Epilepsy Research最新文献_第5页

Effectiveness and tolerability of perampanel as first add-on treatment in pediatric patients with focal and generalized epilepsy perampanel作为小儿局灶性和全身性癫痫患者第一附加治疗的有效性和耐受性。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-24 DOI: 10.1016/j.eplepsyres.2025.107690

Bárbara Blanco Martínez, Elena Arce Portillo, María Muñoz Cabeza, Mercedes López Lobato, Beatriz Muñoz Cabello, Marta Correa Vela, Laura González Hernández, Carmen Cortés Jiménez, Olga Alonso Luengo

Purpose

To compare the effectiveness and safety of perampanel as first add-on vs. late add-on therapy in children with focal or generalized epilepsy.

Methods

Retrospective, single-center study conducted between March 2022 and April 2023, including children ≥ 4 years with focal an generalized epilepsy who started treatment with perampanel in November 2020 or later. Patients were classified into two groups: perampanel as first and as late add-on treatment. Effectiveness and safety data were collected at 3, 6, and 12 months after starting treatment. Primary outcomes were responder rates, seizure-freedom rates, and worsening.

Results

57 patients (45.6 % women) with a mean (SD) age of 8.8 (±3.5) years were included; 27 in the first and 30 in the late add-on group. Effectiveness was consistently higher throughout visits in patients receiving perampanel as first vs. late add-on treatment, with higher response rates (12 months, 95.0 % vs. 55.6 %, p = 0.003), higher seizure-freedom rates (12 months, 65 % vs. 37.0 %, p = 0.058), and fewer patients with worsening (12 months, 0 % vs. 12.8 %, p = 0.031). Retention rates remained high in both groups throughout visits. Sixteen patients discontinued treatment. Reasons were lack of effectiveness, which was more frequent in the late vs. first add-on group, with few patients discontinuing due to adverse events.

Conclusion

The improved effectiveness outcomes of perampanel used as first vs. late add-on therapy in a pediatric population and the favorable safety outcomes support its use as first add-on therapy in pediatric patients with focal and generalized epilepsy.

目的：比较perampanel作为局灶性或全面性癫痫患儿首次附加治疗与晚期附加治疗的有效性和安全性。方法：回顾性、单中心研究于2022年3月至2023年4月进行，纳入≥ 4岁局灶性和全面性癫痫患儿，这些患儿在2020年11月或之后开始使用perampanel治疗。患者分为两组：perampanel作为第一组和晚期附加治疗。在开始治疗后3、6和12个月收集有效性和安全性数据。主要结局是应答率、癫痫解除率和病情恶化。结果：纳入57例患者（45.6% %为女性），平均（SD）年龄为8.8（±3.5）岁；第一个组27人，最后一个组30人。有效性一直在访问病人接受高perampanel作为第一和附加治疗后期,高响应率(12个月,95.0 % 55.6 vs %,p = 0.003),更高的发作率(12个月,65 %与37.0 %,p = 0.058),和更少的患者恶化(12个月,0 % 12.8 vs % p = 0.031)。在整个访问过程中，两组的保留率都很高。16名患者停止治疗。原因是缺乏有效性，这在晚期加药组比首次加药组更常见，很少有患者因不良事件而停药。结论：perampanel作为儿科人群首次与晚期附加治疗的疗效改善以及良好的安全性结果支持其作为局灶性和全面性癫痫儿童患者的首次附加治疗。

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引用次数: 0

Trends, prescribing patterns and projections of antiseizure drug use in Europe 欧洲抗癫痫药物使用的趋势、处方模式和预测。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-23 DOI: 10.1016/j.eplepsyres.2025.107689

Lilly Josephine Bindel, Roland Seifert

Purpose

Epilepsy represents a significant global burden, with antiseizure drugs (ASDs) essential for treatment. This study examines past and recent trends in ASD consumption in 11 European countries, forecasts future developments, analyses Anatomical Therapeutic Chemical Classification (ATC) subgroup use, and offers an initial assessment of treatment sufficiency.

Methods

Publicly available consumption data were collected for ATC group N03A and its subgroups. Past trends in defined daily doses per 1000 inhabitants per day (DID) were analysed, and projections to 2030 were made using Auto Regressive Integrated Moving Average (ARIMA) models. For each country, treatment coverage relative to epilepsy prevalence was estimated.

