Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) causes clustered seizures (late seizures; LS) 3–7 days after early seizure (ES); however, few reports provide continuous electroencephalogram (C-EEG) monitoring details. This study aimed to evaluate the initial/last detection date of LS using C-EEG and determine whether LS EEG features correlate with neurological sequelae.
Materials and methods
We analyzed 28 patients diagnosed with AESD who underwent C-EEG monitoring between 2015 and 2020. Multiple pediatric neurologists and epileptologists evaluated the LS detection timing, duration, and severity. Based on the evaluated data, we compared the clinical characteristics and LS-induced neurological sequelae between the ESEEG+LS (initiated C-EEG immediately after ES) and LSEEG+LS (initiated C-EEG after LS confirmation) groups. Additionally, we compared LS clinical characteristics and severity between severe and non-severe groups for 15 patients (baseline Pediatric Cerebral Performance Category Scale score <3).
Results
LS was detected in 17 of 28 patients. The earliest and latest LS detection dates were 2 and 11 days, respectively, and the longest LS duration was 7 days (median, 0.6 days). Regarding neurological sequelae, the LS duration was markedly longer in the severe group than that in the non-severe group during the distant period. However, LS severity was not associated with neurological sequelae.
Conclusion
This study highlights the importance of C-EEG as it could aid in the early detection of LS. Neurological sequelae correlated with LS duration but not severity.
背景：急性脑病伴双相发作和晚期弥散减少（AESD）会在早期发作（ES）后3-7天引起聚集性发作（晚期发作；LS）；然而，很少有报道提供连续脑电图（C-EEG）监测的详细信息。本研究旨在使用 C-EEG 评估 LS 的初始/最后检测日期，并确定 LS 的脑电图特征是否与神经系统后遗症相关：我们分析了 2015 年至 2020 年期间接受 C-EEG 监测的 28 例确诊为 AESD 的患者。多名儿科神经学家和癫痫专家对 LS 的检测时间、持续时间和严重程度进行了评估。根据评估数据，我们比较了 ESEEG+LS 组（ES 后立即启动 C-EEG）和 LSEEG+LS 组（LS 确认后启动 C-EEG）的临床特征和 LS 引发的神经系统后遗症。此外，我们还比较了 15 名患者（基线小儿脑功能分类量表评分结果）的重度和非重度组 LS 临床特征和严重程度：28 例患者中有 17 例检测出 LS。最早和最晚发现 LS 的日期分别为 2 天和 11 天，最长的 LS 持续时间为 7 天（中位数为 0.6 天）。在神经系统后遗症方面，严重组的 LS 持续时间明显长于远期的非严重组。然而，LS严重程度与神经系统后遗症无关：本研究强调了 C-EEG 的重要性，因为它有助于早期发现 LS。神经系统后遗症与 LS 持续时间相关，但与严重程度无关。
{"title":"Evaluating the late seizures of acute encephalopathy with biphasic seizures and late reduced diffusion via monitoring using continuous electroencephalogram","authors":"Naohiro Yamamoto , Ichiro Kuki , Naoki Yamada , Shizuka Nagase-Oikawa , Masataka Fukuoka , Kim Kiyohiro , Takeshi Inoue , Megumi Nukui , Junichi Ishikawa , Kiyoko Amo , Masao Togawa , Yasunori Otsuka , Shin Okazaki","doi":"10.1016/j.eplepsyres.2024.107483","DOIUrl":"10.1016/j.eplepsyres.2024.107483","url":null,"abstract":"<div><h3>Background</h3><div>Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) causes clustered seizures (late seizures; LS) 3–7 days after early seizure (ES); however, few reports provide continuous electroencephalogram (C-EEG) monitoring details. This study aimed to evaluate the initial/last detection date of LS using C-EEG and determine whether LS EEG features correlate with neurological sequelae.</div></div><div><h3>Materials and methods</h3><div>We analyzed 28 patients diagnosed with AESD who underwent C-EEG monitoring between 2015 and 2020. Multiple pediatric neurologists and epileptologists evaluated the LS detection timing, duration, and severity. Based on the evaluated data, we compared the clinical characteristics and LS-induced neurological sequelae between the ESEEG+LS (initiated C-EEG immediately after ES) and LSEEG+LS (initiated C-EEG after LS confirmation) groups. Additionally, we compared LS clinical characteristics and severity between severe and non-severe groups for 15 patients (baseline Pediatric Cerebral Performance Category Scale score <3).</div></div><div><h3>Results</h3><div>LS was detected in 17 of 28 patients. The earliest and latest LS detection dates were 2 and 11 days, respectively, and the longest LS duration was 7 days (median, 0.6 days). Regarding neurological sequelae, the LS duration was markedly longer in the severe group than that in the non-severe group during the distant period. However, LS severity was not associated with neurological sequelae.</div></div><div><h3>Conclusion</h3><div>This study highlights the importance of C-EEG as it could aid in the early detection of LS. Neurological sequelae correlated with LS duration but not severity.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"209 ","pages":"Article 107483"},"PeriodicalIF":2.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695421","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 : 2024-11-10DOI: 10.1016/j.eplepsyres.2024.107477
Ashley M. Howell, Shelly Wang, John Ragheb, Julia Decker, Erik C. Brown
