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Fluoxetine accelerates epileptogenesis and magnifies disease severity in a rat model of acquired epilepsy 在获得性癫痫大鼠模型中,氟西汀会加速癫痫发生并加重疾病的严重程度。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-05 DOI: 10.1111/epi.18080
Gabi Dezsi, Ezgi Ozturk, Davy Wong, Matthew R. Hudson, Gabriella Martello, Flavia M. M. Gomes, Michael R. Salzberg, Margaret J. Morris, Terence J. O'Brien, Nigel C. Jones

Objective

Many people with epilepsy experience comorbid anxiety and depression, and antidepressants remain a primary treatment for this. Emerging evidence suggests that these agents may modulate epileptogenesis to influence disease severity. Here, we assessed how treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine impacts epileptogenic, behavioral, and pathological sequelae following status epilepticus.

Methods

Male Wistar rats received kainic acid to induce status epilepticus (SE) or vehicle (sham). Animals then received either fluoxetine (10 mg/kg/day) or vehicle for 8 weeks via subcutaneous osmotic pump. Video-electroencephalography was recorded continuously until behavioral testing at day 56, including assessments of anxiety- and depression-like behavior and spatial cognition. Postmortem immunocytochemistry studies examined mossy fiber sprouting.

Results

Fluoxetine treatment significantly accelerated epileptogenesis following SE, reducing the average period to the first spontaneous seizure (from 32 days [vehicle] to 6 days [fluoxetine], p < .01). Also, fluoxetine exposure magnified the severity of the resultant epilepsy, increasing seizure frequency compared to vehicle (p < .01). Exposure to fluoxetine was associated with improved anxiety- and depression-like behaviors but significantly worsened cognition. Mossy fiber sprouting was more pronounced in fluoxetine-treated rats compared to vehicle (p < .0001).

Significance

Our studies demonstrate that, using a model exhibiting spontaneous seizures, epileptogenesis is accelerated and magnified by fluoxetine, an effect that may be related to more severe pathological neuroplasticity. The differential influence of fluoxetine on behavior indicates that different circuitry and mechanisms are responsible for these comorbidities. These findings suggest that caution should be exercised when prescribing SSRI antidepressants to people at risk of developing epilepsy.

目的:许多癫痫患者会合并焦虑和抑郁,而抗抑郁药仍然是治疗这种症状的主要药物。新的证据表明,这些药物可能会调节癫痫的发生,从而影响疾病的严重程度。在此,我们评估了选择性5-羟色胺再摄取抑制剂(SSRI)抗抑郁剂氟西汀的治疗如何影响癫痫状态后的致痫、行为和病理后遗症:雄性 Wistar 大鼠接受凯尼酸诱导癫痫状态(SE)或服用药物(假)。然后,动物通过皮下渗透泵接受氟西汀(10 毫克/千克/天)或药物治疗 8 周。连续记录视频脑电图,直到第 56 天进行行为测试,包括焦虑和抑郁样行为以及空间认知的评估。死后免疫细胞化学研究检测了苔藓纤维的发芽情况:结果:氟西汀治疗明显加速了SE后的癫痫发生,缩短了首次自发癫痫发作的平均时间(从32天[车辆]到6天[氟西汀],p 意义重大:我们的研究表明,利用自发性癫痫发作模型,氟西汀会加速和放大癫痫的发生,这种效应可能与更严重的病理性神经可塑性有关。氟西汀对行为的不同影响表明,这些合并症是由不同的回路和机制造成的。这些研究结果表明,在给有患癫痫风险的人处方 SSRI 抗抑郁药时应谨慎行事。
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引用次数: 0
Role of blood–brain barrier dysfunction in the development of poststroke epilepsy 血脑屏障功能障碍在中风后癫痫发病中的作用。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-05 DOI: 10.1111/epi.18072
Wouter C. Meijer, Jan A. Gorter