Results

In 2023, ASD consumption ranged from 6.9 to 14.0 DID, with varying past and projected trends. The most commonly and increasingly used subgroup was miscellaneous (e.g. levetiracetam). Other subgroup distributions differed across countries, with most showing declines. The analysed countries of Northern Europe had the highest use and share of miscellaneous drugs, while Southern and Eastern Europe showed greater use of barbiturates and benzodiazepines. Adjusted treatment coverage revealed potential undertreatment in several countries, particularly in Eastern Europe.

Conclusion

ASD use has shifted in subgroup patterns without a uniform trend in total volume, with strong regional differences. Evaluating treatment adequacy remains challenging due to non-epilepsy indications. The increase in miscellaneous use appears to be driven by broader applications rather than substitution for older ASDs. Evidence suggests a north-to-south-east gradient, with more rational use in Northern Europe. These disparities likely reflect systemic determinants. The ATC system’s limitations reduce interpretative capability.

目的：癫痫是一项重大的全球负担，抗癫痫药物（ASDs）对治疗至关重要。本研究考察了11个欧洲国家过去和最近的ASD消费趋势，预测了未来的发展，分析了解剖治疗化学分类（ATC）亚组的使用情况，并提供了治疗充分性的初步评估。方法：收集N03A ATC组及其亚组的公开消费资料。分析了每1000名居民每日限定日剂量（DID）的过去趋势，并使用自动回归综合移动平均（ARIMA）模型对2030年进行了预测。对每个国家的治疗覆盖率与癫痫患病率的关系进行了估计。结果：2023年，ASD的消费范围为6.9 - 14.0 DID，过去和预测趋势不同。最常用和越来越多地使用的亚组是杂项（例如左乙拉西坦）。其他亚组的分布在不同国家有所不同，大多数都出现了下降。所分析的北欧国家使用各种药物的比例最高，而南欧和东欧使用巴比妥类药物和苯二氮卓类药物的比例更高。调整后的治疗覆盖率显示，在一些国家，特别是东欧，可能存在治疗不足的情况。结论：ASD使用在亚组模式上发生了变化，但在总量上没有统一的趋势，区域差异较大。由于非癫痫适应症，评估治疗的充分性仍然具有挑战性。各种用途的增加似乎是由更广泛的应用驱动的，而不是替代旧的asd。有证据表明，从北到东南的梯度，在北欧更合理地使用。这些差异可能反映了系统性的决定因素。ATC系统的局限性降低了解释能力。

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引用次数: 0

Antiseizure medication effects on the autonomic nervous system in pediatric patients with epilepsy 抗癫痫药物对小儿癫痫患者自主神经系统的影响

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-23 DOI: 10.1016/j.eplepsyres.2025.107688

Fatemeh Mohammad Alizadeh Chafjiri , Stephanie Dailey , Saeid Sadeghian , Adriana Ulate-Campos , Tobias Loddenkemper

Patients with epilepsy (PWE) taking antiseizure medications (ASMs) exhibit altered autonomic nervous system (ANS) parameters. ANS signals may monitor ASM applications and effectiveness non-invasively. Due to limited research, we reviewed the effects of ASMs on the pediatric ANS. We followed PRISMA guidelines and searched PubMed, Web of Science, and Embase for publications until 12/2024. These studies investigated the impact of ASMs on ANS, including heart rate (HR), heart rate variability (HRV), temperature, and sweat. We used Covidence software for screening processes and data extraction. After screening 9837 studies, 23 were included. Zonisamide and topiramate showed reduced sweating and increased temperature. In polytherapy patients, HRV decreased, with reductions in high-frequency (HF) values on valproic acid and low-frequency values on phenobarbital. Higher ASM doses reduced HRV but did not affect HR or sweat glands. One study reported altered cardiac ventricle functioning in PWE on ASMs. Two studies reviewing the effect of levetiracetam found minimal short-term ANS effects within the ECG but improved parasympathetic control and restored balance in HRV parameters over time. Sympathetic and parasympathetic dysfunctions were prominent in some patients, with polytherapy increasing HR and reducing HF values of HRV. In one study, higher ASM concentrations lowered HRV. Overall, ASMs may influence HR, sweat, and temperature, though many studies lacked analysis of specific ASM types. A better understanding of how ASMs affect ANS is essential for assessing medication efficacy, side effects, and their role as confounders in seizure prediction. These biosignal data can support device-based neuromodulation, seizure detection, and prediction algorithms.

