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Repetitive transcranial magnetic stimulation in murine models of epilepsy: A systematic review of methodological aspects and outcomes 小鼠癫痫模型中的重复经颅磁刺激:方法和结果的系统回顾。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-24 DOI: 10.1016/j.eplepsyres.2024.107468
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

Objectives

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.
目的:重复经颅磁刺激(rTMS)的临床研究并没有提供一致的疗效结果,这可能是由于方法参数的差异造成的。我们的目的是系统回顾小鼠癫痫模型的临床前经颅磁刺激方案,为临床试验的优化提供启示:我们检索了从开始到 2023 年 12 月的 MEDLINE、SCOPUS 和 Web of Science,包括有临床或脑电图(EEG)结果的英文撰写和同行评审研究:在 480 项搜索结果中,有 23 项符合条件的研究同时使用了小鼠和大鼠。癫痫诱导方法包括注射戊四唑、凯因酸、微毒毒素和锂-匹罗卡品、电点燃(杏仁核/海马内侧)、电休克以及失神和颞叶癫痫遗传模型。在确定运动阈值(MT)时,使用了肌电图和运动诱发电位以及单脉冲 TMS。刺激强度介于 MT 的 40% 和 200% 之间,或 0.125-2.5 T。高频经颅磁刺激(≥5 Hz)对癫痫发作的抑制没有效果,或有促进作用,可促进癫痫发生,但 20 Hz 经颅磁刺激与劳拉西泮联用可终止癫痫状态。低频经颅磁刺激(结论:经颅磁刺激具有有效神经调节的潜力,但关键取决于刺激频率和癫痫类型。从临床前方案中获得的转化知识可在未来的临床试验中为经颅磁刺激治疗癫痫的应用提供信息并进行优化。
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引用次数: 0
Differential electrographic seizure patterns in malformations of cortical development, early life brain injury, and later life brain injury 大脑皮层发育畸形、早期脑损伤和晚期脑损伤的不同电图癫痫发作模式。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-22 DOI: 10.1016/j.eplepsyres.2024.107470
Melody T. Trudgen, Brenna R. McKaig, Rishabh Jain, Wesley T. Kerr, James F. Castellano
Structural epilepsy is a chronic neurologic condition that may be caused by in utero malformations of cortical development (MCD) or post-natal brain injuries resulting in encephalomalacia. We hypothesized that the timing of epileptogenic insult would lead to distinct electrographic seizure patterns. Specifically, we predicted that later life insults would lead to longer duration seizures with higher proportion of focal: focal to bilateral tonic-clonic (FBTC) seizures and low rates of bihemispheric onset seizures, as compared to early life insults. We performed a retrospective chart review of 70 adult patients – 33 with epilepsy secondary to brain injury (9 with injury occurring before 16 years and 24 with injury occurring at or after 16 years) with resultant encephalomalacia on MR imaging and 37 with epilepsy secondary to MCD – admitted to the University of Pittsburgh Epilepsy Monitoring Unit for presurgical evaluation. There were no significant differences in duration of epilepsy or number of trialed seizure medications between the groups. We examined scalp EEG data for all patients, as well as intracranial EEG data in a subset. We analyzed seizure duration, seizure frequency, and seizure type (focal, FBTC, and bihemispheric onset) in three cohorts: MCD patients, patients with brain injury occurring in early life (<16 years old), and patients with brain injury occurring in later life (≥16 years old). Patients with later life brain injury had significantly longer and less frequent seizures as compared to MCD cohorts. There were no differences between MCD and early life brain injury cohorts. Seizure duration findings were corroborated in a subset of patients who additionally underwent intracranial EEG monitoring. Additionally, later life brain injury patients had significantly different seizure types as compared to MCD cohorts, with high rates of FBTC and low rates of bihemispheric onset. Again, there was no significant differences in seizure type between early life brain injury and MCD cohorts. These novel findings indicate the relevance of timing of epileptogenic insult on the electrophysiological characteristics of structural epilepsies.
结构性癫痫是一种慢性神经系统疾病,可能由子宫内皮质发育畸形(MCD)或出生后脑损伤导致的脑畸形引起。我们假设,致痫损伤的时间会导致不同的电图癫痫发作模式。具体来说,我们预测晚期脑损伤将导致持续时间较长的癫痫发作,与早期脑损伤相比,局灶性:局灶性至双侧强直阵挛性(FBTC)癫痫发作的比例较高,而双半球发病率较低。我们对 70 名成年患者进行了回顾性病历审查,其中 33 名患者因脑损伤继发癫痫(9 名患者的损伤发生在 16 岁之前,24 名患者的损伤发生在 16 岁时或之后),磁共振成像结果显示为脑畸形,37 名患者因 MCD 继发癫痫,这些患者被送往匹兹堡大学癫痫监护室进行手术前评估。两组患者的癫痫持续时间或试用癫痫发作药物的次数没有明显差异。我们检查了所有患者的头皮脑电图数据,以及一部分患者的颅内脑电图数据。我们分析了三个组群的癫痫发作持续时间、发作频率和发作类型(局灶性、FBTC 和双半球发病):MCD患者、早年脑损伤患者
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引用次数: 0
Effects of sleeve gastrectomy and Roux-en-Y gastric bypass on pharmacokinetics of lamotrigine and valproate: A cohort study 袖带胃切除术和 Roux-en-Y 胃旁路术对拉莫三嗪和丙戊酸钠药代动力学的影响:一项队列研究。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.eplepsyres.2024.107469
Georgios Schoretsanitis , Magnus Strømmen , Hege-Merete Krabseth , Olav Spigset , Arne Helland

