Pub Date : 2025-11-13DOI: 10.1016/j.eplepsyres.2025.107692
Hendriëtte van Loo-Flier , Christoph Stephan Dietze , Anne Marthe Meppelink
Objective
To investigate whether Tailored Provocation (TP) can result in habitual seizures during electroencephalogram (EEG) recording in patients with a probable diagnosis of functional seizures (FS) and if future research is feasible.
Background
The integrative model for FS suggests that seizures can be triggered by internal and external stimuli like a conditioned reflex. Using these individual stimuli as TP to provoke habitual seizures may improve diagnostic yield during EEG recording.
Methods
We identified individual TP and evaluated practical applicability. If possible we applied TP and analyzed the occurrence of habitual seizures and the perceived burden on participants. TP was conducted during EEG recording, in addition to standard photic stimulation and hyperventilation.
Results
We included 15 of 38 patients (39 %). Of these patients, 9 (60 %) experienced a habitual seizure after TP, confirming the diagnosis of FS. Epilepsy was diagnosed in 2 patients (13.3 %). All participants supported the goal of TP, and none found TP to be very or excessively burdensome.
Conclusion
TP seems promising to increase diagnostic yield during EEG-diagnostics. Further research is needed to confirm this in larger cohorts. Still, delineating whether FS provocation is directly linked to TP or to related factors, like the effect of verbal suggestion or repeated provocation, remains challenging.
{"title":"Tailored provocation in functional seizures, a pilot study","authors":"Hendriëtte van Loo-Flier , Christoph Stephan Dietze , Anne Marthe Meppelink","doi":"10.1016/j.eplepsyres.2025.107692","DOIUrl":"10.1016/j.eplepsyres.2025.107692","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether Tailored Provocation (TP) can result in habitual seizures during electroencephalogram (EEG) recording in patients with a probable diagnosis of functional seizures (FS) and if future research is feasible.</div></div><div><h3>Background</h3><div>The integrative model for FS suggests that seizures can be triggered by internal and external stimuli like a conditioned reflex. Using these individual stimuli as TP to provoke habitual seizures may improve diagnostic yield during EEG recording.</div></div><div><h3>Methods</h3><div>We identified individual TP and evaluated practical applicability. If possible we applied TP and analyzed the occurrence of habitual seizures and the perceived burden on participants. TP was conducted during EEG recording, in addition to standard photic stimulation and hyperventilation.</div></div><div><h3>Results</h3><div>We included 15 of 38 patients (39 %). Of these patients, 9 (60 %) experienced a habitual seizure after TP, confirming the diagnosis of FS. Epilepsy was diagnosed in 2 patients (13.3 %). All participants supported the goal of TP, and none found TP to be very or excessively burdensome.</div></div><div><h3>Conclusion</h3><div>TP seems promising to increase diagnostic yield during EEG-diagnostics. Further research is needed to confirm this in larger cohorts. Still, delineating whether FS provocation is directly linked to TP or to related factors, like the effect of verbal suggestion or repeated provocation, remains challenging.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107692"},"PeriodicalIF":2.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.eplepsyres.2025.107691
Zhimin Xu , Stéphane Jean , Yihai Dai , Weihong Liu , Weitao Chen , Xiaoqiang Wei , Xinrong Fang , Shiwei Song
Objective
To evaluate the relationship between multimodal diagnostic concordance and postoperative seizure outcomes in patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG)-guided volumetric radiofrequency thermocoagulation (RFTC).
Methods
In this multicenter retrospective study, 63 patients with DRE (43 children and 20 adults) underwent SEEG-guided volumetric RFTC between January 2020 and January 2024. All patients received comprehensive presurgical evaluations, including high-resolution MRI, PET, interictal and ictal video-EEG (VEEG), interictal and ictal SEEG, and electrically elicited seizures (EES). Pairwise concordance among these modalities was analyzed to assess diagnostic alignment. Postoperative seizure outcomes were evaluated after a minimum follow-up period of 12 months.
