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Plasma neurofilament heavy chain is a prognostic biomarker for the development of severe epilepsy after experimental traumatic brain injury. 血浆神经丝重链是实验性脑外伤后发生严重癫痫的预后生物标志物。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-14 DOI: 10.1111/epi.18149
Mette Heiskanen, Ivette Banuelos, Eppu Manninen, Pedro Andrade, Elina Hämäläinen, Noora Puhakka, Asla Pitkänen

Objective: This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF-H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy.

Methods: Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF-H by enzyme-linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video-electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T2 magnetic resonance imaging were performed to assess comorbidities and lesion severity.

Results: Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI-). Plasma pNF-H concentrations were higher in TBI+ rats than in TBI- rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF-H concentration distinguished TBI+ rats from TBI- rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF-H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF-H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF-H concentration on D2 correlated with greater T2 signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF-H concentration on D2 did not correlate with Morris water maze performance on D37-D39.

Significance: Plasma pNF-H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.

研究目的本研究旨在检测损伤后血浆中磷酸化神经丝重链(pNF-H)的浓度(pNF-H是轴突损伤的标志物)是否是创伤后癫痫发生的预后生物标志物:方法:在创伤性脑损伤(TBI)48小时后,对143只大鼠(10只天真大鼠、21只对照组大鼠、112只侧液叩击伤大鼠)的尾静脉血浆进行采样,通过酶联免疫吸附试验对pNF-H进行定量。在受伤后第 6 个月,对大鼠进行为期 30 天的连续视频脑电图监测,以检测无诱因癫痫发作并评估癫痫严重程度。此外,还进行了躯体运动(综合神经评分)和空间记忆(莫里斯水迷宫)测试以及定量 T2 磁共振成像,以评估合并症和病变严重程度:112只创伤性脑损伤大鼠中,25%(28/112)出现癫痫(创伤性脑损伤+),75%(84/112)未出现癫痫(创伤性脑损伤-)。TBI+ 大鼠的血浆 pNF-H 浓度高于 TBI- 大鼠(p 2 D2 信号异常体积(p 意义:血浆 pNF-H 是一种有希望转化为临床预后的生物标志物,可用于诊断频繁发作或发作集群的创伤后癫痫。
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引用次数: 0
One-year follow-up of neurobehavioral therapy in functional seizures or epilepsy with traumatic brain injury: A nonrandomized controlled trial. 脑外伤功能性癫痫发作或癫痫的神经行为疗法一年随访:非随机对照试验。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-10 DOI: 10.1111/epi.18137
Ryan Van Patten, Andrew Blum, Stephen Correia, Noah S Philip, Jane B Allendorfer, Tyler E Gaston, Adam Goodman, Leslie P Grayson, Krista Tocco, Valerie Vogel, Amber Martin, Samantha Fry, Mark Bolding, Lawrence Ver Hoef, Grayson L Baird, Jerzy P Szaflarski, W Curt LaFrance

Objective: Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy.

Methods: In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life.

Results: Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-only comparisons improved on only one of 19 (5.3%).

Significance: NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures.

目的:创伤性脑损伤(TBI)患者通常伴有癫痫发作(功能性和/或癫痫),但针对TBI合并癫痫发作患者的治疗方法却很有限。我们研究了创伤性脑损伤+功能性癫痫发作(FS)和创伤性脑损伤+癫痫患者接受神经行为疗法(NBT)后的治疗阶段和一年后的疗效:在这项多中心、前瞻性、三组、非随机对照试验中,共招募了三组成年人,进行了为期一年的入组后随访:创伤性脑损伤+视频脑电图(EEG)证实的FS(n = 89)、创伤性脑损伤+EEG证实的癫痫(n = 29)以及图表/病史证实的无癫痫发作的创伤性脑损伤(n = 75)。排除标准为近期精神错乱或自伤行为、当前有自杀倾向、未决诉讼或长期残疾、活动性药物使用障碍以及无法参与研究程序。创伤性脑损伤+FS组和创伤性脑损伤+癫痫组完成了针对癫痫发作的NBT治疗,这是一种以证据为基础的多模式心理治疗,为期12个疗程,而无癫痫发作的创伤性脑损伤组参与者则接受标准的医疗护理。主要结果是癫痫发作频率的变化;次要结果是心理健康、创伤性脑损伤相关症状、残疾和生活质量的变化:结果:在治疗期间,TBI + FS 参与者的每月平均癫痫发作次数有所减少(p = .002),并且从基线(平均值 = 16.75;95% 置信区间 [CI] = 11.44-24.53)到注册后 12 个月(平均值 = 7.28,95% 置信区间 = 4.37-12.13,p = .002,d = .38)期间的减少幅度显著。在治疗期间,创伤性脑损伤+癫痫参与者的每月癫痫发作次数有所减少(p = .002);从基线(平均 = 2.38,95% CI = 1.12-5.04)到入组后 12 个月(平均 = .98,95% CI = .40-2.42,p = .07,d = .22),减少幅度无统计学意义。关于次要结果测量中治疗阶段的变化,TBI + FS参与者在19个变量中的10个变量(52.6%)有显著改善,TBI +癫痫参与者在19个变量中的5个变量(26.3%)有改善,而仅TBI比较者在19个变量中仅有1个变量(5.3%)有改善:NBT使创伤性脑损伤+FS和创伤性脑损伤+癫痫患者受益。TBI+FS患者在接受 NBT 治疗 1 年后病情有所改善。NBT对癫痫发作患者可能是一种临床有用的治疗方法。
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引用次数: 0
Electroencephalographic source imaging of spikes with concurrent high-frequency oscillations is concordant with the clinical ground truth. 脑电波源成像显示尖峰同时伴有高频振荡,这与临床实际情况相符。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-10 DOI: 10.1111/epi.18141
Colton B Gonsisko, Zhengxiang Cai, Xiyuan Jiang, Andrea M Duque Lopez, Gregory A Worrell, Bin He

