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Cannabis use, sleep and mood disturbances among persons with epilepsy – A clinical and polysomnography study from a Canadian tertiary care epilepsy center 癫痫患者吸食大麻、睡眠和情绪障碍--加拿大一家三级护理癫痫中心的临床和多导睡眠图研究
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-20 DOI: 10.1016/j.eplepsyres.2024.107479
Garima Shukla , Rishabh Sablok , Zaitoon Shivji , Stuart Fogel , Gavin P. Winston , Lysa Boissé Lomax , Ana Johnson , Helen Driver

Objective

Interest in anti-seizure properties of cannabinoids is increasing, with the rise in prevalence of recreational and medical cannabis use, especially across Canada. In a recent study on people with epilepsy (PWE), cannabis use showed a strong association with poor psychosocial health. Sleep and mood comorbidities are highly prevalent in epilepsy, and are common motivations for cannabis use. The primary objective of this study was to assess demographic, subjective and objectively assessed sleep quality and mood related differences among PWE who regularly use cannabis compared to those who do not.

Methods

Consecutive consenting patients with a confirmed epilepsy diagnosis, admitted to our Epilepsy Monitoring Unit, over a 3-year period (2019–2022) were enrolled. Detailed epilepsy-related data and self-reported sleep [Pittsburgh Sleep quality index (PSQI)], Epworth Sleepiness Scale (ESS)], mood [(Beck’s Depression Inventory (BDI) and Beck’s Anxiety inventory (BAI)] and cannabis use related data were collected. Overnight polysomnography (PSG) was conducted on the first night of admission, with simultaneous 18-channel video-EEG. Sleep (PSG) scoring followed American Academy of Sleep Medicine guidelines by a scorer blinded to clinical details.

Results

Among 51 patients with similar seizure control, 25 (13 F) reported cannabis use (mean age 36.3+14.8 years) and were significantly younger than 26 (18 F) non-users (mean age 48.3+15 years). Cannabis users had significantly better subjective sleep quality (mean PSQI scores 7.2+2.9 vs 10.2+5.2 respectively). Most patients endorsed sleepiness (Cannabis users with ESS scores greater than 10; 91.3 %, 77.3 % in non-users) and moderate to extreme depression (BDI) scores. No significant differences were observed in objective sleep parameters. BDI score significantly predicted PSQI and ESS scores on multiple logistic regression analysis.

Significance

Despite a significant age difference, self-reported sleep quality is better among PWE who report regular cannabis use compared to non-users. However, there is no significant difference in objective sleep quantity and quality from PSG between the two groups. Additionally, severity of depressive symptoms is a significant predictor of sleep quality and of excessive daytime sleepiness among PWE.
目的随着娱乐性和医用大麻使用率的上升,人们对大麻素抗癫痫特性的兴趣与日俱增,尤其是在加拿大。在最近一项针对癫痫患者(PWE)的研究中,大麻的使用与不良的社会心理健康密切相关。睡眠和情绪并发症在癫痫患者中非常普遍,也是吸食大麻的常见动机。本研究的主要目的是评估经常使用大麻的癫痫患者与不使用大麻的癫痫患者在人口统计学、主观和客观评估的睡眠质量和情绪方面的差异。收集了详细的癫痫相关数据和自我报告的睡眠[匹兹堡睡眠质量指数(PSQI)]、埃普沃斯嗜睡量表(ESS)]、情绪[贝克抑郁量表(BDI)和贝克焦虑量表(BAI)]以及大麻使用相关数据。入院第一晚进行了夜间多导睡眠图(PSG)检查,并同时进行了 18 通道视频脑电图检查。结果在 51 名发作控制情况相似的患者中,有 25 人(13 名女性)报告吸食大麻(平均年龄为 36.3+14.8 岁),他们的年龄明显小于 26 名(18 名女性)非吸食者(平均年龄为 48.3+15 岁)。吸食大麻者的主观睡眠质量明显更好(平均 PSQI 分数分别为 7.2+2.9 与 10.2+5.2)。大多数患者都认可嗜睡(吸食大麻者的ESS评分大于10;91.3%,非吸食者为77.3%)和中度至极度抑郁(BDI)评分。在客观睡眠参数方面没有观察到明显差异。在多重逻辑回归分析中,BDI 分数可明显预测 PSQI 和 ESS 分数。意义尽管存在明显的年龄差异,但与不吸食大麻者相比,报告经常吸食大麻的残疾人自我报告的睡眠质量更好。然而,根据 PSG 的客观睡眠数量和质量,两组之间没有明显差异。此外,抑郁症状的严重程度也是影响残疾人睡眠质量和白天过度嗜睡的一个重要预测因素。
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引用次数: 0
Evaluating the late seizures of acute encephalopathy with biphasic seizures and late reduced diffusion via monitoring using continuous electroencephalogram 通过连续脑电图监测,评估急性脑病晚期发作与双相发作和晚期弥散功能减退的关系。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-19 DOI: 10.1016/j.eplepsyres.2024.107483
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

