Epilepsy Research最新文献_第7页

Health care burden of access barriers to epilepsy care in the United States: A claims-based analysis of payer channels 美国癫痫治疗可及性障碍的卫生保健负担：基于索赔的付款人渠道分析

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-08-09 DOI: 10.1016/j.eplepsyres.2025.107639

Herbert Peeples , Emily Achter , Christopher Dieyi , Keshia Maughn

Objective

To describe access challenges, barriers to antiseizure medications (ASMs), and impact of ASM formulary policies for patients with epilepsy (PWE).

Methods

Observational study of de-identified claims from an all-payer claims database (2014–2021) and a formulary/payer policy database. Adults prescribed ≥ 1 ASM following initial epilepsy diagnosis, with continuous medical/pharmacy benefits, were included. Demographic characteristics, proximity to/use of a neurology health care professional (HCP), health care resource utilization (HCRU), and costs were assessed.

Results

In total, 35,351, 33,339, and 24,722 PWE with commercial, Medicare, and Medicaid insurance, respectively, were included. The Medicare group was older, had a higher comorbidity index score, more males, and fewer non-White and Hispanic individuals versus other groups. Most (> 58 %) commercially-insured PWE had coverage to all six first-generation ASMs examined, six to 12 second-generation ASMs, and all four third-generation ASMs; coverage rates were higher for Medicaid while data for Medicare were incomplete. Most commercial and Medicaid PWE had no access requirements to first-generation ASMs; approximately two-thirds and half of patients had access requirements for second- and third-generation ASMs, respectively. Although > 90 % of PWE used a neurology HCP during follow-up, only about one-third lived within proximity. Of PWE with formulary data (N = 77,787), > 80 % and < 8.0 % were prescribed second- and third-generation ASMs, respectively. There were no clear patterns in epilepsy-related HCRU/cost.

Conclusions

Data revealed difficulties in neurologist access and predominant use of second-generation ASMs, despite access restrictions for many PWE, suggesting obstacles in accessing treatment and specialist care.

目的探讨抗癫痫药物的可及性、障碍及抗癫痫药物处方政策对癫痫患者的影响。方法对2014-2021年全付款人索赔数据库和处方/付款人政策数据库中的去识别索赔进行观察研究。纳入初始癫痫诊断后处方≥ 1 ASM的成人，并持续获得医疗/药学益处。评估了人口统计学特征、接近/使用神经内科卫生保健专业人员（HCP）、卫生保健资源利用率（HCRU）和费用。结果共纳入35,351名、33,339名、24,722名具有商业、医疗和医疗补助保险的PWE。与其他组相比，医疗保险组年龄较大，合并症指数得分较高，男性较多，非白人和西班牙裔个体较少。大多数（> 58% %）商业保险的PWE覆盖了所有6个第一代asm， 6到12个 第二代asm和所有4个第三代asm；医疗补助的覆盖率更高，而医疗保险的数据不完整。大多数商业和医疗补助PWE没有获得第一代asm的要求；大约三分之二和一半的患者分别有获得第二代和第三代asm的需求。虽然>； 90 %的PWE在随访期间使用了神经病学HCP，但只有约三分之一的人住在附近。在有公式数据的PWE中（N = 77,787），>； 80 %和<； 8.0 %分别开第二代和第三代ASMs。与癫痫相关的HCRU/cost没有明确的模式。结论数据显示，尽管许多PWE有准入限制，但神经科医生难以获得和主要使用第二代asm，这表明在获得治疗和专科护理方面存在障碍。

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引用次数: 0

Fenfluramine for developmental and epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS): An exploratory study 芬氟拉明治疗伴有睡眠峰波激活的发展性和癫痫性脑病（DEE-SWAS）：一项探索性研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.eplepsyres.2025.107687

Paloma Parra-Díaz , Antonio Gil-Nagel , Irene Sánchez-Miranda Román , Irene Pascual-Zapatero , Adrián Valls-Carbó , Ángel Aledo-Serrano , Álvaro Beltrán-Corbellini

Objective

To evaluate the safety and potential efficacy of fenfluramine (FFA) in patients with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS).

Methods

We conducted an open-label, interventional, exploratory study of FFA in pediatric patients with DEE-SWAS. We assessed changes in seizure frequency, intensity, and spike-wave index (SWI), as well as non-seizure outcomes including a neuropsychological evaluation with BRIEF®-2 and Vineland-3 questionnaires, assessment of sleep habits, and caregiver-reported changes in cognitive, behavioral and motor symptoms. Adverse effects and changes in concomitant antiseizure medications (ASMs) were recorded.