Objective: Epilepsy raises critical challenges to accurately localize the epileptogenic zone (EZ) to guide presurgical planning. Previous research has suggested that interictal spikes overlapping with high-frequency oscillations, referred to here as pSpikes, serve as a reliable biomarker for EZ estimation, but there remains a question as to whether and to how pSpikes perform as compared to other types of epileptic spikes. This study aims to address this question by investigating the source imaging capabilities of pSpikes alongside other spike types.

Methods: A total of 2819 interictal spikes from 76-channel scalp electroencephalography (EEG) were analyzed in a cohort of 24 drug-resistant focal epilepsy patients. All patients received surgical resection, and 16 were declared seizure-free based on at least 1 year of postoperative follow-up. A recently developed electrophysiological source imaging algorithm-fast spatiotemporal iteratively reweighted edge sparsity (FAST-IRES)-was used for source imaging of the detected interictal spikes. The performance of 217 pSpikes was compared with 772 nSpikes (spikes with irregular high-frequency activations), 1830 rSpikes (spikes with no high-frequency activity), and all 2819 aSpikes (all interictal spikes).

Results: The localization and extent estimation using pSpikes are concordant with the clinical ground truth; using pSpikes yields the best performance compared with nSpikes, rSpikes, and conventional spike imaging (aSpikes). For multiple spike type seizure-free patients, the mean localization error for pSpike imaging was 6.8 mm, compared with 15.0 mm for aSpikes. The sensitivity, precision, and specificity were .41, .67, and .93 for pSpikes compared with .32, .48, and .93 for aSpikes.

Significance: These results demonstrate the merits of noninvasive EEG source localization, and that (1) pSpike is a superior biomarker, outperforming conventional spike imaging for the localization of epileptic sources, and especially those with multiple irritative zones; and (2) FAST-IRES provides accurate source estimation that is highly concordant with clinical ground truth, even in situations of single spike analysis with low signal-to-noise ratio.

目的:癫痫给准确定位致痫区(EZ)以指导术前规划带来了严峻挑战。先前的研究表明,与高频振荡重叠的发作间期尖峰(在此称为 pSpikes)是估测 EZ 的可靠生物标志物,但与其他类型的癫痫尖峰相比,pSpikes 的表现是否和如何仍然存在问题。本研究旨在通过研究 pSpikes 与其他类型尖峰的源成像能力来解决这一问题:方法:在一组 24 名耐药局灶性癫痫患者中分析了 76 通道头皮脑电图(EEG)中的 2819 个发作间期尖峰。所有患者都接受了手术切除,其中16名患者在术后至少1年的随访中被宣布无癫痫发作。最近开发的电生理学源成像算法--快速时空迭代加权边缘稀疏性(FAST-IRES)--被用于对检测到的发作间期尖峰进行源成像。将 217 个 pSpikes 的性能与 772 个 nSpikes(具有不规则高频激活的尖峰)、1830 个 rSpikes(没有高频活动的尖峰)和全部 2819 个 aSpikes(所有发作间期尖峰)进行了比较:结果:使用 pSpikes 进行的定位和范围估计与临床基本事实相符;与 nSpikes、rSpikes 和传统尖峰成像(aSpikes)相比,使用 pSpikes 的效果最好。对于无多棘波类型癫痫发作的患者,pSpike 成像的平均定位误差为 6.8 毫米,而 aSpikes 为 15.0 毫米。pSpikes 的灵敏度、精确度和特异性分别为 0.41、0.67 和 0.93,而 aSpikes 的灵敏度、精确度和特异性分别为 0.32、0.48 和 0.93:这些结果表明了无创脑电图源定位的优点:(1) pSpike 是一种优越的生物标志物,在癫痫源定位方面优于传统的尖峰成像,尤其是那些具有多个刺激区的癫痫源;(2) FAST-IRES 提供了准确的源估计,即使在信噪比较低的单个尖峰分析情况下,也能与临床基本事实高度一致。
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引用次数: 0
Establishing the minimum clinically important difference of the Quality of Life in Childhood Epilepsy Questionnaire. 确定儿童癫痫生活质量问卷的最小临床意义差异。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-09 DOI: 10.1111/epi.18140
Mariela Leda, Klajdi Puka, Karen Bax, Joel J Gagnier, Karina Tassiopoulos, Kathy Nixon Speechley

Objective: To estimate the minimum clinically important difference (MCID) for the parent-reported 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and its shortened 16-item version, QOLCE-16.

