Drug Resistant Epilepsy

耐药性癫痫
  • 文章类型: Journal Article
    神经损伤后小儿大脑的功能变化证明了可塑性的显着壮举。作为这种可塑性基础的神经生物学机制的研究主要集中在病变半影或对比病灶的激活上,同位区。这里,我们采用全脑方法评估因耐药儿童癫痫而进行大面积单侧皮质切除的患者的皮质可塑性.我们比较了患者在功能磁共振成像(fMRI)扫描仪中观看和收听电影摘录时,保留半球的功能连通性(FC)与匹配对照的相应半球。使用两种不同的解剖图册将保存的半球分为180和200个包裹。我们计算了包裹之间的所有成对多元统计相关性,或包裹边缘,在22到7个更大规模的功能网络之间,或网络边缘,从较小的包裹边聚合。相对于匹配的对照组,左半球和右半球保留的患者组的FC普遍减少。特别是对于网络内边缘。病例系列分析进一步揭示了相对于对照组具有独特边缘变化的患者亚簇,说明个体术后连接概况。保存的半球网络的大规模差异可能反映了维持和/或保留的认知功能的可塑性。
    Functional changes in the pediatric brain following neural injuries attest to remarkable feats of plasticity. Investigations of the neurobiological mechanisms that underlie this plasticity have largely focused on activation in the penumbra of the lesion or in contralesional, homotopic regions. Here, we adopt a whole-brain approach to evaluate the plasticity of the cortex in patients with large unilateral cortical resections due to drug-resistant childhood epilepsy. We compared the functional connectivity (FC) in patients\' preserved hemisphere with the corresponding hemisphere of matched controls as they viewed and listened to a movie excerpt in a functional magnetic resonance imaging (fMRI) scanner. The preserved hemisphere was segmented into 180 and 200 parcels using two different anatomical atlases. We calculated all pairwise multivariate statistical dependencies between parcels, or parcel edges, and between 22 and 7 larger-scale functional networks, or network edges, aggregated from the smaller parcel edges. Both the left and right hemisphere-preserved patient groups had widespread reductions in FC relative to matched controls, particularly for within-network edges. A case series analysis further uncovered subclusters of patients with distinctive edgewise changes relative to controls, illustrating individual postoperative connectivity profiles. The large-scale differences in networks of the preserved hemisphere potentially reflect plasticity in the service of maintained and/or retained cognitive function.
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  • 文章类型: Journal Article
    结论:尽管睡眠在调节癫痫活动中的作用已得到证实,许多癫痫学家忽视了在耐药性癫痫患者的术前癫痫评估中考虑睡眠的重要性.这里,我们从2000年1月至2023年5月使用PubMed电子数据库进行了全面的文献综述,并汇编了证据,强调需要修改当前的临床方法.所有文章均由两名独立审稿人进行资格评估。我们的目的是阐明将睡眠监测纳入立体脑电图术前评估的临床价值。我们介绍了在立体脑电图记录中观察到的睡眠与各种形式的癫痫活动之间重要的双向相互作用的最新进展。具体来说,癫痫活动由不同的睡眠阶段调节,在非快速眼动睡眠中达到顶峰,同时在快速眼动睡眠中被抑制。然而,这种调制可以在不同的大脑区域变化,强调需要考虑睡眠,以在术前评估期间准确确定癫痫发生区。最后,我们提供实用的解决方案,例如仅使用立体脑电图数据的自动睡眠评分算法,将睡眠监测无缝整合到常规临床实践中。希望这篇综述将为临床医生提供一个易于获得的路线图,以了解有关立体脑电图背景下睡眠监测的临床实用性的最新证据,并帮助开发治疗和诊断策略以改善患者的手术效果。
    CONCLUSIONS: Although the role of sleep in modulating epileptic activity is well established, many epileptologists overlook the significance of considering sleep during presurgical epilepsy evaluations in cases of drug-resistant epilepsy. Here, we conducted a comprehensive literature review from January 2000 to May 2023 using the PubMed electronic database and compiled evidence to highlight the need to revise the current clinical approach. All articles were assessed for eligibility by two independent reviewers. Our aim was to shed light on the clinical value of incorporating sleep monitoring into presurgical evaluations with stereo-electroencephalography. We present the latest developments on the important bidirectional interactions between sleep and various forms of epileptic activity observed in stereo-electroencephalography recordings. Specifically, epileptic activity is modulated by different sleep stages, peaking in non-rapid eye movement sleep, while being suppressed in rapid eye movement sleep. However, this modulation can vary across different brain regions, underlining the need to account for sleep to accurately pinpoint the epileptogenic zone during presurgical assessments. Finally, we offer practical solutions, such as automated sleep scoring algorithms using stereo-electroencephalography data alone, to seamlessly integrate sleep monitoring into routine clinical practice. It is hoped that this review will provide clinicians with a readily accessible roadmap to the latest evidence concerning the clinical utility of sleep monitoring in the context of stereo-electroencephalography and aid the development of therapeutic and diagnostic strategies to improve patient surgical outcomes.
