Epilepsies, Partial

癫痫,部分
  • 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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  • 文章类型: English Abstract
    BACKGROUND: At least 20% of paediatric patients with epilepsy present resistance to multiple anti-crisis drugs in trials, which has a negative impact on their neuropsychological state, quality of life and prognosis; it is therefore necessary to document their neuropsychological profile in order to improve the clinical approach to them.
    OBJECTIVE: To describe the neuropsychological profile (cognitive, academic, behavioural, emotional, adaptive, sleep disturbances and quality of life) of paediatric patients with drug-resistant focal epilepsy in the frontal, temporal and occipital lobes, and to compare performance between patients with frontal and temporal foci, and to assess the link between the duration of the condition, the frequency of seizures and the amount of anti-crisis drugs and the neuropsychological profile.
    METHODS: The neuropsychological profile of 19 paediatric patients with a diagnosis of pharmacoresistant epilepsy with a mean age of 10.89 years was evaluated.
    RESULTS: 57.9% of the 19 patients were men. 63.2% presented frontal focus; 26.3% presented temporal focus; and 10.5% presented occipital focus. Deficiencies in attention, comprehension, verbal memory, working memory and processing speed, in addition to adaptive difficulties were observed. When the patients with frontal and temporal focus were compared, the former were found to present greater deficits in planning, while the patients with temporal focus presented more severe symptoms of anxiety. Patients with a longer disease duration were found to present greater impairment to their intelligence quotient and adaptive behavioural skills.
    CONCLUSIONS: Pharmacoresistant epilepsy in paediatric patients affects intelligence quotient and adaptive skills, as well as attention, memory and executive functions, and neuropsychological intervention programmes must therefore be implemented to improve these patients\' quality of life.
    BACKGROUND: Perfil neuropsicológico de pacientes pediátricos mexicanos con epilepsia focal farmacorresistente.
    Introducción. Al menos el 20% de los pacientes pediátricos con epilepsia muestra resistencia a los ensayos de múltiples fármacos anticrisis, que impactan negativamente en su estado neuropsicológico, calidad de vida y pronóstico; por tal motivo, es necesario documentar ampliamente su perfil neuropsicológico para mejorar su abordaje clínico. Objetivos. Describir el perfil neuropsicológico (cognitivo, académico, conductual, emocional, adaptativo, alteraciones del sueño y calidad de vida) de pacientes pediátricos con epilepsia focal farmacorresistente de los lóbulos frontal, temporal y occipital, así como comparar el desempeño entre los pacientes con foco frontal y temporal, y evaluar la asociación entre la duración del padecimiento, la frecuencia de las crisis y la cantidad de fármacos anticrisis con el perfil neuropsicológico. Pacientes y métodos. Se evaluó el perfil neuropsicológico de 19 pacientes pediátricos con diagnóstico de epilepsia farmacorresistente, con una edad promedio de 10,89 años. Resultados. De los 19 pacientes, el 57,9% fueron hombres. El 63,2% presentó foco frontal; el 26,3%, temporal; y el 10,5%, occipital. Se encontraron deficiencias en atención, comprensión, memoria verbal, memoria de trabajo y velocidad de procesamiento, además de dificultades adaptativas. Al comparar a los pacientes con foco frontal y temporal, se encontró que los primeros presentaron mayores deficiencias en planificación, mientras que los pacientes con foco temporal presentaron mayores síntomas de ansiedad. Con respecto a la duración de la enfermedad, se encontró que los pacientes con mayor duración del padecimiento presentaron mayor afectación en el cociente intelectual y en las habilidades en la conducta adaptativa. Conclusiones. La epilepsia farmacorresistente en pacientes pediátricos afecta el cociente intelectual y las habilidades adaptativas, así como a la atención, la memoria y las funciones ejecutivas, por lo que es necesaria la implementación de programas de intervención neuropsicológica para mejorar la calidad de vida de estos pacientes.