Methods: Data came from 74 children with epilepsy (CWE) (ages 4-10, mean age = 8 [SD = 1.8]) enrolled in the Making Mindfulness Matter in Epilepsy (M3-E) trial, a pilot, parallel randomized-controlled trial of a mindfulness-based intervention. Both anchor-based and distribution-based methods were used to estimate MCID values for the QOLCE-55 and QOLCE-16. For the anchor-based approach, the Patient Centered Global Ratings of Change (PCGRC) scale and linear regression analysis were used to estimate the MCID. For the distribution-based approach, .5 SD of the health-related quality of life (HRQOL) change score distribution was used to estimate the MCID.

Results: For the QOLCE-55, the MCID obtained using an anchor-based approach was 10 points and using a distribution-based method was 6 points. For the QOLCE-16, the MCID obtained using an anchor-based method was 13 points and using a distribution-based method was 7 points.

Significance: This is the first study to estimate MCID values for the QOLCE-55 and the QOLCE-16. It has been well documented that CWE are at risk of experiencing psychological, behavioral, and cognitive impairments, which can negatively impact their HRQOL. Reporting MCID values for the QOLCE-55 and QOLCE-16 is important in determining whether changes in HRQOL observed are meaningful to CWE themselves, as a key factor in shaping the nature of epilepsy care delivered.

目的估算家长报告的 55 项儿童癫痫生活质量问卷(QOLCE-55)及其 16 项缩短版 QOLCE-16 的最小临床重要性差异(MCID):数据来自 74 名癫痫患儿(CWE)(4-10 岁,平均年龄 = 8 [SD = 1.8]),他们参加了 "让正念在癫痫中发挥作用"(M3-E)试验,这是一项基于正念的干预措施的试点、平行随机对照试验。在估算 QOLCE-55 和 QOLCE-16 的 MCID 值时,使用了基于锚的方法和基于分布的方法。在基于锚的方法中,使用了以患者为中心的全球变化评分量表 (PCGRC) 和线性回归分析来估算 MCID。对于基于分布的方法,使用健康相关生活质量(HRQOL)变化得分分布的 0.5 SD 来估计 MCID:结果:对于 QOLCE-55,使用基于锚的方法得出的 MCID 为 10 分,使用基于分布的方法得出的 MCID 为 6 分。对于 QOLCE-16,使用基于锚的方法得出的 MCID 为 13 分,使用基于分布的方法得出的 MCID 为 7 分:这是第一项估算 QOLCE-55 和 QOLCE-16 MCID 值的研究。有大量文件表明,化武受害者有可能出现心理、行为和认知障碍,这可能会对他们的 HRQOL 产生负面影响。报告 QOLCE-55 和 QOLCE-16 的 MCID 值对于确定观察到的 HRQOL 变化对 CWE 自身是否有意义非常重要,因为这是决定所提供的癫痫护理性质的关键因素。
{"title":"Establishing the minimum clinically important difference of the Quality of Life in Childhood Epilepsy Questionnaire.","authors":"Mariela Leda, Klajdi Puka, Karen Bax, Joel J Gagnier, Karina Tassiopoulos, Kathy Nixon Speechley","doi":"10.1111/epi.18140","DOIUrl":"https://doi.org/10.1111/epi.18140","url":null,"abstract":"<p><strong>Objective: </strong>To estimate the minimum clinically important difference (MCID) for the parent-reported 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and its shortened 16-item version, QOLCE-16.</p><p><strong>Methods: </strong>Data came from 74 children with epilepsy (CWE) (ages 4-10, mean age = 8 [SD = 1.8]) enrolled in the Making Mindfulness Matter in Epilepsy (M3-E) trial, a pilot, parallel randomized-controlled trial of a mindfulness-based intervention. Both anchor-based and distribution-based methods were used to estimate MCID values for the QOLCE-55 and QOLCE-16. For the anchor-based approach, the Patient Centered Global Ratings of Change (PCGRC) scale and linear regression analysis were used to estimate the MCID. For the distribution-based approach, .5 SD of the health-related quality of life (HRQOL) change score distribution was used to estimate the MCID.</p><p><strong>Results: </strong>For the QOLCE-55, the MCID obtained using an anchor-based approach was 10 points and using a distribution-based method was 6 points. For the QOLCE-16, the MCID obtained using an anchor-based method was 13 points and using a distribution-based method was 7 points.</p><p><strong>Significance: </strong>This is the first study to estimate MCID values for the QOLCE-55 and the QOLCE-16. It has been well documented that CWE are at risk of experiencing psychological, behavioral, and cognitive impairments, which can negatively impact their HRQOL. Reporting MCID values for the QOLCE-55 and QOLCE-16 is important in determining whether changes in HRQOL observed are meaningful to CWE themselves, as a key factor in shaping the nature of epilepsy care delivered.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Longitudinal evaluation of retinal neuroaxonal loss in epilepsy using optical coherence tomography. 利用光学相干断层扫描对癫痫患者视网膜神经轴突缺失情况进行纵向评估。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-09 DOI: 10.1111/epi.18139
Livia Stauner, Han Bao, Luisa Delazer, Isabel Kirsch, Tara Christmann, Soheyl Noachtar, Joachim Havla, Michael Lauseker, Elisabeth Kaufmann

Objective: People with epilepsy (PwE) suffer from progressive brain atrophy, which is reflected as neuroaxonal loss on the retinal level. This study aims to provide initial insight into the longitudinal dynamics of the retinal neuroaxonal loss and possible driving factors.