Stroke is a major contributor to mortality and morbidity worldwide and the most common cause of epilepsy in the elderly in high income nations. In recent years, it has become increasingly evident that both ischemic and hemorrhagic strokes induce dysfunction of the blood–brain barrier (BBB), and that this impairment can contribute to epileptogenesis. Nevertheless, studies directly comparing BBB dysfunction and poststroke epilepsy (PSE) are largely absent. Therefore, this review summarizes the role of BBB dysfunction in the development of PSE in animal models and clinical studies. There are multiple mechanisms whereby stroke induces BBB dysfunction, including increased transcytosis, tight junction dysfunction, spreading depolarizations, astrocyte and pericyte loss, reactive astrocytosis, angiogenesis, matrix metalloproteinase activation, neuroinflammation, adenosine triphosphate depletion, oxidative stress, and finally cell death. The degree to which these effects occur is dependent on the severity of the ischemia, whereby cell death is a more prominent mechanism of BBB disruption in regions of critical ischemia. BBB dysfunction can contribute to epileptogenesis by increasing the risk of hemorrhagic transformation, increasing stroke size and the amount of cerebral vasogenic edema, extravasation of excitatory compounds, and increasing neuroinflammation. Furthermore, albumin extravasation after BBB dysfunction contributes to epileptogenesis primarily via increased transforming growth factor β signaling. Finally, seizures themselves induce BBB dysfunction, thereby contributing to epileptogenesis in a cyclical manner. In repairing this BBB dysfunction, pericyte migration via platelet-derived growth factor β signaling is indispensable and required for reconstruction of the BBB, whereby astrocytes also play a role. Although animal stroke models have their limitations, they provide valuable insights into the development of potential therapeutics designed to restore the BBB after stroke, with the ultimate goal of improving outcomes and minimizing the occurrence of PSE. In pursuit of this goal, rapamycin, statins, losartan, semaglutide, and metformin show promise, whereby modulation of pericyte migration could also be beneficial.

中风是导致全球死亡率和发病率的主要因素,也是高收入国家老年人癫痫的最常见病因。近年来,越来越多的研究表明,缺血性和出血性脑卒中都会引起血脑屏障(BBB)功能障碍,而这种障碍会导致癫痫的发生。然而,直接比较血脑屏障功能障碍和脑卒中后癫痫(PSE)的研究在很大程度上并不存在。因此,本综述总结了动物模型和临床研究中 BBB 功能障碍在 PSE 发生中的作用。脑卒中诱导 BBB 功能障碍的机制有多种,包括跨细胞增多、紧密连接功能障碍、扩散性去极化、星形胶质细胞和周细胞丢失、反应性星形胶质细胞增多、血管生成、基质金属蛋白酶激活、神经炎症、三磷酸腺苷耗竭、氧化应激以及最终的细胞死亡。这些影响发生的程度取决于缺血的严重程度,在严重缺血的区域,细胞死亡是更突出的 BBB 破坏机制。BBB 功能障碍会增加出血性转变的风险、增加中风面积和脑血管源性水肿的数量、兴奋性化合物外渗以及增加神经炎症,从而导致癫痫发生。此外,BBB 功能障碍后的白蛋白外渗主要通过增加转化生长因子 β 信号传导促进癫痫发生。最后,癫痫发作本身会诱发 BBB 功能障碍,从而以周期性的方式导致癫痫发生。在修复这种 BBB 功能障碍的过程中,通过血小板源性生长因子 β 信号传导的周细胞迁移是不可或缺的,也是重建 BBB 所必需的,星形胶质细胞也在其中发挥了作用。尽管动物中风模型有其局限性,但它们为开发旨在恢复中风后 BBB 的潜在疗法提供了宝贵的见解,其最终目标是改善预后并最大限度地减少 PSE 的发生。为了实现这一目标,雷帕霉素、他汀类药物、洛沙坦、司马鲁肽和二甲双胍都显示出了前景,而调节周细胞的迁移也可能是有益的。
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引用次数: 0
The hemodynamic response to co-occurring interictal epileptiform discharges and high-frequency oscillations localizes the seizure-onset zone 对同时出现的发作间期癫痫样放电和高频振荡的血流动力学反应可定位癫痫发作起始区。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-05 DOI: 10.1111/epi.18071
William Wilson, Daniel J. Pittman, Perry Dykens, Victoria Mosher, Laura Gill, Joseph Peedicail, Antis G. George, Craig A. Beers, Bradley Goodyear, Pierre LeVan, Paolo Federico, the Calgary Comprehensive Epilepsy Program collaborators