Results

Six patients were included (2 females, median age 10 years, range 4–11 years), with a median follow-up of 12 months (9–13 months). FFA was well tolerated; only two patients experienced mild, transient adverse events, and all participants continued treatment throughout the study. SWI improved in 4/6 patients (66.7 %), with ≥ 50 % reduction in two (near-resolution in one). Seizures were reported as less severe, although their frequency remained unchanged. The total dose of concomitant corticosteroids and ASMs was reduced in 66.7 % of patients. Executive functioning showed a tendency to improvement in 4/6 patients (66.7 %) based on BRIEF®-2 scores, although Vineland-3 scores remained stable. Caregivers also reported perceived improvements in behavior, cognition, and sleep.

Conclusion

FFA was a safe and potentially effective treatment in our cohort of patients with DEE-SWAS. We observed a reduction of SWI in most patients, along with modest improvements in executive function. These preliminary findings support the need for larger studies to confirm efficacy and explore long-term outcomes.

目的评价芬氟拉明（FFA）治疗发育性和癫痫性脑病伴睡眠峰波激活（DEE-SWAS）的安全性和潜在疗效。方法我们对小儿DEE-SWAS患者的FFA进行了一项开放标签、介入性、探索性研究。我们评估了癫痫发作频率、强度和峰波指数（SWI）的变化，以及非癫痫发作结果，包括使用BRIEF®-2和Vineland-3问卷进行神经心理学评估、睡眠习惯评估和护理者报告的认知、行为和运动症状的变化。记录不良反应及伴随抗癫痫药物（asm）的变化。结果纳入6例患者（2例女性，中位年龄10岁，范围4 ~ 11岁），中位随访时间为12个月（9 ~ 13个月）。FFA耐受良好；只有两名患者经历了轻微的、短暂的不良事件，所有参与者在整个研究过程中都继续接受治疗。4/6例患者SWI改善（66.7 %），2例患者SWI降低≥ 50 %（1例接近缓解）。据报道，癫痫发作的严重程度较轻，但发作频率保持不变。同时使用皮质类固醇和asm的患者总剂量降低了66.7 %。根据BRIEF®-2评分，4/6患者（66.7 %）的执行功能有改善的趋势，尽管Vineland-3评分保持稳定。护理人员也报告了行为、认知和睡眠方面的改善。结论ffa在我们的DEE-SWAS患者队列中是一种安全且潜在有效的治疗方法。我们观察到大多数患者的SWI减少，同时执行功能略有改善。这些初步发现支持需要进行更大规模的研究来确认疗效并探索长期结果。

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引用次数: 0

Antiseizure medication effects on the autonomic nervous system in pediatric patients with epilepsy 抗癫痫药物对小儿癫痫患者自主神经系统的影响

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-10-23 DOI: 10.1016/j.eplepsyres.2025.107688

Fatemeh Mohammad Alizadeh Chafjiri , Stephanie Dailey , Saeid Sadeghian , Adriana Ulate-Campos , Tobias Loddenkemper

Patients with epilepsy (PWE) taking antiseizure medications (ASMs) exhibit altered autonomic nervous system (ANS) parameters. ANS signals may monitor ASM applications and effectiveness non-invasively. Due to limited research, we reviewed the effects of ASMs on the pediatric ANS. We followed PRISMA guidelines and searched PubMed, Web of Science, and Embase for publications until 12/2024. These studies investigated the impact of ASMs on ANS, including heart rate (HR), heart rate variability (HRV), temperature, and sweat. We used Covidence software for screening processes and data extraction. After screening 9837 studies, 23 were included. Zonisamide and topiramate showed reduced sweating and increased temperature. In polytherapy patients, HRV decreased, with reductions in high-frequency (HF) values on valproic acid and low-frequency values on phenobarbital. Higher ASM doses reduced HRV but did not affect HR or sweat glands. One study reported altered cardiac ventricle functioning in PWE on ASMs. Two studies reviewing the effect of levetiracetam found minimal short-term ANS effects within the ECG but improved parasympathetic control and restored balance in HRV parameters over time. Sympathetic and parasympathetic dysfunctions were prominent in some patients, with polytherapy increasing HR and reducing HF values of HRV. In one study, higher ASM concentrations lowered HRV. Overall, ASMs may influence HR, sweat, and temperature, though many studies lacked analysis of specific ASM types. A better understanding of how ASMs affect ANS is essential for assessing medication efficacy, side effects, and their role as confounders in seizure prediction. These biosignal data can support device-based neuromodulation, seizure detection, and prediction algorithms.