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  • 文章类型: Journal Article
    我们重新审视了基底颞叶语言区(BTLA)的解剖功能特征,首先由Lüders等人描述。(1986),在日语和语义网络的背景下使用电皮层刺激(ECS)。我们招募了11例局灶性癫痫患者,他们接受了慢性硬膜下电极植入和ECS映射,并进行了多种语言任务,以进行术前评估。半定量语言功能密度图描绘了BTLA的解剖功能特征(66个电极,距颞叶平均3.8厘米)。在以下任务中,ECS引起的损伤概率更高,按降序列出:口语图片匹配,图片命名,汉字单词阅读,段落阅读,口头命令,和假名单词阅读。前梭形回(FG),相邻颞下回(ITG),以及FG和ITG融合的前端,以视觉和听觉任务中刺激引起的损伤为特征,需要口头输出与否,而中间FG的特征主要是视觉输入。海马旁回是基底颞区三个回中受损最少的。我们认为BTLA具有功能梯度,前部参与模态语义加工,后部参与,尤其是单峰语义处理中的中间FG。
    We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.
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  • 文章类型: Journal Article
    正确诊断和分类癫痫发作和癫痫是至关重要的,以确保为癫痫患者量身定制的方法。ILAE癫痫发作分类由两个主要组组成:局灶性和全身性。确定癫痫发作是局灶性还是全身性发作对于癫痫类型和癫痫综合征的分类至关重要,提供更个性化的治疗和预后咨询。脑电图是该分类过程和进一步定位癫痫灶的最重要工具之一。然而,一些脑电图的发现具有误导性,可能会推迟正确的诊断和适当的治疗。了解局灶性和全身性癫痫中最常见的脑电图陷阱对临床实践很有价值。避免误解。一些非典型特征在局灶性癫痫中可能具有挑战性,例如二次双边同步,过度通气和光刺激引起的局灶性癫痫样活动,和非焦点减速。另一方面,超过60%的特发性全身性癫痫患者有至少一种非典型异常.在这份手稿中,我们描述并说明了一些最常见的脑电图发现,这些发现甚至可以使经验丰富的癫痫学家不仅质疑癫痫灶在哪里,而且还质疑患者是否患有局灶性或全身性癫痫.这篇综述总结了这些危险,并提供了一些珍珠来帮助EEG读者。
    Correctly diagnosing and classifying seizures and epilepsies is vital to ensure a tailored approach to patients with epilepsy. The ILAE seizure classification consists of two main groups: focal and generalized. Establishing if a seizure is focal or generalized is essential to classify the epilepsy type and the epilepsy syndrome, providing more personalized treatment and counseling about prognosis. EEG is one of the most essential tools for this classification process and further localization of the epileptogenic focus. However, some EEG findings are misleading and may postpone the correct diagnosis and proper treatment. Knowing the most common EEG pitfalls in focal and generalized epilepsies is valuable for clinical practice, avoiding misinterpretations. Some atypical features can be challenging in focal epilepsies, such as secondary bilateral synchrony, focal epileptiform activity induced by hyperventilation and photic stimulation, and non-focal slowing. On the other hand, more than 60 % of persons with idiopathic generalized epilepsies have at least one type of atypical abnormality. In this manuscript, we describe and illustrate some of the most common EEG findings that can make even experienced epileptologists question not only where the epileptogenic focus is but also if the patient has focal or generalized epilepsy. This review summarizes the perils and provide some pearls to assist EEG readers.
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  • 文章类型: Journal Article
    目的:与普通人群相比,癫痫患者的自杀意念(SI)和行为风险增加。这种关系在青少年中仍未得到探索。我们调查了新诊断的局灶性癫痫青少年在治疗开始后4个月内和随后36个月内的自杀率。
    方法:这是对人类癫痫项目的登记和随访数据的事后分析,一个国际,2012年至2017年招募参与者的多机构研究。招募的参与者年龄为11-17岁,在局灶性癫痫治疗开始后4个月内。我们使用了哥伦比亚自杀严重程度评定量表(C-SSRS)的数据,在登记时和36个月的随访期内进行,还有医疗记录中的数据.
