Evidence map›Paper›PMID 34388852›Full record

ArticleNeuropathology and applied neurobiology2022

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

Andre Altmann, Mina Ryten, Martina Di Nunzio, Teresa Ravizza, Daniele Tolomeo, Regina H Reynolds, Alyma Somani, Marco Bacigaluppi, Valentina Iori, Edoardo Micotti and 92 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropathology and applied neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Palmitic Acid Amplifies Microglial Inflammatory Activation Involving C5aR1-Sensitive Inflammatory Signaling and JMJD3/H3K27me3-Related Epigenetic Changes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

102 authors at 20 institutions in 14 countries.

Andre AltmannCentre for Medical Image Computing, University College London, London, UK.ORCID 0000-0002-9265-2393
Mina RytenDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Martina Di NunzioDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Teresa RavizzaDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Daniele TolomeoDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Regina H ReynoldsDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Alyma SomaniDivision of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.
Marco BacigaluppiDepartment of Neurology, San Raffaele Scientific Institute and Vita Salute San Raffaele University, Milan, Italy.
Valentina IoriDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Edoardo MicottiDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Rossella Di SapiaDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.ORCID 0000-0001-7481-5198
Milica CerovicDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Eleonora PalmaDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Gabriele RuffoloDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Juan A BotíaDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Julie AbsilDepartment of Radiology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
Saud AlhusainiDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Marina K M AlvimDepartment of Neurology, University of Campinas, Campinas, Brazil.
Pia AuvinenEpilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland.
Nuria BargalloMagnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Emanuele BartoliniPediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Benjamin BenderDepartment of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany.ORCID 0000-0002-3205-4631
Felipe P G BergoDepartment of Neurology, University of Campinas, Campinas, Brazil.
Tauana BernardesDepartment of Neurology, University of Campinas, Campinas, Brazil.
Andrea BernasconiNeuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Neda BernasconiNeuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Boris C BernhardtMultimodal Imaging and Connectome Analysis Lab, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Karen BlackmonPsychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
Barbara BragaDepartment of Neurology, University of Campinas, Campinas, Brazil.
Maria Eugenia CaligiuriNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Anna CalvoMagnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Chad CarlsonComprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, New York, USA.
Sarah J A CarrDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Gianpiero L CavalleriDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Fernando CendesDepartment of Neurology, University of Campinas, Campinas, Brazil.
Jian ChenDepartment of Computer Science and Engineering, The Ohio State University, Columbus, Ohio, USA.
Shuai ChenCognitive Science Department, Xiamen University, Xiamen, China.
Andrea CherubiniNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Luis ConchaInstituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Philippe DavidDepartment of Radiology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
Norman DelantyDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Chantal DepondtDepartment of Neurology, Hôpital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
Orrin DevinskyDepartment of Neurology, Langone School of Medicine, New York University, New York, NY, USA.
Colin P DohertyFutureNeuro Research Centre, RCSI, Dublin, Ireland.
Martin DominFunctional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Niels K FockeDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Sonya FoleyThe Welsh Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff, UK.
Wendy FrancaDepartment of Neurology, University of Campinas, Campinas, Brazil.
Antonio GambardellaNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Renzo GuerriniPediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Khalid HamandiThe Welsh Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff, UK.
Derrek P HibarImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Dmitry IsaevImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Graeme D JacksonThe Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, Victoria, Australia.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Reetta KälviäinenEpilepsy Center, Department of Neurology, Kuopio University, Kuopio, Finland.
Simon S KellerInstitute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Peter KochunovMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Raviteja KotikalapudiDepartment of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany.
Magdalena A KowalczykThe Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, Victoria, Australia.
Ruben KuznieckyDepartment of Neurology, Zucker Hofstra School of Medicine, New York, New York, USA.
Patrick KwanDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Angelo LabateNeuroscience Research Center, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
Soenke LangnerFunctional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Matteo LengePediatric Neurology Unit, Children's Hospital A. Meyer-University of Florence, Florence, Italy.
Min LiuNeuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Pascal MartinDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Mario Mascalchi"Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
Stefano MelettiDepartment of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy.
Marcia E Morita-ShermanDepartment of Neurology, University of Campinas, Campinas, Brazil.
Terence J O'BrienDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Jose C ParienteMagnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Mark P RichardsonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Raul Rodriguez-CrucesMultimodal Imaging and Connectome Analysis Lab, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Christian RummelSupport Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland.
Taavi SaavalainenInstitute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Mira K SemmelrochThe Florey Institute of Neuroscience and Mental Health, Austin Campus, Melbourne, Victoria, Australia.
Mariasavina SeverinoNeuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genoa, Italy.ORCID 0000-0003-4730-5322
Pasquale StrianoPediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Thomas ThesenComprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, New York, USA.
Rhys H ThomasInstitute of Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK.
Manuela TondelliCleveland Clinic Neurological Institute, Cleveland, USA.
Domenico TortoraNeuroradiology Unit, Department of Head and Neck and Neurosciences, Istituto Giannina Gaslini, Genoa, Italy.
Anna Elisabetta VaudanoDepartment of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, NOCSE Hospital, Modena, Italy.
Lucy VivashDepartment of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Felix von PodewilsDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Jan WagnerDepartment of Neurology, University of Ulm and Universitäts- and Rehabilitationskliniken Ulm, Ulm, Germany.
Bernd WeberInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany.
Roland WiestSupport Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland.
Clarissa L YasudaDepartment of Neurology, University of Campinas, Campinas, Brazil.
Guohao ZhangDepartment of Computer Science and Electrical Engineering, University of Maryland, Baltimore County, Baltimore, Maryland, USA.
Junsong ZhangCognitive Science Department, Xiamen University, Xiamen, China.
ENIGMA-Epilepsy Working Group
Costin LeuGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Andreja AvbersekStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
EpiPGX Consortium
Maria ThomDivision of Neuropathology, UCL Queen Square Institute of Neurology, London, UK.ORCID 0000-0001-7712-2629
Christopher D WhelanDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Paul ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Carrie R McDonaldMultimodal Imaging Laboratory, University of California San Diego, San Diego, California, USA.
Annamaria VezzaniDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Sanjay M SisodiyaDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Mario Negri Institute for Pharmacological Research · ITUniversidade Estadual de Campinas (UNICAMP) · BRUniversity of Southern California · USMontreal Neurological Institute and Hospital · CAMagna Graecia University · ITNational Hospital for Neurology and Neurosurgery · GBUniversitätsmedizin Greifswald · DEBroad Institute · USMeyer Children's Hospital · ITRoyal College of Surgeons in Ireland · IEThe University of Melbourne · AUUniversité Libre de Bruxelles · BEUniversity of Eastern Finland · FICleveland Clinic · USConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESIstituto Giannina Gaslini · ITKing's College London · GBSapienza University of Rome · ITUniversity Hospital of Wales · GBUniversity of Bern · CH