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  • 文章类型: Journal Article
    结论:立体脑电图是一个既定的,研究难治性癫痫的假设驱动方法。有一些特殊的考虑因素和一些限制适用于接受立体脑电图检查的儿童。立体脑电图的关键原则是采取个体化方法研究难治性癫痫。个性化小儿癫痫手术成功的关键因素是了解它的一些基本和独特方面,包括,但不限于,不同的病因,癫痫综合征,成熟,和年龄相关的特征以及神经可塑性。这些特征反映在符号学和电生理学的个体发育中。此外,在儿童的皮层刺激过程中需要特别考虑。立体脑电图可以指导量身定制的手术干预,足以使患者无癫痫发作,但也可以减少附带损害,而功能缺陷最小或没有。尽管在非侵入性检测方式方面取得了进步,但癫痫手术的结果仍然停滞不前。立体脑电图“思维方式”和指导指导可能会对结果产生积极影响。
    CONCLUSIONS: Stereoelectroencephalography is an established, hypothesis-driven method for investigating refractory epilepsy. There are special considerations and some limitations that apply to children who undergo stereoelectroencephalography. A key principle in stereoelectroencephalography is taking an individualized approach to investigating refractory epilepsy. A crucial factor for success in a personalized pediatric epilepsy surgery is understanding some of the fundamental and unique aspects of it, including, but not limited to, diverse etiology, epilepsy syndromes, maturation, and age-related characteristics as well as neural plasticity. Such features are reflected in the ontogeny of semiology and electrophysiology. In addition, special considerations are taken into account during cortical stimulation in children. Stereoelectroencephalography can guide a tailored surgical intervention where it is sufficient to render the patient seizure-free but it also lessens collateral damage with a minimum or no functional deficit. Epilepsy surgery outcomes remain stagnant despite advances in noninvasive testing modalities. A stereoelectroencephalography \"way of thinking\" and guided mentorship may influence outcomes positively.
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  • 文章类型: Journal Article
    目的:立体脑电图(SEEG)广泛用于需要侵入性癫痫发作定位的医学难治性癫痫患者。尽管在世界各地的许多中心越来越多的采用,没有标准化的电极命名惯例存在,在临床和研究团队之间产生混乱。
    方法:我们开发了一种新的命名法,命名为SEEG应用系统的标准化电极命名法。简洁,独特,翔实,和明确的标签提供有关入口点的信息,深层目标,和电极之间的关系。通过将10个随机抽样的病例(包括136个电极)的原始电极名称与另外4个盲目评估者前瞻性分配的电极名称进行比较,来评估评估者之间的一致性。
    结果:在我们机构接受SEEG监测的40名连续患者中,前瞻性地实施了SEEG应用系统的标准化电极命名法,在所有情况下创建唯一的电极名称,促进植入设计,SEEG记录和绘图解释,和神经外科医生的治疗计划,神经学家,和神经生理学家。两位神经外科医生对电极名称的评分者百分比一致,两位癫痫神经学家,一名神经外科研究员的比例为97.5%。
    结论:这种标准化的命名约定,SEEG应用的标准化电极命名法,提供了一个简单的,简洁,可重复,以及用于指定每个患者中每个SEEG电极的目标和相对位置的信息方法,允许在临床和研究环境中成功共享信息。普遍采用这一术语可以为改善机构之间的沟通和合作铺平道路。
    OBJECTIVE: Stereoelectroencephalography (SEEG) is widely performed on individuals with medically refractory epilepsy for whom invasive seizure localization is desired. Despite increasing adoption in many centers across the world, no standardized electrode naming convention exists, generating confusion among both clinical and research teams.