    结果:共有66名青少年参与者入组并完成了C-SSRS。在入学时,14人(21%)有终身SI,5人(8%)有终身自杀行为(SB)。在接下来的36个月里,6名青少年报告新发SI,5名青少年报告新发SB。因此,该人群中SI的终生患病率从21%增加到30%(14-20名青少年),SB的终生患病率从8%增加到15%(5-10)。
    结论:我们的研究中报道的青少年新诊断局灶性癫痫的自杀率与先前在癫痫中观察到的显著自杀率的发现是一致的。我们在癫痫诊断时和随后几年将青少年确定为高危人群。
    OBJECTIVE: Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months.
    METHODS: This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records.
    RESULTS: A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10).
    CONCLUSIONS: The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.
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  • 文章类型: Systematic Review
    目的:顶叶癫痫(PLE)手术可以有效治疗某些难治性癫痫患者,但可能与严重神经功能缺损的风险有关。我们对文献进行了系统的回顾,以全面总结接受PLE切除手术的患者术后新的神经功能缺损的频率和类型。
    方法:我们搜索了MEDLINE,Embase,和Cochrane中央控制试验登记册,用于1990年1月1日至2022年4月28日之间发表的文章。我们纳入了报道局限于顶叶的PLE切除手术后神经系统结果的研究。我们要求研究包括≥5名患者。收集的数据包括人口统计信息和术后神经功能缺损的具体细节。如果可用,收集个体患者数据.我们使用非随机干预研究中的偏倚风险工具来评估偏倚风险和建议评估分级。发展,和评估,以评估证据的质量。
    结果:在筛选的3,461篇文章中,33项研究符合纳入标准。共纳入370名患者。100名患者(27.0%)术后出现新的缺陷。大约一半的缺陷患者仅经历短暂的缺陷。运动缺陷是最常见的缺陷。PLE手术后出现的运动障碍率为5.7%,3.2%,瞬态为2.2%,长期的,和持续时间未指定,分别。感觉和视野缺陷也普遍报道。4.9%的患者在术后发现了Gerstmann综合征,几乎总是一过性的。个别患者数据增加了有关顶叶次区域术后神经系统预后的信息。
    结论:我们的系统综述提供了与PLE手术相关的神经功能缺损的频率和类型的全面总结。很大比例的术后缺陷是短暂的。除了预期的感官和视觉缺陷,PLE手术与明显的运动缺陷风险相关。现有文献存在重要不足。我们的研究突出了文献中的差距,并为未来的方向提供了建议。
    该系统综述已在PROSPERO上注册(CRD42022313108,2022年5月26日)。
    OBJECTIVE: Parietal lobe epilepsy (PLE) surgery can be an effective treatment for selected patients with intractable epilepsy but can be associated with the risk of serious neurologic deficits. We performed a systematic review of the literature to obtain a comprehensive summary of the frequency and types of new postoperative neurologic deficits in patients undergoing PLE resective surgery.
    METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published between January 1, 1990, and April 28, 2022. We included studies that reported postoperative neurologic outcome following PLE resective surgery confined to the parietal lobe. We required that studies included ≥5 patients. The data collected included demographic information and specific details of postoperative neurologic deficits. When available, individual patient data were collected. We used the Risk of Bias in Nonrandomized Studies of Interventions tool to assess the risk of bias and Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of the evidence.