癫痫患者（PWE）服用抗癫痫药物（asm）表现出改变自主神经系统（ANS）参数。ANS信号可以非侵入性地监测ASM的应用和有效性。由于研究有限，我们回顾了asm对儿科ANS的影响，遵循PRISMA指南，检索了PubMed， Web of Science和Embase的出版物，直到2024年12月。这些研究调查了asm对ANS的影响，包括心率（HR）、心率变异性（HRV）、体温和汗液。我们使用covid软件进行筛选过程和数据提取。筛选9837项研究后，纳入23项。唑尼沙胺和托吡酯显示出汗减少和体温升高。在多药治疗的患者中，HRV下降，丙戊酸降低高频（HF）值，苯巴比妥降低低频值。较高的ASM剂量降低HRV，但不影响HR或汗腺。一项研究报告了脑血管痉挛时PWE患者心室功能的改变。两项研究回顾了左乙拉西坦的作用，发现心电图的短期ANS效应很小，但随着时间的推移，副交感神经控制得到改善，HRV参数恢复平衡。部分患者交感神经和副交感神经功能障碍突出，多药治疗HRV的HR值升高，HF值降低。在一项研究中，较高的ASM浓度降低了HRV。总体而言，ASM可能影响人力资源、出汗和体温，尽管许多研究缺乏对ASM具体类型的分析。更好地了解asm如何影响ANS对于评估药物疗效、副作用及其在癫痫发作预测中作为混杂因素的作用至关重要。这些生物信号数据可以支持基于设备的神经调节、癫痫检测和预测算法。

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引用次数: 0

Periodic limb movements among persons with epilepsy: A retrospective polysomnographic study 癫痫患者的周期性肢体运动：一项回顾性多导睡眠图研究。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI: 10.1016/j.eplepsyres.2025.107662

Manav Jain , Laurel Charlesworth , Helen Driver , Gavin P. Winston , Lysa Boissé Lomax , Garima Shukla

<div><h3>Introduction</h3><div>Persons with epilepsy (PWE) frequently contend with disrupted sleep related to multiple seizure related as well as other factors like medications and comorbidities. Such disturbances often lead to fragmented sleep, which can adversely affect quality of life and compromise seizure management. Previous</div><div>Although previous research has addressed conditions like sleep apnea and insomnia among PWE, less attention has been paid to periodic limb movements (PLMs), a requirement for diagnosis of the periodic limb movement disorder and also commonly observed in restless legs syndrome (RLS) as well as other conditions. This study aims to determine the prevalence and specific features of PLMs in PWE and to explore how these movements correlate with objective sleep measurements.</div></div><div><h3>Methods</h3><div>This investigation employed a retrospective chart review of consecutive adult patients diagnosed with epilepsy who underwent polysomnography at a tertiary-care sleep laboratory over a ten-year span. The control group consisted of individuals evaluated for possible obstructive sleep apnea, who were matched to cases based on age, sex, and the severity of sleep apnea. Patient records were initially identified using keywords related to “epilepsy” or “seizures.” Epilepsy diagnosis was confirmed through detailed chart review, which also yielded clinical details likety duration of epilepsy, seizure classification, and antiseizure medication usage. Sleep parameters such as sleep efficiency, spontaneous arousal index, periodic limb movement index, periodic limb movement with arousal index, and apnea-hypopnea index were extracted from archived polysomnography reports. The subsequent analysis was carried out using descriptive statistical methods using RStudio version 4.4.1.</div></div><div><h3>Results</h3><div>A total of 152 relevant patient records were found in the database. Of these, 61 patients with epilepsy (mean age 41.4 ± 17.2 years, including 31 females) met the inclusion criteria and were matched with 61 patients suspected for OSA. Within the epilepsy cohort, 43 patients experienced focal-onset epilepsy while 16 had generalized epilepsy. 25 patients were prescribed two or more antiseizure medications, and 12 were categorized as medically refractory. PLMs were detected in 23 % of patients with epilepsy compared to 26 % in the control group, with mean PLMI values of 6.1 ± 16.8 and 8.8 ± 20.7, respectively. The PLMAI was also similar between the two groups (0.5 ± 1.0 vs. 1.1 ± 2.4). Other sleep parameters, including the mean AHI (16.0 ± 20.0 in the epilepsy group vs. 19.7 ± 19.4 in the control group), did not exhibit significant differences between groups. Within the epilepsy cohort, the only factor linked to the presence of periodic limb movements was older age, with no observed association with seizure type, number of antiseizure medications, or seizure control.</div></div><div><h3>Conclusions</h3><div>PLMs are a