Background

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。
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引用次数: 0
Validation of hemispherectomy outcome prediction scale in treatment of medically intractable epilepsy 治疗药物难治性癫痫的半球切除术结果预测量表的验证。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-10 DOI: 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.
半球切除术结果预测量表(HOPS)是为了帮助临床医生和患者确定药物难治性癫痫半球手术的成功几率而开发的。产生 HOPS 的原始研究采用了多机构、大规模队列的形式,对患者进行了近乎完美的分层。有证据表明,用于创建此类预测模型的方法(包括交叉验证以及利用用于生成模型的相同数据进行分层)可能会面临一种不良建模现象的风险,这种现象被称为过拟合。我们提出了过拟合是否会影响 HOPS 结果的问题,并试图利用本机构未纳入原始 HOPS 研究的患者参数进行外部验证的初步证据。我们发现 HOPS 对我们有限的术后队列进行了充分的分层。然而,HOPS 预测成功几率最大的患者完全摆脱癫痫发作的可能性为 75%,比最初的 HOPS 群体低了约 20 个百分点。HOPS 预测的绝对成功几率的降低可能代表了某种程度的过度拟合。利用完全独立于用于生成模型的患者队列对 HOPS 进行外部验证,将具有参考价值。对 HOPS 和类似模型进行外部验证可优化干预后成功率的实际预测。
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引用次数: 0
MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept study 微RNA是治疗成人耐药性癫痫的改良阿特金斯饮食反应的潜在生物标志物:概念验证研究
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-08 DOI: 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.
背景:需要准确预测对改良阿特金斯饮食(MAD)的反应。微RNA是癫痫的潜在生物标志物。本研究旨在探索循环miR-146a、miR-155、miR-22、miR-21和miR-134水平在预测MAD反应中的价值:从MAD专科门诊随访的DRE成人前瞻性队列中挑选出完成3个月MAD治疗的患者。如果随访时癫痫发作频率有所减少(通过癫痫发作日历计算),则将患者归类为应答者。此外,还探讨了癫痫发作减少 >50% 的分界线。此外,还分析了癫痫发作和认知能力方面的定性优势。在启动 MAD 之前采集了血液样本,并通过 qRT-PCR 对 microRNA 进行了量化:共纳入 39 名患者(56% 为男性,平均年龄(33.1±8.5)岁,62% 为局灶性癫痫,59% 为结构性病因):20名患者(51%)为应答者[癫痫发作频率平均减少54%(17-100%);10名患者减少≥50%];25名患者(64%)报告了癫痫发作的质量效益,21名患者(54%)报告了认知效益。在治疗前的基线上,结合所有研究的微RNA血清水平的小组预测了癫痫发作的减少(AUC=0.839,p结论:在治疗前的基线上,结合所有研究的微RNA血清水平的小组预测了癫痫发作的减少(AUC=0.839,p结论):将治疗前血清中的 miR-146a、miR-155、miR-134、miR-21 和 miR-22 水平组合在一起,可预测罹患 DRE 的成人在接受 MAD 治疗 3 个月后癫痫发作的减少情况。该研究小组可能是一种很有前景的生物标志物,也是选择患者的有用工具。
{"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 ,&nbsp;Ana Cavalheiro ,&nbsp;Cristina Santos ,&nbsp;Joana Lopes ,&nbsp;Catarina Teixeira ,&nbsp;Maria Manuel Tavares ,&nbsp;Cláudia Carvalho ,&nbsp;Carolina Lemos ,&nbsp;Paulo Pinho e Costa ,&nbsp;Sara Cavaco ,&nbsp;João Chaves ,&nbsp;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 &gt;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&lt;0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p&lt;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 &lt;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}
