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Eating habits and behaviors in children with Dravet syndrome: A case-control study. 德雷维综合征患儿的饮食习惯和行为:病例对照研究
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-06 DOI: 10.1111/epi.18179
Alexandra Laliberté, Lyna Siafa, Arij Soufi, Christelle Dassi, Sophie J Russ-Hall, Ingrid E Scheffer, Kenneth A Myers

This study evaluated food preferences and eating behaviors of individuals with Dravet syndrome. Patients diagnosed with Dravet syndrome were recruited, as well as a control group composed of siblings of patients with epilepsy (any form). The Food Preference Questionnaire and the Child Eating Behavior Questionnaire were completed by caregivers along with two open-ended questions regarding eating challenges. Seventy-eight participants (45 with Dravet syndrome and 33 controls) were included. Compared to controls, mean scores for food preference were lower for fruits (p = .000099), meats and fish (p = .00094), and snacks (p = .000027) in Dravet syndrome. People with Dravet syndrome also had less emotional overeating (p = .0085) and food enjoyment (p = .0012), but more slowness in eating (p = .00021) and food fussiness (p = .0064). In a subgroup analysis of only pediatric (age <18 years) patients, similar results were observed for both food preferences and eating habits. In qualitative data, caregivers most commonly reported difficulties with fixation on specific foods. This study demonstrates specific food preferences and challenging eating behaviors in individuals with Dravet syndrome. These data provide potential avenues for nutritional interventions and behavioral therapies to increase the quality of life of patients and their families.

本研究评估了德雷维综合征患者的食物偏好和饮食行为。研究人员招募了被确诊患上德拉维特综合征的患者,以及由癫痫患者(任何形式)的兄弟姐妹组成的对照组。照顾者填写了食物偏好问卷和儿童进食行为问卷,以及两个有关进食挑战的开放式问题。研究共纳入 78 名参与者(45 名患有德雷维综合征,33 名为对照组)。与对照组患者相比,患有本病的患者对水果(p = .000099)、肉类和鱼类(p = .00094)以及零食(p = .000027)的食物偏好平均得分较低。此外,患有本病的人情绪暴饮暴食(p = .0085)和享受食物(p = .0012)的情况较少,但进食缓慢(p = .00021)和对食物大惊小怪(p = .0064)的情况较多。在一项分组分析中,只有儿童(年龄
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引用次数: 0
Histopathological substrate of increased T2 signal in the anterior temporal lobe white matter in temporal lobe epilepsy associated with hippocampal sclerosis. 与海马硬化相关的颞叶癫痫前颞叶白质中 T2 信号增加的组织病理学基础。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-06 DOI: 10.1111/epi.18162
Ricardo C Wainberg, William Alves Martins, Francine H de Oliveira, Eliseu Paglioli, Ricardo Paganin, Ricardo Soder, Rafael Paglioli, Thomas M Frigeri, Matteo Baldisseroto, André Palmini

Objective: This study was undertaken to analyze the histology underlying increased T2 signal intensity (iT2SI) in anterior temporal lobe white matter (aTLWM) epilepsy due to hippocampal sclerosis (TLE/HS).

Methods: Twenty-three patients were included: 16 with increased T2 signal in the aTLWM and seven with HS only. Magnetic resonance imaging (MRI) findings were consistent across two neuroradiologists (kappa = .89, p < .001). Quantification of neuronal cells, astrocytes, oligodendrocytes, and vacuolization in the white matter of temporal lobe specimens was performed by immunohistochemistry (neuronal nuclear antigen, glial fibrillary acidic protein, oligodendrocyte transcription factor, and basic myelin protein, respectively). Surgical specimens from TLE/HS patients with and without iT2SI in the aTLWM were compared. Samples of aTLWM were divided into three groups, according to MRI features: G1 = samples of iT2SI, G2 = samples with normal T2 signal intensity from patients without white matter imaging abnormalities, and G3 = samples with normal T2 signal intensity adjacent to areas with iT2SI.