引言：癫痫患者（PWE）经常与多次发作相关的睡眠中断以及其他因素（如药物和合并症）作斗争。这种干扰通常会导致睡眠碎片化，这可能会对生活质量产生不利影响，并危及癫痫发作的管理。虽然以前的研究已经解决了PWE中的睡眠呼吸暂停和失眠等疾病，但对周期性肢体运动（PLMs）的关注较少，周期性肢体运动（PLMs）是诊断周期性肢体运动障碍的必要条件，也是不宁腿综合征（RLS）以及其他疾病中常见的症状。本研究旨在确定PWE中PLMs的患病率和具体特征，并探讨这些运动如何与客观睡眠测量相关联。方法：本研究采用回顾性图表回顾，对连续10年在三级保健睡眠实验室接受多导睡眠描记术诊断为癫痫的成年患者进行调查。对照组由可能患有阻塞性睡眠呼吸暂停的个体组成，他们根据年龄、性别和睡眠呼吸暂停的严重程度与病例相匹配。患者记录最初使用与“癫痫”或“癫痫发作”相关的关键词进行识别。通过详细的病历回顾，确认癫痫诊断，并获得癫痫病程、发作类型和抗癫痫药物使用的临床细节。从存档的多导睡眠图报告中提取睡眠效率、自发觉醒指数、周期性肢体运动指数、周期性肢体运动伴觉醒指数和呼吸暂停低通气指数等睡眠参数。后续分析采用描述性统计方法，使用RStudio 4.4.1版本进行。结果：数据库共检索到相关病历152例。其中61例癫痫患者（平均年龄41.4 ± 17.2岁，包括31例女性）符合纳入标准，与61例疑似OSA患者匹配。在癫痫队列中，43例发生局灶性癫痫，16例发生全身性癫痫。25名患者服用了两种或两种以上的抗癫痫药物，12名患者被归类为难治性药物。23 %的癫痫患者检测到PLMs，对照组为26 %，PLMI平均值分别为6.1 ± 16.8和8.8 ± 20.7。两组间PLMAI也相似（0.5 ± 1.0 vs. 1.1 ± 2.4）。其他睡眠参数，包括平均AHI（癫痫组为16.0 ± 20.0，对照组为19.7 ± 19.4），组间无显著差异。在癫痫队列中，与周期性肢体运动存在相关的唯一因素是年龄较大，与癫痫发作类型、抗癫痫药物数量或癫痫发作控制没有观察到关联。结论：在PWE的多导睡眠图研究中，PLMs是一个经常观察到的现象，主要与年龄的增长有关。考虑到癫痫组和年龄和性别匹配的阻塞性睡眠呼吸暂停队列的周期性肢体运动指数的可比性，研究结果表明，阻塞性睡眠呼吸暂停可能是PWE中周期性肢体运动的主要因素。

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引用次数: 0

Attention-deficit/hyperactivity disorder in adults with epilepsy: Preliminary prevalence and associated factors in a Czech sample 成人癫痫患者的注意缺陷/多动障碍：捷克样本的初步患病率和相关因素

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-08-31 DOI: 10.1016/j.eplepsyres.2025.107645

Karin Daniele , Jaroslava Raudenská , Alena Javůrková

Objective

This study investigated the prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in Czech adult people with epilepsy (PWE) and examined factors potentially contributing to the co-occurrence of these two conditions. Although previous research has consistently reported elevated rates of ADHD in epilepsy populations, data from adult samples in Czech Republic remain limited.

Methods

Fifty-six adults with epilepsy completed validated self-report questionnaires assessing ADHD symptoms (ASRS), anxiety (GAD-2), and depression (NDDIE-2). Epilepsy-related clinical factors, such as seizure frequency, anti-seizure medication (ASM), type of epilepsy and epilepsy duration, were also analyzed in relation to ADHD symptoms.

Results

A high prevalence of ADHD symptoms n = 25 (44.6 %) was found in the sample. No significant associations were observed between ADHD symptoms and epilepsy-related variables or depressive symptoms, but a regression model of clinical and sociodemographic variables can explain 34.2 % of the variance in ASRS scores (Adj. R² = 0.342), with only anxiety emerging as a significant predictor (β = 0.517, SE = 0.50, t = 3.23, p = .003).

Conclusion

These preliminary findings suggest a possible link between epilepsy and ADHD, which may be further explored in future research through shared emotional or neurobiological mechanisms. The results underscore the need for integrated screening approaches and further research into the co-occurrence of epilepsy and ADHD in adult populations.