Results
Compared to the other modalities, SEEG-based modalities (ictal SEEG, interictal SEEG, and EES) demonstrated the highest concordance and sensitivity, often approaching 100 %, but were associated with lower specificity and elevated false-positive rates. MRI and VEEG offered more balanced diagnostic profiles, with moderate sensitivity and higher specificity. PET showed moderate concordance (79.66 %–88.52 %) and sensitivity (77.78 %–92.31 %), but low specificity (13.64 %–27.27 %) and high false-positive rates (72.73 %–86.36 %). SEEG-based assessments had the lowest false-negative rates, reinforcing their critical role in localizing the epileptogenic zone (EZ).
Conclusion
Higher concordance among presurgical diagnostic modalities, particularly those involving SEEG-based techniques, is linked to more accurate EZ localization. The perfect (100 %) concordance between interictal/ictal SEEG and EES-induced seizures suggests EES can reliably replicate epileptiform activity. This supports its potential to reduce inpatient monitoring by triggering seizures without waiting for spontaneous events. By comparing prior VEEG semiology with interictal SEEG, clinicians can confirm whether EES accurately mirrors clinical and electrical features, allowing faster EZ identification and streamlined presurgical evaluation.
{"title":"Multimodal diagnostic concordance and seizure outcomes following stereo-encephalography-guided volumetric radiofrequency thermocoagulation in drug-resistant epilepsy","authors":"Zhimin Xu , Stéphane Jean , Yihai Dai , Weihong Liu , Weitao Chen , Xiaoqiang Wei , Xinrong Fang , Shiwei Song","doi":"10.1016/j.eplepsyres.2025.107691","DOIUrl":"10.1016/j.eplepsyres.2025.107691","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the relationship between multimodal diagnostic concordance and postoperative seizure outcomes in patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG)-guided volumetric radiofrequency thermocoagulation (RFTC).</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study, 63 patients with DRE (43 children and 20 adults) underwent SEEG-guided volumetric RFTC between January 2020 and January 2024. All patients received comprehensive presurgical evaluations, including high-resolution MRI, PET, interictal and ictal video-EEG (VEEG), interictal and ictal SEEG, and electrically elicited seizures (EES). Pairwise concordance among these modalities was analyzed to assess diagnostic alignment. Postoperative seizure outcomes were evaluated after a minimum follow-up period of 12 months.</div></div><div><h3>Results</h3><div>Compared to the other modalities, SEEG-based modalities (ictal SEEG, interictal SEEG, and EES) demonstrated the highest concordance and sensitivity, often approaching 100 %, but were associated with lower specificity and elevated false-positive rates. MRI and VEEG offered more balanced diagnostic profiles, with moderate sensitivity and higher specificity. PET showed moderate concordance (79.66 %–88.52 %) and sensitivity (77.78 %–92.31 %), but low specificity (13.64 %–27.27 %) and high false-positive rates (72.73 %–86.36 %). SEEG-based assessments had the lowest false-negative rates, reinforcing their critical role in localizing the epileptogenic zone (EZ).</div></div><div><h3>Conclusion</h3><div>Higher concordance among presurgical diagnostic modalities, particularly those involving SEEG-based techniques, is linked to more accurate EZ localization. The perfect (100 %) concordance between interictal/ictal SEEG and EES-induced seizures suggests EES can reliably replicate epileptiform activity. This supports its potential to reduce inpatient monitoring by triggering seizures without waiting for spontaneous events. By comparing prior VEEG semiology with interictal SEEG, clinicians can confirm whether EES accurately mirrors clinical and electrical features, allowing faster EZ identification and streamlined presurgical evaluation.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107691"},"PeriodicalIF":2.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 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。
{"title":"Effectiveness and tolerability of perampanel as first add-on treatment in pediatric patients with focal and generalized epilepsy","authors":"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","doi":"10.1016/j.eplepsyres.2025.107690","DOIUrl":"10.1016/j.eplepsyres.2025.107690","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the effectiveness and safety of perampanel as first add-on vs. late add-on therapy in children with focal or generalized epilepsy.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 %, <em>p</em> = 0.003), higher seizure-freedom rates (12 months, 65 % vs. 37.0 %, <em>p</em> = 0.058), and fewer patients with worsening (12 months, 0 % vs. 12.8 %, <em>p</em> = 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107690"},"PeriodicalIF":2.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 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.