Background

Bariatric surgeries may affect the pharmacokinetics of medications through alterations of the gastrointestinal physiology. Pharmacokinetic changes of first-line antiseizure medications such as lamotrigine and valproate following bariatric treatment have received little research attention so far.

Methods

In our prospective case study we included lamotrigine- or valproate-treated patients undergoing bariatric surgery at hospitals in Central Norway. Lamotrigine and valproate concentrations were assessed using serial blood samples over a dose interval, before and one, six and twelve months following surgery. Primary outcomes included changes in area under the time-concentration curve (AUC) with secondary outcomes comprising full pharmacokinetic profiling.

Results

Six lamotrigine-treated obese patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 3) and sleeve gastrectomy (SG) (n = 3), as well as two valproate-treated patients (one undergoing RYGB and one SG) were included. Largest changes for dose-adjusted AUC values after surgery were seen in RYGB-treated patients on lamotrigine (average increases of 38 % one month and 32 % 12 months postoperatively). In the patients on valproate, AUC values were decreased by 22 % after 6 months and by 30 % after 12 months. The interindividual variation was high. Formal statistical testing was not done due to few cases.

Conclusion

Postoperative pharmacokinetic changes for lamotrigine and valproate were modest, but for lamotrigine changes may be larger in patients undergoing RYGB than in those undergoing SG. Given the substantial interindividual variation, therapeutic drug monitoring should be used to capture pharmacokinetic changes and guide dose adjustments after bariatric surgery.
背景:减肥手术可能会通过改变胃肠道生理机能来影响药物的药代动力学。迄今为止,减肥治疗后拉莫三嗪和丙戊酸钠等一线抗癫痫药物的药代动力学变化很少受到研究关注:在前瞻性病例研究中,我们纳入了在挪威中部医院接受减肥手术的拉莫三嗪或丙戊酸钠治疗患者。在手术前、手术后1个月、6个月和12个月期间,通过连续血样评估拉莫三嗪和丙戊酸钠的浓度。主要结果包括时间-浓度曲线下面积(AUC)的变化,次要结果包括完整的药代动力学分析:结果:纳入了六名接受 Roux-en-Y 胃旁路术(RYGB)(n = 3)和袖状胃切除术(SG)(n = 3)的拉莫三嗪治疗肥胖患者,以及两名丙戊酸钠治疗患者(一名接受 RYGB,一名接受 SG)。接受拉莫三嗪治疗的 RYGB 患者术后剂量调整后的 AUC 值变化最大(术后 1 个月和 12 个月的平均增幅分别为 38% 和 32%)。在服用丙戊酸钠的患者中,6 个月后 AUC 值下降了 22%,12 个月后下降了 30%。个体间差异很大。由于病例较少,因此没有进行正式的统计学测试:拉莫三嗪和丙戊酸钠的术后药代动力学变化不大,但拉莫三嗪在接受 RYGB 治疗的患者中的变化可能大于接受 SG 治疗的患者。考虑到个体间的巨大差异,减肥手术后应使用治疗药物监测来捕捉药代动力学变化并指导剂量调整。
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引用次数: 0
An advocacy based cross sectional study of healthcare professionals of factors impacting on medication adherence across nine Sub-Saharan African countries 对九个撒哈拉以南非洲国家的医护专业人员进行了一项基于宣传的横断面研究,探讨影响坚持用药的因素
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.eplepsyres.2024.107459
Niki Sotiropoulou , Michael Kinney , Tolu Olaniyan , Kehinde Salako , Shadrach Akinola , Miria Chikasama , Farmanga Ngobeh , Margaret Sipilon , Millie Kumenda , Edward Shabangu , Richard Laugharne , Rohit Shankar

Background

Adherence to anti-seizure medication (ASM) by people diagnosed with epilepsy in sub-Saharan Africa remains low. The factors for low adherence are not well understood. To improve adherence, it is important to understand the perceptions and views of healthcare professionals delivering epilepsy care to this population. The aim was to investigate the factors influencing ASM adherence.

Methods

This study uses a brief online questionnaire which asked healthcare professionals (both from nursing and medical backgrounds) who work in sub-Saharan African countries to rate a set of pre-established options designed with the feedback of a local focus group of epilepsy experts from countries targeted. The questionnaire consisted of six questions and was a mix of multiple choice and Likert scale questions.

