{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:19:29Z","timestamp":1776125969671,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020102","name":"TSC Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["487762"],"award-info":[{"award-number":["487762"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC\u2010related clinical manifestations. Reliable biomarkers are lacking to monitor and predict evolution and response to treatment for epilepsy in pwTSC. Inflammation has been implicated in epileptogenesis in non\u2013TSC\u2010related epilepsy. We aimed to characterize the relation between markers of neuroglial activation\/injury, markers of peripheral inflammation, and active epilepsy in pwTSC to identify accessible biomarkers and potential new therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a cross\u2010sectional study to investigate markers of central nervous system (CNS) (neurofilament light [NfL] and glial fibrillary acidic protein [GFAP]) and peripheral (45 cytokines) inflammation in the peripheral blood of pwTSC (<jats:italic>n<\/jats:italic>\u2009=\u200946) vs age\u2010 and sex\u2010matched healthy controls (HCs) (<jats:italic>n<\/jats:italic>\u2009=\u200926). In pwTSC, markers associated with active epilepsy (<jats:italic>n<\/jats:italic>\u2009=\u200923\/46) were compared to non\u2010TSC epilepsy controls (<jats:italic>n<\/jats:italic>\u2009=\u200918). Observations on markers of neuroglial activation\/injury (GFAP, NfL) were confirmed in an independent TSC cohort (<jats:italic>n<\/jats:italic>\u2009=\u200945; 69% with active epilepsy).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report that TSC is characterized by elevated serum levels of marker of astrogliosis (GFAP), pro\u2010inflammatory molecules (interleukin 1\u03b2 [IL\u20101\u03b2], CXCL8) and trophic factor (epidermal growth factor [EGF]) compared to HCs and to non\u2013TSC\u2010related epilepsy controls. Among pwTSC, renal angiomyolipoma presence and size was associated with IL\u201015. It is notable that active epilepsy in pwTSC was associated with higher levels of GFAP compared to pwTSC without epilepsy, which was confirmed in an external validation cohort, and with elevated levels of pro\u2010inflammatory cytokines (IL\u201017A, IL\u201017C, tumor necrosis factor \u03b1 [TNF\u2010\u03b1]), not significantly related to seizure activity or treatment with mTOR inhibitor. These associations remained significant after adjusting for age and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These results suggest that key inflammatory mediators could contribute to epileptogenesis and represent novel biomarkers and therapeutic targets in TSC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18261","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T19:06:32Z","timestamp":1737054392000},"page":"1288-1303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Distinct peripheral pro\u2010inflammatory profile associated with tuberous sclerosis complex and epilepsy"],"prefix":"10.1111","volume":"66","author":[{"given":"Renaud","family":"Balthazard","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Centre de Recherche du Centre 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Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montreal Quebec Canada"},{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM)  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8386-8897","authenticated-orcid":false,"given":"Jimmy","family":"Li","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montreal Quebec Canada"},{"name":"Division of Neurology Centre Hospitalier de l'Universit\u00e9 de Sherbrooke (CHUS)  Sherbrooke Quebec Canada"},{"name":"School of Public Health Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Tastet","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute  Montr\u00e9al Quebec 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Maria","family":"Sreng Flores","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montreal Quebec Canada"},{"name":"Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montreal Quebec Canada"},{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM)  Montreal Quebec Canada"},{"name":"Department of Medicine, Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Division of Infectious Diseases, Department of Medicine Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Major","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Division of Neurology Centre Hospitalier Universitaire (CHU) Sainte Justine  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"House","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Western University and London Health Sciences Centre  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"L\u00e9tourneau\u2010Guillon","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CRCHUM)  Montreal Quebec Canada"},{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al (CHUM)  Montreal Quebec 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