Methods: PwE and healthy controls (HC; 18-55 years of age) underwent spectral domain optical coherence tomography at baseline and 7.0 ± 1.5 and 6.7 ± 1.0 months later, respectively. The change in retinal thickness/volume and annualized percentage change (APC) were calculated for the peripapillary retinal nerve fiber layer (pRNFL), the macular RNFL (mRNFL), the ganglion cell inner plexiform layer (GCIP), the inner nuclear layer, and the total macular volume (TMV). Group comparisons and multiple linear models with stepwise backward selection were performed to evaluate associations with demographic and clinical parameters.

Results: PwE (n = 44, 21 females, mean age = 35.6 ± 10.9 years) revealed a significant decrease in the pRNFL, mRNFL, GCIP, and TMV thickness or volume in the study interval. When compared to HC (n = 56, 37 females, mean age = 32.7 ± 8.3 years), the APC of the pRNFL (-.98 ± 3.13%/year) and the GCIP (-1.24 ± 2.56%/year) were significantly more pronounced in PwE (p = .01 and p = .046, respectively). Of note, atrophy of the mRNFL was significantly influenced by the number of antiseizure medications (ASMs; p = .047) and increasing age of PwE (p = .03). Contradictory results, however, were revealed for the impact of seizures.

Significance: In epilepsy, progression of retinal neuroaxonal loss was already detectable at short-term follow-up. PwE who receive a high number of ASMs seem to be at risk for accelerated neuroaxonal loss, stressing the importance of well-considered and effective antiseizure therapy.

目的:癫痫患者(PwE)患有进行性脑萎缩,这种萎缩反映为视网膜神经轴突的缺失。本研究旨在初步了解视网膜神经轴突丢失的纵向动态变化以及可能的驱动因素:方法:患者和健康对照组(HC;18-55 岁)分别在基线和 7.0 ± 1.5 个月后及 6.7 ± 1.0 个月后接受光谱域光学相干断层扫描。计算了毛细血管周围视网膜神经纤维层 (pRNFL)、黄斑 RNFL (mRNFL)、神经节细胞丛状内层 (GCIP)、核内层和黄斑总体积 (TMV) 的视网膜厚度/体积变化和年化百分比变化 (APC)。通过分组比较和逐步后向选择的多重线性模型来评估与人口统计学和临床参数之间的关联:PwE(n = 44,21 名女性,平均年龄 = 35.6 ± 10.9 岁)的 pRNFL、mRNFL、GCIP 和 TMV 厚度或体积在研究期间显著下降。与 HC(n = 56,37 名女性,平均年龄 = 32.7 ± 8.3 岁)相比,PwE 的 pRNFL(-.98 ± 3.13%/年)和 GCIP(-1.24 ± 2.56%/年)的 APC 明显更明显(分别为 p = .01 和 p = .046)。值得注意的是,mRNFL 的萎缩受到抗癫痫药物(ASMs)的数量(p = .047)和 PwE 年龄增加(p = .03)的显著影响。然而,在癫痫发作的影响方面却出现了相互矛盾的结果:重要意义:在癫痫患者中,视网膜神经轴突丢失的进展在短期随访中已经可以检测到。接受大量 ASM 的癫痫患者似乎面临着神经轴突加速丧失的风险,这强调了经过深思熟虑的有效抗癫痫治疗的重要性。
{"title":"Longitudinal evaluation of retinal neuroaxonal loss in epilepsy using optical coherence tomography.","authors":"Livia Stauner, Han Bao, Luisa Delazer, Isabel Kirsch, Tara Christmann, Soheyl Noachtar, Joachim Havla, Michael Lauseker, Elisabeth Kaufmann","doi":"10.1111/epi.18139","DOIUrl":"https://doi.org/10.1111/epi.18139","url":null,"abstract":"<p><strong>Objective: </strong>People with epilepsy (PwE) suffer from progressive brain atrophy, which is reflected as neuroaxonal loss on the retinal level. This study aims to provide initial insight into the longitudinal dynamics of the retinal neuroaxonal loss and possible driving factors.</p><p><strong>Methods: </strong>PwE and healthy controls (HC; 18-55 years of age) underwent spectral domain optical coherence tomography at baseline and 7.0 ± 1.5 and 6.7 ± 1.0 months later, respectively. The change in retinal thickness/volume and annualized percentage change (APC) were calculated for the peripapillary retinal nerve fiber layer (pRNFL), the macular RNFL (mRNFL), the ganglion cell inner plexiform layer (GCIP), the inner nuclear layer, and the total macular volume (TMV). Group comparisons and multiple linear models with stepwise backward selection were performed to evaluate associations with demographic and clinical parameters.</p><p><strong>Results: </strong>PwE (n = 44, 21 females, mean age = 35.6 ± 10.9 years) revealed a significant decrease in the pRNFL, mRNFL, GCIP, and TMV thickness or volume in the study interval. When compared to HC (n = 56, 37 females, mean age = 32.7 ± 8.3 years), the APC of the pRNFL (-.98 ± 3.13%/year) and the GCIP (-1.24 ± 2.56%/year) were significantly more pronounced in PwE (p = .01 and p = .046, respectively). Of note, atrophy of the mRNFL was significantly influenced by the number of antiseizure medications (ASMs; p = .047) and increasing age of PwE (p = .03). Contradictory results, however, were revealed for the impact of seizures.</p><p><strong>Significance: </strong>In epilepsy, progression of retinal neuroaxonal loss was already detectable at short-term follow-up. PwE who receive a high number of ASMs seem to be at risk for accelerated neuroaxonal loss, stressing the importance of well-considered and effective antiseizure therapy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Health utilities of patients with epilepsy in a Canadian population. 加拿大癫痫患者的健康效用。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-07 DOI: 10.1111/epi.18132
Olayinka I Arimoro, Samuel Wiebe, Chantelle Q Y Lin, Colin B Josephson, Tolulope T Sajobi