    METHODS: We have developed a novel nomenclature, named the Standardized Electrode Nomenclature for SEEG Applications system. Concise, unique, informative, and unambiguous labels provide information about entry point, deep targets, and relationships between electrodes. Inter-rater agreement was evaluated by comparing original electrode names from 10 randomly sampled cases (including 136 electrodes) with those prospectively assigned by four additional blinded raters.
    RESULTS: The Standardized Electrode Nomenclature for SEEG Application system was prospectively implemented in 40 consecutive patients undergoing SEEG monitoring at our institution, creating unique electrode names in all cases, and facilitating implantation design, SEEG recording and mapping interpretation, and treatment planning among neurosurgeons, neurologists, and neurophysiologists. The inter-rater percent agreement for electrode names among two neurosurgeons, two epilepsy neurologists, and one neurosurgical fellow was 97.5%.
    CONCLUSIONS: This standardized naming convention, Standardized Electrode Nomenclature for SEEG Application, provides a simple, concise, reproducible, and informative method for specifying the target(s) and relative position of each SEEG electrode in each patient, allowing for successful sharing of information in both the clinical and research settings. General adoption of this nomenclature could pave the way for improved communication and collaboration between institutions.
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  • 文章类型: Journal Article
    目的:在美国,立体定向脑电图(SEEG)越来越多地用于难治性癫痫的颅内评估。2022年全国癫痫中心协会三级转诊(NAECIV级)中心对SEEG实践的调查发现,各机构的实践基本相似。然而,在技术和患者护理实践中注意到一些显著差异,以及SEEG背景培训水平。自出版以来的一年,我们回顾了SEEG实践所面临的挑战,并提出了具体的纠正措施。
    结论:立体定向脑电图已迅速成为美国癫痫手术中心颅内脑电图监测的主要方法。SEEG的采用率目前高于侵入性监测的总体增长。大多数报告了SEEG的类似适应症,尽管人员专业知识以及技术和患者护理实践存在显著差异。共识声明,指导方针,迫切需要对研究生培训课程进行审查,以对SEEG实践进行基准测试,并在美国下一代从业者中开发适当的技能。
    OBJECTIVE: Stereotactic EEG (SEEG) is being increasingly used in the intracranial evaluation of refractory epilepsy in the United States. A 2022 survey of SEEG practices among National Association of Epilepsy Centers tertiary referral (NAEC level IV) centers found largely similar practices across institutions. However, a few significant differences were noted in technical and patient care practice, and in the level of SEEG background training. In the year since publication, we review the identified challenges facing SEEG practice and suggest specific corrective action.
    CONCLUSIONS: Stereotactic EEG has rapidly become the principal method for intracranial EEG monitoring in epilepsy surgery centers in the United States. The rate of adoption of SEEG is currently higher than the growth of invasive monitoring overall. Most report similar indications for SEEG, although significant variability exists in personnel expertise and technical and patient care practice. Consensus statements, guidelines, and review of postgraduate training curricula are urgently needed to benchmark SEEG practice and develop appropriate skillsets in the next generation of practitioners in the United States.
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  • 文章类型: Journal Article