The Hemispherectomy Outcome Prediction Scale (HOPS) was developed to aid both clinicians and patients in determining the chance of success after hemispheric surgery for medically refractory epilepsy. The original study generating HOPS had a multi-institutional, large cohort format yielding near perfect patient stratification. Evidence suggests that methodologies utilized to create such predictive models, including cross-validation as well as stratification utilizing the same data employed for model generation, may be at risk of an undesirable modeling phenomenon known as overfitting. We posed the question of whether overfitting may be influencing HOPS results and aimed for preliminary evidence of external validation with parameters from patients at our institution not included in the original HOPS study. We found HOPS to stratify our limited post-operative cohort adequately. However, the likelihood of complete seizure freedom among the patients predicted by HOPS to be at greatest chance of success was ∼75 %, about 20 points lower than in the original HOPS cohort. This reduction in absolute chance of success predicted by HOPS may represent some degree of overfitting. It will be informative to aim for external validation of HOPS utilizing patient cohorts entirely separate from those used for model generation. External validation of HOPS and similar models could optimize realistic prediction of success after intervention.
{"title":"Validation of hemispherectomy outcome prediction scale in treatment of medically intractable epilepsy","authors":"Ashley M. Howell, Shelly Wang, John Ragheb, Julia Decker, Erik C. Brown","doi":"10.1016/j.eplepsyres.2024.107477","DOIUrl":"10.1016/j.eplepsyres.2024.107477","url":null,"abstract":"<div><div>The Hemispherectomy Outcome Prediction Scale (HOPS) was developed to aid both clinicians and patients in determining the chance of success after hemispheric surgery for medically refractory epilepsy. The original study generating HOPS had a multi-institutional, large cohort format yielding near perfect patient stratification. Evidence suggests that methodologies utilized to create such predictive models, including cross-validation as well as stratification utilizing the same data employed for model generation, may be at risk of an undesirable modeling phenomenon known as overfitting. We posed the question of whether overfitting may be influencing HOPS results and aimed for preliminary evidence of external validation with parameters from patients at our institution not included in the original HOPS study. We found HOPS to stratify our limited post-operative cohort adequately. However, the likelihood of complete seizure freedom among the patients predicted by HOPS to be at greatest chance of success was ∼75 %, about 20 points lower than in the original HOPS cohort. This reduction in absolute chance of success predicted by HOPS may represent some degree of overfitting. It will be informative to aim for external validation of HOPS utilizing patient cohorts entirely separate from those used for model generation. External validation of HOPS and similar models could optimize realistic prediction of success after intervention.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107477"},"PeriodicalIF":2.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644216","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 : 2024-11-08DOI: 10.1016/j.eplepsyres.2024.107478
Raquel Samões , Ana Cavalheiro , Cristina Santos , Joana Lopes , Catarina Teixeira , Maria Manuel Tavares , Cláudia Carvalho , Carolina Lemos , Paulo Pinho e Costa , Sara Cavaco , João Chaves , Bárbara Leal
Background
Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD.
Methods
Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR.
Results
Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17–100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %.
Conclusions
A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.
{"title":"MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept study","authors":"Raquel Samões , Ana Cavalheiro , Cristina Santos , Joana Lopes , Catarina Teixeira , Maria Manuel Tavares , Cláudia Carvalho , Carolina Lemos , Paulo Pinho e Costa , Sara Cavaco , João Chaves , Bárbara Leal","doi":"10.1016/j.eplepsyres.2024.107478","DOIUrl":"10.1016/j.eplepsyres.2024.107478","url":null,"abstract":"<div><h3>Background</h3><div>Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD.</div></div><div><h3>Methods</h3><div>Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR.</div></div><div><h3>Results</h3><div>Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17–100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %.</div></div><div><h3>Conclusions</h3><div>A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107478"},"PeriodicalIF":2.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616803","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 : 2024-11-08DOI: 10.1016/j.eplepsyres.2024.107474
Chi-Yuan Chang , Boyu Zhang , Robert Moss , Rosalind Picard , M. Brandon Westover , Daniel Goldenholz
Background
This study aims to illustrate the connection between seizure frequency (SF) and performance metrics in seizure forecasting, and to compare the effectiveness of a moving average (MA) model versus the commonly used permutation benchmark.