Objective: Health state utilities are required to obtain quality adjusted life years, a common metric that informs clinical decision-making at individual, group, and health policy levels. Health state utilities are different from health-related quality of life, and their distribution across patients with epilepsy, as well as the factors that impact them, have not been studied in depth. We aimed to describe the distribution of health state utilities in people with epilepsy and the impact of different combinations of clinical and demographic factors on health state evaluation.

Methods: We performed a retrospective analysis of patients' data prospectively collected in the Calgary Comprehensive Epilepsy Program registry. Patient-reported health state utilities were measured using the 5-level EuroQol 5-Dimension scale (EQ-5D-5L) completed at their initial assessment. EQ-5D-5L index scores were derived via the time trade-off approach based on Canadian norms, and their distribution across different health states and patient characteristics was obtained. The Tobit regression model was used to evaluate the determinants of EQ-5D-5L index scores.

Results: Of 1446 patients included in this analysis, 724 (50.5%) were female. The median (interquartile range) Canada-normed EQ-5D-5L index score was .87 (.71-.91). Patients with significantly lower health utilities were more likely to be female (p = .008), to be older (p = .034), to be unmarried (p = .013), to have failed to achieve 1-year seizure freedom (p < .001), to have no postsecondary education (p = .028), to be depressed (p < .001), to have antiseizure medication side effects (p = .001), to be unemployed (p < .001), and to be unable to drive (p < .001). A look-up table of health utilities based on combinations of clinical-demographic characteristics was produced.

Significance: Health utility estimates for combinations of different health states in people with epilepsy attending specialty clinics are now available. These can help guide clinical decision-making in routine clinical practice, economic evaluations of treatment interventions, and health care policies.

目的:健康状态效用是获得质量调整生命年的必要条件,质量调整生命年是一种通用指标,可为个人、群体和卫生政策层面的临床决策提供依据。健康状态效用不同于健康相关生活质量,其在癫痫患者中的分布以及影响因素尚未得到深入研究。我们旨在描述癫痫患者健康状态效用的分布情况,以及临床和人口学因素的不同组合对健康状态评估的影响:我们对卡尔加里综合癫痫计划登记处前瞻性收集的患者数据进行了回顾性分析。患者报告的健康状况效用采用患者初次评估时填写的五级EuroQol 5维量表(EQ-5D-5L)进行测量。EQ-5D-5L指数得分是根据加拿大标准通过时间权衡法得出的,其在不同健康状况和患者特征中的分布情况也是根据加拿大标准得出的。采用 Tobit 回归模型评估 EQ-5D-5L 指数得分的决定因素:结果:在纳入分析的 1446 名患者中,724 名(50.5%)为女性。加拿大标准化 EQ-5D-5L 指数得分的中位数(四分位间距)为 0.87(0.71-0.91)。健康效用明显较低的患者更有可能是女性(p = .008)、年龄较大(p = .034)、未婚(p = .013)、未能实现 1 年癫痫发作自由(p 有意义:现在已经有了在专科门诊就诊的癫痫患者不同健康状况组合的健康效用估计值。这些数据有助于指导常规临床实践中的临床决策、治疗干预的经济评估以及医疗保健政策。
{"title":"Health utilities of patients with epilepsy in a Canadian population.","authors":"Olayinka I Arimoro, Samuel Wiebe, Chantelle Q Y Lin, Colin B Josephson, Tolulope T Sajobi","doi":"10.1111/epi.18132","DOIUrl":"https://doi.org/10.1111/epi.18132","url":null,"abstract":"<p><strong>Objective: </strong>Health state utilities are required to obtain quality adjusted life years, a common metric that informs clinical decision-making at individual, group, and health policy levels. Health state utilities are different from health-related quality of life, and their distribution across patients with epilepsy, as well as the factors that impact them, have not been studied in depth. We aimed to describe the distribution of health state utilities in people with epilepsy and the impact of different combinations of clinical and demographic factors on health state evaluation.</p><p><strong>Methods: </strong>We performed a retrospective analysis of patients' data prospectively collected in the Calgary Comprehensive Epilepsy Program registry. Patient-reported health state utilities were measured using the 5-level EuroQol 5-Dimension scale (EQ-5D-5L) completed at their initial assessment. EQ-5D-5L index scores were derived via the time trade-off approach based on Canadian norms, and their distribution across different health states and patient characteristics was obtained. The Tobit regression model was used to evaluate the determinants of EQ-5D-5L index scores.</p><p><strong>Results: </strong>Of 1446 patients included in this analysis, 724 (50.5%) were female. The median (interquartile range) Canada-normed EQ-5D-5L index score was .87 (.71-.91). Patients with significantly lower health utilities were more likely to be female (p = .008), to be older (p = .034), to be unmarried (p = .013), to have failed to achieve 1-year seizure freedom (p < .001), to have no postsecondary education (p = .028), to be depressed (p < .001), to have antiseizure medication side effects (p = .001), to be unemployed (p < .001), and to be unable to drive (p < .001). A look-up table of health utilities based on combinations of clinical-demographic characteristics was produced.</p><p><strong>Significance: </strong>Health utility estimates for combinations of different health states in people with epilepsy attending specialty clinics are now available. These can help guide clinical decision-making in routine clinical practice, economic evaluations of treatment interventions, and health care policies.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antiepileptic drugs, folate one-carbon metabolism, genetics, and epigenetics: Congenital, developmental, and neuropsychological risks and antiepileptic action. 抗癫痫药物、叶酸一碳代谢、遗传学和表观遗传学:先天、发育和神经心理学风险与抗癫痫作用。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-07 DOI: 10.1111/epi.18120
Edward H Reynolds
{"title":"Antiepileptic drugs, folate one-carbon metabolism, genetics, and epigenetics: Congenital, developmental, and neuropsychological risks and antiepileptic action.","authors":"Edward H Reynolds","doi":"10.1111/epi.18120","DOIUrl":"https://doi.org/10.1111/epi.18120","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of epileptic seizures on the quality of biosignals recorded from wearables. 癫痫发作对可穿戴设备记录的生物信号质量的影响。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-07 DOI: 10.1111/epi.18138
Sebastian Böttcher, Nicolas Zabler, Michele Jackson, Elisa Bruno, Andrea Biondi, Nino Epitashvili, Solveig Vieluf, Matthias Dümpelmann, Mark P Richardson, Benjamin H Brinkmann, Tobias Loddenkemper, Andreas Schulze-Bonhage