Results: Patients with increased T2 signal had a significantly younger age at epilepsy onset (p < .035). Histological analysis revealed a higher percentage of vacuolar area in these patients (p < .004) along with a lower number of ectopic neurons (p = .042). No significant differences were found in astrocyte or oligodendrocyte counts among groups.

Significance: A higher proportion of vacuoles in regions with iT2SI may be the histopathologic substrate of this signal alteration in the white matter of the temporal lobe in patients with TLE/HS. This method of quantifying vacuoles using digital image analysis proved reliable and cost-effective.

研究目的本研究旨在分析海马硬化导致的前颞叶白质(aTLWM)癫痫(TLE/HS)T2信号强度增加(iT2SI)的组织学基础:纳入23名患者:方法:共纳入23名患者:16名aTLWM中T2信号增高的患者和7名仅患有HS的患者。两名神经放射学专家的磁共振成像(MRI)结果一致(kappa = .89,p 结果:T2信号增高的患者的T2信号比TLE/HS患者的T2信号高:T2信号增高的患者癫痫发病年龄明显较小(p 有意义:iT2SI区域空泡比例较高可能是TLE/HS患者颞叶白质信号改变的组织病理学基础。事实证明,这种利用数字图像分析量化空泡的方法既可靠又经济。
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引用次数: 0
Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study. 耐药性癫痫的血脑屏障功能障碍成像:多中心可行性研究
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-06 DOI: 10.1111/epi.18145
Nir Cafri, Sheida Mirloo, Daniel Zarhin, Lyna Kamintsky, Yonatan Serlin, Laith Alhadeed, Ilan Goldberg, Mark A Maclean, Ben Whatley, Ilia Urman, Colin P Doherty, Chris Greene, Claire Behan, Declan Brennan, Matthew Campbell, Chris Bowen, Gal Ben-Arie, Ilan Shelef, Britta Wandschneider, Matthias Koepp, Alon Friedman, Felix Benninger

Objective: Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals.

Methods: We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls.

Results: Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10).

Significance: These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

目的:血脑屏障功能障碍(BBBD)与包括癫痫在内的多种神经系统疾病有关。本研究旨在利用动态对比增强磁共振成像(DCE-MRI)来识别和比较癫痫患者(PWE)和健康人存在血脑屏障功能障碍的脑区:我们使用 DCE-MRI 扫描了来自全球四个专业癫痫中心的 50 名耐药性癫痫 (DRE) 患者和 58 名对照组参与者。方法:我们使用 DCE-MRI 扫描了来自全球四个专业癫痫中心的 50 名耐药性癫痫患者和 58 名对照组参与者,分析并比较了 PWE 和健康对照组之间 BBBD 的存在和程度:结果:与健康对照组相比,PWE 患者的脑容量更大,具有 BBBD 的脑区数量更多(p -7)。在被诊断为局灶性癫痫发作或全身性癫痫的患者中,尽管受影响的区域不同,但未观察到伴有BBBD的总脑容量存在差异。与无病变病例相比,有磁共振成像可见病灶的PWE患者有BBBD的总脑容量没有差异。82%的患者(n = 39)在怀疑与癫痫发作有关的脑区观察到了BBBD,并且通常在怀疑致痫病灶(n = 10)所在、邻近和/或同一半球中发现:这些研究结果与临床前研究一致,临床前研究强调了 BBBD 在 DRE 发病中的作用,并将稳定微血管确定为一种潜在的治疗策略。
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引用次数: 0
Long-term neuroplasticity in language networks after anterior temporal lobe resection. 前颞叶切除术后语言网络的长期神经可塑性。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-06 DOI: 10.1111/epi.18147
Maria Sablik, Marine N Fleury, Lawrence P Binding, David P Carey, Giovanni d'Avossa, Sallie Baxendale, Gavin P Winston, John S Duncan, Meneka K Sidhu

Objective: Anterior temporal lobe resection (ATLR) is an effective treatment for drug-resistant temporal lobe epilepsy (TLE), although language deficits may occur after both left and right ATLR. Functional reorganization of the language network has been observed in the ipsilateral and contralateral hemispheres within 12 months after ATLR, but little is known of longer-term plasticity effects. Our aim was to examine the plasticity of language functions up to a decade after ATLR, in relation to cognitive profiles.