Objective

To use intracranial electroencephalography (EEG) to characterize functional magnetic resonance imaging (fMRI) activation maps associated with high-frequency oscillations (HFOs) (80–250 Hz) and examine their proximity to HFO- and seizure-generating tissue.

Methods

Forty-five patients implanted with intracranial depth electrodes underwent a simultaneous EEG-fMRI study at 3 T. HFOs were detected algorithmically from cleaned EEG and visually confirmed by an experienced electroencephalographer. HFOs that co-occurred with interictal epileptiform discharges (IEDs) were subsequently identified. fMRI activation maps associated with HFOs were generated that occurred either independently of IEDs or within ±200 ms of an IED. For all significant analyses, the Maximum, Second Maximum, and Closest activation clusters were identified, and distances were measured to both the electrodes where the HFOs were observed and the electrodes involved in seizure onset.

Results

We identified 108 distinct groups of HFOs from 45 patients. We found that HFOs with IEDs produced fMRI clusters that were closer to the local field potentials of the corresponding HFOs observed within the EEG than HFOs without IEDs. In addition to the fMRI clusters being closer to the location of the EEG correlate, HFOs with IEDs generated Maximum clusters with greater z-scores and larger volumes than HFOs without IEDs. We also observed that HFOs with IEDs resulted in more discrete activation maps.

Significance

Intracranial EEG-fMRI can be used to probe the hemodynamic response to HFOs. The hemodynamic response associated with HFOs that co-occur with IEDs better identifies known epileptic tissue than HFOs that occur independently.

目的利用颅内脑电图(EEG)描述与高频振荡(HFO)(80-250 Hz)相关的功能磁共振成像(fMRI)激活图,并检查其与高频振荡和癫痫发作生成组织的接近程度:45名植入颅内深度电极的患者接受了3 T同步脑电图-核磁共振成像研究。通过算法从清洁的脑电图中检测出 HFO,并由经验丰富的脑电图学家进行视觉确认。随后对与发作间期痫样放电(IED)同时出现的 HFO 进行识别。生成与 HFO 相关的 fMRI 激活图,这些激活图要么独立于 IED 出现,要么在 IED 出现后的±200 毫秒内出现。在所有重要分析中,我们确定了最大、次最大和最接近的激活集群,并测量了与观察到 HFO 的电极和涉及癫痫发作的电极之间的距离:结果:我们从 45 名患者中识别出 108 组不同的 HFOs。我们发现,与无 IED 的 HFO 相比,有 IED 的 HFO 产生的 fMRI 簇更接近于在脑电图中观察到的相应 HFO 的局部场电位。与无 IED 的 HFO 相比,有 IED 的 HFO 除了产生的 fMRI 簇更接近脑电图相关位置外,还产生了 Z 值更大和体积更大的最大簇。我们还观察到,有 IED 的 HFO 会产生更多离散的激活图:意义:颅内 EEG-fMRI 可用于探测 HFO 的血流动力学反应。与独立发生的 HFO 相比,与 IED 同时发生的 HFO 相关的血液动力学反应能更好地识别已知的癫痫组织。
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引用次数: 0
Investigating current clinical opinions in stereoelectroencephalography-informed epilepsy surgery 调查目前立体脑电图癫痫手术的临床观点。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-03 DOI: 10.1111/epi.18076
John Thomas, Chifaou Abdallah, Zhengchen Cai, Kassem Jaber, Jean Gotman, Sandor Beniczky, Birgit Frauscher

Objective

Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions.