目的调查捷克成年癫痫患者（PWE）注意力缺陷/多动障碍（ADHD）症状的患病率，并探讨可能导致这两种情况同时发生的因素。尽管先前的研究一直报道癫痫人群中多动症的发病率升高，但捷克共和国成人样本的数据仍然有限。方法56例成人癫痫患者完成了评估ADHD症状（ASRS）、焦虑（GAD-2）和抑郁（NDDIE-2）的有效自我报告问卷。分析癫痫相关临床因素，如癫痫发作频率、抗癫痫药物（ASM）、癫痫类型和癫痫持续时间与ADHD症状的关系。结果本组儿童ADHD患病率较高，分别为 = 25（44.6% %）。ADHD症状与癫痫相关变量或抑郁症状之间没有明显的关联，但临床和社会人口学变量的回归模型可以解释ASRS评分中34.2% %的方差（Adj. R²= 0.342），只有焦虑是一个显著的预测因子（β = 0.517, SE = 0.50, t = 3.23,p = .003）。结论这些初步发现提示癫痫与ADHD之间可能存在联系，未来的研究可以通过共同的情绪或神经生物学机制进一步探索这一联系。这些结果强调需要综合筛查方法，并进一步研究成人人群中癫痫和ADHD的共发情况。

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引用次数: 0

Electrographic seizures on responsive neurostimulation: An early and objective measure of response to cenobamate 反应性神经刺激的电图癫痫发作：一种早期和客观的测量对cenobamate反应的方法

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-08-30 DOI: 10.1016/j.eplepsyres.2025.107647

Sami Aboumatar , Jay R. Gavvala , Zeenat Jaisani , Ruben Kuzniecky , Michael Privitera , Madeline Ring , William E. Rosenfeld , Jacob Pellinen

Objectives

Responsive neurostimulation (RNS) electrocorticographic (ECoG) data may have a role in objectively assessing the efficacy of add-on antiseizure medications (ASMs). This retrospective, multicenter, observational, 24-week study is the first to report the effects of cenobamate on RNS-detected events (RDE).

Methods

Patients included adults (≥18 years) with a history of recurrent focal seizures and implanted RNS who initiated adjunctive cenobamate ≥ 3 months after RNS implant between 4/1/20–12/15/23 and who received ≥ 2 weeks of cenobamate (≥50 mg/day). RDE (“long episodes,” “long episodes with saturation,” and “saturation”) obtained from the NeuroPace Patient Data Management System were reviewed to select only electrographic seizures (ESs) based on electrographic ictal patterns. RDEs and ESs were counted during the 8-week baseline period, every 2 weeks for 12 weeks after starting cenobamate, and at study end. The main outcome was percent change from baseline to the end of the 16-week treatment period (12 + weeks) for overall ESs, ESs ≥ 50 seconds, and ESs < 50 seconds. Patient-reported clinical seizure frequency was recorded when available.

Results

Thirty-seven patients (mean age 36.7 years) were included. Median cenobamate dose was 150 mg/day (range, 50–250 mg/day). There was a significant median percent reduction from baseline to the end of cenobamate treatment in ESs (94.4 %; p < 0.0001), ESs ≥ 50 s (100.0 %; p < 0.0001), and ESs < 50 s (100.0 %; p < 0.0001). Among patients with available seizure data (n = 24), median percent reduction in clinical seizures per 28 days from baseline to end of treatment was 72.2 % (p < 0.0001). Adverse events were reported in 27 % (10/37) of patients; dizziness, fatigue, and sleepiness were most reported.

Significance

Patients with uncontrolled seizures after RNS had a significant reduction in ESs and clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis support the potential use of RNS ECoG data as an objective measure to supplement clinical data when determining cenobamate efficacy and may provide a strategy for monitoring responses to ASMs more generally in this population.

Data Availability

The data for the analyses described in this paper are available by request from the corresponding author or from SK Life Science, Inc., the company sponsoring the clinical development of cenobamate for the treatment of focal epilepsy.