Methods
Metrics of calibration and discrimination were computed for each dataset, comparing MA and permutation performance across SF values. Three datasets were used: (1) self-reported seizure diaries from 3994 Seizure Tracker patients, (2) automatically detected and sometimes manually reported or edited generalized tonic-clonic seizures from 2350 Empatica Embrace 2 and Mate App users, and (3) simulated datasets with varying SFs.
Results
Most metrics were found to depend on SF. The MA model outperformed or matched the permutation model in all cases. These more advanced metrics show that comparison to permutation will falsely elevate poor forecasting models.
Conclusions
The findings highlight SF's role in seizure forecasting accuracy and the MA model's suitability as a benchmark. This study underscores the need for considering patient SF in forecasting studies and suggests the MA model may provide a better standard for evaluating future seizure forecasting models.
背景：本研究旨在说明癫痫发作频率（SF）与癫痫发作预测中的性能指标之间的联系，并比较移动平均（MA）模型与常用的置换基准的有效性：方法：计算每个数据集的校准和判别指标，比较不同 SF 值的移动平均模型和置换模型的性能。使用了三个数据集：(1) 来自 3994 名 Seizure Tracker 患者的自我报告发作日记；(2) 来自 2350 名 Empatica Embrace 2 和 Mate App 用户的自动检测和有时手动报告或编辑的全身强直阵挛发作；(3) 具有不同 SF 的模拟数据集：结果：发现大多数指标取决于 SF。在所有情况下，MA 模型都优于或与 permutation 模型相当。这些更先进的指标表明，与置换模型进行比较会错误地抬高差劲的预测模型：研究结果强调了 SF 在癫痫发作预测准确性中的作用以及 MA 模型作为基准的适用性。这项研究强调了在预测研究中考虑患者 SF 的必要性，并建议 MA 模型可为评估未来的癫痫发作预测模型提供更好的标准。
{"title":"Necessary for seizure forecasting outcome metrics: Seizure frequency and benchmark model","authors":"Chi-Yuan Chang , Boyu Zhang , Robert Moss , Rosalind Picard , M. Brandon Westover , Daniel Goldenholz","doi":"10.1016/j.eplepsyres.2024.107474","DOIUrl":"10.1016/j.eplepsyres.2024.107474","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to illustrate the connection between seizure frequency (SF) and performance metrics in seizure forecasting, and to compare the effectiveness of a moving average (MA) model versus the commonly used permutation benchmark.</div></div><div><h3>Methods</h3><div>Metrics of calibration and discrimination were computed for each dataset, comparing MA and permutation performance across SF values. Three datasets were used: (1) self-reported seizure diaries from 3994 Seizure Tracker patients, (2) automatically detected and sometimes manually reported or edited generalized tonic-clonic seizures from 2350 Empatica Embrace 2 and Mate App users, and (3) simulated datasets with varying SFs.</div></div><div><h3>Results</h3><div>Most metrics were found to depend on SF. The MA model outperformed or matched the permutation model in all cases. These more advanced metrics show that comparison to permutation will falsely elevate poor forecasting models.</div></div><div><h3>Conclusions</h3><div>The findings highlight SF's role in seizure forecasting accuracy and the MA model's suitability as a benchmark. This study underscores the need for considering patient SF in forecasting studies and suggests the MA model may provide a better standard for evaluating future seizure forecasting models.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107474"},"PeriodicalIF":2.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616826","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 : 2024-11-08DOI: 10.1016/j.eplepsyres.2024.107476
Fan Wu , Xinna Ji , Mengxiao Shen , Peidi Cheng , Yanyan Gao , Wanting Liu , Jinxiao Chen , Shuo Feng , Huanhuan Wu , Fei Di , Yunlin Li , Jianhua Wang , Xue Zhang , Qian Chen
Background
Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome that predisposes patients to seizures. We aimed to estimate the prevalence, clinical characteristics and outcomes of seizures in NF1 patients, and analyze prognostic factors of seizures.
Methods
Systematic searches were conducted in the PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and grey literature databases from inception to April 2024. We identified observational studies that included NF1 patients with seizures. Clinical characteristics of seizures were summarized and meta-analyses of prevalence and outcomes were conducted. We assessed publication bias using funnel plots and conducted sensitivity analysis to assess stability and reliability. Individual patient data were analyzed to evaluate prognostic factors.
Results
Fourteen studies were identified from 1021 records. A total of 337 patients with seizures from 4946 NF1 patients were included. Meta-analysis indicated the overall prevalence of seizures in NF1 patients was 8.1 % (95 % CI= 5.9–10.3 %). The first seizure usually occurs in childhood, with a median age range of 3.5–12.0 years. Focal seizures (54.2 %) and generalized tonic-clonic seizures (16.8 %) were the most common types. The seizure freedom rate was 68.5 % (95 % CI= 57.5–79.5 %), mostly with one or two antiseizure medications. Cortical malformation/hippocampus sclerosis emerged as an independent risk factor for persistent seizures (OR=5.19, 95 %CI=1.27–21.18, P=0.02).
