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The diagnostic value of sleep-deprived EEG in epilepsy: A meta-analysis 睡眠剥夺脑电图对癫痫的诊断价值:荟萃分析
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-29 DOI: 10.1016/j.seizure.2024.08.023
Yi Zhang , Ginger Qinghong Zeng , Ruodi Lu , Xiaofei Ye , Xiaochu Zhang

Sleep deprivation has been studied as a method to induce sleep before EEG testing to improve the diagnosis of epilepsy. However, the effectiveness of sleep deprivation in diagnosing epilepsy through EEG in humans showed conflicting findings in previous studies. This meta-analysis aimed to provide statistical evidence for the diagnostic value of sleep-deprived EEG in epilepsy. A systematic search of the Web of Science and PubMed databases identified 12 relevant studies from May 1997 to the present. These studies were included to examine the diagnostic value of sleep-deprived EEG in epilepsy and its associated clinical variables, such as patient age, duration of sleep deprivation, and EEG recording duration. The results of the random effects model did not show a significant overall diagnostic effect for sleep-deprived EEG in epilepsy, but revealed high heterogeneity among the studies. Notably, this heterogeneity was not accounted for by the clinical variables analyzed. Upon excluding outliers, a trend suggesting a modest diagnostic value of sleep-deprived EEG emerged. The high heterogeneity among studies indicates the need for a standardized protocol for sleep deprivation in future studies. Overall, while sleep deprivation may have a small positive effect on EEG-based epilepsy diagnosis, further research is needed to better understand its impact and optimize its use in clinical practice.

睡眠剥夺法是一种在脑电图测试前诱导睡眠以改善癫痫诊断的方法。然而,在以往的研究中,睡眠剥夺对通过脑电图诊断人类癫痫的有效性显示出相互矛盾的结果。本荟萃分析旨在为睡眠剥夺脑电图在癫痫诊断中的价值提供统计学证据。通过对 Web of Science 和 PubMed 数据库进行系统搜索,发现了 1997 年 5 月至今的 12 项相关研究。纳入这些研究是为了考察睡眠剥夺脑电图对癫痫的诊断价值及其相关临床变量,如患者年龄、睡眠剥夺持续时间和脑电图记录持续时间。随机效应模型的结果表明,睡眠剥夺脑电图对癫痫的总体诊断效果并不显著,但却显示出研究之间的高度异质性。值得注意的是,分析的临床变量并不能解释这种异质性。在排除异常值后,出现了一种趋势,表明睡眠剥夺脑电图具有适度的诊断价值。各研究之间的高度异质性表明,在未来的研究中需要对睡眠剥夺制定标准化方案。总之,虽然剥夺睡眠可能对基于脑电图的癫痫诊断有微小的积极影响,但仍需进一步研究,以更好地了解其影响并优化其在临床实践中的应用。
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引用次数: 0
The aging brain and late onset drug-refractory epilepsies. 大脑老化与晚发性药物难治性癫痫。
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-28 DOI: 10.1016/j.seizure.2024.08.021
Heidrun Potschka

While late-onset epilepsies are characterized by a good pharmacoresponsiveness, a relevant subgroup of this patient population suffers from drug-refractory epilepsy with its impact on overall quality of life and a high risk of seizure-related injuries. Particular attention should be paid to accurate diagnosis and thorough exclusion of pseudoresistance. Challenges include the likelihood of multimorbidities and polypharmacotherapy in an elderly patient population. Network, cellular, molecular, and metabolic alterations associated with aging and age-related disorders have the potential to affect the intrinsic severity of late-onset epilepsies, neural network function, and the pharmacodynamics and pharmacokinetics of antiseizure medications (ASMs). Whereas age-related changes in pharmacokinetics tend to favor responsiveness to low doses, respective changes in network excitability and pharmacodynamics of ASMs are more likely to contribute to drug resistance. There are particular gaps in our knowledge of the mechanisms of drug resistance and the impact of influencing factors in this patient population. Therefore, experimental and clinical research needs to be intensified to advance our understanding of drug-resistant epilepsy in patients with late-onset epilepsies and to develop multivariate prediction algorithms. In this context, the heterogeneity of an elderly patient population should be taken into account, considering differences in etiology, comorbidities, co-medications, frailty, activity and environmental factors.