    RESULTS: Of the 3,461 articles screened, 33 studies met the inclusion criteria. A total of 370 patients were included. One hundred patients (27.0%) had a new deficit noted postoperatively. Approximately half of the patients with deficits experienced only transient deficits. Motor deficits were the most commonly identified deficit. The rates of motor deficits noted after PLE surgery were 5.7%, 3.2%, and 2.2% for transient, long-term, and duration not specified, respectively. Sensory and visual field deficits were also commonly reported. Gerstmann syndrome was noted postoperatively in 4.9% of patients and was almost always transient. Individual patient data added information on parietal lobe subregion postoperative neurologic outcome.
    CONCLUSIONS: Our systematic review provides a comprehensive summary of the frequency and types of neurologic deficits associated with PLE surgery. A significant percentage of postoperative deficits are transient. In addition to the expected sensory and visual deficits, PLE surgery is associated with a notable risk of motor deficits. The available literature has important deficiencies. Our study highlights gaps in the literature and provides recommendations for future directions.
    UNASSIGNED: This systematic review was registered on PROSPERO (CRD42022313108, May 26, 2022).
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  • 文章类型: Journal Article
    目的:微状态代表头皮记录的脑电图的脑电活动的整体和地形分布。本研究旨在探讨局灶性癫痫患者用药前的脑电图微观状态,并使用提取的微状态指标来预测奥卡西平单药治疗的结果。
    方法:本研究纳入了25例新诊断的局灶性癫痫患者(13例女性),年龄12至68岁,病因各异。根据首次随访结果,将患者分为无癫痫(NSF)和无癫痫(SF)组。从用药前的脑电图,通过聚类鉴定了四种代表性的微状态.提取并分析了微观状态的时间参数和转移概率,以辨别群体差异。使用生成样本方法,支持向量机(SVM)逻辑回归(LR),和朴素贝叶斯(NB)分类器用于预测治疗结果。
    结果:在NSF组中,微状态1(MS1)表现出明显更长的持续时间(平均值±std。=0.092±0.008vs.0.085±0.008,p=0.047),发生率(平均值±std.=2.587±0.334vs.2.260±0.278,p=0.014),和覆盖率(平均值±标准。=0.240±0.046vs.与SF组相比,0.194±0.040,p=0.014)。此外,从微态2(MS2)和微态3(MS3)到MS1的转移概率增加。在MS2中,NSF组显示出较强的相关性(平均值±std。=0.618±0.025vs.0.571±0.034,p<0.001)和更高的全局解释方差(平均值±std。=0.083±0.035vs.0.055±0.023,p=0.027)比SF组。相反,SF组中的微状态4(MS4)表现出明显更大的覆盖率(平均值±std。=0.388±0.074vs.0.334±0.052,p=0.046)和从MS2到MS4的更频繁转换,表明不同的模式。时间参数在预测奥卡西平的治疗结果方面具有重要的预测作用,LR实现的曲线下面积(AUC)为0.95、0.70和0.86,NB和SVM,分别。
    结论:本研究强调了脑电图微状态作为新诊断局灶性癫痫患者奥卡西平治疗反应的预测生物标志物的潜力。
    OBJECTIVE: Microstates represent the global and topographical distribution of electrical brain activity from scalp-recorded EEG. This study aims to explore EEG microstates of patients with focal epilepsy prior to medication, and employ extracted microstate metrics for predicting treatment outcomes with Oxcarbazepine monotherapy.
    METHODS: This study involved 25 newly-diagnosed focal epilepsy patients (13 females), aged 12 to 68, with various etiologies. Patients were categorized into Non-Seizure-Free (NSF) and Seizure-Free (SF) groups according to their first follow-up outcomes. From pre-medication EEGs, four representative microstates were identified by using clustering. The temporal parameters and transition probabilities of microstates were extracted and analyzed to discern group differences. With generating sample method, Support Vector Machine (SVM), Logistic Regression (LR), and Naïve Bayes (NB) classifiers were employed for predicting treatment outcomes.