Conclusion
Though NF1 patients face a higher risk of seizures than the general population, the majority achieve seizure freedom. Patients with cortical malformation or hippocampus sclerosis were at a higher risk of persistent seizures.
{"title":"Prevalence, clinical characteristics and outcomes of seizures in neurofibromatosis type 1: A systematic review and single arm meta-analysis","authors":"Fan Wu , Xinna Ji , Mengxiao Shen , Peidi Cheng , Yanyan Gao , Wanting Liu , Jinxiao Chen , Shuo Feng , Huanhuan Wu , Fei Di , Yunlin Li , Jianhua Wang , Xue Zhang , Qian Chen","doi":"10.1016/j.eplepsyres.2024.107476","DOIUrl":"10.1016/j.eplepsyres.2024.107476","url":null,"abstract":"<div><h3>Background</h3><div>Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome that predisposes patients to seizures. We aimed to estimate the prevalence, clinical characteristics and outcomes of seizures in NF1 patients, and analyze prognostic factors of seizures.</div></div><div><h3>Methods</h3><div>Systematic searches were conducted in the PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and grey literature databases from inception to April 2024. We identified observational studies that included NF1 patients with seizures. Clinical characteristics of seizures were summarized and meta-analyses of prevalence and outcomes were conducted. We assessed publication bias using funnel plots and conducted sensitivity analysis to assess stability and reliability. Individual patient data were analyzed to evaluate prognostic factors.</div></div><div><h3>Results</h3><div>Fourteen studies were identified from 1021 records. A total of 337 patients with seizures from 4946 NF1 patients were included. Meta-analysis indicated the overall prevalence of seizures in NF1 patients was 8.1 % (95 % CI= 5.9–10.3 %). The first seizure usually occurs in childhood, with a median age range of 3.5–12.0 years. Focal seizures (54.2 %) and generalized tonic-clonic seizures (16.8 %) were the most common types. The seizure freedom rate was 68.5 % (95 % CI= 57.5–79.5 %), mostly with one or two antiseizure medications. Cortical malformation/hippocampus sclerosis emerged as an independent risk factor for persistent seizures (OR=5.19, 95 %CI=1.27–21.18, P=0.02).</div></div><div><h3>Conclusion</h3><div>Though NF1 patients face a higher risk of seizures than the general population, the majority achieve seizure freedom. Patients with cortical malformation or hippocampus sclerosis were at a higher risk of persistent seizures.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107476"},"PeriodicalIF":2.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616931","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 : 2024-11-08DOI: 10.1016/j.eplepsyres.2024.107471
Deeksha Sharma , Sudhir Chandra Sarangi , Surabhi Sinha , Soumya Sucharita Pattnaik , Yajnaseni Dash , Aruna Nambirajan , Tapas Chandra Nag , Surender Singh , Matthew C. Walker
Objective
4-butylcyclohexane carboxylic acid (4-BCCA), a low-affinity inhibitor of AMPA receptors at the trans-membrane domain have been suggested as potential therapeutic option for epilepsy, but its potential impact on status epilepticus and disease-modification and neurodegeneration following status epilepticus have not been investigated.
Methods
This study established the effect of 4-BCCA along with standard antiseizure medications (ASMs) [valproate (VPA) and perampanel (PER)] in Li-pilocarpine induced status epilepticus rat model. We first established the effective dose of 4-BCCA in status epilepticus followed by an acute and long-term effect study. Assessments of neurobehaviour (by elevated plus maze and passive avoidance), neurodegeneration [by transmission electron microscopy (TEM) and immunohistochemistry in hippocampal slices], total antioxidant capacity (TAC) and neuronal loss [by neuron specific enolase (NSE) in cerebral tissue] were performed.
Results
4-BCCA at 200 mg/kg. i.p. was found to be an effective dose and in comparison, to other ASMs it showed better seizure control in terms of latency and number of stage 3/4 seizures. PER group and 4-BCCA+PER showed better memory retention but without significant difference among the drug-treated groups. In TEM, 4-BCCA+PER and 4-BCCA+VPA group showed less nucleus and cytoplasmic changes. In immunohistochemistry 4-BCCA, PER and combination groups showed better neuronal viability. 4-BCCA+ PER showed higher TAC and lower NSE level.
Significance
4-BCCA alone and its combination with ASMs especially perampanel in status epilepticus model in rats showed better seizure control and neuroprotection.