虽然晚发性癫痫具有良好的药敏性,但这一患者群体中有一个相关的亚群患有药物难治性癫痫,对整体生活质量造成了影响,并且具有发作相关伤害的高风险。应特别注意准确诊断和彻底排除假性抗药性。面临的挑战包括老年患者可能患有多种疾病和接受多种药物治疗。与衰老和年龄相关疾病有关的网络、细胞、分子和代谢改变有可能影响晚发性癫痫的内在严重性、神经网络功能以及抗癫痫药物(ASMs)的药效学和药代动力学。与年龄相关的药代动力学变化倾向于对小剂量药物产生反应,而神经网络兴奋性和抗癫痫药物药效学的各自变化则更有可能导致耐药性。我们对这一患者群体的耐药机制和影响因素的影响的认识还存在特别大的差距。因此,需要加强实验和临床研究,以加深我们对晚发癫痫患者耐药性癫痫的了解,并开发多变量预测算法。在这方面,应考虑到老年患者群体的异质性,考虑到病因、合并症、联合用药、体弱、活动和环境因素的差异。
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引用次数: 0
Symptomatic syringomyelia after disconnective epilepsy surgery 断开癫痫手术后的症状性鞘翅肌瘤
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-25 DOI: 10.1016/j.seizure.2024.08.019
Steven Smeijers , Johannes van Loon , Marec von Lehe , Tom Theys
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引用次数: 0
Does epilepsy differentially affect different types of memory? 癫痫是否会对不同类型的记忆产生不同影响?
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.seizure.2024.08.020
Kirsty H T Phillips , Karalyn Patterson , Christopher R Butler , Emma Woodberry , Matthew A Lambon Ralph , Thomas E Cope

Despite the recognition that epilepsy can substantially disrupt memory, there are few published accounts of whether and how this disruption varies across different types of memory and/or different types of epilepsy. This review explores four main questions: (1) Are working, episodic and semantic memory differentially affected by epilepsy? (2) Do various types of epilepsy, and their treatment, have different, specifiable effects on memory? (3) Are the usual forms of neuropsychological assessments of memory – many or most designed for other conditions – appropriate for patients with epilepsy? (4) How can research on epilepsy contribute to our understanding of the neuroscience of memory?

We conclude that widespread and multifactorial problems are seen in working memory in all patient groups, while patients with temporal lobe epilepsy seem particularly prone to episodic memory deficit, and those with frontal lobe epilepsy to executive function deficits that may in turn impair semantic control. Currently, it is difficult to make individual patient predictions about likely memory deficits based on seizure aetiology and type, but it is possible to guide and tailor neuropsychological assessments in an individualised way. We make recommendations for future directions in validating and optimising neuropsychological assessments, and consider how to approach effective shared decision making about the pros and cons of seizure treatment strategies, especially at crucial educational stages such as adolescence.

尽管人们认识到癫痫会严重破坏记忆,但关于这种破坏是否以及如何因不同类型的记忆和/或不同类型的癫痫而异,已发表的论述却很少。本综述探讨了四个主要问题:(1)工作记忆、情节记忆和语义记忆是否受到癫痫的不同影响?(2) 各种类型的癫痫及其治疗对记忆是否有不同的、具体的影响?(3) 记忆的神经心理学评估的通常形式--许多或大多数是为其他情况设计的--是否适合癫痫患者?(4) 对癫痫的研究如何有助于我们理解记忆的神经科学?我们的结论是,所有患者群体的工作记忆都存在广泛和多因素的问题,而颞叶癫痫患者似乎特别容易出现外显记忆缺陷,额叶癫痫患者则容易出现执行功能缺陷,这可能反过来损害语义控制。目前,很难根据癫痫发作的病因和类型来预测每个患者可能出现的记忆缺陷,但有可能以个体化的方式指导和调整神经心理学评估。我们就验证和优化神经心理学评估的未来方向提出了建议,并考虑了如何就癫痫发作治疗策略的利弊进行有效的共同决策,尤其是在青春期等关键教育阶段。
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引用次数: 0
PPP3CA gene-related developmental and epileptic encephalopathy: Expanding the electro-clinical phenotype 与 PPP3CA 基因相关的发育性癫痫脑病:扩展电临床表型。
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.seizure.2024.08.017
Jacopo Favaro , Alessandro Iodice , Margherita Nosadini , Francesca Asta , Irene Toldo , Claudio Ancona , Elena Cavaliere , Maria Federica Pelizza , Gianluca Casara , Lucio Parmeggiani , Stefano Sartori