Methods

We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders.

Results

A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis.

Significance

This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.

目的:立体脑电图(SEEG)在全球癫痫手术规划中的应用日益广泛。关于 SEEG 术语和解释的国际指南尚未提出。在 SEEG 的定义、癫痫手术计划中特征的应用以及手术结果的解释方面,世界各地存在着差异。这阻碍了 SEEG 发现的临床解释和合作研究。我们旨在评估全球对 SEEG 术语的看法、手术前特征应用的差异以及手术结果评分解释的差异,并分析临床专家的人口统计学如何影响这些观点:我们通过调查评估了接受过 SEEG 专业培训的癫痫专家的做法和观点。我们对数据进行了定性分析,并根据地理区域和经验年限对亚组进行了研究。主要结果包括对 SEEG 术语、用于癫痫手术的特征和结果评分解释的看法。此外,我们还进行了多层次回归和后分层分析,以确定未回复者的特征:结果:共分析了来自 39 个国家的 321 份专家回复。我们观察到不同地理区域和 SEEG 专业水平的专家在术语、实践和术前特征使用方面存在很大差异。大多数专家(220 位,68.5%)赞成 Lüders 致痫区定义。对于癫痫发作区的定义,专家们意见不一,179 位专家(55.8%)赞成单纯发作,135 位专家(42.1%)支持发作和早期传播。在手术前 SEEG 特征方面,专家们明显倾向于发作期特征而非发作间期特征。有 265 名专家(82.5%)认为癫痫发作模式是最重要的特征。在使用回归分析对未应答者进行校正后,我们发现了类似的趋势:本研究强调了在 SEEG 信息化癫痫手术中标准化术语、解释和结果评估的必要性。通过强调 SEEG 中的不同观点和实践,该研究为制定全球公认的术语和指南奠定了坚实的基础,推动了该领域在癫痫手术中的交流和标准化。
{"title":"Investigating current clinical opinions in stereoelectroencephalography-informed epilepsy surgery","authors":"John Thomas,&nbsp;Chifaou Abdallah,&nbsp;Zhengchen Cai,&nbsp;Kassem Jaber,&nbsp;Jean Gotman,&nbsp;Sandor Beniczky,&nbsp;Birgit Frauscher","doi":"10.1111/epi.18076","DOIUrl":"10.1111/epi.18076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Re-PROGRAM: The evaluation of a brief intervention program for patients with functional seizures in an outpatient hospital setting Re-PROGRAM:对医院门诊环境中功能性癫痫发作患者的简短干预计划进行评估。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-03 DOI: 10.1111/epi.18073
Lana Higson, Terence J O'Brien, Genevieve Rayner, Rubina Alpitsis, Toby Winton-Brown

Objective

Functional seizures (FS) account for 20%–25% of referrals to specialist epilepsy clinics. They are associated with major disability, increased mortality, and frequent and costly health care use. Current guidelines emphasize the importance of implementing clinical pathways to coordinate and deliver effective treatment, but there are few targeted evidence-based interventions that reliably improve patient outcomes, and treatment resources are limited. We conducted a retrospective evaluation of Re-PROGRAM, a novel, brief intervention for functional seizure patients, to assess its feasibility in an outpatient setting.

Methods

Twenty-nine patients with FS undertook Re-PROGRAM between August 2020 and January 2022 at the Alfred Hospital Functional Seizures Clinic, Melbourne, Australia. The intervention comprised five 60–90-min consecutive weekly appointments via telehealth, where psychologists engaged patients in a structured program of seizure management skills, lifestyle modification, and behavioral activation strategies. Following the intervention, patient feedback was collected in routine clinical follow-up as well as with a 24-item self-report pre-/postintervention comparison questionnaire.

