Evidence map›Paper›PMID 39817839›Full record

ArticleEpilepsia2025

Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.

Renaud Balthazard, Rose-Marie Drouin-Engler, Samuel Bertrand, Faycal Zine-Eddine, Jimmy Li, Olivier Tastet, Audrey Daigneault, Victoria H Mamane, Gloria Gabrielle Ortega-Delgado, Alina Maria Sreng Flores and 7 more

Abstract read
In one paragraph

Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Renaud BalthazardDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Rose-Marie Drouin-EnglerDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Samuel BertrandCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Faycal Zine-EddineCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Jimmy LiCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-8386-8897
Olivier TastetMontreal Heart Institute, Montréal, Quebec, Canada.
Audrey DaigneaultCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Victoria H MamaneDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Gloria Gabrielle Ortega-DelgadoCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Alina Maria Sreng FloresCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Daniel E KaufmannCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Philippe MajorDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Andrew A HouseDivision of Nephrology, Department of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada.
Laurent Létourneau-GuillonCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Nathalie ArbourDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Mark R KeezerDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Catherine LarochelleDepartment of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.

Funding

CIHR 487762LES NEUROLOGUES ASSOCIÉS DU CHUM, S.E.N.C.R.LTSC Alliance
6 · The paper itself

Abstract

objectiveTuberous 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-related 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-TSC-related 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.

methodsWe performed a cross-sectional 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 (n = 46) vs age- and sex-matched healthy controls (HCs) (n = 26). In pwTSC, markers associated with active epilepsy (n = 23/46) were compared to non-TSC epilepsy controls (n = 18). Observations on markers of neuroglial activation/injury (GFAP, NfL) were confirmed in an independent TSC cohort (n = 45; 69% with active epilepsy).

resultsWe report that TSC is characterized by elevated serum levels of marker of astrogliosis (GFAP), pro-inflammatory molecules (interleukin 1β [IL-1β], CXCL8) and trophic factor (epidermal growth factor [EGF]) compared to HCs and to non-TSC-related epilepsy controls. Among pwTSC, renal angiomyolipoma presence and size was associated with IL-15. 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-inflammatory cytokines (IL-17A, IL-17C, tumor necrosis factor α [TNF-α]), not significantly related to seizure activity or treatment with mTOR inhibitor. These associations remained significant after adjusting for age and sex. SIGNIFICANCE: These results suggest that key inflammatory mediators could contribute to epileptogenesis and represent novel biomarkers and therapeutic targets in TSC.

Indexed as

CytokinesEpilepsyInflammationTuberous SclerosisAdolescentAdultBiomarkersCross-Sectional StudiesFemaleGlial Fibrillary Acidic ProteinHumansMaleMiddle AgedYoung AdultBiomarkersCytokinesGlial Fibrillary Acidic ProteinEpilepsyGFAPNeuroinflammationTuberous sclerosis complex

Identifiers

PMID39817839
PMCPMC11997944

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LicenceCC BY-NC
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.