目的反应性神经刺激（RNS）皮质电图（ECoG）数据可能在客观评估附加抗癫痫药物（asm）的疗效方面发挥作用。这项回顾性、多中心、观察性、为期24周的研究首次报道了cenobamate对rns检测事件（RDE）的影响。方法患者包括有复发性局灶性癫痫发作和植入RNS病史的成人（≥18岁），在RNS植入后4/1 - 20 / 12/15/23期间开始辅助使用辛奥巴马酸≥ 3个月，并接受≥ 2周的辛奥巴马酸（≥50 mg/天）。回顾从NeuroPace患者数据管理系统获得的RDE（“长发作”、“长发作伴饱和”和“饱和”），仅根据电图的心电图模式选择电图癫痫发作（ESs）。RDEs和ESs分别在基线期8周、开始治疗12周后每2周和研究结束时进行计数。主要结局是从基线到16周治疗期结束（12 +周）的总体ESs、ESs≥ 50 秒和ESs <； 50 秒的百分比变化。患者报告的临床癫痫发作频率被记录下来。结果纳入37例患者，平均年龄36.7岁。中位剂量为150 mg/天（范围50-250 mg/天）。显著值还原率从基线到年底cenobamate治疗ESs(94.4 %;p & lt; 0.0001),ESs≥50  年代(100.0 %;p & lt; 0.0001),和ESs & lt;  50年代(100.0 %;p & lt; 0.0001)。在可获得癫痫发作数据的患者中（n = 24），从基线到治疗结束，每28天临床癫痫发作减少的中位数百分比为72.2 % （p <； 0.0001）。27 %（10/37）的患者报告了不良事件；最常见的症状是头晕、疲劳和嗜睡。意义：RNS后癫痫发作不受控制的患者在辅助治疗期间，ESs和临床报告的癫痫发作显著减少。该分析的结果支持RNS ECoG数据作为一种客观测量的潜在用途，以补充临床数据，以确定药物疗效，并可能为更广泛地监测该人群对asm的反应提供策略。数据可得性本文中描述的分析数据可从通讯作者或SK生命科学公司获得，该公司赞助了用于治疗局灶性癫痫的cenobamate的临床开发。

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引用次数: 0

Deep brain stimulation of the anterior nucleus of the thalamus in animal models of mesial temporal lobe epilepsy: A literature review 中颞叶癫痫动物模型中丘脑前核的深部脑刺激：文献综述

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-10-03 DOI: 10.1016/j.eplepsyres.2025.107670

Emma Acerbo , Thomas Eggers , Alejandra M. Fernandez , Robert E. Gross , Claire-Anne Gutekunst

Epilepsy affects approximately 1 % of the global population, presenting as a complex and heterogeneous disorder characterized by spontaneous, recurrent seizures. Focal onset seizures comprise half of all epilepsy cases. Mesial temporal lobe epilepsy (MTLE), the most prevalent form of focal seizures in adults, originates in the temporal lobe and is challenging to manage with standard antiseizure medications. Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has emerged as a therapeutic option for drug-resistant cases. Although clinical effects are well documented, pre-clinical research remains limited. To date, only 28 studies have been published, mostly in rodents and few in primates and sheep. This narrative review examines the anatomical organization of the ANT across human, rodent, and non-human primate models and synthesizes findings from the preclinical studies investigating ANT-DBS in experimental MTLE animal models. Collectively, these studies demonstrate an approximate 50 % reduction in seizure frequency, mirroring recent clinical outcomes. However, the majority of studies have focused on high-frequency stimulation (>100 Hz), with few exploring multiple stimulation frequencies. Additionally, outcomes from intermittent ON/OFF stimulation were inconclusive or showed worsening effects in two out of three studies. Thus, several crucial parameters, including stimulation frequency, pattern, and other variables remain inadequately explored in preclinical MTLE models yet hold potential to enhance therapeutic efficacy and patient outcomes.

癫痫影响全球约1 %的人口，是一种复杂的异质性疾病，其特征是自发、反复发作。局灶性癫痫发作占所有癫痫病例的一半。中颞叶癫痫（MTLE）是成人最常见的局灶性癫痫，起源于颞叶，使用标准抗癫痫药物治疗具有挑战性。针对丘脑前核（ANT）的深部脑刺激（DBS）已成为耐药病例的治疗选择。虽然临床效果有充分的证据，但临床前研究仍然有限。迄今为止，仅发表了28项研究，主要针对啮齿动物，很少针对灵长类动物和绵羊。本文综述了人类、啮齿动物和非人类灵长类动物模型中ANT的解剖组织，并综合了在实验性MTLE动物模型中调查ANT- dbs的临床前研究结果。总的来说，这些研究表明癫痫发作频率降低了大约50% %，反映了最近的临床结果。然而，大多数研究都集中在高频刺激（>100 Hz）上，很少探索多种刺激频率。此外，在三分之二的研究中，间歇性开/关刺激的结果是不确定的或显示出恶化的效果。因此，在临床前MTLE模型中，包括刺激频率、模式和其他变量在内的几个关键参数仍未得到充分探索，但仍有可能提高治疗效果和患者预后。

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引用次数: 0

Perceptions of health disparities among neurologists treating Black patients with epilepsy: A survey study in the United States 对治疗黑人癫痫患者的神经科医生健康差异的看法：美国的一项调查研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-08-05 DOI: 10.1016/j.eplepsyres.2025.107637

Ima Ebong , Pam Eads , Georgette Charles

Objective

Many factors influence patients’ experience with epilepsy, including inequities based on socially defined race and ethnicity. We sought to better understand factors contributing to health disparities in Black people living with epilepsy (PWE), as perceived by neurologists, and the value of programs to help healthcare providers (HCPs) reduce these disparities.

