Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY

European Stroke Journal Pub Date : 2024-09-01 Epub Date: 2024-04-01 DOI:10.1177/23969873241244584

Laura Abraira, Samuel López-Maza, Manuel Quintana, Elena Fonseca, Manuel Toledo, Daniel Campos-Fernández, Sofía Lallana, Laia Grau-López, Jordi Ciurans, Marta Jiménez, Juan Luis Becerra, Alejandro Bustamante, Marta Rubiera, Anna Penalba, Joan Montaner, José Álvarez Sabin, Estevo Santamarina

{"title":"Exploratory study of blood biomarkers in patients with post-stroke epilepsy.","authors":"Laura Abraira, Samuel López-Maza, Manuel Quintana, Elena Fonseca, Manuel Toledo, Daniel Campos-Fernández, Sofía Lallana, Laia Grau-López, Jordi Ciurans, Marta Jiménez, Juan Luis Becerra, Alejandro Bustamante, Marta Rubiera, Anna Penalba, Joan Montaner, José Álvarez Sabin, Estevo Santamarina","doi":"10.1177/23969873241244584","DOIUrl":null,"url":null,"abstract":"Introduction: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE.Patients and methods: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE.Results: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865).Discussion and conclusion: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.","PeriodicalId":46821,"journal":{"name":"European Stroke Journal","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418466/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Stroke Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/23969873241244584","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE.

Patients and methods: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE.

Results: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865).

Discussion and conclusion: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

查看原文本刊更多论文

脑卒中后癫痫患者血液生物标志物的探索性研究。

简介：除临床因素外，基于血液的生物标志物可提供有关卒中后癫痫（PSE）发病风险的有用信息。我们的目的是确定中风发病时的血清生物标志物，这些标志物有助于预测中风后癫痫风险较高的患者：先前的一项研究对 895 名急性中风患者进行了随访，其中 51 名患者出现了 PSE。我们选择了 15 例 PSE 患者和 15 例无癫痫的对照组。在发现生物标志物的过程中，我们使用了 5 个 Olink 面板（每个面板包含 96 种蛋白质）来确定蛋白质水平。在 50 名 PSE 患者和 50 名对照者的样本中，使用酶联免疫吸附试验验证了 PSE 患者中下调和过表达的生物标记物，以及与其他蛋白质相互作用最强的生物标记物。采用 ROC 曲线分析评估了重要生物标志物对 PSE 发病的预测能力：PSE发现队列的平均年龄为68.56±15.1岁，40%为女性，基线NIHSS为12[IQR 1-25]。九种蛋白质表达量下降：CASP-8、TNFSF-14、STAMBP、ENRAGE、EDA2R、SIRT2、TGF-α、OSM 和 CLEC1B。VEGFa、CD40 和 CCL4 与其余蛋白质的相互作用最大。在验证分析中，TNFSF-14 是唯一一个在 PSE 患者中显示出显著统计学下调水平的生物标记物（p = 0.006），它对 PSE 的发生显示出良好的预测能力（AUC 0.733，95% CI 0.601-0.865）：讨论与结论：PSE 患者的蛋白表达与非癫痫性中风患者的蛋白表达不同，这表明中风后癫痫的发生涉及多种不同的蛋白。TNFSF-14是预测PSE的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Stroke Journal Multiple-

CiteScore

7.50

自引率

6.60%

发文量

102

期刊介绍： Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.