    RESULTS: In the NSF group, Microstate 1 (MS1) exhibited a significantly higher duration (mean±std. = 0.092±0.008 vs. 0.085±0.008, p = 0.047), occurrence (mean±std. = 2.587±0.334 vs. 2.260±0.278, p = 0.014), and coverage (mean±std. = 0.240±0.046 vs. 0.194±0.040, p = 0.014) compared to the SF group. Additionally, the transition probabilities from Microstate 2 (MS2) and Microstate 3 (MS3) to MS1 were increased. In MS2, the NSF group displayed a stronger correlation (mean±std. = 0.618±0.025 vs. 0.571±0.034, p < 0.001) and a higher global explained variance (mean±std. = 0.083±0.035 vs. 0.055±0.023, p = 0.027) than the SF group. Conversely, Microstate 4 (MS4) in the SF group demonstrated significantly greater coverage (mean±std. = 0.388±0.074 vs. 0.334±0.052, p = 0.046) and more frequent transitions from MS2 to MS4, indicating a distinct pattern. Temporal parameters contribute major predictive role in predicting treatment outcomes of Oxcarbazepine, with area under curves (AUCs) of 0.95, 0.70, and 0.86, achieved by LR, NB and SVM, respectively.
    CONCLUSIONS: This study underscores the potential of EEG microstates as predictive biomarkers for Oxcarbazepine treatment responses in newly-diagnosed focal epilepsy patients.
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  • 文章类型: Journal Article
    背景:准确识别异常脑电图(EEG)活动对于诊断和治疗癫痫至关重要。最近的研究表明,将大脑活动分解为周期性(振荡)和非周期性(跨所有频率的趋势)成分可以阐明光谱活动变化的驱动因素。
    方法:我们分析了234名受试者的颅内脑电图(iEEG)数据,创建一个规范的地图。将该图与考虑进行神经外科手术的63例难治性局灶性癫痫患者的队列进行了比较。使用三种方法计算规范图:(I)相对完整频带功率,(ii)去除非周期性分量的相对频带功率,和(iii)非周期性指数。在患者队列中计算每种方法的异常。我们评估了空间剖面,评估了他们定位异常的能力,并使用脑磁图(MEG)复制了这些发现。
    结果:相对完整频带功率和相对周期频带功率的规范图表现出相似的空间分布,而非周期性的规范图显示颞叶的指数值较高。通过完全频带功率估计的异常可有效区分好结果和坏结果患者。结合周期性和非周期性异常增强性能,就像完整的波段功率方法。
    结论:保留周期性和非周期性活动异常的脑组织可能导致不良的手术结果。周期性和非周期性分量都不能单独携带足够的信息。相对完整的频带功率解决方案被证明是用于此目的的最可靠的方法。未来的研究可以研究大脑位置或病理如何影响周期性或非周期性异常。
    BACKGROUND: Accurate identification of abnormal electroencephalographic (EEG) activity is pivotal for diagnosing and treating epilepsy. Recent studies indicate that decomposing brain activity into periodic (oscillatory) and aperiodic (trend across all frequencies) components can illuminate the drivers of spectral activity changes.
    METHODS: We analysed intracranial EEG (iEEG) data from 234 subjects, creating a normative map. This map was compared to a cohort of 63 patients with refractory focal epilepsy under consideration for neurosurgery. The normative map was computed using three approaches: (i) relative complete band power, (ii) relative band power with the aperiodic component removed, and (iii) the aperiodic exponent. Abnormalities were calculated for each approach in the patient cohort. We evaluated the spatial profiles, assessed their ability to localize abnormalities, and replicated the findings using magnetoencephalography (MEG).
    RESULTS: Normative maps of relative complete band power and relative periodic band power exhibited similar spatial profiles, while the aperiodic normative map revealed higher exponent values in the temporal lobe. Abnormalities estimated through complete band power effectively distinguished between good and bad outcome patients. Combining periodic and aperiodic abnormalities enhanced performance, like the complete band power approach.