Methods

An online, blinded, cross-sectional survey was administered to neurologists (November 8–18, 2022) whose population of PWE included ≥ 20 % of Black individuals and who had managed ≥ 10 PWE in the last 30 days. Questions assessed recognition of health disparities in PWE and the value of HCP-focused programs to address disparities. Statistical comparisons were performed by practice setting (academic vs. community).

Results

Of 101 neurologists, 48.5 % and 51.5 % worked in academic and community settings, respectively, 2.0 % of all neurologists were Black, and 28.3 % of neurologists’ patients were Black. Situations most commonly having a major/severe negative health impact were ‘inconsistent treatment adherence/compliance’ and ‘have significant comorbidities’ in all PWE, and ‘missed appointments’ and ‘mistrust in the healthcare system’ in Black PWE. In total, 27.7 % of neurologists (42.9 % academic vs. 13.5 % community-based; p < 0.05) completely agreed that racism is a social determinant of health (SDOH). HCP-focused programs were generally considered as somewhat/very important to improve outcomes in Black PWE.

Conclusions

Fewer than a third of neurologists completely agreed that racism is an SDOH, variably suggesting no perceived differences in their patient populations (leading to disagreement) or providing evidence of implicit/unconscious bias. Increasing neurologists' participation in HCP-focused programs may help counter health disparities in Black PWE, or at a minimum improve awareness that disparities exist.

许多因素影响患者的癫痫经历，包括基于社会定义的种族和民族的不平等。我们试图更好地了解神经科医生认为黑人癫痫患者（PWE）健康差异的因素，以及帮助医疗保健提供者（HCPs）减少这些差异的项目的价值。方法对患有PWE的神经科医生（2022年11月8日至18日）进行在线、盲法、横断面调查，这些医生的PWE人群包括≥ 20% %的黑人，并且在过去30天内处理过≥ 10例PWE。评估了对PWE中健康差异的认识以及以hcp为重点的解决差异的方案的价值。通过实践环境（学术与社区）进行统计比较。结果101名神经科医生中，在学术和社区工作的分别占48.5% %和51.5% %，所有神经科医生中黑人占2.0% %，神经科医生的患者中黑人占28.3% %。最常见的对健康产生重大/严重负面影响的情况是所有PWE中“不一致的治疗依从性/依从性”和“有显著的合并症”，以及黑色PWE中“错过预约”和“对医疗系统的不信任”。总的来说，27.7% %的神经科医生(42.9% %学术vs 13. %社区；p <； 0.05)完全同意种族主义是健康的社会决定因素（SDOH）。以hcp为重点的项目通常被认为对改善黑人PWE的结果有些/非常重要。结论：不到三分之一的神经科医生完全同意种族主义是一种SDOH，这可能表明他们的患者群体没有感知到差异（导致分歧），或者提供了隐性/无意识偏见的证据。增加神经科医生参与以hcp为重点的项目可能有助于消除黑人PWE的健康差异，或者至少提高对差异存在的认识。

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引用次数: 0

Exploring metabolic biomarkers and pathways in pharmacoresistant epilepsy: A systematic review 探索抗药癫痫的代谢生物标志物和途径：系统综述

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.eplepsyres.2025.107656

Zheng-Dong Lim , Nur Asyiqin Syafiqa Abdullah , Kheng-Seang Lim , Paul Chi-Lui Ho , Alina Arulsamy , Si-Lei Fong , Hui-Yin Yow

Drug-resistant epilepsy (DRE) is characterized by the failure to attain sustained seizure freedom despite adequate trials of two antiseizure medication (ASM) regimens that are well tolerated and appropriately chosen and administered, either as monotherapies or in combination. Despite being a cornerstone of epilepsy treatment, ASMs are ineffective in achieving seizure remission in nearly one-third of patients, who are consequently classified as having DRE. This systematic review aims to determine potential metabolic biomarkers and pathways linked to DRE, which could inform personalized treatment and optimize therapeutic outcomes. A comprehensive search of databases, namely Medline, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) based on predefined inclusion and exclusion criteria yielded 29 eligible studies after full-text screening. The risk of bias from these studies was reviewed using the Office of Health Assessment and Translation (OHAT) risk of bias rating tool. Key information, including study groups, sample size, model types, and main findings were tabulated. Several metabolites were identified, including amino acids (glycine, glutamate, isoleucine), organic acids (lactate), and glucose, which may serve as potential biomarkers for DRE. MetaboAnalyst 6.0 pathway analysis identified the alanine, aspartate and glutamate metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis pathways, emerged with significant impact score (≥0.5, p < 0.05). The findings highlight the promising role of these metabolites and pathways as predictive biomarkers for DRE and potential therapeutic targets for novel drug development.