Objective: Wearable nonelectroencephalographic biosignal recordings captured from the wrist offer enormous potential for seizure monitoring. However, signal quality remains a challenging factor affecting data reliability. Models trained for seizure detection depend on the quality of recordings in peri-ictal periods in performing a feature-based separation of ictal periods from interictal periods. Thus, this study aims to investigate the effect of epileptic seizures on signal quality, ensuring accurate and reliable monitoring.

Methods: This study assesses the signal quality of wearable data during peri-ictal phases of generalized tonic-clonic and focal to bilateral tonic-clonic seizures (TCS), focal motor seizures (FMS), and focal nonmotor seizures (FNMS). We evaluated accelerometer (ACC) activity and the signal quality of electrodermal activity (EDA) and blood volume pulse (BVP) data. Additionally, we analyzed the influence of peri-ictal movements as assessed by ACC (ACC activity) on signal quality and examined intraictal subphases of focal to bilateral TCS.

Results: We analyzed 386 seizures from 111 individuals in three international epilepsy monitoring units. BVP signal quality and ACC activity levels differed between all seizure types. We found the largest decrease in BVP signal quality and increase in ACC activity when comparing the ictal phase to the pre- and postictal phases for TCS. Additionally, ACC activity was strongly negatively correlated with BVP signal quality for TCS and FMS, and weakly for FNMS. Intraictal analysis revealed that tonic and clonic subphases have the lowest BVP signal quality and the highest ACC activity.

Significance: Motor elements of seizures significantly impair BVP signal quality, but do not have significant effect on EDA signal quality, as assessed by wrist-worn wearables. The results underscore the importance of signal quality assessment methods and careful selection of robust modalities to ensure reliable seizure detection. Future research is needed to explain whether seizure detection models' decisions are based on signal responses induced by physiological processes as opposed to artifacts.