Results

All 29 patients who enrolled in Re-PROGRAM completed the scheduled sessions. Of those who returned the postintervention questionnaire (n = 16), 15 reported a reduction in seizure frequency. Four patients were lost to follow-up. Of the remaining nine, eight reported seizure frequency reduction during clinical follow-up. Qualitative analysis of the feedback revealed the majority of patients reported reduced seizure duration, intensity, and bothersomeness, and patients felt improvements in their sense of control over seizures, confidence to use seizure control strategies, assertive communication, problem solving, coping skills, relationships with others, and their day-to-day functioning.

Significance

This retrospective evaluation demonstrates the feasibility and acceptability of Re-PROGRAM as a brief intervention for individuals diagnosed with FS delivered in a clinical outpatient setting and warrants further investigation in larger scale, randomized controlled studies.

目的:功能性癫痫发作(FS)占癫痫专科门诊转诊人数的 20%-25%。功能性癫痫发作与严重残疾、死亡率上升以及频繁使用昂贵的医疗服务有关。现行指南强调实施临床路径以协调和提供有效治疗的重要性,但能可靠改善患者预后的针对性循证干预措施却很少,而且治疗资源有限。我们对针对功能性癫痫发作患者的新型简短干预措施 Re-PROGRAM 进行了回顾性评估,以评估其在门诊环境中的可行性:2020年8月至2022年1月期间,29名FS患者在澳大利亚墨尔本阿尔弗雷德医院功能性癫痫诊所接受了Re-PROGRAM干预。干预措施包括通过远程医疗连续进行五次每周 60-90 分钟的预约,由心理学家指导患者学习癫痫发作管理技能、生活方式调整和行为激活策略等结构化计划。干预结束后,通过常规临床随访以及 24 项自我报告的干预前后对比问卷收集患者反馈:结果:所有 29 名参加 Re-PROGRAM 的患者都完成了预定的疗程。在返回干预后调查问卷的患者(16 人)中,15 人报告癫痫发作频率有所降低。四名患者失去了随访机会。其余九名患者中,有八名在临床随访期间报告癫痫发作频率有所降低。对反馈信息的定性分析显示,大多数患者报告癫痫发作的持续时间、强度和烦扰程度都有所减少,而且患者认为他们对癫痫发作的控制感、使用癫痫发作控制策略的信心、自信的沟通能力、解决问题的能力、应对技能、与他人的关系以及日常功能都有所改善:这项回顾性评估表明,Re-PROGRAM 作为一种简短的干预措施,在临床门诊环境中对确诊为 FS 的患者进行干预是可行的、可接受的,值得在更大规模的随机对照研究中进一步探讨。
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引用次数: 0
Neurocardiac pathologies associated with potassium channelopathies 与钾离子通道病变有关的神经心脏病。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 DOI: 10.1111/epi.18066
Veronica Singh, David S. Auerbach

Voltage-gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A-type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode Kv7.x and Kv11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti-seizure therapies available on the market, one-third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug-resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi-system pathologies, such as epileptogenesis, Kv7 channel modulators provide a potential anti-seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of Kv channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP).