Results

There were 217 healthcare professionals who replied to the questionnaire. The most important factors believed to be influencing adherence from a healthcare professional perspective are; lack of availability of medication for epilepsy (71 %), affordability of medication (60 %), the patient, family, carer lacking in understanding of medication (43 %), cultural misconceptions about epilepsy (40 %) and side effects of the medication (32 %). The survey was answered by many different healthcare professionals; 65 participants were doctors and 152 were other healthcare professionals such as nurses (59 %) pharmacists (10 %) and when comparing them, the three most important categories were consistent across groups.

Conclusion

Healthcare workers in Sub-Saharan Africa identify that the primary factors impacting adherence to ASMs, in their view, is affordability and availability of ASMs.Addressing this issue may reduce the treatment gap.
背景撒哈拉以南非洲地区的癫痫患者对抗癫痫药物(ASM)的依从性仍然很低。导致依从性低的因素尚不十分明确。为了提高依从性,了解为这一人群提供癫痫护理的医疗保健专业人员的看法和观点非常重要。本研究使用了一份简短的在线问卷,要求在撒哈拉以南非洲国家工作的医护专业人员(包括护理和医疗专业人员)对一组预先确定的选项进行评分,这些选项是根据目标国家当地癫痫专家焦点小组的反馈意见设计的。问卷由六个问题组成,混合了多项选择题和李克特量表题。从医护专业人员的角度来看,认为影响坚持用药的最重要因素是:缺乏治疗癫痫的药物(71%)、药物的可负担性(60%)、患者、家属、护理人员对药物缺乏了解(43%)、文化上对癫痫的误解(40%)和药物的副作用(32%)。参与调查的有许多不同的医疗保健专业人员;65 名参与者是医生,152 名参与者是其他医疗保健专业人员,如护士(59%)和药剂师(10%)。
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引用次数: 0
Evaluating the efficacy of transcranial direct current stimulation for refractory epilepsy: A meta-analysis of RCTs and non-RCTs 评估经颅直流电刺激治疗难治性癫痫的疗效:对研究性试验和非研究性试验的荟萃分析。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.eplepsyres.2024.107456
Yuteng Sun , Xian Tang , Ye Li , Chao Gao , Zhiyuan Shen , Xiaosu Guo , Xin Guo , Zibin Wei , Yicun Jia , Mengyi Zheng , Yaxin Zhang , Yuan Xing , Shujuan Tian
An increasing number of research indicate that non-invasive neurostimulation techniques, like transcranial direct current stimulation (tDCS), can effectively control refractory epilepsy. While previous meta-analyses have primarily focused on randomized controlled trials (RCTs), this study expands the scope by including both RCTs and non-RCTs to provide a more comprehensive assessment of tDCS efficacy in treating refractory epilepsy. Through a systematic search of "PUBMED, Embase and Cochrane", we sought relevant studies related to the research topic. We utilized the Cochrane Collaboration tool to assess the risk of bias for the RCTs and the Methodological Index for Non-Randomized Studies (MINORS) tool to evaluate the quality of the non-RCTs included in this meta-analysis. In addition, a protocol for this meta-analysis was registered on PROSPERO (CRD42024496837 http://www.crd.york.ac.uk/ PROSPERO). A total of 14 studies, including 8 RCTs and 6 non-RCTs , involving 307 subjects with refractory epilepsy, were included in this meta-analysis. The combined analysis of RCTs and non-RCTs indicated that tDCS was effective in reducing seizure frequency (SF) in refractory epilepsy patients, with significant improvements observed both four weeks (MD = −4.54; p < 0.01; 95 % CI = −5.69 to −3.38) and eight weeks (MD = −3.49; p < 0.01; 95 % CI = −5.37 to −1.61) after stimulation.
There were no statistically significant differences in Interictal Epileptiform Discharges (IEDs) shortly after stimulation (MD = −3.59; p = 0.42; 95 % CI = −12.33–5.16). However, a reduction was observed at four weeks (MD = −5.28; p < 0.01; 95 % CI = −6.88 to −3.68) and eight weeks post-stimulation (MD = −3.37; p < 0.01; 95 % CI = −5.35 to −1.40). The patient's adverse reactions were mild, and they could be relieved shortly after discontinuation of the stimulus. The quality of evidence across outcomes was assessed as moderate. The results indicate that tDCS demonstrates promising efficacy and safety in managing seizures in refractory epilepsy. While this meta-analysis provides valuable findings, additional large-scale randomized controlled trials are needed to further confirm the efficacy of tDCS for refractory epilepsy.
越来越多的研究表明,经颅直流电刺激(tDCS)等非侵入性神经刺激技术可以有效控制难治性癫痫。以往的荟萃分析主要关注随机对照试验(RCT),而本研究通过同时纳入随机对照试验和非随机对照试验,扩大了荟萃分析的范围,从而更全面地评估了经颅直流电刺激治疗难治性癫痫的疗效。通过对 "PUBMED、Embase 和 Cochrane "进行系统检索,我们找到了与研究主题相关的研究。我们利用 Cochrane 协作工具评估了 RCT 的偏倚风险,并利用非随机研究方法学指数 (MINORS) 工具评估了纳入本荟萃分析的非 RCT 的质量。此外,本荟萃分析的方案已在 PROSPERO 上注册(CRD42024496837 http://www.crd.york.ac.uk/ PROSPERO)。本次荟萃分析共纳入 14 项研究,包括 8 项研究性临床试验和 6 项非研究性临床试验,涉及 307 名难治性癫痫患者。对研究性临床试验和非研究性临床试验的综合分析表明,tDCS能有效降低难治性癫痫患者的发作频率(SF),刺激后四周(MD = -4.54;p < 0.01;95 % CI = -5.69至-3.38)和八周(MD = -3.49;p < 0.01;95 % CI = -5.37至-1.61)均观察到显著改善。刺激后不久,发作间期癫痫样放电(IEDs)的差异无统计学意义(MD = -3.59;p = 0.42;95 % CI = -12.33-5.16)。然而,在刺激后四周(MD = -5.28;p < 0.01;95 % CI = -6.88 至 -3.68)和八周(MD = -3.37;p < 0.01;95 % CI = -5.35 至 -1.40)观察到了减少。患者的不良反应轻微,在停止刺激后不久即可缓解。所有结果的证据质量均被评为中等。结果表明,tDCS 在控制难治性癫痫发作方面具有良好的疗效和安全性。虽然这项荟萃分析提供了有价值的发现,但还需要更多大规模随机对照试验来进一步证实 tDCS 对难治性癫痫的疗效。
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引用次数: 0
Risk of recurrence after a first unprovoked seizure with different risk factors: A 10-year prospective cohort study 不同风险因素导致的首次无诱因癫痫发作后的复发风险:一项为期 10 年的前瞻性队列研究。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-06 DOI: 10.1016/j.eplepsyres.2024.107457
Xin-yu Chen , Feng-huang Zhou , Ge Tan , Deng Chen , Ling Liu