癫痫患者（PWE）服用抗癫痫药物（asm）表现出改变自主神经系统（ANS）参数。ANS信号可以非侵入性地监测ASM的应用和有效性。由于研究有限，我们回顾了asm对儿科ANS的影响，遵循PRISMA指南，检索了PubMed， Web of Science和Embase的出版物，直到2024年12月。这些研究调查了asm对ANS的影响，包括心率（HR）、心率变异性（HRV）、体温和汗液。我们使用covid软件进行筛选过程和数据提取。筛选9837项研究后，纳入23项。唑尼沙胺和托吡酯显示出汗减少和体温升高。在多药治疗的患者中，HRV下降，丙戊酸降低高频（HF）值，苯巴比妥降低低频值。较高的ASM剂量降低HRV，但不影响HR或汗腺。一项研究报告了脑血管痉挛时PWE患者心室功能的改变。两项研究回顾了左乙拉西坦的作用，发现心电图的短期ANS效应很小，但随着时间的推移，副交感神经控制得到改善，HRV参数恢复平衡。部分患者交感神经和副交感神经功能障碍突出，多药治疗HRV的HR值升高，HF值降低。在一项研究中，较高的ASM浓度降低了HRV。总体而言，ASM可能影响人力资源、出汗和体温，尽管许多研究缺乏对ASM具体类型的分析。更好地了解asm如何影响ANS对于评估药物疗效、副作用及其在癫痫发作预测中作为混杂因素的作用至关重要。这些生物信号数据可以支持基于设备的神经调节、癫痫检测和预测算法。

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引用次数: 0

Altered synaptic functions in a humanized mouse model of down syndrome (TcMAC21): Implications for seizure susceptibility 唐氏综合征人源化小鼠模型（TcMAC21）突触功能改变：对癫痫易感性的影响

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-17 DOI: 10.1016/j.eplepsyres.2025.107686

Li-Rong Shao , Carl E. Stafstrom

It is not understood why children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of seizures, including infantile spasms and tonic-clonic seizures. Using a novel humanized mouse model of DS (TcMAC21), we recently showed that TcMAC21 mice express an increased propensity to infantile spasms and demonstrate an increased neocortical synaptic excitation-to-inhibition ratio. To understand the pathophysiology of DS that may predispose animals to increased seizure susceptibility, we investigated 1) kainic-acid receptor (KAR)-mediated excitation, 2) gamma-aminobutyric acid receptors A and B (GABA_AR and GABA_BR)-mediated inhibition, and 3) synaptojanin 1 (SYNJ1) function in TcMAC21 mice, as genes encoding KAR, GABA_BR and SYNJ1 are among those triplicated in DS. Layer V neocortical neurons were recorded using whole-cell patch-clamp recordings to test KAR, GABA_AR, GABA_BR, and SYNJ functions. TcMAC21 neurons responded to focal KA application with significantly larger currents than control euploid neurons. GABA_AR-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) were less frequent in TcMAC21 than in euploid neurons while sIPSC amplitudes remained unchanged. Bath application of a GABA_BR agonist, baclofen, caused similar hyperpolarization in TcMAC21 and euploid neurons. During repetitive synaptic stimulation, excitatory postsynaptic currents (EPSCs) in TcMAC21 neurons decayed slower and to a lesser extent than control euploid neurons, indicating less transmitter depletion (i.e., enhanced synaptic vesicle trafficking). These data provide the first physiological evidence for gain-of-function of KAR and SYNJ1, and altered GABA-mediated synaptic function in TcMAC21 mice, and may represent some important DS-specific mechanisms of seizure pathogenesis.