    一些研究最近提出了神经炎症在癫痫发生中的核心作用。本系统综述探讨了炎症介质在癫痫发生中的作用。它与癫痫发作严重程度的关联,及其与耐药癫痫(DRE)的相关性。该研究分析了2019年至2024年JCR期刊上发表的文章。搜索策略包括MESH,“神经炎症”的免费条款,并选择性搜索先前从相关文献中选择的以下单个生物标志物:“高迁移率组框1/HMGB1”,“Toll样受体4/TLR-4”,“白细胞介素-1/IL-1”,“白细胞介素-6/IL-6”,“转化生长因子β/TGF-β”,和“肿瘤坏死因子-α/TNF-α”。这些查询都与MESH术语“癫痫发生”和“癫痫”相结合。我们发现了243篇与癫痫发生和神经炎症有关的文章,356篇文章来自生物标志物类型的选择性搜索。消除重复项之后,对324篇文章进行了评估,其中272个排除在外,55个由作者评估。共有21篇文章被纳入定性评价,包括18项病例对照研究,2个案例系列,和1个前瞻性研究。作为结论,本系统综述为五种生物标志物提供了可接受的支持,包括TNF-α及其一些可溶性受体(sTNFr2),HMGB1、TLR-4、CCL2和IL-33。某些受体,细胞因子,和趋化因子是神经炎症相关生物标志物的例子,这些生物标志物可能对难治性癫痫的早期诊断至关重要,或者可能与癫痫发作的控制有关.它们的价值将在未来的研究中得到更好的定义。
    A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of \"Neuroinflammation\", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: \"High mobility group box 1/HMGB1\", \"Toll-Like-Receptor 4/TLR-4\", \"Interleukin-1/IL-1\", \"Interleukin-6/IL-6\", \"Transforming growth factor beta/TGF-β\", and \"Tumour necrosis factor-alpha/TNF-α\". These queries were all combined with the MESH terms \"Epileptogenesis\" and \"Epilepsy\". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
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  • 文章类型: Case Reports
    磷脂酰肌醇聚糖A类(PIGA)基因中的种系变体,参与糖基磷脂酰肌醇(GPI)的生物合成,导致多种先天性异常-张力减退-癫痫发作综合征2(MCAHS2),并伴有X连锁隐性遗传。现有文献已经描述了携带PIGA变体的母亲中几乎100%X染色体失活的模式。这里,我们报道了一名男性婴儿MCAHS2,由他母亲遗传的一种新的PIGA变异体引起,具有X失活的非偏斜模式。通过流式细胞术测试获得了支持该变体致病性的表型证据。我们建议在中性粒细胞中评估GPI锚定蛋白(GPI-AP)的表达,在携带者母亲中具有未知意义的变异并随机X失活的情况下,尤其是CD16,以阐明PIGA或与GPI-AP合成相关的其他基因变异的致病作用。
    Germline variants in the phosphatidylinositol glycan class A (PIGA) gene, which is involved in glycosylphosphatidylinositol (GPI) biosynthesis, cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) with X-linked recessive inheritance. The available literature has described a pattern of almost 100% X-chromosome inactivation in mothers carrying PIGA variants. Here, we report a male infant with MCAHS2 caused by a novel PIGA variant inherited from his mother, who has a non-skewed pattern of X inactivation. Phenotypic evidence supporting the pathogenicity of the variant was obtained by flow-cytometry tests. We propose that the assessment in neutrophils of the expression of GPI-anchored proteins (GPI-APs), especially CD16, should be considered in cases with variants of unknown significance with random X-inactivation in carrier mothers in order to clarify the pathogenic role of PIGA or other gene variants linked to the synthesis of GPI-APs.
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  • 文章类型: Journal Article
    大约40%的新发作癫痫是药物难治性的。如果癫痫手术不是一种选择或失败,可以考虑迷走神经刺激(VNS)。据报道,在50-56%的患者中,VNS功效降低超过50%的癫痫发作频率。在较新的模型的特点提供了额外的治疗优化的可能性。副作用包括声音嘶哑,咳嗽,和呼吸困难.对于患有睡眠呼吸暂停或肺部疾病的患者,建议谨慎。VNS有关于MRI的特定限制。这篇综述概述了丹麦的VNS治疗,并讨论了未来的挑战。
    About 40 % of new-onset epilepsy is drug refractory. If epilepsy surgery is not an option or fails, vagal nerve stimulation (VNS) can be considered. VNS efficacy is reported as more than 50 % seizure frequency reduction in 50-56 % of patients. Features in the newer models offer additional treatment optimization possibilities. Side effects include hoarseness, cough, and dyspnoea. Caution is advised for patients with sleep apnoea or lung disease. VNS has specific limitations concerning MRI. This review presents an overview of VNS treatment in Denmark and discusses future challenges.
