Pediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Italy
Leyden K.M.:
Multimodal Imaging Laboratory, University of California San Diego, San Diego, CA, United States
Department of Psychiatry, University of California San Diego, San Diego, CA, United States
Liu M.:
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, Mcgill University, Montreal, QC, Canada
Loi R.Q.:
Multimodal Imaging Laboratory, University of California San Diego, San Diego, CA, United States
Department of Psychiatry, University of California San Diego, San Diego, CA, United States
Martin P.:
Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Mascalchi M.:
Neuroradiology Unit, Children's Hospital A. Meyer, Florence, Italy
'Mario Serio' Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy
Morita M.E.:
Department of Neurology, University of Campinas, Campinas, Brazil
Pariente J.C.:
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
Rodríguez-Cruces R.:
Instituto de Neurobiología, Universidad Nacional Autónoma de México. Querétaro, Querétaro, Mexico
Rummel C.:
Support Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
Saavalainen T.:
Institute of Clinical Medicine Neurology, University of Eastern Finland, Kuopio, Finland
Central Finland Central Hospital, Medical Imaging Unit, Jyväskylä, Finland
Semmelroch M.K.:
Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, VIC, Australia
Severino M.:
Neuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genova, Italy
Thomas R.H.:
Institute of Psychological Medicine and Clinical Neurosciences, Hadyn Ellis Building, Maindy Road, Cardiff, United Kingdom
Department of Neurology, University Hospital of Wales, Cardiff, United Kingdom
Tondelli M.:
Department of Biomedical Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy
Tortora D.:
Neuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genova, Italy
Vaudano A.E.:
Department of Biomedical Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy
Vivash L.:
Melbourne Brain Centre, Department of Medicine, University of Melbourne, Parkville, VIC, Australia
Department of Neurology, Royal Melbourne Hospital, Parkville, Australia
Department of Medicine, University of Melbourne, Parkville, VIC, Australia
Von Podewils F.:
Department of Neurology, University Medicine Greifswald, Greifswald, Germany
Wagner J.:
Department of Epileptology, University Hospital Bonn, Bonn, Germany
Department of Neurology, Philips University of Marburg, Marburg, Germany
Weber B.:
Department of Epileptology, University Hospital Bonn, Bonn, Germany
Department of Neurocognition / Imaging, LifeandBrain Research Centre, Bonn, Germany
Yao Y.:
Affiliated Chenggong Hospital of Xiamen University, Xiamen, China
Yasuda C.L.:
Department of Neurology, University of Campinas, Campinas, Brazil
Zhang G.:
Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, United States
Bargalló N.:
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
Centre de Diagnostic per la Imatge (CDIC), Hospital Clinic, Barcelona, Spain
Bender B.:
Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
Bernasconi N.:
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, Mcgill University, Montreal, QC, Canada
Bernasconi A.:
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, Mcgill University, Montreal, QC, Canada
Bernhardt B.C.:
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, Mcgill University, Montreal, QC, Canada
Multimodal Imaging and Connectome Analysis Lab, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
Blümcke I.:
Department of Neuropathology, University Hospital Erlangen, Germany
Carlson C.:
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, United States
Medical College of Wisconsin, Department of Neurology, Milwaukee, WI, United States
Cavalleri G.L.:
Department of Molecular and Cellular Therapeutics, Royal College of Sur. in Ireland, Dublin, Ireland
FutureNeuro Research Centre, RCSI, Dublin, Ireland
Cendes F.:
Department of Neurology, University of Campinas, Campinas, Brazil
Concha L.:
Instituto de Neurobiología, Universidad Nacional Autónoma de México. Querétaro, Querétaro, Mexico
Delanty N.:
Department of Molecular and Cellular Therapeutics, Royal College of Sur. in Ireland, Dublin, Ireland
FutureNeuro Research Centre, RCSI, Dublin, Ireland
Division of Neurology, Beaumont Hospital, Dublin 9, Ireland
Depondt C.:
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Devinsky O.:
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, United States
Doherty C.P.:
FutureNeuro Research Centre, RCSI, Dublin, Ireland
Neurology Department, St. James's Hospital, Dublin 8, Ireland
Focke N.K.:
Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Department of Clinical Neurophysiology, University Medicine Göttingen, Göttingen, Germany
Gambardella A.:
Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy
Institute of Neurology, University Magna Græcia, Catanzaro, Italy
Guerrini R.:
Pediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Italy
IRCCS Stella Maris Foundation, Pisa, Italy
Hamandi K.:
Institute of Psychological Medicine and Clinical Neurosciences, Hadyn Ellis Building, Maindy Road, Cardiff, United Kingdom
Department of Neurology, University Hospital of Wales, Cardiff, United Kingdom
Jackson G.D.:
Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, VIC, Australia
Florey Department of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
Kälviäinen R.:
Epilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland
Institute of Clinical Medicine Neurology, University of Eastern Finland, Kuopio, Finland
Kochunov P.:
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Maryland, United States
Kwan P.:
Department of Neurology, Royal Melbourne Hospital, Parkville, Australia
Labate A.:
Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Catanzaro, Italy
Institute of Neurology, University Magna Græcia, Catanzaro, Italy
McDonald C.R.:
Multimodal Imaging Laboratory, University of California San Diego, San Diego, CA, United States
Department of Psychiatry, University of California San Diego, San Diego, CA, United States
Meletti S.:
Department of Biomedical Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy
O'Brien T.J.:
Department of Neurology, Royal Melbourne Hospital, Parkville, Australia
Department of Medicine, University of Melbourne, Parkville, VIC, Australia
Ourselin S.:
Translational Imaging Group, Centre for Medical Image Computing, University College London, London, United Kingdom
Richardson M.P.:
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
Department of Neurology, King's College Hospital, London, United Kingdom
Striano P.:
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy
Thesen T.:
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, United States
Department of Physiology, Neuroscience and Behavioral Science, St. George's University, Grenada, Grenada
Wiest R.:
Support Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
Zhang J.:
Cognitive Science Department, Xiamen University, Xiamen, China
Fujian Key Laboratory of the Brain-like Intelligent Systems, China
Vezzani A.:
Dept of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, Milan, Italy
Ryten M.:
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
Thompson P.M.:
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
Sisodiya S.M.:
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Box 29 Queen Square, London, United Kingdom
Chalfont Centre for Epilepsy, Bucks, United Kingdom
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