{"title":"Effect of trans 4-butylcyclohexane carboxylic acid (4-BCCA) upon neurodegeneration, oxidative stress related to epileptogenesis in pilocarpine-induced status epilepticus","authors":"Deeksha Sharma , Sudhir Chandra Sarangi , Surabhi Sinha , Soumya Sucharita Pattnaik , Yajnaseni Dash , Aruna Nambirajan , Tapas Chandra Nag , Surender Singh , Matthew C. Walker","doi":"10.1016/j.eplepsyres.2024.107471","DOIUrl":"10.1016/j.eplepsyres.2024.107471","url":null,"abstract":"<div><h3>Objective</h3><div>4-butylcyclohexane carboxylic acid (4-BCCA), a low-affinity inhibitor of AMPA receptors at the trans-membrane domain have been suggested as potential therapeutic option for epilepsy, but its potential impact on status epilepticus and disease-modification and neurodegeneration following status epilepticus have not been investigated.</div></div><div><h3>Methods</h3><div>This study established the effect of 4-BCCA along with standard antiseizure medications (ASMs) [valproate (VPA) and perampanel (PER)] in Li-pilocarpine induced status epilepticus rat model. We first established the effective dose of 4-BCCA in status epilepticus followed by an acute and long-term effect study. Assessments of neurobehaviour (by elevated plus maze and passive avoidance), neurodegeneration [by transmission electron microscopy (TEM) and immunohistochemistry in hippocampal slices], total antioxidant capacity (TAC) and neuronal loss [by neuron specific enolase (NSE) in cerebral tissue] were performed.</div></div><div><h3>Results</h3><div>4-BCCA at 200 mg/kg. i.p. was found to be an effective dose and in comparison, to other ASMs it showed better seizure control in terms of latency and number of stage 3/4 seizures. PER group and 4-BCCA+PER showed better memory retention but without significant difference among the drug-treated groups. In TEM, 4-BCCA+PER and 4-BCCA+VPA group showed less nucleus and cytoplasmic changes. In immunohistochemistry 4-BCCA, PER and combination groups showed better neuronal viability. 4-BCCA+ PER showed higher TAC and lower NSE level.</div></div><div><h3>Significance</h3><div>4-BCCA alone and its combination with ASMs especially perampanel in status epilepticus model in rats showed better seizure control and neuroprotection.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"209 ","pages":"Article 107471"},"PeriodicalIF":2.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700284","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 : 2024-11-02DOI: 10.1016/j.eplepsyres.2024.107475
Xiang Ji , Yuanyuan Dang , Ming Song , Aijun Liu , Hulin Zhao , Tianzi Jiang
Background
Precisely localizing the seizure onset zone (SOZ) is critical for focal epilepsy surgery. Existing methods mainly focus on high-frequency activities in stereo-electroencephalography, but often fail when seizures are not driven by high-frequency activities. Recognized as biomarkers of epileptic seizures, ictal spikes in SOZ induce epileptiform discharges in other brain regions. Based on this understanding, we aim to develop a universal algorithm to localize SOZ and investigate how ictal spikes within the SOZ induce seizures.
Methods
We proposed a novel metric called standard deviation of spike amplitude (SDSA) and utilized channel-averaged SDSA to describe seizure processes and detect seizures. By integrating SDSA values in specific intervals, the score for each channel located within SOZ was calculated. Channels with high SOZ scores were clustered as SOZ. The localization accuracy was asserted using area under the receiver operating characteristic (ROC) curve. Further, we analyzed early ictal signals from SOZ channels and investigated factors influencing their duration to reveal the seizure inducing conditions.
Results
We analyzed data from 15 patients with focal epilepsy. The channel-averaged SDSA successfully detected all 28 seizures without false alarms. Using SDSA integration, we achieved precise SOZ localization with an average area under ROC curve (AUC) of 0.96, significantly outperforming previous methods based on high-frequency activities. Further, we discovered that energy of ictal spikes in SOZ was concentrated at a specific frequency distributed in [6, 12 Hz]. Additionally, we found that the higher the energy per second in this frequency band, the faster ictal spikes could induce seizures.
Conclusion
The SDSA metric offered precise SOZ localization with robustness and low computational cost, making it suitable for clinical practice. By studying the propagation patterns of ictal spikes between the SOZ and non-SOZ, we suggest that ictal spikes from SOZ need to accumulate energy at a specific central frequency to induce epileptic spikes in non-SOZ, which may have significant implications for understanding the seizure onset pattern.