引用次数: 0
Necessary for seizure forecasting outcome metrics: Seizure frequency and benchmark model 癫痫发作预测结果指标的必要条件:癫痫发作频率和基准模型。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-08 DOI: 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。
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引用次数: 0
Prevalence, clinical characteristics and outcomes of seizures in neurofibromatosis type 1: A systematic review and single arm meta-analysis 1型神经纤维瘤病癫痫发作的患病率、临床特征和预后:系统综述和单臂荟萃分析。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-08 DOI: 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.
背景:神经纤维瘤病1型(NF1)是一种常见的神经皮肤综合征,易导致患者癫痫发作。我们的目的是估计 NF1 患者癫痫发作的患病率、临床特征和结果,并分析癫痫发作的预后因素:方法:我们在 PubMed、EMBASE、Web of Science、Scopus、Cochrane Library 和灰色文献数据库中进行了系统检索,检索时间从开始到 2024 年 4 月。我们确定了纳入 NF1 癫痫发作患者的观察性研究。我们总结了癫痫发作的临床特征,并对发病率和结果进行了荟萃分析。我们使用漏斗图评估了发表偏倚,并进行了敏感性分析以评估稳定性和可靠性。我们对患者的个体数据进行了分析,以评估预后因素:从 1021 份记录中确定了 14 项研究。共纳入了 4946 名 NF1 患者中的 337 名癫痫发作患者。元分析表明,NF1患者癫痫发作的总患病率为8.1%(95% CI= 5.9-10.3%)。首次癫痫发作通常发生在儿童时期,中位年龄为 3.5-12.0 岁。最常见的类型是局灶性发作(54.2%)和全身强直阵挛发作(16.8%)。癫痫发作自由率为 68.5%(95 % CI= 57.5-79.5%),大多数情况下只需服用一种或两种抗癫痫药物。皮质畸形/海马硬化是癫痫持续发作的独立风险因素(OR=5.19,95 %CI=1.27-21.18,P=0.02):尽管NF1患者面临的癫痫发作风险高于普通人群,但大多数患者都能摆脱癫痫发作。皮质畸形或海马硬化的患者癫痫持续发作的风险较高。
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引用次数: 0
Effect of trans 4-butylcyclohexane carboxylic acid (4-BCCA) upon neurodegeneration, oxidative stress related to epileptogenesis in pilocarpine-induced status epilepticus 反式 4-丁基环己烷羧酸(4-BCCA)对皮质类药物诱发的癫痫状态中与癫痫发生相关的神经变性和氧化应激的影响
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-08 DOI: 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.