Objective

To evaluate the recurrence risk following a first unprovoked seizure using both single-factor and multiple-factor approaches, as well as to further analyze the potential risk factors associated with recurrence.

Methods

In a prospective cohort study, a total of 201 individuals who experienced their initial unprovoked seizure were recruited from January 2010 to December 2019. The cumulative recurrence rates were calculated by Kaplan–Meier survival curves. Multivariate analyses for recurrence risk were conducted utilizing the Cox regression model. Additionally, interaction effects were evaluated by quantifying the attributable proportion due to interaction (AP).

Results

The cumulative recurrence rates were as follows: 29.4 % at 6 months, 35.8 % at 1 year, 41.1 % at 2 years, 47.9 % at 5 years, and 57.5 % at 10 years. Notably, the majority of recurrences, specifically 61.2 %, manifested within the initial 6 months following the onset, with 74.4 % occurring within the first year, and 82.6 % within the initial 2 years. The recurrence risk of patients with epileptic abnormal discharges on VEEG, nocturnal seizure, abnormal MRI, prior brain insult and focal seizure was 71.9 %, 61.4 %, 61.5 %, 75.0 %, and 69.7 %, respectively. Epileptiform discharges (RR 2.5, 95 % CI 1.4–4.3, P=0.001) and prior brain insult (RR 2.1, 95 % CI 1.2–3.7, P=0.007) were predictors of recurrence. Interaction analysis showed the combination of epileptiform discharges and prior brain insult was associated with a 7-fold increased risk of recurrence (RR 7.0, 95 %CI 3.5–14.2),with AP estimated at 0.34, the combination of epileptiform discharges and nocturnal seizure was associated with a 4-fold increased risk of recurrence(RR 4.3, 95 %CI 2.4–7.4), with AP estimated at −0.25,and the combination of prior brain insult and nocturnal seizures was associated with a 4-fold increased risk of recurrence(RR 4.1, 95 %CI 1.9–8.9), with AP estimated at −0.03.