Methods: We examined 24 TLE patients (12 left [LTLE]) and 10 controls across four time points: pre-surgery, 4 months, 12 months, and ~9 years post-ATLR. Participants underwent standard neuropsychological assessments (naming, phonemic, and categorical fluency tests) and a verbal fluency functional magnetic resonance imaging (fMRI) task. Using a flexible factorial design, we analyzed longitudinal fMRI activations from 12 months to ~9 years post-ATLR, relative to controls, with separate analyses for people with hippocampal sclerosis (HS). Change in cognitive profiles was correlated with the long-term change in fMRI activations to determine the "efficiency" of reorganized networks.

Results: LTLE patients had increased long-term engagement of the left extra-temporal and contralateral temporal regions, with better language performance linked to bilateral activation. Those with HS exhibited more widespread bilateral activations. RTLE patients showed plasticity in the left extra-temporal regions, with better language outcomes associated with these areas. Both groups of patients achieved cognitive stability over 9 years, with more than 50% of LTLE patients improving. Older age, longer epilepsy duration, and lower pre-operative cognitive reserve negatively affected long-term language performance.

Significance: Neuroplasticity continues for up to ~9 years post-epilepsy surgery in LTLE and RTLE, with effective language recovery linked to bilateral engagement of temporal and extra-temporal regions. This adaptive reorganization is associated with improved cognitive outcomes, challenging the traditional view of localized surgery effects. These findings emphasize the need for early intervention, tailored pre-operative counseling, and the potential for continued cognitive gains with extended post-ATLR rehabilitation.

目的:前颞叶切除术(ATLR)是治疗耐药性颞叶癫痫(TLE)的有效方法,但左右颞叶切除术后都可能出现语言障碍。在ATLR术后12个月内,同侧和对侧大脑半球都观察到了语言网络的功能重组,但对长期的可塑性影响却知之甚少。我们的目的是研究 ATLR 后十年内语言功能的可塑性与认知特征的关系:我们对 24 名 TLE 患者(12 名左侧患者 [LTLE])和 10 名对照组患者进行了检查,共分为四个时间点:ATLR 术前、术后 4 个月、术后 12 个月和术后约 9 年。受试者接受了标准的神经心理学评估(命名、音位和分类流利性测试)和言语流利性功能磁共振成像(fMRI)任务。我们采用灵活的因子设计,分析了ATLR后12个月至约9年期间相对于对照组的纵向fMRI激活情况,并对海马硬化症(HS)患者进行了单独分析。认知概况的变化与fMRI激活的长期变化相关联,以确定重组网络的 "效率":结果:LTLE 患者左侧颞外和对侧颞区的长期参与度增加,语言能力的提高与双侧激活有关。HS患者则表现出更广泛的双侧激活。RTLE患者的左侧颞外区域表现出可塑性,语言成绩的提高与这些区域有关。两组患者的认知能力在9年内都趋于稳定,其中超过50%的LTLE患者的认知能力有所改善。年龄越大、癫痫持续时间越长、术前认知储备越低,对长期语言表现的影响越不利:LTLE和RTLE患者在癫痫手术后的神经可塑性可持续长达约9年,语言的有效恢复与颞区和颞外区的双侧参与有关。这种适应性重组与认知结果的改善有关,挑战了手术局部效应的传统观点。这些发现强调了早期干预、量身定制的术前咨询的必要性,以及通过延长ATLR术后康复来继续提高认知能力的潜力。
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引用次数: 0
Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy. 预测新生儿缺氧缺血性脑病初期发作的机器学习。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-04 DOI: 10.1111/epi.18163
Danilo Bernardo, Jonathan Kim, Marie-Coralie Cornet, Adam L Numis, Aaron Scheffler, Vikram R Rao, Edilberto Amorim, Hannah C Glass

Objective: This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features.

Methods: We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions.

Results: The UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power.

Significance: This study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.