目的:从手腕采集的可穿戴式非脑电图生物信号记录为癫痫发作监测提供了巨大的潜力。然而,信号质量仍然是影响数据可靠性的一个挑战性因素。在对发作期和发作间期进行基于特征的分离时,为癫痫发作检测而训练的模型依赖于发作周期的记录质量。因此,本研究旨在调查癫痫发作对信号质量的影响,确保准确可靠的监测:本研究评估了全身强直-阵挛发作(TCS)、局灶至双侧强直-阵挛发作(TCS)、局灶运动性发作(FMS)和局灶非运动性发作(FNMS)围发作期可穿戴数据的信号质量。我们评估了加速计 (ACC) 活动以及皮电活动 (EDA) 和血容量脉搏 (BVP) 数据的信号质量。此外,我们还分析了由 ACC 评估的发作期运动(ACC 活动)对信号质量的影响,并检查了局灶至双侧 TCS 的发作期亚相:我们分析了三个国际癫痫监测单位 111 人的 386 次癫痫发作。所有发作类型的 BVP 信号质量和 ACC 活动水平均有所不同。我们发现,当将 TCS 的发作期与发作前和发作后进行比较时,BVP 信号质量的下降幅度最大,而 ACC 活动的增加幅度最大。此外,TCS 和 FMS 的 ACC 活动与 BVP 信号质量呈强负相关,而 FNMS 的 ACC 活动与 BVP 信号质量呈弱相关。发作期分析表明,强直和阵挛亚相的 BVP 信号质量最低,而 ACC 活性最高:重要意义:根据腕戴式可穿戴设备的评估,癫痫发作的运动因素会严重影响 BVP 信号质量,但对 EDA 信号质量的影响不大。结果强调了信号质量评估方法和谨慎选择稳健模式对确保可靠的癫痫发作检测的重要性。未来的研究还需要解释癫痫发作检测模型的决策是否基于生理过程而非伪装引起的信号反应。
{"title":"Effects of epileptic seizures on the quality of biosignals recorded from wearables.","authors":"Sebastian Böttcher, Nicolas Zabler, Michele Jackson, Elisa Bruno, Andrea Biondi, Nino Epitashvili, Solveig Vieluf, Matthias Dümpelmann, Mark P Richardson, Benjamin H Brinkmann, Tobias Loddenkemper, Andreas Schulze-Bonhage","doi":"10.1111/epi.18138","DOIUrl":"10.1111/epi.18138","url":null,"abstract":"<p><strong>Objective: </strong>Wearable nonelectroencephalographic biosignal recordings captured from the wrist offer enormous potential for seizure monitoring. However, signal quality remains a challenging factor affecting data reliability. Models trained for seizure detection depend on the quality of recordings in peri-ictal periods in performing a feature-based separation of ictal periods from interictal periods. Thus, this study aims to investigate the effect of epileptic seizures on signal quality, ensuring accurate and reliable monitoring.</p><p><strong>Methods: </strong>This study assesses the signal quality of wearable data during peri-ictal phases of generalized tonic-clonic and focal to bilateral tonic-clonic seizures (TCS), focal motor seizures (FMS), and focal nonmotor seizures (FNMS). We evaluated accelerometer (ACC) activity and the signal quality of electrodermal activity (EDA) and blood volume pulse (BVP) data. Additionally, we analyzed the influence of peri-ictal movements as assessed by ACC (ACC activity) on signal quality and examined intraictal subphases of focal to bilateral TCS.</p><p><strong>Results: </strong>We analyzed 386 seizures from 111 individuals in three international epilepsy monitoring units. BVP signal quality and ACC activity levels differed between all seizure types. We found the largest decrease in BVP signal quality and increase in ACC activity when comparing the ictal phase to the pre- and postictal phases for TCS. Additionally, ACC activity was strongly negatively correlated with BVP signal quality for TCS and FMS, and weakly for FNMS. Intraictal analysis revealed that tonic and clonic subphases have the lowest BVP signal quality and the highest ACC activity.</p><p><strong>Significance: </strong>Motor elements of seizures significantly impair BVP signal quality, but do not have significant effect on EDA signal quality, as assessed by wrist-worn wearables. The results underscore the importance of signal quality assessment methods and careful selection of robust modalities to ensure reliable seizure detection. Future research is needed to explain whether seizure detection models' decisions are based on signal responses induced by physiological processes as opposed to artifacts.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Matrix-assisted laser desorption/ionization mass spectrometry imaging as a new tool for molecular histopathology in epilepsy surgery. 基质辅助激光解吸电离质谱成像是癫痫手术中分子组织病理学的新工具。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-05 DOI: 10.1111/epi.18136
Cinzia Cagnoli, Dalia De Santis, Claudio Caccia, Italia Bongarzone, Giulia Capitoli, Laura Rossini, Michele Rizzi, Francesco Deleo, Laura Tassi, Marco de Curtis, Rita Garbelli

Objective: Epilepsy surgery is a treatment option for patients with seizures that do not respond to pharmacotherapy. The histopathological characterization of the resected tissue has an important prognostic value to define postoperative seizure outcome in these patients. However, the diagnostic classification process based on microscopic assessment remains challenging, particularly in the case of focal cortical dysplasia (FCD). Imaging mass spectrometry is a spatial omics technique that could improve tissue phenotyping and patient stratification by investigating hundreds of biomolecules within a single tissue sample, without the need for target-specific reagents.

Methods: An in situ proteomic technique called matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is here investigated as a potential new tool to expand conventional diagnosis on standard paraffin brain tissue sections. Unsupervised and region of interest-based MALDI-MSI analyses of sections from 10 FCD type IIb (FCDIIb) cases were performed, and the results were validated by immunohistochemistry.

Results: MALDI-MSI identified distinct histopathological features and the boundaries of the dysplastic lesion. The capability to visualize the spatial distribution of well-known diagnostic markers enabling multiplex measurements on single tissue sections was demonstrated. Finally, a fingerprint list of potential discriminant peptides that distinguish FCD core from peri-FCD tissue was generated.

Significance: This is the first study that explores the potential application of MALDI-MSI in epilepsy postsurgery fixed tissue, by utilizing the well-characterized FCDIIb features as a model. Extending these preliminary analyses to a larger cohort of patients will generate spectral libraries of molecular signatures that discriminate tissue features and will contribute to patient phenotyping.