Purpose

The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE).

Methods

We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain.

Results

Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy.

Conclusion

Our study emphasizes the critical role of pathogenic variants’ type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies.
目的:本研究旨在描述受罕见的 PPP3CA 基因相关发育性癫痫脑病(DEE)影响的个体的电-临床表型:方法:我们对以前未报道过的四例受试者进行了详细的电-临床描述,这四例受试者的脑部核磁共振成像(MRI)结构均无异常,先天性代谢异常筛查结果也正常,但他们携带了编码钙神经蛋白的 PPP3CA 基因调控域内的致病变体。我们还通过PubMed和SCOPUS(截至2023年12月)进行了文献综述,收集了所有报告PPP3CA基因调控域致病变体受试者临床细节的研究:我们的深入研究发现了两种不同的电临床表型,它们具有独特的发作间期和发作模式。钙调蛋白结合域的致病变异导致儿童发病型癫痫,伴有局灶性和全身性癫痫发作、发育和智力障碍。调节结构域中的致病变异会导致早发性耐药性严重癫痫,并可能造成致命后果。与现有文献的比较分析证实,截短突变(主要发生在调节结构域,但也可能发生在钙调素结合结构域)始终与更严重的残疾和耐药性癫痫有关:我们的研究强调了致病变异的类型和位置对 PPP3CA 相关 DEE 严重程度的关键作用。我们还根据特殊的脑电图模式推测了涉及钙神经蛋白功能障碍和钙平衡的潜在病理生理机制。为了提高我们对这种罕见 DEE 的认识,我们需要共同努力收集更多的队列并开展进一步的实验研究。
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引用次数: 0
Prescription patterns of home rescue benzodiazepines for febrile seizures 发热性癫痫发作的家庭抢救性苯并二氮杂卓处方模式
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.seizure.2024.08.018
Iván Sánchez Fernández, Taha Fathima Khan, Amanda Romeu, Tahir Sheikh, Alcy Torres, Rinat Jonas, Laurie Douglass

Objective

To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription.

Methods

Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up.

Results

There were a total of 82,835 patients [median (p25-p75) age 1.0 (1.0–2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p25-p75) time from first febrile seizure to non-IV-rBZD prescription was 27 (2–186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24–3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29–3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient's residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription.

Conclusion

Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.