Funding

Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
SOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0M
Multimodal Imaging of Language in the Preoperative Evaluation of EpilepsyR01NS065838 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MCDONALD, CARRIE R · 2010 to 2018
$4.4M
Lifespan 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
$3.8M
A Nomogram to Predict Seizure Outcomes After Resective Epilepsy SurgeryR01NS097719 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI JEHI, LARA · 2017 to 2021
$3.6M
Hybrid GPU/CPU Computing Resource to Support Connectomic and GenomicsS10OD023696 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI KOCHUNOV, PETER V. · 2018 to 2018
$593k
Prediction of seizure lateralization and postoperative outcome through the use of deep learning applied to multi-site MRI/DTI data: An ENIGMA-Epilepsy studyR21NS107739 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BONILHA, LEONARDO F, MCDONALD, CARRIE R · 2019 to 2019
$444k
Medical Research Council MR/L016311/1Medical Research Council MR/N008324/1Medical Research Council Clinician Scientist Fellowship MR/N008324/1NIBIB NIH HHS R01 EB015611NIBIB NIH HHS U54 EB020403NIH HHS R01 NS065838NIH HHS R01 NS097719NIH HHS S10 OD023696NIH HHS U54 EB020403NINDS NIH HHS R01 NS065838NINDS NIH HHS R01 NS097719NINDS NIH HHS R01 NS122827NINDS NIH HHS R21 NS107739
6 · The paper itself

Abstract

aimsThe 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.

methodsImaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy.

resultsWe identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia.

conclusionsThese convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Indexed as

EpilepsyMicrogliaAnimalsBrainEndothelial CellsMiceSeizurescortical thinninggene expressionMRIpost mortem

Identifiers

PMID34388852
PMCPMC8983060
OpenAlexW3190489139

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