耐药癫痫（DRE）的特点是，尽管对两种抗癫痫药物（ASM）方案进行了充分的试验，但仍未能实现持续的癫痫发作自由，这两种抗癫痫药物（ASM）方案具有良好的耐受性，并且可以作为单一疗法或联合疗法进行适当的选择和施用。尽管asm是癫痫治疗的基石，但在近三分之一的患者中，asm对癫痫发作的缓解是无效的，因此这些患者被归类为DRE。本系统综述旨在确定与DRE相关的潜在代谢生物标志物和途径，从而为个性化治疗提供信息并优化治疗结果。综合检索数据库，即Medline， Web of Science和Cochrane Central Register of Controlled Trials (Central)，基于预定义的纳入和排除标准，在全文筛选后获得29项符合条件的研究。使用健康评估和翻译办公室（OHAT）偏倚风险评级工具对这些研究的偏倚风险进行了审查。关键信息，包括研究组、样本量、模型类型和主要发现被制成表格。鉴定出几种代谢物，包括氨基酸（甘氨酸、谷氨酸、异亮氨酸）、有机酸（乳酸）和葡萄糖，它们可能作为DRE的潜在生物标志物。MetaboAnalyst 6.0通路分析发现丙氨酸、天冬氨酸和谷氨酸代谢，以及苯丙氨酸、酪氨酸和色氨酸的生物合成通路，出现显著影响评分（≥0.5,p <； 0.05）。这些发现强调了这些代谢物和途径作为DRE的预测性生物标志物和新药开发的潜在治疗靶点的有希望的作用。

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引用次数: 0

Ganaxolone in Epilepsy: Insights into a Neurosteroid-Based Therapy 加那洛酮治疗癫痫：以神经类固醇为基础的治疗。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 10.1016/j.eplepsyres.2025.107669

Giovanni Battista Dell’Isola , Margherita Siciliano , Gianluca D’Onofrio , Pietro Ferrara , Pasquale Striano , Marco Carotenuto , Alberto Verrotti

Neurological and neuropsychiatric disorders, particularly drug-resistant epilepsies and rare genetic syndromes such as CDKL5 deficiency disorder, pose significant therapeutic challenges. Ganaxolone (GNX), a synthetic neurosteroid and positive allosteric modulator of GABA-A receptors, has emerged as a promising treatment option due to its unique pharmacological properties. This review explores GNX's pharmacokinetic profile, preclinical evidence, and clinical applications. Preclinical studies have demonstrated its efficacy in reducing seizure frequency and severity across various epilepsy models, including amygdala kindling and status epilepticus, as well as its neuroprotective effects in hypoxic-ischemic encephalopathy. Clinical trials have confirmed GNX's benefits, particularly in CDD, where it significantly reduces seizure frequency, leading to its FDA and EMA approval. Additionally, GNX has shown potential in focal epilepsy, status epilepticus, and other drug-resistant epilepsies, although with variable results. Beyond epilepsy, GNX's modulation of GABAergic signaling suggests potential applications in neuropsychiatric conditions. Its favorable safety profile further supports its therapeutic value.

神经和神经精神疾病，特别是耐药癫痫和罕见的遗传综合征，如CDKL5缺乏症，构成了重大的治疗挑战。Ganaxolone （GNX）是一种合成的神经类固醇和GABA-A受体的阳性变构调节剂，由于其独特的药理特性而成为一种有希望的治疗选择。本文综述了GNX的药代动力学特征、临床前证据和临床应用。临床前研究表明，它可以降低各种癫痫模型的发作频率和严重程度，包括杏仁核点燃和癫痫持续状态，以及它对缺氧缺血性脑病的神经保护作用。临床试验已经证实了GNX的益处，特别是在CDD方面，它显著降低了癫痫发作频率，从而获得了FDA和EMA的批准。此外，GNX在局灶性癫痫、癫痫持续状态和其他耐药癫痫中显示出潜力，尽管结果不尽相同。除癫痫外，GNX对gaba能信号的调节表明其在神经精神疾病中的潜在应用。其良好的安全性进一步支持了其治疗价值。

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引用次数: 0