研究目的本研究旨在开发一种机器学习(ML)模型,利用临床和定量脑电图(QEEG)特征预测新生儿缺氧缺血性脑病(HIE)的初始癫痫发作:我们开发了一种梯度提升 ML 模型(Neo-GB),利用临床特征和 QEEG 预测随时间变化的癫痫发作风险。临床变量包括脐带血气值、Apgar 评分、胎龄、经后年龄 (PMA)、产后年龄和出生体重。QEEG 特征包括统计矩、频谱功率和复发量化分析 (RQA) 特征。我们在加州大学旧金山分校(UCSF)的新生儿 HIE 数据集上对 Neo-GB 进行了训练和评估,并利用科克大学和赫尔辛基大学医院公开提供的新生儿脑电图(EEG)数据集对训练进行了补充。我们通过诊断性能指标和接收器工作特征曲线下的事件/动态面积(iAUC)分析,评估了 Neo-GB 在提供动态和静态预测方面的性能。对模型进行了解释,以评估 QEEG 特征和通道对模型预测的贡献:加州大学旧金山分校的数据集包括 60 名患有 HIE 的新生儿(30 名患有癫痫发作)。在脑电图开始后 30 分钟的受试者级静态预测中,无时间依赖特征的基线 Neo-GB 的接收器操作特征曲线下面积 (AUROC) 为 0.76,而有时间依赖特征的 Neo-GB 的接收器操作特征曲线下面积 (AUROC) 为 0.89。在对 24 小时发作发生期内的初始发作进行时间依赖性评估时,使用 Neo-GB 进行动态预测的中位 iAUC = .79(四分位距 [IQR] .75-.82)和一致性指数 (C-index) = .82,而 30 分钟的基线静态预测的中位 iAUC = .75(四分位距 [IQR] .72-.76)和 C-index = .69。模型解释分析表明,频谱功率、PMA、RQA 和脐带血气体值对 Neo-GB 预测的贡献最大。在最有影响力的脑电图通道中,随着发作前期向最终发作的推进,宽带频谱功率呈上升趋势:本研究展示了一种结合 QEEG 和临床特征的多重多重模式,可预测新生儿 HIE 中随时间变化的初始癫痫发作风险。频谱功率演变是新生儿 HIE 癫痫发作风险的早期脑电图标记。
{"title":"Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.","authors":"Danilo Bernardo, Jonathan Kim, Marie-Coralie Cornet, Adam L Numis, Aaron Scheffler, Vikram R Rao, Edilberto Amorim, Hannah C Glass","doi":"10.1111/epi.18163","DOIUrl":"https://doi.org/10.1111/epi.18163","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features.</p><p><strong>Methods: </strong>We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions.</p><p><strong>Results: </strong>The UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power.</p><p><strong>Significance: </strong>This study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567118","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
Distinct comorbidity phenotypes among post-9/11 Veterans with epilepsy are linked to diverging outcomes and mortality risks. 9/11事件后退伍军人癫痫患者不同的合并症表型与不同的治疗结果和死亡风险有关。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1111/epi.18170
Mary Jo Pugh, Heidi Munger Clary, Madeleine Myers, Eamonn Kennedy, Megan Amuan, Alicia A Swan, Sidney Hinds, W Curt LaFrance, Hamada Altalib, Alan Towne, Amy Henion, Abigail White, Christine Baca, Chen-Pin Wang

Objective: To investigate phenotypes of comorbidity before and after an epilepsy diagnosis in a national cohort of post-9/11 Service Members and Veterans and explore phenotypic associations with mortality.

Methods: Among a longitudinal cohort of Service Members and Veterans receiving care in the Veterans Health Administration (VHA) from 2002 to 2018, annual diagnoses for 26 conditions associated with epilepsy were collected over 5 years, ranging from 2 years prior to 2 years after the year of first epilepsy diagnosis. Latent class analysis (LCA) was used to identify probabilistic comorbidity phenotypes with distinct health trajectories. Descriptive statistics were used to describe the characteristics of each phenotype. Fine and Gray cause-specific survival models were used to measure mortality outcomes for each phenotype up to 2021.

