A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies,Neuropathology and Applied Neurobiology

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A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies
Neuropathology and Applied Neurobiology ( IF 5 ) Pub Date : 2021-08-13 , DOI: 10.1111/nan.12758
Andre Altmann ₁ , Mina Ryten ₂ , Martina Di Nunzio ₃ , Teresa Ravizza ₃ , Daniele Tolomeo ₃ , Regina H Reynolds ₂ , Alyma Somani ₄ , Marco Bacigaluppi ₅ , Valentina Iori ₃ , Edoardo Micotti ₃ , Rossella Di Sapia ₃ , Milica Cerovic ₃ , Eleonora Palma ₆ , Gabriele Ruffolo ₆ , Juan A Botía _{2,

7} , Julie Absil ₈ , Saud Alhusaini _{9,

10} , Marina K M Alvim ₁₁ , Pia Auvinen _{12,

13} , Nuria Bargallo _{14,

15} , Emanuele Bartolini _{16,

17} , Benjamin Bender ₁₈ , Felipe P G Bergo ₁₁ , Tauana Bernardes ₁₁ , Andrea Bernasconi ₁₉ , Neda Bernasconi ₁₉ , Boris C Bernhardt ₂₀ , Karen Blackmon ₂₁ , Barbara Braga ₁₁ , Maria Eugenia Caligiuri ₂₂ , Anna Calvo ₁₄ , Chad Carlson _{23,

24} , Sarah J A Carr ₂₅ , Gianpiero L Cavalleri _{9,

26} , Fernando Cendes ₁₁ , Jian Chen ₂₇ , Shuai Chen _{28,

29} , Andrea Cherubini ₂₂ , Luis Concha ₃₀ , Philippe David ₈ , Norman Delanty _{9,

26,

31} , Chantal Depondt ₃₂ , Orrin Devinsky ₃₃ , Colin P Doherty _{26,

34} , Martin Domin ₃₅ , Niels K Focke _{36,

37} , Sonya Foley ₃₈ , Wendy Franca ₁₁ , Antonio Gambardella _{22,

39} , Renzo Guerrini ₁₆ , Khalid Hamandi _{38,

40} , Derrek P Hibar ₄₁ , Dmitry Isaev ₄₁ , Graeme D Jackson _{42,

43} , Neda Jahanshad ₄₁ , Reetta Kälviäinen _{12,

13} , Simon S Keller ₄₄ , Peter Kochunov ₄₅ , Raviteja Kotikalapudi _{18,

35,

36} , Magdalena A Kowalczyk ₄₂ , Ruben Kuzniecky ₄₆ , Patrick Kwan ₄₇ , Angelo Labate _{22,

39} , Soenke Langner ₃₅ , Matteo Lenge ₁₆ , Min Liu ₁₉ , Pascal Martin ₃₆ , Mario Mascalchi ₄₈ , Stefano Meletti ₄₉ , Marcia E Morita-Sherman _{11,

50} , Terence J O'Brien _{47,

51} , Jose C Pariente ₁₄ , Mark P Richardson _{25,

52} , Raul Rodriguez-Cruces _{20,

30} , Christian Rummel ₅₃ , Taavi Saavalainen _{13,

54} , Mira K Semmelroch _{42,

43} , Mariasavina Severino ₅₅ , Pasquale Striano ₅₆ , Thomas Thesen ₂₃ , Rhys H Thomas ₅₇ , Manuela Tondelli ₅₀ , Domenico Tortora ₅₅ , Anna Elisabetta Vaudano ₄₉ , Lucy Vivash _{47,

58} , Felix von Podewils ₅₉ , Jan Wagner ₆₀ , Bernd Weber ₆₁ , Roland Wiest ₅₃ , Clarissa L Yasuda ₁₁ , Guohao Zhang ₆₂ , Junsong Zhang _{28,

29} , , Costin Leu _{63,

64,

65} , Andreja Avbersek ₆₄ , , Maria Thom _{4,

65} , Christopher D Whelan _{9,

41} , Paul Thompson ₄₁ , Carrie R McDonald _{66,

67} , Annamaria Vezzani ₃ , Sanjay M Sisodiya _{65,

68}

Affiliation

Centre for Medical Image Computing, University College London, London, UK.
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Division of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.
Department of Neurology, San Raffaele Scientific Institute and Vita Salute San Raffaele University, Milan, Italy.
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, Murcia, Spain.
Department of Radiology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Neurology Department, Yale University School of Medicine, New Haven, CT, USA.
Department of Neurology, University of Campinas, Campinas, Brazil.
Epilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland.
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Centre de Diagnostic Per la Imatge (CDIC), Hospital Clinic, Barcelona, Spain.
Pediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Neurology Unit, USL Centro Toscana, Nuovo Ospedale Santo Stefano, Prato, Italy.
Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany.
Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Multimodal Imaging and Connectome Analysis Lab, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
Neuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, New York, USA.
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
FutureNeuro Research Centre, RCSI, Dublin, Ireland.
Department of Computer Science and Engineering, The Ohio State University, Columbus, Ohio, USA.
Cognitive Science Department, Xiamen University, Xiamen, China.
Fujian Key Laboratory of the Brain-like Intelligent Systems, Xiamen, China.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Division of Neurology, Beaumont Hospital, Dublin 9, Ireland.
Department of Neurology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
Department of Neurology, Langone School of Medicine, New York University, New York, NY, USA.
School of Medicine, Trinity College Dublin, Dublin, Ireland.
Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
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.
The Welsh Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff, UK.
Institute of Neurology, University "Magna Graecia", Catanzaro, Italy.
Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
The Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, Victoria, Australia.
Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Neurology, Zucker Hofstra School of Medicine, New York, New York, USA.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
"Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy.
Cleveland Clinic Neurological Institute, Cleveland, USA.
The Department of Medicine (The Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia.
Department of Neurology, King's College Hospital, London, UK.
Support Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland.
Medical Imaging Unit, Central Finland Central Hospital, Jyväskylä, Finland.
Neuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genoa, Italy.
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Institute of Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK.
Melbourne Brain Centre, Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
Department of Neurology, University of Ulm and Universitäts- and Rehabilitationskliniken Ulm, Ulm, Germany.
Institute of Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany.
Department of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Multimodal Imaging Laboratory, University of California San Diego, San Diego, California, USA.
Department of Psychiatry, University of California San Diego, San Diego, California, USA.
Chalfont Centre for Epilepsy, Bucks, UK.

The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis.

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