Conclusions

Patients with epileptiform discharges VEEG, nocturnal seizures, abnormal MRI findings, prior brain insult, or focal seizures exhibited a substantial recurrence rate. Specifically, the presence of epileptiform discharges in VEEG recordings, and a history of prior brain insult were identified as independent risk factors associated with recurrence following an initial unprovoked seizure. Notably, individuals with multiple risk factors exhibited a significantly higher recurrence risk compared to those with no or a single risk factor.
目的采用单因素和多因素方法评估首次无诱因癫痫发作后的复发风险,并进一步分析与复发相关的潜在风险因素:在一项前瞻性队列研究中,从 2010 年 1 月至 2019 年 12 月共招募了 201 名经历过首次无诱因癫痫发作的患者。通过卡普兰-梅耶生存曲线计算累计复发率。利用 Cox 回归模型对复发风险进行了多变量分析。此外,还通过量化交互作用(AP)导致的可归因比例来评估交互作用效应:结果:累积复发率如下:结果:累积复发率如下:6 个月时为 29.4%,1 年时 35.8%,2 年时 41.1%,5 年时 47.9%,10 年时 57.5%。值得注意的是,大多数复发(61.2%)发生在发病后的最初 6 个月内,74.4%发生在第一年内,82.6%发生在最初两年内。VEEG显示有癫痫异常放电、夜间发作、核磁共振成像异常、脑损伤和局灶性发作的患者的复发风险分别为71.9%、61.4%、61.5%、75.0%和69.7%。癫痫样放电(RR 2.5,95 % CI 1.4-4.3,P=0.001)和既往脑损伤(RR 2.1,95 % CI 1.2-3.7,P=0.007)是复发的预测因素。交互分析显示,痫样放电和先前脑损伤的组合与复发风险增加 7 倍相关(RR 7.0,95 %CI 3.5-14.2),AP 估计为 0.34,痫样放电和夜间发作的组合与复发风险增加 4 倍相关(RR 4.3,95%CI为2.4-7.4),AP估计为-0.25;既往脑损伤和夜间癫痫发作的组合与复发风险增加4倍相关(RR为4.1,95%CI为1.9-8.9),AP估计为-0.03:有癫痫样放电 VEEG、夜间癫痫发作、核磁共振成像结果异常、既往脑损伤或局灶性癫痫发作的患者复发率很高。具体而言,VEEG 记录中出现痫样放电和既往脑损伤史被确定为与初次无诱因癫痫发作后复发相关的独立风险因素。值得注意的是,与没有或只有一个风险因素的人相比,有多个风险因素的人复发风险明显更高。
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引用次数: 0
Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I 依地美酮可减轻鱼藤酮角膜点燃耐药模型中的线粒体难治性癫痫:绕过线粒体复合体 I 的方法
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-05 DOI: 10.1016/j.eplepsyres.2024.107458
Arshbir Kaur, Arvinder Kaur, Samriti, Rajesh Kumar Goel

Objective

To assess the potential of bypassing mitochondrial complex I with idebenone to overcome drug resistance in a Rotenone corneal kindling (RCK) mouse model of mitochondrial refractory epilepsy.

Material and method

Resistance was developed by administering rotenone 2.5 mg/kg intraperitoneally once and corneal kindling twice daily. The kindling development took 15 days, and pre-treatment resistance validation was carried out with five different antiseizure drugs: pregabalin, levetiracetam, valproate, lamotrigine, and phenytoin. The treatment drug, Idebenone (IDB) was given at doses of 10, 20, and 40 mg/kg intraperitoneally for 10 days. The post-treatment resistance validation was evaluated with same standard drugs in same order along with other parameters assessment, such as NAD(P)H: quinone oxidoreductase 1 (NQO1), ATP, GSH, and TBARS.

Results

The pre-treatment resistance validation shows an inability of standard drugs to attenuate seizure scores by rotenone kindling, justifying the development of drug resistance. IDB successfully abolished the resistance developed in RCK model. IDB elevated the levels of ATP and NQO1 and showed antioxidant activity by elevating GSH and attenuating TBARS.

Conclusion & future direction

IDB have successfully elevated the level of ATP, NQO1 in RCK model, hence proving the complex I bypass hypothesis. Thus, IDB can be the drug of choice for mitochondrial epilepsies involving drug refractoriness as adjuvant with anticonvulsant drugs.
材料与方法通过腹腔注射鱼藤酮 2.5 毫克/千克,每天 1 次,角膜点燃 2 次,产生耐药性。角膜点燃过程历时 15 天,治疗前用五种不同的抗癫痫药物:普瑞巴林、左乙拉西坦、丙戊酸钠、拉莫三嗪和苯妥英进行耐药性验证。治疗药物艾地苯醌(IDB)的剂量分别为 10、20 和 40 毫克/千克,腹腔注射 10 天。结果治疗前的耐药性验证表明,标准药物无法减轻鱼藤酮点燃的癫痫发作评分,这证明耐药性的产生是有道理的。IDB 成功消除了 RCK 模型中产生的耐药性。IDB 提高了 ATP 和 NQO1 的水平,并通过提高 GSH 和降低 TBARS 显示出抗氧化活性。因此,IDB 可以作为抗惊厥药物的辅助药物,用于治疗涉及药物难治性的线粒体癫痫。
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引用次数: 0
Epidemiology and real-world management of childhood epilepsy in Japan: A descriptive study using a health claim database 日本儿童癫痫的流行病学和实际管理:利用健康索赔数据库进行的描述性研究。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-09-30 DOI: 10.1016/j.eplepsyres.2024.107455
Takashi Saito , Nozomi Miyagawa , Kyoko Kanazawa , Masaki Iwasaki , Eiji Nakagawa

Introduction

The purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning.

Materials and methods

The study encompassed insured individuals aged 0–17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January—December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated.

Results

Among 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80–2.15) in the 0–2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98–9.72) in the 15–17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %–91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age.