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  • 文章类型: Journal Article
    目的:尽管颞叶前叶切除加杏仁核海马切除术(ATL+AH)对颞叶癫痫(TLE)患者有益处,大约高达5%的患者可能有偏瘫作为其术后并发症。本文旨在描述具有AH的ATL的哪个步骤/s具有最大的MEP振幅减小的最大概率。
    方法:本研究采用横断面设计,从接受ATL+AH和TcMEP监测的TLE患者中获取数据。评估以下每个步骤的MEP振幅的降低:1)硬脑膜开口,2)打开下喇叭,2)垂直颞叶切除3)下静脉夹层,4)颞叶茎切除术,5)颞叶外侧切除术,6)海马切除术,7)杏仁核切除术,8)子宫切除和9)硬膜闭合。
    结果:本研究纳入了19例患者。根据弗里德曼测试,一个或多个步骤的平均MEP幅度降低显著不同(Friedman=50.7,p=0.0001).与基线(100%,截止p=0.005),海马切除(z=-3.81,p<0.0001),T1下解剖(z=-3.2,p=0.0010),肠切除(z=-3.48,p=0.0002),颞叶茎切除(z=-3.26,p=0.001),颞叶外侧切除术(z=-3.13,p=0.002)和杏仁核切除术(-z=-3.37,p=0.0005)明显较低。其中,海马切除术,肠切除和杏仁核切除术被认为是非常重要的。
    结论:在杏仁核期间,MEP振幅趋于降低,由于手术操作脉络膜动脉可能导致偏瘫,因此在这些步骤中应仔细注意MEP的变化。
    OBJECTIVE: Despite the benefits of anterior temporal lobectomy with amygdalohippocampectomy (ATL+AH) in patients with temporal lobe epilepsy (TLE), approximately up to 5% may have hemiparesis as its postoperative complication. This paper aims to describe which step/s of the ATL with AH have the highest probability of having greatest decrease in MEP amplitude.
    METHODS: This study utilized a cross-sectional design of obtaining data from TLE patients who underwent ATL+AH with TcMEP monitoring. Each of the following steps were evaluated for reduction in MEP amplitude: 1) Dural Opening, 2) Opening the inferior horn, 2) Vertical temporal lobe resection 3) Subpial dissection, 4) Temporal lobe stem resection, 5) Lateral temporal lobe resection, 6) Hippocampal Resection, 7) Amygdala Resection, 8) Uncus resection and 9) Dural Closure.
    RESULTS: Nineteen patients were included in the study. Based on Friedman Test, one or more steps had significantly different average MEP amplitude reductions (Friedman=50.7, p=0.0001). When compared to baseline (100%, cut off p=0.005), hippocampal resection (z=-3.81, p<0.0001), T1 subpial dissection (z=-3.2, p=0.0010), uncus resection (z=-3.48, p=0.0002), temporal stem resection (z=-3.26, p=0.001), lateral temporal lobe resection (z=-3.13, p=0.002) and amygdalectomy (-z=-3.37, p=0.0005) were significantly lower. Of these, hippocampal resection, uncus resection and amygdalectomy were deemed highly significant.
    CONCLUSIONS: MEP amplitude tends to decrease during amygdala, hippocampal and uncal resection because of surgical manipulation of choroidal arteries which can potentially cause hemiparesis so careful attention should be paid to changes in MEP during these steps.
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  • 文章类型: Journal Article
    立体脑电图(SEEG)是描述局灶性耐药癫痫手术目标的金标准。SEEG使用直接放置在大脑中的电极来识别癫痫发作区(SOZ)。然而,它的主要限制是大脑覆盖有限,可能导致对“真实”SOZ的错误识别。这里,我们提出了一个框架,通过将癫痫生物标志物与其空间分布耦合并测量系统对这种耦合扰动的反应,来评估充分的SEEG采样.我们证明,当虚拟地去除测量的SOZ时,系统的反应在良好采样的患者中是最强的。然后我们介绍空间摄动图,一种能够对植入覆盖率进行定性评估的工具。概率模型显示,在无癫痫发作的患者或非无癫痫发作的SOZ切除不完全的患者中,植入良好的SOZ的可能性更高,与完全切除的非癫痫患者相比。这突出了该框架在避免患者因SEEG覆盖率差而导致的不成功手术方面的价值。
    Stereo-electroencephalography (SEEG) is the gold standard to delineate surgical targets in focal drug-resistant epilepsy. SEEG uses electrodes placed directly into the brain to identify the seizure-onset zone (SOZ). However, its major constraint is limited brain coverage, potentially leading to misidentification of the \'true\' SOZ. Here, we propose a framework to assess adequate SEEG sampling by coupling epileptic biomarkers with their spatial distribution and measuring the system\'s response to a perturbation of this coupling. We demonstrate that the system\'s response is strongest in well-sampled patients when virtually removing the measured SOZ. We then introduce the spatial perturbation map, a tool that enables qualitative assessment of the implantation coverage. Probability modelling reveals a higher likelihood of well-implanted SOZs in seizure-free patients or non-seizure free patients with incomplete SOZ resections, compared to non-seizure-free patients with complete resections. This highlights the framework\'s value in sparing patients from unsuccessful surgeries resulting from poor SEEG coverage.
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