{"title":"Trends, prescribing patterns and projections of antiseizure drug use in Europe","authors":"Lilly Josephine Bindel, Roland Seifert","doi":"10.1016/j.eplepsyres.2025.107689","DOIUrl":"10.1016/j.eplepsyres.2025.107689","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107689"},"PeriodicalIF":2.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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。
{"title":"Antiseizure medication effects on the autonomic nervous system in pediatric patients with epilepsy","authors":"Fatemeh Mohammad Alizadeh Chafjiri , Stephanie Dailey , Saeid Sadeghian , Adriana Ulate-Campos , Tobias Loddenkemper","doi":"10.1016/j.eplepsyres.2025.107688","DOIUrl":"10.1016/j.eplepsyres.2025.107688","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107688"},"PeriodicalIF":2.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 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 (GABAAR and GABABR)-mediated inhibition, and 3) synaptojanin 1 (SYNJ1) function in TcMAC21 mice, as genes encoding KAR, GABABR and SYNJ1 are among those triplicated in DS. Layer V neocortical neurons were recorded using whole-cell patch-clamp recordings to test KAR, GABAAR, GABABR, and SYNJ functions. TcMAC21 neurons responded to focal KA application with significantly larger currents than control euploid neurons. GABAAR-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) were less frequent in TcMAC21 than in euploid neurons while sIPSC amplitudes remained unchanged. Bath application of a GABABR 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.
{"title":"Altered synaptic functions in a humanized mouse model of down syndrome (TcMAC21): Implications for seizure susceptibility","authors":"Li-Rong Shao , Carl E. Stafstrom","doi":"10.1016/j.eplepsyres.2025.107686","DOIUrl":"10.1016/j.eplepsyres.2025.107686","url":null,"abstract":"<div><div>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<sub>A</sub>R and GABA<sub>B</sub>R)-mediated inhibition, and 3) synaptojanin 1 (SYNJ1) function in TcMAC21 mice, as genes encoding KAR, GABA<sub>B</sub>R and SYNJ1 are among those triplicated in DS. Layer V neocortical neurons were recorded using whole-cell patch-clamp recordings to test KAR, GABA<sub>A</sub>R, GABA<sub>B</sub>R, and SYNJ functions. TcMAC21 neurons responded to focal KA application with significantly larger currents than control euploid neurons. GABA<sub>A</sub>R-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<sub>B</sub>R 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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107686"},"PeriodicalIF":2.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Fenfluramine for developmental and epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS): An exploratory study","authors":"Paloma Parra-Díaz , Antonio Gil-Nagel , Irene Sánchez-Miranda Román , Irene Pascual-Zapatero , Adrián Valls-Carbó , Ángel Aledo-Serrano , Álvaro Beltrán-Corbellini","doi":"10.1016/j.eplepsyres.2025.107687","DOIUrl":"10.1016/j.eplepsyres.2025.107687","url":null,"abstract":"<div><h3>Objective</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107687"},"PeriodicalIF":2.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-11DOI: 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.
{"title":"Reassessing anhedonia in Genetic Absence Epilepsy: Sucrose preference unaltered by spike-wave discharges in WAG/Rij rats","authors":"Maria Pupikina, Evgenia Sitnikova","doi":"10.1016/j.eplepsyres.2025.107683","DOIUrl":"10.1016/j.eplepsyres.2025.107683","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107683"},"PeriodicalIF":2.0,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 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.
{"title":"Epilepsy in children and adolescents with B-cell acute lymphoblastic leukemia","authors":"Sun Ah Choi , Aditi Trivedi , Daanish Unwalla , Anuja Jindal , Maria A. Montenegro , Shifteh Sattar","doi":"10.1016/j.eplepsyres.2025.107671","DOIUrl":"10.1016/j.eplepsyres.2025.107671","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to evaluate seizure outcomes and identify predisposing factors for epilepsy in patients diagnosed with B-cell acute lymphoblastic leukemia (B-ALL).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107671"},"PeriodicalIF":2.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-09DOI: 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.
{"title":"Histological and electrophysiological effects of sulbactam and valproate in the PTZ-induced epileptic rat model","authors":"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","doi":"10.1016/j.eplepsyres.2025.107676","DOIUrl":"10.1016/j.eplepsyres.2025.107676","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"Article 107676"},"PeriodicalIF":2.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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