Anticonvulsants

抗惊厥药
  • 文章类型: Journal Article
    研究目的是评估癫痫患者的处方模式和抗癫痫药物(ASM)的使用,并评估ASM剂量的变化是否对癫痫发作的控制有有益的影响。通过ASM的治疗药物监测[TDM]水平观察。
    分析了癫痫发作患者血液中抗癫痫发作药物及其治疗水平的详细信息。
    基于医院的病例记录回顾性分析。
    三级护理公立教学医院的治疗药物监测OPD。
    2016-2021年918例癫痫患者的病例记录。
    对年龄在18-75岁之间的男性(53%)和女性(47%)的数据进行了评估约62%(566/918)的患者服用左乙拉西坦,最常用的抗癫痫药物。每当ASM剂量根据TDM水平增加或减少时,它与突发性癫痫发作频率显著增加相关[OR-5(95%CI:1.28~19.46)].然而,当患者服用相同维持剂量的抗癫痫药物[OR-0.2(95%CI:0.06~0.63)]时,癫痫发作得到显著控制.每当新的抗癫痫药物被处方或从现有的抗癫痫药物中删除时,它没有显著影响癫痫发作控制.
    对每位患者进行个体化药物治疗和治疗药物监测,以及患者的因素,如药物依从性,伴随药物和疾病史,和药物遗传学评估,应该是癫痫患者更好控制癫痫发作的理想做法。
    没有声明。
    UNASSIGNED: The study objective was to evaluate the prescription pattern and use of anti-seizure medications (ASMs) in patients with a seizure disorder and to evaluate if a change in the ASM dose had a beneficial effect on seizure control, observed through Therapeutic Drug Monitoring [TDM] level of ASMs.
    UNASSIGNED: Details of anti-seizure medications with their therapeutic levels in the blood of patients with seizure disorder were analysed.
    UNASSIGNED: Hospital-based retrospective analysis of patient case records.
    UNASSIGNED: Therapeutic Drug Monitoring OPD of a tertiary care public teaching hospital.
    UNASSIGNED: Case records of 918 patients with seizure disorder from 2016-2021.
    UNASSIGNED: Data of men (53%) and women (47%) aged between 18-75 years was assessed About 62% (566/918) of patients were on levetiracetam, the most frequently prescribed anti-seizure medication. Whenever the ASMs dose was increased or decreased based on TDM levels, it was associated with a significant increase in the frequency of break-through seizures [OR- 5 (95% CI: 1.28-19.46)]. However, significant seizure control was observed when the patients were on the same maintenance dose of the anti-seizure medication [OR- 0.2 (95% CI: 0.06-0.63)]. Whenever an additional new anti-epileptic drug was prescribed or removed from the pre-existing anti-epileptic medications, it did not significantly impact seizure control.
    UNASSIGNED: Individualising drug therapy and therapeutic drug monitoring for each patient, along with patient factors such as medication compliance, concomitant drug and disease history, and pharmacogenetic assessment, should be the ideal practice in patients with seizures for better seizure control.
    UNASSIGNED: None declared.
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  • 文章类型: Journal Article
    鼻内途径由于其广泛的表面积而表现出优异的全身生物利用度,内皮膜的多孔性质,大量的血液流动,规避首过代谢。在传统的医学实践中,BacopaMonnieri,也被称为Brahmi,以增强认知功能和癫痫的潜在影响而闻名。本研究旨在开发和优化用于递送BacosideA的热敏原位鼻凝胶,从Bacopamonnieri中提取的主要活性化合物。该制剂掺入泊洛沙姆407作为热胶凝剂和HPMCK4M作为粘膜粘附聚合物。采用32阶乘设计方法进行优化。在配方中。F7表现出通过鼻粘膜的最有效的离体渗透,达到94.69±2.54%的渗透,并在约30.48°C下经历溶胶-凝胶转变。研究的析因设计表明,胶凝温度和粘膜粘附强度是影响性能的关键因素。使用PTZ诱导的惊厥模型在体内研究中证明了原位鼻凝胶(优化批次F7)治疗癫痫的潜力。该制剂降低了癫痫发作的发生率和强度。优化的配方F7展示了作为巴果苷A的有效鼻腔给药系统的显着前景,提供增强的生物利用度和潜在的提高癫痫治疗的疗效。
    The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study\'s factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.