目的描述发热性癫痫发作时家庭非静脉注射抢救性苯二氮卓类药物(non-IV-rBZDs)的处方模式,以及与处方相关的因素。方法使用 MarketScan 商业数据库进行回顾性描述性研究,该数据库是美国雇主赞助的私人投保患者的大型数据库。我们使用了 2006 年 1 月 1 日至 2022 年 12 月 31 日的数据。我们研究了以发热性癫痫发作作为就医主要代码(通过国际疾病分类代码识别)、年龄在 6 个月至 5 岁之间、随访至少 1 个月的患者。结果共有 82,835 名患者[中位数(p25-p75)年龄为 1.0(1.0-2.0)岁,56.7% 为男性]至少有一次发热性癫痫发作,其中 9,737 人(11.8%)至少开了一张非 IV-rBZD 处方。在 9,737 名至少开过一次处方的患者中,从首次发热发作到开出非 IV-rBZD 处方的中位时间(p25-p75)为 27(2-186)天。在首次发热发作时已知的因素中,复杂性发热发作(OR:3.51,95 % CI:3.24-3.79)和首次因发热发作住院(OR:3.53,95 % CI:3.29-3.79)是与开具非 IV-rBZD 处方关系最大的因素。相比之下,性别、农村患者居住地和工薪阶层(相对于其他职业阶层)与开具非 IV-rBZD 处方并无独立关联。在随访结束时已知的因素中,复杂发热发作、初次就诊类型和最终诊断为癫痫是与开具非 IV-rBZD 处方相关的主要独立因素。与开具处方独立相关的主要因素包括复杂发热发作、入院、反复发热发作以及最终诊断为癫痫。
{"title":"Prescription patterns of home rescue benzodiazepines for febrile seizures","authors":"Iván Sánchez Fernández,&nbsp;Taha Fathima Khan,&nbsp;Amanda Romeu,&nbsp;Tahir Sheikh,&nbsp;Alcy Torres,&nbsp;Rinat Jonas,&nbsp;Laurie Douglass","doi":"10.1016/j.seizure.2024.08.018","DOIUrl":"10.1016/j.seizure.2024.08.018","url":null,"abstract":"<div><h3>Objective</h3><p>To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription.</p></div><div><h3>Methods</h3><p>Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up.</p></div><div><h3>Results</h3><p>There were a total of 82,835 patients [median (p<sub>25</sub>-p<sub>75</sub>) age 1.0 (1.0–2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p<sub>25</sub>-p<sub>75</sub>) time from first febrile seizure to non-IV-rBZD prescription was 27 (2–186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24–3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29–3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient's residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription.</p></div><div><h3>Conclusion</h3><p>Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.</p></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"121 ","pages":"Pages 197-203"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Seizure outcome in drug-resistant epilepsy in the setting of polymicrogyria 多微畸形情况下耐药性癫痫的发作结果
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.seizure.2024.08.016
Thandar Aung , Jin Bo , William Bingaman , Imad Najm , Andreas Alexopoulos , Juan C. Bulacio

Objective

We aimed to analyze seizure outcomes and define ictal onset with intracranial electroencephalography (ICEEG) in patients with polymicrogyria (PMG)-related drug-resistant epilepsy (DRE), considering surrounding cortex and extent of surgical resection.

Methods

Retrospective study of PMG-diagnosed patients (2001 to June 2018) at a single epilepsy center was performed. Primary outcome was complete seizure freedom (SF), based on Engel classification with follow-up of ≥ 1 year. Univariate analyses identified predictive clinical variables, later integrated into multivariate Cox proportional hazards models.

Results

Thirty-five patients with PMG-related DRE (19 adults/16 pediatric: 20 unilateral/15 bilateral) were studied. In surgical group (n = 23), 52 % achieved SF (mean follow-up:47 months), whereas none in non-resective treatment group (n = 12) attained SF (mean follow-up:39.3 months) (p = 0.002). In surgical group, there were no significant differences in SF, based on the laterality of the PMG [uni or bilateral,p = 0.35], involvement of perisylvian region(p = 0.714), and extent of the PMG resection [total vs. partial,p = 0.159]. Patients with ictal ICEEG onset in both PMG and non-PMG cortices, and those limited to non- PMG cortices had a greater chance of achieving SF compared to those limited to the PMG cortices.

Conclusion

Resective surgery guided by ICEEG for defining the epileptogenic zone (EZ), in DRE patients with PMG, leads to favorable seizure outcomes. ICEEG-guided focal surgical resection(s) may lead to SF in patients with bilateral or extensive unilateral PMG. ICEEG aids in EZ localization within and/or outside the MRI-identified PMG. Complete removal of PMG identified on MRI does not guarantee SF. Hence, developing preimplantation hypotheses based on epileptogenic networks evaluation during presurgical assessment is crucial in this patient population.

