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
ISSN: 00068950
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 141 Número: 2
Páginas: 391-408
WOS Id: 000424217900017
ID de PubMed: 29365066