目的:癫痫手术是药物治疗无效的癫痫患者的一种治疗选择。切除组织的组织病理学特征对于确定这些患者术后癫痫发作的预后具有重要价值。然而,基于显微镜评估的诊断分类过程仍具有挑战性,尤其是在局灶性皮质发育不良(FCD)的情况下。成像质谱是一种空间全息技术,可通过研究单个组织样本中的数百种生物大分子来改善组织表型和患者分层,而无需靶向特异性试剂:方法:本文研究了一种名为基质辅助激光解吸电离质谱成像(MALDI-MSI)的原位蛋白质组学技术,将其作为一种潜在的新工具来扩展标准石蜡脑组织切片的常规诊断。研究人员对10例FCD IIb型(FCDIIb)病例的切片进行了无监督和基于兴趣区域的MALDI-MSI分析,并通过免疫组化对结果进行了验证:结果:MALDI-MSI确定了不同的组织病理学特征和发育不良病变的边界。结果表明,MALDI-MSI能识别出明显的组织病理学特征和发育不良病变的边界,并能观察到知名诊断标记物的空间分布,从而实现对单个组织切片的多重测量。最后,还生成了一份潜在的鉴别肽指纹列表,用于区分 FCD 核心组织和 FCD 周围组织:这是第一项探索 MALDI-MSI 在癫痫术后固定组织中的潜在应用的研究,它利用了特征明确的 FCDIIb 特征作为模型。将这些初步分析扩展到更大的患者群,将生成可区分组织特征的分子特征光谱库,并将有助于患者的表型分析。
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引用次数: 0
Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study 循环微RNA和isomiRs作为四种实验性癫痫模型初始损伤和癫痫发生的生物标记物:EPITARGET 研究。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-01 DOI: 10.1111/epi.18134
Erwin A. van Vliet, Mirte Scheper, James D. Mills, Noora Puhakka, Kinga Szydlowska, Manuela Ferracin, Francesca Lovisari, Marie Soukupova, Silvia Zucchini, Prashant K. Srivastava, Michael R. Johnson, Katarzyna Lukasiuk, Jan A. Gorter, Eleonora Aronica, Asla Pitkänen, Michele Simonato

Objective

Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.

Methods

Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long-term video-electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome-wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers.

Results

Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model-specific manner. One miRNA, miR-3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, p < .05).

Significance

Identified plasma miRNAs and isomiRs are mostly etiology-specific rather than common prognostic biomarkers of epileptogenesis. These data imply that in preclinical and clinical studies, it may be necessary to identify specific biomarkers for different epilepsy etiologies. Importantly, circulating miRNAs like miR-3085 with high negative predictive value for epileptogenesis in different etiologies could be useful candidates for initial screening purposes of epileptogenesis risk.

目的:结构性癫痫可在最初的致痫损伤发生后数月或数年才出现,因此适合进行二级预防。然而,由于缺乏生物标志物来识别致痫损伤后患痫风险最高的人群,预防性治疗的开发一直面临挑战:方法:研究了四种不同的癫痫发生大鼠模型,以确定作为癫痫发生生物标志物的不同表达的循环微RNA(miRNA)和isomiR图谱。利用全基因组小RNA测序平台,以无监督方式鉴定和测量了miRNA和isomiRs。对推测的生物标志物的性能进行了接收者操作特征分析:结果:致痫损伤两天后,血浆中几种miRNA和isomiRs水平的改变以模型特异性的方式预测了癫痫的发生。一种 miRNA,即 miR-3085,作为癫痫发生的预后生物标志物,在所有四种模型中都显示出良好的灵敏度(但特异性较低)(曲线下面积 = .729,灵敏度 = 83%,特异性 = 64%,p 意义重大:鉴定出的血浆 miRNA 和 isomiRs 大多是癫痫发生的病因特异性生物标志物,而不是常见的预后生物标志物。这些数据表明,在临床前和临床研究中,可能有必要针对不同的癫痫病因确定特定的生物标志物。重要的是,循环 miRNA(如 miR-3085)对不同病因的癫痫发生具有较高的阴性预测值,可作为癫痫发生风险初步筛查的有用候选指标。
{"title":"Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study","authors":"Erwin A. van Vliet,&nbsp;Mirte Scheper,&nbsp;James D. Mills,&nbsp;Noora Puhakka,&nbsp;Kinga Szydlowska,&nbsp;Manuela Ferracin,&nbsp;Francesca Lovisari,&nbsp;Marie Soukupova,&nbsp;Silvia Zucchini,&nbsp;Prashant K. Srivastava,&nbsp;Michael R. Johnson,&nbsp;Katarzyna Lukasiuk,&nbsp;Jan A. Gorter,&nbsp;Eleonora Aronica,&nbsp;Asla Pitkänen,&nbsp;Michele Simonato","doi":"10.1111/epi.18134","DOIUrl":"10.1111/epi.18134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long-term video-electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome-wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model-specific manner. One miRNA, miR-3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, <i>p</i> &lt; .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Identified plasma miRNAs and isomiRs are mostly etiology-specific rather than common prognostic biomarkers of epileptogenesis. These data imply that in preclinical and clinical studies, it may be necessary to identify specific biomarkers for different epilepsy etiologies. Importantly, circulating miRNAs like miR-3085 with high negative predictive value for epileptogenesis in different etiologies could be useful candidates for initial screening purposes of epileptogenesis risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 11","pages":"3406-3420"},"PeriodicalIF":6.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Epilepsia
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