目的我们旨在分析多小脑症(PMG)相关耐药癫痫(DRE)患者的发作结果,并通过颅内脑电图(ICEEG)确定发作起始时间,同时考虑周围皮质和手术切除范围。方法对一家癫痫中心确诊的PMG患者(2001年至2018年6月)进行了回顾性研究。主要结果是完全癫痫发作自由度(SF),基于恩格尔分类,随访时间≥1年。单变量分析确定了预测性临床变量,随后将其纳入多变量 Cox 比例危险模型。在手术组(n = 23)中,52%的患者实现了SF(平均随访时间:47个月),而在非切除治疗组(n = 12)中,没有一人实现了SF(平均随访时间:39.3个月)(p = 0.002)。在手术组中,根据原发性脑积水的偏侧[单侧或双侧,p = 0.35]、原发性脑积水周围区域受累(p = 0.714)和原发性脑积水切除范围[全部或部分切除,p = 0.159],SF无显著差异。与局限于永磁皮质的患者相比,在永磁和非永磁皮质均有发作性 ICEEG 的患者以及局限于非永磁皮质的患者获得 SF 的机会更大。ICEEG引导下的病灶手术切除可使双侧或广泛单侧永磁发电机患者获得SF。ICEEG 有助于在磁共振成像确定的 PMG 内部和/或外部进行 EZ 定位。完全切除磁共振成像确定的原发性骨髓增生异常并不能保证原发性骨髓增生异常。因此,在术前评估时,根据致痫网络评估提出植入前假设对这类患者至关重要。
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引用次数: 0
Combined generalized and focal epilepsy with reflex features in Adaptor protein complex 4-associated hereditary spastic paraplegias: A cohort observational study 自适应蛋白复合物 4 相关遗传性痉挛性截瘫患者中具有反射特征的全身性和局灶性综合癫痫:一项队列观察研究
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.seizure.2024.08.009
Emanuele Bartolini , Anna Rita Ferrari , Filippo Maria Santorelli , Carmen Salluce , Guja Astrea , Gemma Marinella , Francesca Maria Agostina Papoff , Alessandro Orsini , Roberta Battini

Background

Patients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far.

Purpose

We aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency.

Methods

Observational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications.

Results

Patients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %).

Conclusion

In AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.

背景适配蛋白复合物 4(AP-4)基因缺乏症患者表现出早发性发育迟缓、痉挛性偏瘫、智力障碍和语言障碍。其表型与其他遗传性痉挛性截瘫和脑瘫重叠。发病时常见发热性癫痫发作。半数以上的病例出现癫痫,多在婴儿期出现,常伴有癫痫状态,但迄今为止尚未发现典型的癫痫发作半身像或脑电图特征。方法对AP-4亚基双等位基因致病变异和癫痫患者进行队列观察研究。结果患者携带 AP4S1(5 例)或 AP4M1(1 例)致病变异。表型包括痉挛性瘫痪、智力障碍、言语/语言障碍、小头畸形和胼胝体发育不良的磁共振成像证据。66%的患者在癫痫发病前有发热性发作,发病时间从婴儿期到青春期不等(范围=14个月-13岁)。失神发作(66%)和局灶性运动性发作(50%)很常见。没有患者符合耐药性标准。癫痫发病后出现了特殊的脑电图特征,并在长期随访中持续存在:双侧不同步的局灶性放电合并独立的弥漫性棘波放电(100%)和反射异常(66%)。预后良好。我们观察到一种常见的脑电图特征--合并局灶性/全身性和反射性异常--这可能是 AP-4 缺乏症合并癫痫的生物标志物,适用于基因检测和鉴别诊断。
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引用次数: 0
Pathophysiological mechanisms underlying the development of focal cortical dysplasia and their association with epilepsy: Experimental models as a research approach 局灶性皮质发育不良的病理生理机制及其与癫痫的关系:作为研究方法的实验模型
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.seizure.2024.08.013
Kaiyi Kang , Yuxin Wu , Hui Gan , Baohui Yang , Han Xiao , Difei Wang , Hanli Qiu , Xinyu Dong , Haotian Tang , Xuan Zhai

Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.