{"title":"A universal method for seizure onset zone localization in focal epilepsy using standard deviation of spike amplitude","authors":"Xiang Ji , Yuanyuan Dang , Ming Song , Aijun Liu , Hulin Zhao , Tianzi Jiang","doi":"10.1016/j.eplepsyres.2024.107475","DOIUrl":"10.1016/j.eplepsyres.2024.107475","url":null,"abstract":"<div><h3>Background</h3><div>Precisely localizing the seizure onset zone (SOZ) is critical for focal epilepsy surgery. Existing methods mainly focus on high-frequency activities in stereo-electroencephalography, but often fail when seizures are not driven by high-frequency activities. Recognized as biomarkers of epileptic seizures, ictal spikes in SOZ induce epileptiform discharges in other brain regions. Based on this understanding, we aim to develop a universal algorithm to localize SOZ and investigate how ictal spikes within the SOZ induce seizures.</div></div><div><h3>Methods</h3><div>We proposed a novel metric called standard deviation of spike amplitude (SDSA) and utilized channel-averaged SDSA to describe seizure processes and detect seizures. By integrating SDSA values in specific intervals, the score for each channel located within SOZ was calculated. Channels with high SOZ scores were clustered as SOZ. The localization accuracy was asserted using area under the receiver operating characteristic (ROC) curve. Further, we analyzed early ictal signals from SOZ channels and investigated factors influencing their duration to reveal the seizure inducing conditions.</div></div><div><h3>Results</h3><div>We analyzed data from 15 patients with focal epilepsy. The channel-averaged SDSA successfully detected all 28 seizures without false alarms. Using SDSA integration, we achieved precise SOZ localization with an average area under ROC curve (AUC) of 0.96, significantly outperforming previous methods based on high-frequency activities. Further, we discovered that energy of ictal spikes in SOZ was concentrated at a specific frequency distributed in [6, 12 Hz]. Additionally, we found that the higher the energy per second in this frequency band, the faster ictal spikes could induce seizures.</div></div><div><h3>Conclusion</h3><div>The SDSA metric offered precise SOZ localization with robustness and low computational cost, making it suitable for clinical practice. By studying the propagation patterns of ictal spikes between the SOZ and non-SOZ, we suggest that ictal spikes from SOZ need to accumulate energy at a specific central frequency to induce epileptic spikes in non-SOZ, which may have significant implications for understanding the seizure onset pattern.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107475"},"PeriodicalIF":2.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593409","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 : 2024-10-30DOI: 10.1016/j.eplepsyres.2024.107472
Luca Zanuttini , Federico Mason , Lorenzo Ferri , Elena Pasini , Lidia Di Vito , Roberto Mai , Laura Tassi , Laura Castana , Gianfranco Vornetti , Lorenzo Muccioli , Luigi Cirillo , Francesca Bisulli , Roberto Michelucci , Raffaele Lodi , Francesco Cardinale , Matteo Martinoni
Objective
Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is an invasive procedure based on stereotactic lesioning of cortical targets in the brain using bipolar current through electrode contacts within the SEEG implant. To date, several RF-TC protocols have been described in the literature; however, a consensus has yet to be reached. This work aims to analyze the electrical parameters during RF-TC processes, offering a method to objectively describe and compare different SEEG-guided RF-TC protocols.
Methods
The study included patients who underwent RF-TC procedures at the IRCCS Istituto delle Scienze Neurologiche di Bologna from February 2022 to May 2023. During each procedure, modifications of the following parameters were measured: voltage, current, impedance, and electric power. An ad-hoc algorithm was implemented to detect abrupt impedance raises, which reflects the occurrence of the thermocoagulation. A two-sample t-test was used to compare parameter curves in RF-TC of different brain structures.
Results
A total of ninety-two RF-TC procedures were performed in eight patients according to a standardized protocol. During each procedure, impedance levels started at about and rose up to , displaying an erratic pattern characterized by one or multiple raises. All measured parameters exhibited similar trends until the first peak, after which changes were influenced by the frequency of impedance raises. No significant correlations were observed between parameter modifications in distinct anatomical sites of RF-TC.
Significance
The systematic analysis of electrical parameters may represent a reliable tool to compare different RF-TC protocols, paving the way for identifying optimal configurations for SEEG-guided RF-TC procedures in the future.