    CONCLUSIONS: Sparing cerebral tissue with abnormalities in both periodic and aperiodic activity may result in poor surgical outcomes. Both periodic and aperiodic components do not carry sufficient information in isolation. The relative complete band power solution proved to be the most reliable method for this purpose. Future studies could investigate how cerebral location or pathology influences periodic or aperiodic abnormalities.
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  • 文章类型: Journal Article
    目的:我们先前分析了三项辅助布立西坦(BRV)成人第11期临床试验的数据,表明药物相关的中枢神经系统治疗引起的不良事件(TEAE)的发生率和患病率在BRV治疗开始后的几周内迅速达到峰值并下降。然而,该分析未评估抗癫痫药物(ASM)治疗可能发生的精神和行为副作用。这里,我们调查了BRV治疗周的精神和行为TEAE的时程,以及如何管理这些TEAE.
    方法:数据来自3项试验(N01252[NCT00490035];N01253[NCT00464269];N01358[NCT01261325])在接受BRV辅助治疗的成年患者(≥16岁)的局灶性发作性癫痫发作。该事后分析报告了在12周治疗期间接受50-200mg/天(无滴定)的BRV剂量或安慰剂(PBO)的患者随时间的药物相关精神病或行为TEAE的发生率和患病率。使用逻辑回归模型来确定精神病或行为合并症是否为药物相关精神病或行为TEAE的预测因子。或BRV因精神病或行为TEAE而停药。
    结果:共有803名患者接受了50-200毫克/天的BRV,459例患者接受PBO。11.0%的患者在辅助性BRV治疗期间报告了药物相关的精神或行为TEAE(PBO:4.8%),在BRV开始后早期发作(至首次药物相关的精神或行为TEAE发作的中位时间:15天)。发病率在第1周达到峰值,并在开始BRV后的前4周内下降。患病率在第4周达到峰值,然后在第5-12周之间保持稳定。在排除合并左乙拉西坦患者的分析中(BRV:n=744;PBO:n=422),药物相关的精神病或行为TEAE的发生率与总体人群的发生率相似.最常见的药物相关精神或行为TEAE是易怒,失眠,抑郁症,和焦虑。只有2%的患者因精神病或行为TEAE而停止BRV(PBO:1.3%),而大多数报告药物相关精神或行为TEAE的BRV患者不需要改变剂量(84.1%;PBO:63.6%).精神病或行为合并症病史(在开始BRV时未持续)与药物相关的精神病或行为TEAE的可能性增加无关,或BRV因精神病或行为TEAE而停药。BRV开始时持续的精神或行为共病状况增加了药物相关精神或行为TEAE的可能性,但不是由于精神病或行为TEAE而停用BRV的可能性。
    结论:药物相关的精神和行为TEAE在BRV治疗早期发生,大多数患者不需要改变BRV剂量.这些数据可以帮助指导临床医生在启动BRV后进行监测和患者预期。
    OBJECTIVE: We previously analyzed data from three phase lll trials of adjunctive brivaracetam (BRV) in adults showing that the incidence and prevalence of drug-related central nervous system treatment-emergent adverse events (TEAEs) quickly peaked and decreased over several weeks following BRV treatment initiation. However, that analysis did not assess psychiatric and behavioral side effects which can occur with antiseizure medication (ASM) treatment. Here, we investigate the time-course of psychiatric and behavioral TEAEs by week of BRV treatment and how these TEAEs were managed.
    METHODS: Data were pooled from three trials (N01252 [NCT00490035]; N01253 [NCT00464269]; N01358 [NCT01261325]) in adult patients (≥16 years of age) with focal-onset seizures receiving BRV adjunctive therapy. This post hoc analysis reports data on the incidence and prevalence of drug-related psychiatric or behavioral TEAEs over time in patients who received BRV doses of 50-200 mg/day (without titration) or placebo (PBO) during the 12-week treatment period. A logistic regression model was used to determine if psychiatric or behavioral comorbid conditions were predictors for drug-related psychiatric or behavioral TEAEs, or BRV discontinuation due to psychiatric or behavioral TEAEs.