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  • 文章类型: Case Reports
    附睾结核是罕见的,通常存在诊断困难。它可能表明感染的传播形式,我们的病人就是这样.一个19岁的男人,没有既往病史,因左侧阴囊肿胀疼痛而入院,该阴囊已经演变了8个月。他接受了睾丸切除术,解剖病理学检查与附睾结核一致。放射学检查揭示了感染的其他定位:淋巴,肺,顶骨和骨关节结核。介绍了抗结核治疗。然而,在治疗的第四个月,患者出现癫痫发作。进行了脑部磁共振成像,最后是脑结核瘤.抗结核治疗继续与抗惊厥药相关,结果良好。我们观察的独创性在于传播的漏状结核病的揭示模式,通过附睾定位,在一个有免疫能力的病人身上。
    Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:癫痫持续状态(SE)可能危及生命,然而,目前尚不清楚哪些抗癫痫药物(AEDs)应该用作二线AEDs.
    目的:我们进行了一项网络荟萃分析(NMA)的随机对照试验(RCTs),比较多个二线AED对SE的疗效。
    方法:我们搜索了MEDLINE,中部,ClinicalTrials.gov,和世界卫生组织国际临床试验平台搜索门户,并于2023年12月31日纳入了年龄≥15岁SE患者的随机对照试验。我们比较了SE的多个二线AED,包括fphenytoin(fPHT),拉科沙胺(LCM),左乙拉西坦(LEV),苯妥英(PHT),苯巴比妥(PHB),和丙戊酸盐(VPA)。主要和次要结果是癫痫发作终止,包括在30分钟和60分钟没有癫痫发作复发。以及与AED相关的不良事件,分别,以95%置信区间(CI)表示为相对风险(RR)。我们使用基于频率的方法和多元随机效应进行了NMA,并根据建议的等级评估确定性,评估,发展,和评估框架。
    结果:包括七个RCT(n=780),并且在VPA与PHB(RR,0.67;95%CI,0.53-0.85;确定性非常低),fPHTvs.PHB(RR,0.66;95%CI,0.48-0.90;确定性非常低),LCMvs.PHB(RR,0.62;95%CI,0.41-0.93;确定性非常低),和LEVvs.PHB(RR,0.69;95%CI,0.51-0.94;确定性非常低)。此外,PHB在癫痫发作终止排名中最高。对于不良事件,由于AED的选择,没有观察到显著的减少,虽然PHB的排名最低。
    结论:PHB作为成人SE患者的二线AED可能是最有效的癫痫发作终止方法。然而,几乎所有比较的确定性都是“非常低”,仔细的解释是必不可少的。
    BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs.
    OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs.
    METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework.
    RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest.
    CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was \"very low\", and careful interpretation is essential.
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  • 文章类型: Journal Article
    目的:癫痫的负担是复杂的,包括与急性癫痫发作直接相关的因素以及与慢性神经系统疾病相关的因素。本系统评价的目的是描述癫痫发作的短期负担,并探讨急性治疗除了降低癫痫持续状态的风险外,减轻这些负担的潜在价值。
    结果:使用PubMed进行了系统的文献检索,以确定从2017年1月1日至2023年6月22日发表的文章,这些文章描述了癫痫发作的短期负担和急性治疗。主要结果包括与癫痫发作的短期负担和急性治疗以减少短期负担有关的结果。在通过PubMed确定的1332篇文章和通过其他来源确定的17篇文章中,27例具有相关结果,并被纳入定性综合。癫痫紧急情况对短期生活质量和进行正常日常生活活动的能力产生负面影响,并与身体(伤害)和财务(紧急运输,住院)负担。急性治疗的使用与患者和护理人员快速恢复(≤1小时)至正常功能/自我相关,并可能降低医疗保健利用率和成本。癫痫发作行动计划可以提高癫痫发作护理的知识和舒适度,赋予患者和护理人员权力。癫痫发作的短期负担可能对患者和护理人员产生重大负面影响。急性治疗除了其充分描述的减少癫痫发作活动和癫痫持续状态风险的作用外,还可以减少癫痫发作的短期负担。
    OBJECTIVE: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus.
    RESULTS: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures. Primary outcomes included those related to short-term burdens of seizures and the benefits of acute treatments to reduce short-term burdens. Of the 1332 articles identified through PubMed and 17 through other sources, 27 had relevant outcomes and were included in the qualitative synthesis. Seizure emergencies negatively affected short-term quality of life and the ability to conduct normal daily living activities and were associated with physical (injury) and financial (emergency transport, hospitalization) burdens. The use of acute treatment was associated with a rapid return (≤ 1 h) to normal function/self for both patients and caregivers and potentially lower healthcare utilization and costs. Seizure action plans may improve knowledge and comfort with seizure care, empowering patients and caregivers. The short-term burden of seizures can create a substantial negative impact on patients and caregivers. Acute treatments may reduce the short-term burdens of seizures in addition to their well-described role to reduce seizure activity and the risk for status epilepticus.