{"title":"Parameter analysis in stereoelectroencephalography-guided radiofrequency thermocoagulation: A common basis for objective comparison between protocols","authors":"Luca Zanuttini , Federico Mason , Lorenzo Ferri , Elena Pasini , Lidia Di Vito , Roberto Mai , Laura Tassi , Laura Castana , Gianfranco Vornetti , Lorenzo Muccioli , Luigi Cirillo , Francesca Bisulli , Roberto Michelucci , Raffaele Lodi , Francesco Cardinale , Matteo Martinoni","doi":"10.1016/j.eplepsyres.2024.107472","DOIUrl":"10.1016/j.eplepsyres.2024.107472","url":null,"abstract":"<div><h3>Objective</h3><div>Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is an invasive procedure based on stereotactic lesioning of cortical targets in the brain using bipolar current through electrode contacts within the SEEG implant. To date, several RF-TC protocols have been described in the literature; however, a consensus has yet to be reached. This work aims to analyze the electrical parameters during RF-TC processes, offering a method to objectively describe and compare different SEEG-guided RF-TC protocols.</div></div><div><h3>Methods</h3><div>The study included patients who underwent RF-TC procedures at the IRCCS Istituto delle Scienze Neurologiche di Bologna from February 2022 to May 2023. During each procedure, modifications of the following parameters were measured: voltage, current, impedance, and electric power. An ad-hoc algorithm was implemented to detect abrupt impedance raises, which reflects the occurrence of the thermocoagulation. A two-sample t-test was used to compare parameter curves in RF-TC of different brain structures.</div></div><div><h3>Results</h3><div>A total of ninety-two RF-TC procedures were performed in eight patients according to a standardized protocol. During each procedure, impedance levels started at about <span><math><mrow><mn>700</mn><mi>Ω</mi></mrow></math></span> and rose up to <span><math><mrow><mn>1300</mn><mi>Ω</mi></mrow></math></span>, displaying an erratic pattern characterized by one or multiple raises. All measured parameters exhibited similar trends until the first peak, after which changes were influenced by the frequency of impedance raises. No significant correlations were observed between parameter modifications in distinct anatomical sites of RF-TC.</div></div><div><h3>Significance</h3><div>The systematic analysis of electrical parameters may represent a reliable tool to compare different RF-TC protocols, paving the way for identifying optimal configurations for SEEG-guided RF-TC procedures in the future.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107472"},"PeriodicalIF":2.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578071","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 : 2024-10-29DOI: 10.1016/j.eplepsyres.2024.107473
Rohan Jha , Melissa M.J. Chua , David D. Liu , R. Mark Richardson , Steven Tobochnik , John D. Rolston
Introduction
Patients considering therapeutic epilepsy surgery often seek to decrease the number of anti-seizure medications (ASMs) they need. Predicting such reductions remains challenging. Although predictors of seizure freedom after epilepsy surgery are well-established, long-term outcomes remain modest and factors associated with ASM reduction, even in the absence of seizure freedom, may improve surgical planning to align with patient goals.
Methods
We studied a large multi-institutional cohort of patients who underwent epilepsy surgery between 2001 and 2022, with a minimum of two years follow-up. Preoperative features, including duration of epilepsy, epilepsy etiology, non-invasive investigation data, and total number of ASMs prescribed immediately prior to surgery were extracted for each patient. Primary endpoints included likelihood of ASM reduction and ASM freedom at multiple post-operative time points up to 15 years and stratified by seizure control.
Results
A total of 250 patients were followed for a median of 6.0 (range 2, 22) years after intracranial EEG (iEEG) surgery. Significant ASM reduction was only observed in those who underwent subsequent resection, whereas those undergoing neuromodulation saw their ASM usage maintained. Engel I outcomes were the strongest driver of ASM reduction. In patients with persistent seizures, patients with lateralized seizure onset zones (SOZs) also achieved sustained ASM reduction over time. Similarly, an increased number of preoperative ASMs also corresponded to a higher likelihood of ASM reduction across all follow-up periods. Other preoperative factors, including seizure etiology, did not independently influence ASM reduction.
Conclusions
Even patients with persistent seizures after epilepsy surgery can observe meaningful ASM reduction during long-term follow-up. ASM reduction may be a relevant secondary outcome measure for epilepsy surgery.
{"title":"Beyond seizure freedom: Reduction in anti-seizure medication after epilepsy surgery","authors":"Rohan Jha , Melissa M.J. Chua , David D. Liu , R. Mark Richardson , Steven Tobochnik , John D. Rolston","doi":"10.1016/j.eplepsyres.2024.107473","DOIUrl":"10.1016/j.eplepsyres.2024.107473","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients considering therapeutic epilepsy surgery often seek to decrease the number of anti-seizure medications (ASMs) they need. Predicting such reductions remains challenging. Although predictors of seizure freedom after epilepsy surgery are well-established, long-term outcomes remain modest and factors associated with ASM reduction, even in the absence of seizure freedom, may improve surgical planning to align with patient goals.</div></div><div><h3>Methods</h3><div>We studied a large multi-institutional cohort of patients who underwent epilepsy surgery between 2001 and 2022, with a minimum of two years follow-up. Preoperative features, including duration of epilepsy, epilepsy etiology, non-invasive investigation data, and total number of ASMs prescribed immediately prior to surgery were extracted for each patient. Primary endpoints included likelihood of ASM reduction and ASM freedom at multiple post-operative time points up to 15 years and stratified by seizure control.</div></div><div><h3>Results</h3><div>A total of 250 patients were followed for a median of 6.0 (range 2, 22) years after intracranial EEG (iEEG) surgery. Significant ASM reduction was only observed in those who underwent subsequent resection, whereas those undergoing neuromodulation saw their ASM usage maintained. Engel I outcomes were the strongest driver of ASM reduction. In patients with persistent seizures, patients with lateralized seizure onset zones (SOZs) also achieved sustained ASM reduction over time. Similarly, an increased number of preoperative ASMs also corresponded to a higher likelihood of ASM reduction across all follow-up periods. Other preoperative factors, including seizure etiology, did not independently influence ASM reduction.</div></div><div><h3>Conclusions</h3><div>Even patients with persistent seizures after epilepsy surgery can observe meaningful ASM reduction during long-term follow-up. ASM reduction may be a relevant secondary outcome measure for epilepsy surgery.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107473"},"PeriodicalIF":2.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553760","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}
Clinical studies of repetitive transcranial magnetic stimulation (rTMS) do not provide consistent efficacy results, possibly due to variability in methodological parameters. Our aim is to systematically review preclinical rTMS protocols in murine models of epilepsy, offering insights from might facilitate the optimization of clinical trials.