局灶性皮质发育不良(FCD)是一种结构性病变,是儿童中最常见的解剖学病变,也是成人耐药性局灶性癫痫患者中第二常见的病变。这些病变的大小、位置和组织病理学表现各不相同。FCD 可分为三个亚型,分别与 PI3K/AKT、TSC1/TSC2、RHEB 和 DEPDC/NPRL2/NPRL3 的功能缺失突变有关。在对 FCD 的数十年研究中,实验模型在研究疾病发病机制、病理生理学和治疗的研究设计中发挥了不可替代的作用。此外,FCD 实验模型的建立还通过(1)揭示 FCD 发病机制的细胞过程和信号通路;(2)改变研究 FCD 蛋白功能的方法和材料,推动了该领域的发展。目前,FCD 实验模型主要以小鼠为主,每种模型都能为 FCD 病变提供独特的见解。本综述简要概述了 FCD 的病理和分子功能,进一步比较了现有的建模方法和指标以及模型的利用情况,然后分析了这些模型与人类 FCD 的相似之处和优缺点。
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引用次数: 0
Factors associated with seizure response in adults with epilepsy on a modified Atkins diet 改良阿特金斯饮食法成人癫痫患者癫痫发作反应的相关因素
IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.seizure.2024.08.014
Nicholas Huerta , Mengyang Lu , Bobbie J. Henry-Barron , Mackenzie C. Cervenka , Tanya J.W. McDonald

Purpose

This study investigated factors associated with improved seizure control in adults with epilepsy following a modified Atkins diet (MAD).

Methods

Follow-up data collected from participants enrolled in a prospective study between March 2016 and November 2023 was analyzed. Demographic and clinical differences between diet responders and non-responders were evaluated. MAD response was defined as ≥ 50 % reduction in seizure frequency from baseline.

Results

MAD use led to clinical response in 48 % of study participants with 2–3 month follow-up and in 56 % of study participants with 6 month follow-up. No significant differences were found for gender, age at diet initiation, age at epilepsy diagnosis, or for number of current or past medications tried. However, a significant relationship emerged between epilepsy type and diet response at 6 months with a response of 100 % seen in adults with generalized epilepsy and a response of only 42 % in adults with focal epilepsy (p = 0.004). Those who responded to the diet showed non-significant increases in many of the measured lipid biomarkers. Levels of apolipoprotein-B and small low-density lipoprotein particles showed significant increases from baseline after 3 months in responders compared to non-responders (p = 0.004 and 0.049, respectively).

Conclusions

These findings support the continued use of MAD particularly for seizure management in adults with generalized epilepsy and highlight potential mechanisms of clinical response involving lipoprotein and energy metabolism.

目的 本研究调查了改良阿特金斯饮食(MAD)后成人癫痫患者癫痫发作控制得到改善的相关因素。方法 分析了从 2016 年 3 月至 2023 年 11 月期间参加前瞻性研究的参与者收集的随访数据。评估了饮食应答者和未应答者之间的人口统计学和临床差异。MAD反应的定义是癫痫发作频率比基线降低≥50%。结果在2-3个月的随访中,48%的研究参与者使用MAD后出现了临床反应,在6个月的随访中,56%的研究参与者使用MAD后出现了临床反应。性别、开始使用饮食的年龄、癫痫确诊年龄、目前或过去尝试过的药物数量均无明显差异。然而,癫痫类型与 6 个月的饮食反应之间存在明显关系,全身性癫痫患者的饮食反应为 100%,而局灶性癫痫患者的饮食反应仅为 42%(p = 0.004)。对饮食有反应的人在许多测量的脂质生物标志物中都显示出非显著性的增加。结论:这些研究结果支持继续使用 MAD,特别是用于控制全身性癫痫成人患者的癫痫发作,并强调了涉及脂蛋白和能量代谢的潜在临床反应机制。
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期刊
Seizure-European Journal of Epilepsy
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