Conclusions

Our findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy.
简介:这项流行病学研究旨在评估儿童癫痫的患病率、合并症和实际管理情况,为加强癫痫管理和医疗资源规划提供见解:该研究涵盖了截至 2018 年 12 月年龄在 0-17 岁的被保险人,他们在 2018 年的任何时间点都在日本健康索赔数据库中进行了登记,时间跨度为 2018 年 1 月至 12 月,至少在这一年的部分时间内进行了登记。癫痫的定义是根据《国际疾病分类》第 10 次修订版的代码诊断为癫痫,且索赔的癫痫管理费或抗癫痫药物(ASM)处方超过 4 周。对癫痫患病率、患者特征(包括合并症)和管理状况(如抗癫痫药物处方)进行了评估:在 1528905 名登记儿童中,有 9279 人被确认患有癫痫。0-2 岁年龄组的癫痫发病率最低,为每千人 1.97 例(95 % 置信区间 [CI] 1.80-2.15),随着年龄的增长,15-17 岁年龄组的发病率增至每千人 9.34 例(95 % 置信区间 [CI] 8.98-9.72),≥12 岁年龄组的男孩发病率明显高于女孩。88.3%-91.9% 的患者服用了 ASM。此外,27 名(0.29%)患者接受了癫痫手术。随着年龄的降低,要求静脉注射 ASMs 和长期脑电图费用的频率也在增加:我们的研究结果表明,幼儿比青少年获得了更多的医疗资源,而癫痫手术却未得到充分利用。进一步的调查将有助于改善癫痫的管理和制定防治措施。
{"title":"Epidemiology and real-world management of childhood epilepsy in Japan: A descriptive study using a health claim database","authors":"Takashi Saito ,&nbsp;Nozomi Miyagawa ,&nbsp;Kyoko Kanazawa ,&nbsp;Masaki Iwasaki ,&nbsp;Eiji Nakagawa","doi":"10.1016/j.eplepsyres.2024.107455","DOIUrl":"10.1016/j.eplepsyres.2024.107455","url":null,"abstract":"<div><h3>Introduction</h3><div>The purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning.</div></div><div><h3>Materials and methods</h3><div>The study encompassed insured individuals aged 0–17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January—December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated.</div></div><div><h3>Results</h3><div>Among 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80–2.15) in the 0–2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98–9.72) in the 15–17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %–91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"207 ","pages":"Article 107455"},"PeriodicalIF":2.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399754","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
Serum matrix metallopeptidase-9 levels in infantile epileptic spasms syndrome of unknown etiology 病因不明的婴儿癫痫痉挛综合征的血清基质金属肽酶-9水平。
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-09-27 DOI: 10.1016/j.eplepsyres.2024.107454
Ryuki Matsuura , Shin-ichiro Hamano , Reiko Koichihara , Rikako Takeda , Hirokazu Takeuchi , Yuko Hirata , Kenjiro Kikuchi , Akira Oka

Purpose

Epileptic spasms are the primary symptom of infantile epileptic spasms syndrome (IESS); however, their direct impact on blood–brain barrier (BBB) function is unknown. Matrix metallopeptidase-9 (MMP-9), degrades type IV collagen, a key component of the blood-brain barrier, while tissue inhibitor of metalloproteinase-1 (TIMP-1) suppresses its activity, protecting BBB integrity. This study aimed to assess serum MMP-9 and TIMP-1 levels in patients with IESS of unknown etiology.

Methods

We prospectively assessed serum MMP-9 and TIMP-1 levels prior to administering vigabatrin or adrenocorticotropic hormone therapy in patients with IESS of unknown etiology at Saitama Children’s Medical Center between February 2012 and December 2023. We compared these biomarkers between patients with epileptic spasms and age-matched controls and performed a curve regression analysis between the biomarkers and the frequency of epileptic spasms. Additionally, we assessed whether MMP-9 and TIMP-1 levels were diagnostic predictors of IESS.

Results

This study included 22 patients with IESS (11 males) and 12 controls. Serum MMP-9 and MMP-9/TIMP-1 ratios were higher in patients with IESS than in controls (p < 0.001 and p = 0.002, respectively). A high frequency of epileptic spasms also led to higher serum MMP-9 levels (y = 0.0871x2 + 0.195x + 195.15, R² = 0.77, p < 0.001). Using MMP >188 ng/mL as the cutoff level, the sensitivity for diagnosing IESS was 95.5 %, the specificity was 75.0 %, the positive likelihood ratio was 3.82 (95 % confidence interval (CI) 1.43–10.22), and the relative risk was 8.75 (95 % CI 1.36–56.5).