尚不清楚为什么患有唐氏综合症（DS， 21号染色体三体）的儿童癫痫发作的风险增加，包括婴儿痉挛和强直阵挛性癫痫发作。利用一种新的人源化小鼠DS模型（TcMAC21），我们最近发现TcMAC21小鼠表现出增加的婴儿痉挛倾向，并表现出增加的新皮质突触兴奋-抑制比。为了了解DS可能使动物易患癫痫的病理生理机制，我们研究了1)kainic-acid受体（KAR）介导的兴奋，2)γ -氨基丁酸受体A和B （GABAAR和GABABR）介导的抑制，以及3)synaptojanin 1 （SYNJ1）在TcMAC21小鼠中的功能，因为编码KAR、GABABR和SYNJ1的基因在DS中是三重复制的。采用全细胞膜片钳记录V层新皮层神经元，检测KAR、GABAAR、GABABR和SYNJ功能。TcMAC21神经元对KA施加的电流响应明显大于对照整倍体神经元。gabaar介导的自发性抑制性突触后电流（sIPSC）在TcMAC21中的频率低于整倍体神经元，而sIPSC振幅保持不变。GABABR激动剂巴氯芬在TcMAC21和整倍体神经元中引起类似的超极化。在重复突触刺激过程中，TcMAC21神经元中的兴奋性突触后电流（EPSCs）衰减速度较慢，且程度低于对照整倍体神经元，这表明递质耗竭较少（即突触囊泡运输增强）。这些数据为TcMAC21小鼠中KAR和SYNJ1的功能获得以及gaba介导的突触功能改变提供了第一个生理学证据，并可能代表了ds特异性癫痫发病机制的一些重要机制。

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引用次数: 0

Fenfluramine for developmental and epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS): An exploratory study 芬氟拉明治疗伴有睡眠峰波激活的发展性和癫痫性脑病（DEE-SWAS）：一项探索性研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-17 DOI: 10.1016/j.eplepsyres.2025.107687

Paloma Parra-Díaz , Antonio Gil-Nagel , Irene Sánchez-Miranda Román , Irene Pascual-Zapatero , Adrián Valls-Carbó , Ángel Aledo-Serrano , Álvaro Beltrán-Corbellini

Objective

To evaluate the safety and potential efficacy of fenfluramine (FFA) in patients with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS).

Methods

We conducted an open-label, interventional, exploratory study of FFA in pediatric patients with DEE-SWAS. We assessed changes in seizure frequency, intensity, and spike-wave index (SWI), as well as non-seizure outcomes including a neuropsychological evaluation with BRIEF®-2 and Vineland-3 questionnaires, assessment of sleep habits, and caregiver-reported changes in cognitive, behavioral and motor symptoms. Adverse effects and changes in concomitant antiseizure medications (ASMs) were recorded.

Results

Six patients were included (2 females, median age 10 years, range 4–11 years), with a median follow-up of 12 months (9–13 months). FFA was well tolerated; only two patients experienced mild, transient adverse events, and all participants continued treatment throughout the study. SWI improved in 4/6 patients (66.7 %), with ≥ 50 % reduction in two (near-resolution in one). Seizures were reported as less severe, although their frequency remained unchanged. The total dose of concomitant corticosteroids and ASMs was reduced in 66.7 % of patients. Executive functioning showed a tendency to improvement in 4/6 patients (66.7 %) based on BRIEF®-2 scores, although Vineland-3 scores remained stable. Caregivers also reported perceived improvements in behavior, cognition, and sleep.

Conclusion

FFA was a safe and potentially effective treatment in our cohort of patients with DEE-SWAS. We observed a reduction of SWI in most patients, along with modest improvements in executive function. These preliminary findings support the need for larger studies to confirm efficacy and explore long-term outcomes.