Results: Six distinct phenotypes were identified: (1) relatively healthy, (2) post-traumatic stress disorder, (3) anxiety and depression, (4) chronic disease, (5) bipolar/substance use disorder, and (6) polytrauma. Accidents were the most common cause of death overall, followed by suicide/mental health and cancer, respectively. Each phenotype exhibited unique associations with mortality and cause of death, highlighting the differential impact of comorbidity patterns on patient outcomes.

Significance: By delineating clinically meaningful epilepsy comorbidity phenotypes, this study offers a framework for clinicians to tailor interventions. Moreover, these data support systems of care that facilitate treatment of epilepsy and comorbidities within an interdisciplinary health team that allows continuity of care. Targeting treatment toward patients with epilepsy who present with specific heightened risks could help mitigate adverse outcomes and enhance overall patient care.

目的调查9/11后军人和退伍军人全国队列中癫痫诊断前后的合并症表型,并探讨表型与死亡率的关联:在2002年至2018年期间接受退伍军人健康管理局(VHA)护理的军人和退伍军人纵向队列中,收集了与癫痫相关的26种疾病的年度诊断,诊断时间为首次癫痫诊断年之前2年至之后2年,历时5年。潜类分析(LCA)用于识别具有不同健康轨迹的概率合并症表型。描述性统计用于描述每种表型的特征。使用 Fine 和 Gray 病因特异性生存模型来测量每个表型直到 2021 年的死亡率结果:结果:确定了六种不同的表型:结果:确定了六种不同的表型:(1) 相对健康;(2) 创伤后应激障碍;(3) 焦虑和抑郁;(4) 慢性疾病;(5) 躁郁症/药物使用障碍;(6) 多重创伤。事故是最常见的死亡原因,其次分别是自杀/精神疾病和癌症。每种表型都与死亡率和死因有独特的关联,凸显了合并症模式对患者预后的不同影响:本研究通过划分具有临床意义的癫痫合并症表型,为临床医生提供了一个量身定制干预措施的框架。此外,这些数据还支持在跨学科医疗团队内促进癫痫和合并症治疗的护理系统,从而实现护理的连续性。对具有特定高风险的癫痫患者进行针对性治疗,有助于减轻不良后果并加强对患者的整体护理。
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引用次数: 0
Role of cholesterol in modulating brain hyperexcitability. 胆固醇在调节大脑过度兴奋中的作用
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1111/epi.18174
James W Wheless, Jong M Rho

Cholesterol is a critical molecule in the central nervous system, and imbalances in the synthesis and metabolism of brain cholesterol can result in a range of pathologies, including those related to hyperexcitability. The impact of cholesterol on disorders of epilepsy and developmental and epileptic encephalopathies is an area of growing interest. Cholesterol cannot cross the blood-brain barrier, and thus the brain synthesizes and metabolizes its own pool of cholesterol. The primary metabolic enzyme for brain cholesterol is cholesterol 24-hydroxylase (CH24H), which metabolizes cholesterol into 24S-hydroxycholesterol (24HC). Dysregulation of CH24H and 24HC can affect neuronal excitability through a range of mechanisms. 24HC is a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors and can increase glutamate release via tumor necrosis factor-α-dependent pathways. Increasing cholesterol metabolism can lead to dysfunction of excitatory amino acid transporter 2 and impair glutamate reuptake. Finally, overstimulation of NMDA receptors can further activate metabolism of cholesterol, leading to a vicious cycle of overactivation. All of these mechanisms increase extracellular glutamate and can lead to hyperexcitability. For these reasons, the cholesterol pathway represents a new potential mechanistic target for antiseizure medications. CH24H inhibition has been shown to decrease seizure behavior and improve survival in multiple animal models of epilepsy and could be a promising new mechanism of action for the treatment of neuronal hyperexcitability and developmental and epileptic encephalopathies.