Conclusion

Patients with IESS had elevated serum MMP-9 levels, suggesting an association between epileptic spasms and blood–brain barrier dysfunction. MMP-9 level measurement may be useful for diagnosing suspected patients.
目的:癫痫痉挛是婴儿癫痫痉挛综合征(IESS)的主要症状;然而,它们对血脑屏障(BBB)功能的直接影响尚不清楚。基质金属肽酶-9(MMP-9)可降解血脑屏障的关键成分 IV 型胶原蛋白,而组织金属蛋白酶抑制剂-1(TIMP-1)可抑制其活性,从而保护血脑屏障的完整性。本研究旨在评估病因不明的 IESS 患者的血清 MMP-9 和 TIMP-1 水平:2012年2月至2023年12月期间,我们在埼玉儿童医学中心对病因不明的IESS患者进行了前瞻性评估,在使用维格巴曲林或促肾上腺皮质激素治疗前评估了血清MMP-9和TIMP-1水平。我们比较了癫痫痉挛患者和年龄匹配对照组的这些生物标志物,并对生物标志物和癫痫痉挛频率进行了曲线回归分析。此外,我们还评估了MMP-9和TIMP-1水平是否是IESS的诊断预测因子:本研究纳入了 22 名 IESS 患者(11 名男性)和 12 名对照组患者。IESS患者的血清MMP-9和MMP-9/TIMP-1比率高于对照组(分别为p < 0.001和p = 0.002)。癫痫痉挛频率高也会导致血清 MMP-9 水平升高(y = 0.0871x2 + 0.195x + 195.15,R² = 0.77,p < 0.001)。以 MMP >188 ng/mL 为临界值,诊断 IESS 的敏感性为 95.5%,特异性为 75.0%,阳性似然比为 3.82(95% 置信区间(CI)为 1.43-10.22),相对风险为 8.75(95% 置信区间(CI)为 1.36-56.5):结论:IESS患者的血清MMP-9水平升高,表明癫痫痉挛与血脑屏障功能障碍有关。测量MMP-9水平可能有助于诊断疑似患者。
{"title":"Serum matrix metallopeptidase-9 levels in infantile epileptic spasms syndrome of unknown etiology","authors":"Ryuki Matsuura ,&nbsp;Shin-ichiro Hamano ,&nbsp;Reiko Koichihara ,&nbsp;Rikako Takeda ,&nbsp;Hirokazu Takeuchi ,&nbsp;Yuko Hirata ,&nbsp;Kenjiro Kikuchi ,&nbsp;Akira Oka","doi":"10.1016/j.eplepsyres.2024.107454","DOIUrl":"10.1016/j.eplepsyres.2024.107454","url":null,"abstract":"<div><h3>Purpose</h3><div>Epileptic spasms are the primary symptom of infantile epileptic spasms syndrome (IESS); however, their direct impact on blood–brain barrier (BBB) function is unknown. Matrix metallopeptidase-9 (MMP-9), degrades type IV collagen, a key component of the blood-brain barrier, while tissue inhibitor of metalloproteinase-1 (TIMP-1) suppresses its activity, protecting BBB integrity. This study aimed to assess serum MMP-9 and TIMP-1 levels in patients with IESS of unknown etiology.</div></div><div><h3>Methods</h3><div>We prospectively assessed serum MMP-9 and TIMP-1 levels prior to administering vigabatrin or adrenocorticotropic hormone therapy in patients with IESS of unknown etiology at Saitama Children’s Medical Center between February 2012 and December 2023. We compared these biomarkers between patients with epileptic spasms and age-matched controls and performed a curve regression analysis between the biomarkers and the frequency of epileptic spasms. Additionally, we assessed whether MMP-9 and TIMP-1 levels were diagnostic predictors of IESS.</div></div><div><h3>Results</h3><div>This study included 22 patients with IESS (11 males) and 12 controls. Serum MMP-9 and MMP-9/TIMP-1 ratios were higher in patients with IESS than in controls (<em>p</em> &lt; 0.001 and <em>p</em> = 0.002, respectively). A high frequency of epileptic spasms also led to higher serum MMP-9 levels (y = 0.0871x<sup>2</sup> + 0.195x + 195.15, <em>R</em>² = 0.77, <em>p</em> &lt; 0.001). Using MMP &gt;188 ng/mL as the cutoff level, the sensitivity for diagnosing IESS was 95.5 %, the specificity was 75.0 %, the positive likelihood ratio was 3.82 (95 % confidence interval (CI) 1.43–10.22), and the relative risk was 8.75 (95 % CI 1.36–56.5).</div></div><div><h3>Conclusion</h3><div>Patients with IESS had elevated serum MMP-9 levels, suggesting an association between epileptic spasms and blood–brain barrier dysfunction. MMP-9 level measurement may be useful for diagnosing suspected patients.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"207 ","pages":"Article 107454"},"PeriodicalIF":2.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344064","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
Face swapping in seizure videos for patient deidentification 在癫痫发作视频中进行人脸互换以识别患者身份
IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-09-18 DOI: 10.1016/j.eplepsyres.2024.107453
Chin-Jou Li , Jen-Cheng Hou , Chien-Chen Chou , Yen-Cheng Shih , Stephane Dufau , Po-Tso Lin , Aileen McGonigal , Hsiang-Yu Yu

Objective

This study aimed to test different AI-based face-swapping models applied to videos of epileptic seizures, with the goal of protecting patient privacy while retaining clinically useful seizure semiology. We hypothesized that specific models would show differences in semiologic fidelity compared to the original clinical videos.