电压门控钾通道遍布人体各处,对生理功能至关重要。这些通道包括延迟整流通道、A 型通道、外向整流通道和内向整流通道。它们影响心脏(复极化)和大脑(复极化和静息膜电位的稳定)的电功能。KCNQx 和 KCNHx 编码 Kv7.x 和 Kv11.x 蛋白,它们形成延迟整流钾通道。KCNQx 和 KCNHx 通道病变与心脏和神经元病变有关。这些病症包括心电图异常、心律失常、心脏性猝死(SCD)、癫痫样放电、癫痫发作、躁狂症和癫痫猝死(SUDEP)。由于 KCNQx 和 KCNHx 通道的表达无处不在,其功能异常尤其有害,会增加猝死的风险。例如,KCNH2 变体在心脏和神经元病变中具有双重作用,而 KCNQ2 和 KCNQ3 变体则与严重的难治性癫痫有关。反复发作和无法控制的癫痫发作会导致继发性异常,包括自主神经、心电功能、呼吸驱动和神经元电活动。即使市场上有多种抗癫痫疗法,全球 7000 多万癫痫患者中仍有三分之一的人癫痫发作无法控制(即难治性/耐药性癫痫),这对神经发育和生活质量造成了负面影响。为了解该领域的现状,本综述研究了 KCNQx 和 KCNHx 在大脑和心脏中的表达模式和电功能。此外,它还讨论了几种已在临床和电生理学上表征的 KCNQx 和 KCNHx 变体。由于这些通道变异与癫痫发生等多系统病变有关,Kv7 通道调节剂提供了一种潜在的抗癫痫疗法,尤其是针对难治性癫痫患者。最终,对 Kv 通道在全身所起作用的进一步了解将推动针对猝死高危人群(SCD 和 SUDEP)的创新、安全和有效疗法的开发。
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引用次数: 0
Farewell from the Editor-in-Chief 主编的告别。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-31 DOI: 10.1111/epi.18060
Michael R. Sperling
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引用次数: 0
Thank you to the outgoing editor-in-chief of Epilepsia, Michael Sperling 感谢即将离任的 Epilepsia 主编 Michael Sperling:国际抗癫痫联盟。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-31 DOI: 10.1111/epi.18057
International League Against Epilepsy
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引用次数: 0
Uses of antiseizure medication among pregnant women with epilepsy and risk of adverse obstetric outcomes: A group-based trajectory analysis 癫痫孕妇使用抗癫痫药物与不良产科结果风险:基于群体的轨迹分析。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-30 DOI: 10.1111/epi.18064
Yi-Chin Lin, Chih-Wan Lin, Lin-Chieh Meng, Shih-Tsung Huang, Yi-Yung Chen, Shuu-Jiun Wang, K. Arnold Chan, Fei-Yuan Hsiao

Objective

This study was undertaken to examine the association between different patterns of antiseizure medication (ASM) use during pregnancy and adverse obstetric outcomes (preterm birth, low birth weight [LBW], and small for gestational age [SGA]).

Methods

This retrospective cohort study used the Birth Certificate Application and National Health Insurance data in Taiwan (January 1, 2004 through December 31, 2018). We retrieved weekly ASM among pregnant women with epilepsy who were prepregnancy chronic users and used group-based trajectory modeling to identify distinct patterns of use. Logistic regressions were adopted to examine the association between patterns of ASM use and risk of preterm birth, LBW, and SGA. In addition, we revealed postnatal ASM utilization pattern among these prepregnancy chronic users as an exploratory study.

Results

Of 2175 pregnant women with epilepsy, we identified four patterns of ASM use during pregnancy: frequent and continuous (64.87%), frequent but discontinuous (7.08%), intermittent (19.72%), and intermittent and discontinuous users (8.32%). Compared to frequent and continuous users, the adjusted odds ratios for preterm birth in frequent but discontinuous, intermittent, and intermittent and discontinuous users were .83 (95% confidence interval [CI] = .47–1.48), .71 (95% CI = .47–1.05), and .88 (95% CI = .52–1.49), respectively. Similar results were observed for LBW and SGA. In the exploratory study, we found that most of our study subjects maintained the same patterns before and after delivery.

Significance

After considering duration and timing of exposure, our study did not find an association between four distinct patterns of ASM use and adverse obstetric outcomes among women with epilepsy. The findings suggested that optimal seizure control could be received for pregnant women with epilepsy after evaluating the risks and benefits.