目的评价芬氟拉明（FFA）治疗发育性和癫痫性脑病伴睡眠峰波激活（DEE-SWAS）的安全性和潜在疗效。方法我们对小儿DEE-SWAS患者的FFA进行了一项开放标签、介入性、探索性研究。我们评估了癫痫发作频率、强度和峰波指数（SWI）的变化，以及非癫痫发作结果，包括使用BRIEF®-2和Vineland-3问卷进行神经心理学评估、睡眠习惯评估和护理者报告的认知、行为和运动症状的变化。记录不良反应及伴随抗癫痫药物（asm）的变化。结果纳入6例患者（2例女性，中位年龄10岁，范围4 ~ 11岁），中位随访时间为12个月（9 ~ 13个月）。FFA耐受良好；只有两名患者经历了轻微的、短暂的不良事件，所有参与者在整个研究过程中都继续接受治疗。4/6例患者SWI改善（66.7 %），2例患者SWI降低≥ 50 %（1例接近缓解）。据报道，癫痫发作的严重程度较轻，但发作频率保持不变。同时使用皮质类固醇和asm的患者总剂量降低了66.7 %。根据BRIEF®-2评分，4/6患者（66.7 %）的执行功能有改善的趋势，尽管Vineland-3评分保持稳定。护理人员也报告了行为、认知和睡眠方面的改善。结论ffa在我们的DEE-SWAS患者队列中是一种安全且潜在有效的治疗方法。我们观察到大多数患者的SWI减少，同时执行功能略有改善。这些初步发现支持需要进行更大规模的研究来确认疗效并探索长期结果。

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引用次数: 0

Reassessing anhedonia in Genetic Absence Epilepsy: Sucrose preference unaltered by spike-wave discharges in WAG/Rij rats 重新评估遗传性缺失性癫痫的快感缺乏：WAG/Rij大鼠的糖偏好未因峰波放电而改变。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-11 DOI: 10.1016/j.eplepsyres.2025.107683

Maria Pupikina, Evgenia Sitnikova

Anhedonia, characterized by reduced pleasure or interest, is linked to various neurological disorders, including genetic epilepsies. Previous studies in genetic rat models of absence epilepsy, such as WAG/Rij rats, have reported anhedonia-like behaviors. Here, we hypothesize that these behaviors depend on experimental factors rather than epilepsy itself. To test this, we conducted sucrose preference tests in WAG/Rij rats using different concentrations (2 % and 20 %), fasting durations (0 and 23 h), and test lengths (1 and 48 h). Rats underwent non-invasive electroencephalographic examination, which revealed typical 8–10 Hz spike-wave discharges (SWD) and a hallmark of absence epilepsy. In Experiment 1 (2 % sucrose), 59 symptomatic and 31 asymptomatic rats were tested at 6 and 12 months. In Experiment 2 (20 % sucrose), 34 rats were tested at 6 months. Surprisingly, there were no significant differences in sucrose preference or consumption between symptomatic and asymptomatic rats, indicating that absence epilepsy in WAG/Rij rats does not cause anhedonia. After a 23-h fast, female rats showed a lower preference for 20 % sucrose than males, suggesting that fasting conditions might introduce stress and metabolic differences that affect males and females differently. Both the 2 % and 20 % sucrose preference tests showed that symptomatic WAG/Rij rats did not exhibit anhedonia and had similar preferences to asymptomatic rats, regardless of concentration or fasting conditions. These findings challenge previous assumptions and emphasize the importance of considering methodological factors when interpreting rodent behavior.

快感缺乏症的特征是快乐或兴趣降低，与多种神经系统疾病有关，包括遗传性癫痫。先前对缺失性癫痫的遗传大鼠模型的研究，如WAG/Rij大鼠，已经报道了快感缺乏样行为。在这里，我们假设这些行为取决于实验因素而不是癫痫本身。为了验证这一点，我们对WAG/Rij大鼠进行了蔗糖偏好试验，使用不同浓度（2 %和20 %）、禁食时间（0和23 h）和试验长度（1和48 h）。大鼠进行了无创脑电图检查，发现典型的8-10 Hz的峰波放电（SWD）和缺席癫痫的标志。实验1（2 %蔗糖），分别于6个月和12个月对59只有症状大鼠和31只无症状大鼠进行实验。实验2（20 %蔗糖），34只大鼠6月龄。令人惊讶的是，有症状大鼠和无症状大鼠对蔗糖的偏好或消耗没有显著差异，这表明WAG/Rij大鼠的缺乏性癫痫不会引起快感缺乏。禁食23小时后，雌性大鼠对20% %蔗糖的偏好低于雄性，这表明禁食条件可能会引入压力和代谢差异，对雄性和雌性产生不同的影响。2 %和20 %蔗糖偏好试验表明，无论浓度或禁食条件如何，有症状的WAG/Rij大鼠没有表现出缺乏症，并且与无症状大鼠具有相似的偏好。这些发现挑战了先前的假设，并强调了在解释啮齿动物行为时考虑方法因素的重要性。