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  • 文章类型: Journal Article
    背景:根根大黄,在韩国药典中被列为“Daehwang”,富含各种蒽醌,以其抗炎和抗氧化特性而闻名。含有Daehwang的制剂传统上用于治疗神经病症。本研究旨在证实丹参根提取物(RTE)对三甲基锡(TMT)诱导的癫痫发作和海马神经变性的抗癫痫和神经保护功效。
    方法:采用超高效液相色谱法(UPLC)对RTE的成分进行鉴定。实验动物分为以下五类:对照,TMT,和三个TMT+RTE组,剂量为10、30和100mg/kg。每天评估癫痫发作的严重程度,以进行组间比较。使用组织学和分子生物学技术检查脑组织样品以确定神经变性和神经炎症的程度。网络药理学分析涉及从多个数据库中提取大王的草药靶标和癫痫的疾病靶标。使用用于检索相互作用基因/蛋白质(STRING)数据库的搜索工具建立了蛋白质-蛋白质相互作用网络,并通过拓扑分析确定关键目标。使用注释数据库进行富集分析,可视化,和集成发现(DAVID)工具来阐明底层机制。
    结果:发现RTE制剂中含有皂甙A,森诺赛德B,大黄酚,大黄素,physcion,(+)-儿茶素,和槲皮素-3-O-葡糖醛酸。RTE在10、30和100mg/kg剂量下有效抑制TMT诱导的癫痫发作,并在30和100mg/kg剂量下减轻海马神经元衰变和神经炎症。此外,RTE显著降低肿瘤坏死因子(TNF-α)的mRNA水平,胶质纤维酸性蛋白(GFAP),和海马组织中的c-fos。网络分析显示TNF,白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),蛋白质c-fos(FOS),RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1),以哺乳动物雷帕霉素靶蛋白(mTOR)为核心靶点。富集分析显示,唐古汀菌成分显著参与神经变性(p=4.35×10-5)和TNF信号通路(p=9.94×10-5)。
    结论:本研究中进行的体内和计算机模拟分析表明,RTE可以潜在地调节TMT诱导的癫痫发作和神经变性。因此,根根是一种有前途的草药治疗选择,用于抗癫痫和神经保护应用。
    BACKGROUND: Rheum tanguticum root, cataloged as \"Daehwang\" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration.
    METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms.
    RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5).
    CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.
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  • 文章类型: Journal Article
    妊娠和产后是癫痫妇女及其婴儿的潜在高危时期。所有患有癫痫的女性都应该有机会接受孕前咨询,以降低风险,为潜在发育中的胎儿优化结果,并做出明智的决策。本文为孕前咨询讨论提供了一个基于证据的框架,包括对诊断和当前抗癫痫药物的审查,与抗癫痫药物和产妇癫痫发作有关的胎儿风险,孕产妇发病率,SUDEP风险,叶酸补充剂,避孕,母乳喂养和安全建议。
    Pregnancy and the postpartum period are potentially high-risk periods for women with epilepsy and their babies. All women with epilepsy should have the opportunity for preconception counselling with the aim of reducing risk, optimising outcomes for the potentially developing fetus and enabling informed decision-making. This article provides an evidence-based framework for preconception counselling discussion, including the review of diagnosis and of current antiseizure medication, the risk to the fetus in relation to antiseizure medication and maternal seizures, maternal morbidity, SUDEP risk, folic acid supplements, contraception, breastfeeding and safety advice.
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  • 文章类型: News
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  • 文章类型: Journal Article
    钾通道最近已成为治疗癫痫疾病的合适靶标。在钾通道中,KCNT1通道被最广泛地表征为负责几种癫痫和发育性脑病。然而,到目前为止,KCNT1阻断剂的药物化学尚不发达。在本次审查中,我们描述和分析了解决KCNT1阻断剂开发和鉴定问题的论文,还证明了其中描述的科学方法的利弊。在简短介绍了癫痫性疾病和钾离子通道的结构功能之后,我们提供了到目前为止所描述的KCNT1阻断剂的化学型的广泛概述,以及用于识别它们的科学方法。
    Potassium channels have recently emerged as suitable target for the treatment of epileptic diseases. Among potassium channels, KCNT1 channels are the most widely characterized as responsible for several epileptic and developmental encephalopathies. Nevertheless, the medicinal chemistry of KCNT1 blockers is underdeveloped so far. In the present review, we describe and analyse the papers addressing the issue of KCNT1 blockers\' development and identification, also evidencing the pros and the cons of the scientific approaches therein described. After a short introduction describing the epileptic diseases and the structure-function of potassium channels, we provide an extensive overview of the chemotypes described so far as KCNT1 blockers, and the scientific approaches used for their identification.
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