目的4-丁基环己烷羧酸(4-BCCA)是一种跨膜结构域的 AMPA 受体低亲和力抑制剂,已被认为是治疗癫痫的潜在选择,但其对癫痫状态、疾病修饰和癫痫状态后神经变性的潜在影响尚未得到研究。方法本研究确定了 4-BCCA 与标准抗癫痫药物(ASMs)[丙戊酸钠(VPA)和过潘奈尔(PER)]在利血平诱导的状态性癫痫大鼠模型中的作用。我们首先确定了 4-BCCA 对癫痫状态的有效剂量,然后进行了急性和长期效应研究。我们对大鼠的神经行为(通过高架迷宫和被动回避)、神经变性(通过海马切片的透射电子显微镜(TEM)和免疫组化)、总抗氧化能力(TAC)和神经元损失(通过脑组织中的神经元特异性烯醇化酶(NSE))进行了评估。结果发现,4-BCCA(200 毫克/千克,静脉注射)是一种有效剂量,与其他 ASM 相比,它在潜伏期和 3/4 期癫痫发作次数方面显示出更好的癫痫发作控制效果。PER 组和 4-BCCA+PER 显示出更好的记忆保持能力,但各药物治疗组之间没有显著差异。在 TEM 中,4-BCCA+PER 组和 4-BCCA+VPA 组的细胞核和细胞质变化较少。在免疫组化中,4-BCCA、PER 和联合组显示出更好的神经元活力。意义4-BCCA单药及其与ASMs(尤其是perampanel)的联合用药在大鼠癫痫状态模型中显示出更好的癫痫控制和神经保护作用。
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引用次数: 0
A universal method for seizure onset zone localization in focal epilepsy using standard deviation of spike amplitude 利用尖峰振幅标准偏差定位局灶性癫痫发作起始区的通用方法
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-02 DOI: 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.
背景精确定位癫痫发作区(SOZ)对局灶性癫痫手术至关重要。现有方法主要关注立体脑电图中的高频活动,但当癫痫发作并非由高频活动驱动时,这些方法往往会失败。作为癫痫发作的生物标志物,SOZ 中的发作性尖峰会诱发其他脑区的痫样放电。基于这一认识,我们旨在开发一种通用算法来定位 SOZ,并研究 SOZ 内的发作性尖峰如何诱发癫痫发作。方法 我们提出了一种名为尖峰振幅标准偏差(SDSA)的新指标,并利用通道平均 SDSA 来描述癫痫发作过程和检测癫痫发作。通过整合特定区间的 SDSA 值,计算出 SOZ 内各通道的得分。SOZ 分数高的通道被归类为 SOZ。利用接收者操作特征曲线(ROC)下的面积来判定定位的准确性。此外,我们还分析了 SOZ 通道的早期发作信号,并研究了影响其持续时间的因素,以揭示癫痫发作的诱发条件。通道平均 SDSA 成功检测到所有 28 次癫痫发作,且无误报。利用 SDSA 集成,我们实现了精确的 SOZ 定位,ROC 曲线下平均面积 (AUC) 为 0.96,明显优于之前基于高频活动的方法。此外,我们还发现 SOZ 中的发作性尖峰能量集中在一个特定的频率上,分布在 [6, 12 Hz]。此外,我们还发现,该频段的每秒能量越高,发作性尖峰诱发癫痫发作的速度就越快。通过研究发作性尖峰在 SOZ 和非 SOZ 之间的传播模式,我们认为来自 SOZ 的发作性尖峰需要在特定的中心频率积累能量才能诱发非 SOZ 的癫痫尖峰,这可能对理解癫痫发作的起始模式具有重要意义。
{"title":"A universal method for seizure onset zone localization in focal epilepsy using standard deviation of spike amplitude","authors":"Xiang Ji ,&nbsp;Yuanyuan Dang ,&nbsp;Ming Song ,&nbsp;Aijun Liu ,&nbsp;Hulin Zhao ,&nbsp;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}
引用次数: 0
Parameter analysis in stereoelectroencephalography-guided radiofrequency thermocoagulation: A common basis for objective comparison between protocols 立体脑电图引导射频热凝术的参数分析:客观比较不同方案的共同基础
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-30 DOI: 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 700Ω and rose up to 1300Ω, 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.