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引用次数: 0

Epilepsy in children and adolescents with B-cell acute lymphoblastic leukemia 患有b细胞急性淋巴细胞白血病的儿童和青少年癫痫

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-10 DOI: 10.1016/j.eplepsyres.2025.107671

Sun Ah Choi , Aditi Trivedi , Daanish Unwalla , Anuja Jindal , Maria A. Montenegro , Shifteh Sattar

Objective

This study aims to evaluate seizure outcomes and identify predisposing factors for epilepsy in patients diagnosed with B-cell acute lymphoblastic leukemia (B-ALL).

Methods

This was a retrospective study conducted at a tertiary care hospital. Inclusion criteria were: age younger than 18 years at the time of B-ALL diagnosis, and occurrence of seizures at any point after B-ALL diagnosis.

Results

A total of 23 patients met the inclusion criteria. The mean age at B-ALL diagnosis was 6.1 years, and 21.7 % received prophylactic brain irradiation. The mean age at first seizure was 8.5 years, with a mean latency of 28 months from B-ALL diagnosis. Of the 23 patients, 17 (73.9 %) experienced provoked seizures, most commonly related to acute or subacute methotrexate (MTX) neurotoxicity. Overall, seven patients (30.4 %) developed epilepsy, and five (21.7 %) had drug-resistant epilepsy (two with focal intractable epilepsy and three with Lennox-Gastaut syndrome). Patients who developed epilepsy had a significantly older age of seizure onset compared to those with only provoked seizures (p = 0.012), suggesting that older age at seizure onset may be a predisposing factor for epilepsy.

Conclusions

Most seizures in patients with B-ALL were provoked and resolved without the need for long-term antiseizure medication treatment. Acute or subacute MTX neurotoxicity accounted for the majority of provoked seizures. However, these rarely progressed to epilepsy. Long-term neurological surveillance is important in B-ALL survivors, especially those with delayed seizure onset or magnetic resonance imaging evidence of leukoencephalopathy.

目的本研究旨在评估b细胞急性淋巴细胞白血病（B-ALL）患者的癫痫发作结局并确定癫痫的易感因素。方法在某三级医院进行回顾性研究。纳入标准为：B-ALL诊断时年龄小于18岁，B-ALL诊断后任何时间发生癫痫发作。结果23例患者符合纳入标准。B-ALL诊断的平均年龄为6.1岁，21.7% %接受预防性脑照射。首次发作的平均年龄为8.5岁，B-ALL诊断后的平均潜伏期为28个月。在23例患者中，17例（73.9 %）经历了诱发性癫痫发作，最常见的是急性或亚急性甲氨蝶呤（MTX）神经毒性。总体而言，7名患者（30.4% %）发生癫痫，5名患者（21.7% %）发生耐药癫痫（2名局灶性难治性癫痫，3名lenox - gastaut综合征）。与仅诱发性癫痫发作的患者相比，癫痫发作的年龄明显大于诱发性癫痫发作的患者（p = 0.012），提示癫痫发作的年龄较大可能是癫痫的易感因素。结论B-ALL患者癫痫发作多为诱发性发作，不需要长期抗癫痫药物治疗。急性或亚急性MTX神经毒性占诱发性癫痫发作的大部分。然而，这些很少发展为癫痫。长期神经监测对B-ALL幸存者很重要，特别是那些延迟发作或磁共振成像证据表明脑白质病的患者。

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引用次数: 0

Histological and electrophysiological effects of sulbactam and valproate in the PTZ-induced epileptic rat model 舒巴坦和丙戊酸钠对ptz诱导癫痫大鼠模型的组织学和电生理影响。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-09 DOI: 10.1016/j.eplepsyres.2025.107676

Yun-Ju Hsieh , Fang-Chia Chang , Chiung-Hui Liu , Yi-Tse Hsiao , Wen-Chieh Liao , Ru-Yin Tsai , Ciptasari Prabawanti , Chih-Li Lin , Ching-Sui Hung , Ying-Jui Ho

An imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters is a key mechanism in epilepsy. Astrocytic glutamate transporter-1 (GLT-1) helps reuptake glutamate in the synaptic cleft to maintain glutamate concentration and prevent neuronal hyperactivity. Sulbactam (SUL), a β-lactam drug, increases GLT-1 expression. Valproate (VPA) is a first-line antiepileptic drug. The current study evaluated the effects of SUL and VPA on histology and electroencephalography in a pentylenetetrazol (PTZ)-induced epilepsy rat model.