胆固醇是中枢神经系统中的重要分子,大脑胆固醇合成和代谢失衡会导致一系列病症,包括与过度兴奋有关的病症。胆固醇对癫痫、发育性和癫痫性脑病的影响是一个日益受到关注的领域。胆固醇无法通过血脑屏障,因此大脑会合成和代谢自身的胆固醇池。大脑胆固醇的主要代谢酶是胆固醇 24- 羟化酶(CH24H),它将胆固醇代谢为 24S- 羟基胆固醇(24HC)。CH24H 和 24HC 的失调可通过一系列机制影响神经元的兴奋性。24HC 是 N-甲基-D-天冬氨酸(NMDA)受体的正异构调节剂,可通过肿瘤坏死因子-α 依赖性途径增加谷氨酸的释放。胆固醇代谢增加会导致兴奋性氨基酸转运体 2 功能失调,影响谷氨酸的再摄取。最后,NMDA 受体的过度刺激会进一步激活胆固醇的代谢,导致过度激活的恶性循环。所有这些机制都会增加细胞外谷氨酸,导致过度兴奋。由于这些原因,胆固醇途径成为抗癫痫药物的一个新的潜在机制靶点。在多种癫痫动物模型中,CH24H 抑制剂已被证明能减少癫痫发作行为并改善存活率,它可能成为治疗神经元过度兴奋以及发育性和癫痫性脑病的一种前景广阔的新作用机制。
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引用次数: 0
Latent cognitive phenotypes in juvenile myoclonic epilepsy: Clinical, sociodemographic, and neuroimaging associations. 青少年肌阵挛性癫痫的潜在认知表型:临床、社会人口学和神经影像学关联。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 10.1111/epi.18167
Aaron F Struck, Camille Garcia-Ramos, Vivek Prabhakaran, Veena Nair, Nagesh Adluru, Anusha Adluru, Dace Almane, Jana E Jones, Bruce P Hermann

Objective: Application of cluster analytic procedures has advanced understanding of the cognitive heterogeneity inherent in diverse epilepsy syndromes and the associated clinical and neuroimaging features. Application of this unsupervised machine learning approach to the neuropsychological performance of persons with juvenile myoclonic epilepsy (JME) has yet to be attempted, which is the intent of this investigation.

Methods: A total of 77 JME participants, 19 unaffected siblings, and 44 unrelated controls, 12 to 25 years of age, were administered a comprehensive neuropsychological battery (intelligence, language, memory, executive function, and processing speed), which was subjected to factor analysis followed by K-means clustering of the resultant factor scores. Identified cognitive phenotypes were characterized and related to clinical, family, sociodemographic, and cortical and subcortical imaging features.

Results: Factor analysis revealed three underlying cognitive dimensions (general ability, speed/response inhibition, and learning/memory), with JME participants performing worse than unrelated controls across all factor scores, and unaffected siblings performing worse than unrelated controls on the general mental ability and learning/memory factors, with no JME vs sibling differences. K-means clustering of the factor scores revealed three latent groups including above average (31.4% of participants), average (52.1%), and abnormal performance (16.4%). Participant groups differed in their distributions across the latent groups (p < 0.001), with 23% JME, 22% siblings, and 2% unrelated controls in the abnormal performance group; and 18% JME, 21% siblings, and 59% unrelated controls in the above average group. Clinical epilepsy variables were unassociated with cluster membership, whereas family factors (lower parental education) and abnormally increased thickness and/or volume in the frontal, parietal, and temporal-occipital regions were associated with the abnormal cognition group.

Significance: Distinct cognitive phenotypes characterize the spectrum of neuropsychological performance of patients with JME for which there is familial (sibling) aggregation. Phenotypic membership was associated with parental (education) and imaging characteristics (increased cortical thickness and volume) but not basic clinical seizure features.