Methods

Three open-source models, SimSwap, MobileFaceSwap and GHOST were adopted for face-swapping. For every model, an AI generated male and female image were used to replace the original faces. One representative seizure per patient from three patients with epilepsy was chosen (3 seizure videos x 3 AI models x 2 M/F swap) and remade to 18 transformed video clips. To evaluate the performance of the three models, we used both objective (AI-based) and subjective (expert clinician) evaluation. The objective assessment included four metrics for facial appearance and four metrics for facial expression changes. Four experienced epileptologists reviewed the clips and scoring according to deidentification and preservation of semiology. Kruskal-Wallis H test was used for statistical analysis among the models.

Results

In the reproduced videos, the swapped face cannot be recognized as the original face, with no significant difference in scores of deidentification either by objective or subjective assessment. Regarding semiology preservation, no significant differences between models were observed in the objective evaluations. The subjective evaluations revealed that the GHOST model outperformed the other two models (p=0.028).

Conclusion

This is the first study evaluating AI face swapping models in epileptic seizure video clips. Optimization of AI face-swapping models could enhance the accessibility of seizure videos for education and research while protecting patient privacy and maintaining semiology.
目标本研究旨在测试应用于癫痫发作视频的不同人工智能换脸模型,目的是在保护患者隐私的同时保留对临床有用的发作符号学。我们假设,与原始临床视频相比,特定模型将显示出在符号学保真度方面的差异。方法我们采用了三种开源模型:SimSwap、MobileFaceSwap 和 GHOST 进行换脸。每个模型都使用人工智能生成的男性和女性图像来替换原始人脸。我们从三名癫痫患者中为每名患者选择了一个具有代表性的发作视频(3 个发作视频 x 3 个人工智能模型 x 2 个男/女交换),并将其重制为 18 个转换视频片段。为了评估三种模型的性能,我们采用了客观(基于人工智能)和主观(临床专家)两种评估方法。客观评估包括四个面部外观指标和四个面部表情变化指标。四位经验丰富的癫痫专家根据去身份化和保留符号学的原则对剪辑和评分进行了审查。结果 在复制的视频中,被调换的面部无法被识别为原始面部,无论是客观评价还是主观评价,在去识别性评分方面都没有显著差异。在保留符号学方面,客观评价没有发现不同模型之间存在显著差异。主观评价显示,GHOST 模型的表现优于其他两个模型(P=0.028)。优化人工智能换脸模型可以提高癫痫发作视频在教育和研究方面的可访问性,同时保护患者隐私并保持半身像。
{"title":"Face swapping in seizure videos for patient deidentification","authors":"Chin-Jou Li ,&nbsp;Jen-Cheng Hou ,&nbsp;Chien-Chen Chou ,&nbsp;Yen-Cheng Shih ,&nbsp;Stephane Dufau ,&nbsp;Po-Tso Lin ,&nbsp;Aileen McGonigal ,&nbsp;Hsiang-Yu Yu","doi":"10.1016/j.eplepsyres.2024.107453","DOIUrl":"10.1016/j.eplepsyres.2024.107453","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to test different AI-based face-swapping models applied to videos of epileptic seizures, with the goal of protecting patient privacy while retaining clinically useful seizure semiology. We hypothesized that specific models would show differences in semiologic fidelity compared to the original clinical videos.</div></div><div><h3>Methods</h3><div>Three open-source models, SimSwap, MobileFaceSwap and GHOST were adopted for face-swapping. For every model, an AI generated male and female image were used to replace the original faces. One representative seizure per patient from three patients with epilepsy was chosen (3 seizure videos x 3 AI models x 2 M/F swap) and remade to 18 transformed video clips. To evaluate the performance of the three models, we used both objective (AI-based) and subjective (expert clinician) evaluation. The objective assessment included four metrics for facial appearance and four metrics for facial expression changes. Four experienced epileptologists reviewed the clips and scoring according to deidentification and preservation of semiology. Kruskal-Wallis H test was used for statistical analysis among the models.</div></div><div><h3>Results</h3><div>In the reproduced videos, the swapped face cannot be recognized as the original face, with no significant difference in scores of deidentification either by objective or subjective assessment. Regarding semiology preservation, no significant differences between models were observed in the objective evaluations. The subjective evaluations revealed that the GHOST model outperformed the other two models (<em>p</em>=0.028).</div></div><div><h3>Conclusion</h3><div>This is the first study evaluating AI face swapping models in epileptic seizure video clips. Optimization of AI face-swapping models could enhance the accessibility of seizure videos for education and research while protecting patient privacy and maintaining semiology.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"207 ","pages":"Article 107453"},"PeriodicalIF":2.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0920121124001682/pdfft?md5=fdbd2e70e749c1faff0aabb208404bb7&pid=1-s2.0-S0920121124001682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Epilepsy Research
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