Male Wistar rats received intraperitoneal injection of PTZ (20–35 mg/kg, every other day) for 25 days (13 injections in total) to establish an epilepsy model. From day 26, saline, SUL (50 or 150 mg/kg), VPA (50 mg/kg), or a combination of SUL and VPA was intraperitoneally administered daily for 25 days. Electroencephalography recordings were taken on day 46 or 47. Brains were used for histological analyses.

Electrophysiological results indicated that during the PTZ challenge session, the epilepsy group had significantly more spikes and seizures and higher delta, theta, and beta power compared with the control group. SUL at 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly reduced the numbers of spikes and seizures. SUL at both 50 and 150 mg/kg and the combination of SUL (50 mg/kg) and VPA (50 mg/kg) significantly inhibited the increase in delta, theta, and beta power. In terms of histology, the epilepsy group exhibited lower neuronal density in the hippocampus, lower GLT-1 expression in astrocytes, lower GABAergic density, and hyperactivity in the subthalamic nucleus. These neurophysiological impairments were restored by treatment with SUL and a combination of SUL and VPA. The results suggest that SUL increases GLT-1 expression in astrocytes and the number of GABAergic neurons, indicating it holds potential as an antiepileptic treatment.

兴奋性谷氨酸和抑制性γ -氨基丁酸（GABA）神经递质之间的不平衡是癫痫的关键机制。星形胶质细胞谷氨酸转运蛋白-1 （GLT-1）有助于突触间隙谷氨酸的再摄取，维持谷氨酸浓度，防止神经元过度活跃。舒巴坦（SUL）是一种β-内酰胺类药物，可增加GLT-1的表达。丙戊酸钠（VPA）是一线抗癫痫药物。本研究评价了SUL和VPA对戊四唑（PTZ）诱导的大鼠癫痫模型的组织学和脑电图的影响。雄性Wistar大鼠腹腔注射PTZ（20-35 mg/kg，每隔一天）25 d（共13针）建立癫痫模型。从第26天开始，每天腹腔注射生理盐水，SUL(50或150 mg/kg)， VPA(50 mg/kg)，或SUL和VPA的组合，持续25天。分别于第46天和第47天进行脑电图记录。脑组织用于组织学分析。电生理结果显示，在PTZ刺激过程中，癫痫组与对照组相比，有更多的尖峰和癫痫发作，以及更高的δ、θ和β功率。SUL（150 mg/kg）和SUL（50 mg/kg）和VPA（50 mg/kg）的组合显著减少了尖峰和癫痫发作的次数。SUL（50 mg/kg）和150 mg/kg以及SUL（50 mg/kg）和VPA（50 mg/kg）联合使用显著抑制了δ、θ和β功率的增加。在组织学上，癫痫组海马神经元密度降低，星形胶质细胞GLT-1表达降低，gaba能密度降低，丘底核多动。这些神经生理损伤可通过骶髂神经传导阻滞和骶髂神经传导阻滞联合治疗得到恢复。结果表明，SUL增加了星形胶质细胞中GLT-1的表达和gaba能神经元的数量，表明它具有抗癫痫治疗的潜力。

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引用次数: 0

Comment on the meta-analysis comparing phenobarbital and valproate for the treatment of generalized convulsive status epilepticus 比较苯巴比妥和丙戊酸治疗广泛性惊厥癫痫持续状态的meta分析评论。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-08 DOI: 10.1016/j.eplepsyres.2025.107674

Arkansh Sharma , Vinay Suresh

引用次数: 0

Author response: Seizure outcome and anti-seizure medication use in post-stroke epilepsy: A retrospective cohort study 作者回应：卒中后癫痫的发作结局和抗发作药物的使用：一项回顾性队列研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-10-03 DOI: 10.1016/j.eplepsyres.2025.107673

Ahmed Khadija, Jacques Theitler, Revital Gandelman-Marton

引用次数: 0