研究目的本研究旨在探讨孕期使用抗癫痫药物(ASM)的不同模式与不良产科结局(早产、低出生体重[LBW]和小于胎龄[SGA])之间的关联:这项回顾性队列研究使用了台湾的出生证明申请和国民健康保险数据(2004 年 1 月 1 日至 2018 年 12 月 31 日)。我们检索了孕前长期使用ASM的癫痫孕妇的每周ASM情况,并使用基于群体的轨迹建模来识别不同的使用模式。我们采用逻辑回归法来研究 ASM 使用模式与早产、低体重儿和 SGA 风险之间的关联。此外,作为一项探索性研究,我们还揭示了这些孕前长期使用 ASM 的孕妇在产后使用 ASM 的模式:在 2175 名患有癫痫的孕妇中,我们发现了孕期使用 ASM 的四种模式:频繁且持续使用(64.87%)、频繁但间断使用(7.08%)、间断使用(19.72%)和间断且间断使用(8.32%)。与经常使用和连续使用的人群相比,经常使用但不连续使用、间断使用和间断及不连续使用的人群早产的调整后几率比分别为 0.83(95% 置信区间 [CI] = 0.47-1.48)、0.71(95% CI = 0.47-1.05)和 0.88(95% CI = 0.52-1.49)。LBW 和 SGA 也观察到了类似的结果。在探索性研究中,我们发现大多数研究对象在分娩前后保持了相同的模式:在考虑了接触ASM的持续时间和时机后,我们的研究没有发现癫痫妇女使用ASM的四种不同模式与不良产科结局之间存在关联。研究结果表明,在对风险和益处进行评估后,癫痫孕妇可以获得最佳的癫痫控制效果。
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引用次数: 0
Automated detection of tonic seizures using wearable movement sensor and artificial neural network 利用可穿戴运动传感器和人工神经网络自动检测强直性癫痫发作。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-30 DOI: 10.1111/epi.18077
Sidsel Armand Larsen, Daniel Højrup Johansen, Sándor Beniczky

Although several validated wearable devices are available for detection of generalized tonic–clonic seizures, automated detection of tonic seizures is still a challenge. In this phase 1 study, we report development and validation of an artificial neural network (ANN) model for automated detection of tonic seizures with visible clinical manifestation using a wearable wristband movement sensor (accelerometer and gyroscope). The dataset prospectively recorded for this study included 70 tonic seizures from 15 patients (seven males, age 3–46 years, median = 19 years). We trained an ANN model to detect tonic seizures. The independent test dataset comprised nocturnal recordings, including 10 tonic seizures from three patients and additional (distractor) data from three subjects without seizures. The ANN model detected nocturnal tonic seizures with visible clinical manifestation with a sensitivity of 100% (95% confidence interval = 69%–100%) and with an average false alarm rate of .16/night. The mean detection latency was 14.1 s (median = 10 s), with a maximum of 47 s. These data suggest that nocturnal tonic seizures can be reliably detected with movement sensors using ANN. Large-scale, multicenter prospective (phase 3) trials are needed to provide compelling evidence for the clinical utility of this device and detection algorithm.

尽管目前已有几种经过验证的可穿戴设备可用于检测全身强直阵挛发作,但强直发作的自动检测仍是一项挑战。在这项第一阶段研究中,我们报告了使用可穿戴腕带运动传感器(加速度计和陀螺仪)自动检测有明显临床表现的强直性发作的人工神经网络(ANN)模型的开发和验证情况。这项研究的前瞻性记录数据集包括 15 名患者(7 名男性,年龄 3-46 岁,中位数 = 19 岁)的 70 次强直性发作。我们训练了一个 ANN 模型来检测强直性癫痫发作。独立测试数据集由夜间记录组成,包括三名患者的 10 次强直性发作和三名无发作受试者的附加(干扰)数据。ANN 模型检测到有明显临床表现的夜间强直性癫痫发作的灵敏度为 100%(95% 置信区间 = 69%-100%),平均误报率为 0.16/夜。平均检测潜伏期为 14.1 秒(中位数 = 10 秒),最长为 47 秒。这些数据表明,使用方差分析网络的运动传感器可以可靠地检测到夜间强直性癫痫发作。需要进行大规模、多中心前瞻性(第 3 期)试验,为该设备和检测算法的临床实用性提供有力证据。
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引用次数: 0
期刊
Epilepsia
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