目的:聚类分析程序的应用增进了人们对各种癫痫综合征固有的认知异质性以及相关临床和神经影像学特征的了解。将这种无监督机器学习方法应用于青少年肌阵挛性癫痫(JME)患者的神经心理学表现尚未尝试过,而这正是本次调查的目的所在:共对 77 名 12 至 25 岁的 JME 患者、19 名未受影响的兄弟姐妹和 44 名无亲属关系的对照组患者进行了全面的神经心理测试(智力、语言、记忆、执行功能和处理速度),并对测试结果进行了因子分析和 K-means 聚类分析。对确定的认知表型进行了特征描述,并将其与临床、家庭、社会人口学、皮层和皮层下成像特征联系起来:因子分析揭示了三个潜在的认知维度(一般能力、速度/反应抑制和学习/记忆),在所有因子得分上,JME参与者的表现都比非相关对照组差,而在一般心智能力和学习/记忆因子上,未受影响的兄弟姐妹的表现比非相关对照组差,JME与兄弟姐妹之间没有差异。因子得分的 K-means 聚类显示了三个潜在的组别,包括高于平均水平组(31.4% 的参与者)、平均水平组(52.1%)和表现异常组(16.4%)。在各潜在组别中,参与者组别的分布存在差异(p 显著性):不同的认知表型描述了存在家族(兄弟姐妹)聚集现象的 JME 患者的神经心理学表现。表型成员与父母(教育程度)和成像特征(皮质厚度和体积增加)有关,但与基本临床发作特征无关。
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引用次数: 0
Transition to seizure in focal epilepsy: From SEEG phenomenology to underlying mechanisms. 局灶性癫痫向发作的过渡:从 SEEG 现象到潜在机制。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-30 DOI: 10.1111/epi.18173
Mehmet Alihan Kayabas, Elif Köksal Ersöz, Maxime Yochum, Fabrice Bartolomei, Pascal Benquet, Fabrice Wendling

Objective: For the pre-surgical evaluation of patients with drug-resistant focal epilepsy, stereo-electroencephalographic (SEEG) signals are routinely recorded to identify the epileptogenic zone network (EZN). This network consists of remote brain regions involved in seizure initiation. However, the pathophysiological mechanisms underlying typical SEEG patterns that occur during the transition from interictal to ictal activity in distant brain nodes of the EZN remain poorly understood. The primary aim is to identify and explain these mechanisms using a novel physiologically-plausible model of the EZN.

Methods: We analyzed SEEG signals recorded from the EZN in 10 patients during the transition from interictal to ictal activity. This transition consisted of a sequence of periods during which SEEG signals from distant neocortical regions showed stereotypical patterns of activity: sustained preictal spiking activity preceding a fast activity occurring at seizure onset, followed by the ictal activity. Spectral content and non-linear correlation of SEEG signals were analyzed. In addition, we developed a novel neuro-inspired computational model consisting of bidirectionally coupled neuronal populations.

Results: The proposed model captured the essential characteristics of the patient signals, including the quasi-synchronous onset of rapid discharges in distant interconnected epileptogenic zones. Statistical analysis confirmed the dynamic correlation/de-decorrelation pattern observed in the patient signals and accurately reproduced in the simulated signals.

Significance: This study provides insight into the abnormal dynamic changes in glutamatergic and γ-aminobutyric acid (GABA)ergic synaptic transmission that occur during the transition to seizures. The results strongly support the hypothesis that bidirectional connections between distant neuronal populations of the EZN (from pyramidal cells to vaso-intestinal peptide-positive interneurons) play a key role in this transition, while parvalbumin-positive interneurons intervene in the emergence of rapid discharges at seizure onset.

