{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:41:09Z","timestamp":1793691669611,"version":"4.5.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"FWF","doi-asserted-by":"publisher","award":["J3499"],"award-info":[{"award-number":["J3499"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Czech Ministry of Health grant","award":["IGA NT\/11443-5"],"award-info":[{"award-number":["IGA NT\/11443-5"]}]},{"name":"Framework Programme","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"name":"DESIRE","award":["602531"],"award-info":[{"award-number":["602531"]}]},{"name":"EPISTOP","award":["602391"],"award-info":[{"award-number":["602391"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is a monogenetic disease that arises due to mutations in either the TSC1 or TSC2 gene and affects multiple organ systems. One of the hallmark manifestations of TSC are cortical malformations referred to as cortical tubers. These tubers are frequently associated with treatment-resistant epilepsy. Some of these patients are candidates for epilepsy surgery. White matter abnormalities, such as loss of myelin and oligodendroglia, have been described in a small subset of resected tubers but mechanisms underlying this phenomenon are unclear. Herein, we analyzed a variety of neuropathologic and immunohistochemical features in gray and white matter areas of resected cortical tubers from 46 TSC patients using semi-automated quantitative image analysis. We observed divergent amounts of myelin basic protein as well as numbers of oligodendroglia in both gray and white matter when compared with matched controls. Analyses of clinical data indicated that reduced numbers of oligodendroglia were associated with lower numbers on the intelligence quotient scale and that lower amounts of myelin-associated oligodendrocyte basic protein were associated with the presence of autism-spectrum disorder. In conclusion, myelin pathology in cortical tubers extends beyond the white matter and may be linked to cognitive dysfunction in TSC patients.<\/jats:p>","DOI":"10.1093\/jnen\/nlaa090","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T06:25:24Z","timestamp":1600669524000},"page":"1054-1064","source":"Crossref","is-referenced-by-count":33,"title":["Myelin Pathology Beyond White Matter in Tuberous Sclerosis Complex (TSC) Cortical Tubers"],"prefix":"10.1093","volume":"79","author":[{"given":"Angelika","family":"M\u00fchlebner","sequence":"first","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackelien","family":"van Scheppingen","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"de Neef","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-4240","authenticated-orcid":false,"given":"Anika","family":"Bongaarts","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till S","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor E","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Brain Center University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G M","family":"Spliet","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center Utrecht (WGMS) Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Krsek","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Zamecnik","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Coras","sequence":"additional","affiliation":[{"name":"Second Faculty of Medicine, Charles University, Motol University Hospital , Prague, Czech Republic; Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Blumcke","sequence":"additional","affiliation":[{"name":"Second Faculty of Medicine, Charles University, Motol University Hospital , Prague, Czech Republic; Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Feucht","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Scholl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria-Elisabeth","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A","family":"Hainfellner","sequence":"additional","affiliation":[{"name":"Institute of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Figen","family":"S\u00f6ylemezo\u011flu","sequence":"additional","affiliation":[{"name":"Medical University of Vienna , Vienna, Austria; Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kotulska","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology , The Children's Memorial Health Institute, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieven","family":"Lagae","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration-Section Pediatric Neurology, University Hospitals KU Leuven , Leuven"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C","family":"Jansen","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit-UZ Brussel , Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiusz","family":"Jozwiak","sequence":"additional","affiliation":[{"name":"Department of Neurology and Epileptology, The Children's Memorial Health Institute"},{"name":"Department of Child Neurology, Medical University of Warsaw Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Curatolo","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University , Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"},{"name":"Stichting Epilepsie Instellingen Nederland (SEIN) , Heemstede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2024032523351462200_nlaa090-B1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMra1004418","article-title":"Drug-resistant epilepsy","volume":"365","author":"Kwan","year":"2011","journal-title":"N Engl J 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