目的立体脑电图引导下射频热凝术(SEEG-guided RF-TC)是一种侵入性手术,其原理是使用双极电流通过 SEEG 植入体内的电极触点对大脑皮层靶点进行立体定向病变。迄今为止,文献中已描述了几种 RF-TC 方案,但尚未达成共识。这项研究旨在分析 RF-TC 过程中的电参数,为客观描述和比较不同的 SEEG 引导的 RF-TC 方案提供一种方法。研究对象包括 2022 年 2 月至 2023 年 5 月期间在博洛尼亚神经科学研究所(IRCCS Istituto delle Scienze Neurologiche di Bologna)接受 RF-TC 手术的患者。在每次手术过程中,都对以下参数进行了测量:电压、电流、阻抗和功率。采用了一种临时算法来检测阻抗的突然升高,这反映了热凝固的发生。采用双样本 t 检验比较不同脑结构 RF-TC 的参数曲线。在每个过程中,阻抗水平从大约 700Ω 开始上升到 1300Ω,表现出不稳定的模式,其特点是一次或多次上升。在达到第一个峰值之前,所有测量参数都呈现出相似的趋势,之后的变化受阻抗上升频率的影响。电参数的系统分析可能是比较不同 RF-TC 方案的可靠工具,为将来确定 SEEG 引导的 RF-TC 程序的最佳配置铺平了道路。
{"title":"Parameter analysis in stereoelectroencephalography-guided radiofrequency thermocoagulation: A common basis for objective comparison between protocols","authors":"Luca Zanuttini ,&nbsp;Federico Mason ,&nbsp;Lorenzo Ferri ,&nbsp;Elena Pasini ,&nbsp;Lidia Di Vito ,&nbsp;Roberto Mai ,&nbsp;Laura Tassi ,&nbsp;Laura Castana ,&nbsp;Gianfranco Vornetti ,&nbsp;Lorenzo Muccioli ,&nbsp;Luigi Cirillo ,&nbsp;Francesca Bisulli ,&nbsp;Roberto Michelucci ,&nbsp;Raffaele Lodi ,&nbsp;Francesco Cardinale ,&nbsp;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}
引用次数: 0
Beyond seizure freedom: Reduction in anti-seizure medication after epilepsy surgery 超越癫痫发作自由:癫痫手术后减少抗癫痫药物用量
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-29 DOI: 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.
导言:考虑接受治疗性癫痫手术的患者通常希望减少所需的抗癫痫药物(ASM)数量。预测这种减少仍然具有挑战性。尽管癫痫手术后癫痫发作自由度的预测因素已经确立,但长期疗效仍然不佳,即使在没有癫痫发作自由度的情况下,与减少抗癫痫药物相关的因素也可能改善手术规划,使之符合患者的目标。方法我们对 2001 年至 2022 年期间接受癫痫手术的大型多机构患者队列进行了研究,随访至少两年。我们提取了每位患者的术前特征,包括癫痫持续时间、癫痫病因、非侵入性检查数据以及手术前立即使用的抗癫痫药物总数。主要终点包括术后多个时间点的 ASM 减少可能性和 ASM 自由度,最长可达 15 年,并根据癫痫发作控制情况进行分层。只有在接受后续切除术的患者中才能观察到 ASM 的显著减少,而接受神经调控术的患者的 ASM 使用量则保持不变。Engel I结果是ASM减少的最大驱动力。在癫痫持续状态患者中,癫痫发作区(SOZ)偏向一侧的患者随着时间的推移也能持续减少 ASM 的使用。同样,术前 ASM 数量的增加也与所有随访期间 ASM 减少的可能性相对应。结论即使是癫痫手术后持续发作的患者,在长期随访期间也能观察到有意义的 ASM 减少。ASM减少可能是癫痫手术的一个相关次要结局指标。
{"title":"Beyond seizure freedom: Reduction in anti-seizure medication after epilepsy surgery","authors":"Rohan Jha ,&nbsp;Melissa M.J. Chua ,&nbsp;David D. Liu ,&nbsp;R. Mark Richardson ,&nbsp;Steven Tobochnik ,&nbsp;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}
引用次数: 0
期刊
Epilepsy Research
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