目的:在对耐药性局灶性癫痫患者进行手术前评估时,通常会记录立体脑电图(SEEG)信号,以确定致痫区网络(EZN)。该网络由参与癫痫发作的偏远脑区组成。然而,人们对 EZN 远处脑节点从发作间期向发作活动过渡期间典型 SEEG 模式的病理生理机制仍然知之甚少。我们的主要目的是利用一个生理上合理的新型 EZN 模型来识别和解释这些机制:我们分析了 10 名患者在发作间期向发作活动过渡期间从 EZN 记录的 SEEG 信号。在这一过渡阶段,来自远处新皮层区域的 SEEG 信号显示出刻板的活动模式:在发作开始时出现快速活动之前有持续的发作前尖峰活动,随后是发作期活动。我们分析了 SEEG 信号的频谱内容和非线性相关性。此外,我们还开发了一个由双向耦合神经元群组成的新型神经启发计算模型:结果:所提出的模型捕捉到了患者信号的基本特征,包括在遥远的相互连接的致痫区内准同步发生的快速放电。统计分析证实了在患者信号中观察到的动态相关性/去相关性模式,并在模拟信号中准确再现:本研究深入揭示了在癫痫发作过渡期间谷氨酸能和γ-氨基丁酸(GABA)能突触传递的异常动态变化。研究结果有力地支持了这一假设:EZN 远距离神经元群(从锥体细胞到血管-肠肽阳性中间神经元)之间的双向连接在这一过渡中起着关键作用,而副斑蝥素阳性中间神经元则在癫痫发作开始时介入快速放电的出现。
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引用次数: 0
Accumulated seizure burden predicts neurodevelopmental outcome at 36 months of age in patients with tuberous sclerosis complex. 累积的癫痫发作负担可预测结节性硬化症复合体患者在 36 个月大时的神经发育结果。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-10-29 DOI: 10.1111/epi.18172
S Katie Z Ihnen, Samuel Alperin, Jamie K Capal, Alexander L Cohen, Jurriaan M Peters, E Martina Bebin, Hope A Northrup, Mustafa Sahin, Darcy A Krueger

Objective: Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear.

Methods: Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of candidate biomarkers to predict 36-month neurodevelopmental subgroup using univariable and multivariable logistic regression. Candidate biomarkers included age at seizure onset, accumulated seizure burden, tuber volume, sex, and earlier neurodevelopmental test scores.

Results: Patients clustered into two neurodevelopmental subgroups at 36 months of age, higher and lower scoring. Subgroup was mostly (75%) the same at 12 months. Significant univariable effects on subgroup were seen only for accumulated seizure burden (largest effect), earlier test scores, and tuber volume. Neither age at seizure onset nor sex significantly distinguished 36-month subgroups, although for girls but not boys there was a significant effect of age at seizure onset. In the multivariable model, accumulated seizure burden and earlier test scores together predicted 36-month neurodevelopmental group with 82% accuracy and an area under the curve of .86.

Significance: These results untangle the contributions of age at seizure onset and accumulated seizure burden to neurodevelopmental outcomes in young children with TSC. Accumulated seizure burden, rather than the age at seizure onset, most accurately predicts neurodevelopmental outcome at 36 months of age. These results emphasize the need to manage seizures aggressively during the first 3 years of life for patients with TSC, not only to promote seizure control but to optimize cognitive function.

目的:在结节性硬化症复合体(TSC)中,癫痫和智力障碍是常见病。虽然已知 TSC 患者的早期癫痫发作与智力障碍相关,但癫痫发作年龄和累积的癫痫发作负担对发育的不同影响仍不清楚:我们对 129 名 TSC 患者从 0 个月到 36 个月的每日发作日记、连续神经发育测试和脑磁共振成像进行了分析。我们使用机器学习方法,根据患者36个月大时的神经发育测试评分确定了患者亚组,并评估了这些亚组在12个月大时的稳定性。我们使用单变量和多变量逻辑回归测试了候选生物标志物预测 36 个月大神经发育亚组的能力。候选生物标志物包括癫痫发作起始年龄、累积癫痫发作负担、块茎体积、性别和早期神经发育测试评分:患者在 36 个月大时分为两个神经发育亚组,即高分和低分。在 12 个月时,亚组大部分(75%)相同。只有累积发作负担(最大影响)、早期测试得分和块茎体积对亚组有显著的单变量影响。癫痫发作年龄和性别对 36 个月亚组的区分均不明显,但对女孩(而非男孩)而言,癫痫发作年龄有显著影响。在多变量模型中,累积发作负担和早期测试得分共同预测了 36 个月的神经发育组别,准确率为 82%,曲线下面积为 0.86:这些结果揭示了发作开始年龄和累积发作负担对TSC幼儿神经发育结果的影响。累积的癫痫发作负担,而不是癫痫发作年龄,最能准确预测患儿在36个月大时的神经发育结局。这些结果表明,有必要在TSC患者出生后的头3年积极控制癫痫发作,这不仅是为了促进癫痫发作控制,也是为了优化认知功能。
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引用次数: 0
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Epilepsia
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