Methods
We searched MEDLINE, SCOPUS and Web of Science from inception until December 2023, including English-written and peer-reviewed studies with clinical or electroencephalographic (EEG) outcomes.
Results
Among 480 search results, in the 23 eligible studies both mice and rats were used. Epilepsy induction methods included injections of pentylenetetrazole, kainic acid, picrotoxin and lithium-pilocarpine, electrical kindling (amygdala/ventral hippocampus), electroconvulsive shock and genetic models of absence and temporal lobe epilepsy. For motor threshold (MT) definition electromyography with motor evoked potentials and single-pulse TMS were used. Stimulation intensity ranged between 40 % and 200 % of MT or 0.125–2.5 T. High-frequency rTMS (≥5 Hz) demonstrated either no effect on seizure suppression or a rather facilitatory effect, promoting ictogenesis, with the exception of 20-Hz-rTMS coupling with lorazepam for status epilepticus cessation. Low-frequency rTMS (<5 Hz), primarily at 0.5 and 1 Hz, exerted an inhibitory effect on both clinical and EEG parameters on various epilepsy models in most studies and also significantly ameliorated performance in behavioral tests.
Conclusions
rTMS holds potential for effective neuromodulation, that is critically dependent on stimulation frequency and epilepsy type. Translational knowledge gained from preclinical protocols may inform and optimize rTMS application for epilepsy management in future clinical trials.
{"title":"Repetitive transcranial magnetic stimulation in murine models of epilepsy: A systematic review of methodological aspects and outcomes","authors":"Vasilis-Spyridon Tseriotis , Vasilios K. Kimiskidis , David-Dimitris Chlorogiannis , Marianthi Arnaoutoglou , Dimitrios Kouvelas , Georgios Konstantis , Sofia Karachrysafi , Faye Malliou , Paraskevas Mavropoulos , Marina Manani , Stavroula Koukou , Chryssa Pourzitaki","doi":"10.1016/j.eplepsyres.2024.107468","DOIUrl":"10.1016/j.eplepsyres.2024.107468","url":null,"abstract":"<div><h3>Objectives</h3><div>Clinical studies of repetitive transcranial magnetic stimulation (rTMS) do not provide consistent efficacy results, possibly due to variability in methodological parameters. Our aim is to systematically review preclinical rTMS protocols in murine models of epilepsy, offering insights from might facilitate the optimization of clinical trials.</div></div><div><h3>Methods</h3><div>We searched MEDLINE, SCOPUS and Web of Science from inception until December 2023, including English-written and peer-reviewed studies with clinical or electroencephalographic (EEG) outcomes.</div></div><div><h3>Results</h3><div>Among 480 search results, in the 23 eligible studies both mice and rats were used. Epilepsy induction methods included injections of pentylenetetrazole, kainic acid, picrotoxin and lithium-pilocarpine, electrical kindling (amygdala/ventral hippocampus), electroconvulsive shock and genetic models of absence and temporal lobe epilepsy. For motor threshold (MT) definition electromyography with motor evoked potentials and single-pulse TMS were used. Stimulation intensity ranged between 40 % and 200 % of MT or 0.125–2.5 T. High-frequency rTMS (≥5 Hz) demonstrated either no effect on seizure suppression or a rather facilitatory effect, promoting ictogenesis, with the exception of 20-Hz-rTMS coupling with lorazepam for status epilepticus cessation. Low-frequency rTMS (<5 Hz), primarily at 0.5 and 1 Hz, exerted an inhibitory effect on both clinical and EEG parameters on various epilepsy models in most studies and also significantly ameliorated performance in behavioral tests.</div></div><div><h3>Conclusions</h3><div>rTMS holds potential for effective neuromodulation, that is critically dependent on stimulation frequency and epilepsy type. Translational knowledge gained from preclinical protocols may inform and optimize rTMS application for epilepsy management in future clinical trials.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"208 ","pages":"Article 107468"},"PeriodicalIF":2.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544487","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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