    RESULTS: A total of 803 patients received BRV 50-200 mg/day, and 459 patients received PBO. Drug-related psychiatric or behavioral TEAEs were reported by 11.0 % of patients during adjunctive BRV treatment (PBO: 4.8 %) with onset early after BRV initiation (median time to onset of first drug-related psychiatric or behavioral TEAE: 15 days). Incidence peaked at week 1 and decreased over the first 4 weeks following BRV initiation. Prevalence peaked at week 4 and then remained stable between weeks 5-12. In an analysis excluding patients on concomitant levetiracetam (BRV: n = 744; PBO: n = 422), the incidence of drug-related psychiatric or behavioral TEAEs was similar to the incidence in the overall population. The most common drug-related psychiatric or behavioral TEAEs were irritability, insomnia, depression, and anxiety. Only 2 % of patients discontinued BRV due to psychiatric or behavioral TEAEs (PBO: 1.3 %), while most patients on BRV who reported drug-related psychiatric or behavioral TEAEs did not require a change in dose (84.1 %; PBO: 63.6 %). A history of psychiatric or behavioral comorbid conditions (not ongoing at BRV initiation) was not associated with an increased likelihood of drug-related psychiatric or behavioral TEAEs, or BRV discontinuation due to psychiatric or behavioral TEAEs. Ongoing psychiatric or behavioral comorbid conditions at BRV initiation increased the likelihood of drug-related psychiatric or behavioral TEAEs, but not the likelihood of BRV discontinuation due to psychiatric or behavioral TEAEs.
    CONCLUSIONS: Drug-related psychiatric and behavioral TEAEs occurred early during BRV treatment, and most patients did not require a change in BRV dose. These data can help guide clinician monitoring and patient expectations after starting BRV.
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  • 文章类型: Journal Article
    对BIA-2093-304研究中包括的亚洲患者的数据进行事后分析,以评估辅助醋酸艾司利卡西平(ESL)在难治性局灶性癫痫发作的成年亚洲患者中的长期安全性/耐受性和有效性。第一部分是一项随机对照试验,其中患者接受ESL(每天一次800或1200mg[QD])或安慰剂,在12周的维护期内评估。完成第一部分的患者可以进入两个开放标签延长期(第二部分,1年;第三部分,≥2年),在此期间,所有人都接受了ESL(400-1600mgQD)。通过评估治疗引起的不良事件(TEAE)来评估安全性/耐受性。功效评估包括响应者和癫痫发作自由率。安全人群包括125、92和23名亚洲患者,II,III,分别。ESL相关TEAE的发生率为61.3%,45.7%,第一部分为17.4%,II,III,分别。ESL相关TEAE(最常见的是,头晕,嗜睡,和头痛)与ESL已知的安全性一致。在第一部分,ESL800(41.7%)和1200mgQD(44.4%)的应答率高于安慰剂(32.6%),虽然没有统计学意义。ESL800(5.5%)和1200mgQD(11.1%)的癫痫发作自由率也高于安慰剂(0%)(ESL1200mgQD与安慰剂的p<0.05)。在第二部分的结尾,响应者和癫痫发作自由率分别为60.3%和14.7%,分别。总之,患有难治性局灶性癫痫发作的成年亚洲患者对ESL作为辅助治疗有反应,并且通常在长达3年的时间内表现出良好的治疗耐受性.没有观察到新的/意外的安全性发现。
    A post hoc analysis of data from Asian patients included in the study BIA-2093-304 was conducted to evaluate the long-term safety/tolerability and efficacy of adjunctive eslicarbazepine acetate (ESL) in adult Asian patients with refractory focal seizures. Part I was a randomized controlled trial, in which patients received ESL (800 or 1200 mg once daily [QD]) or placebo, assessed over a 12-week maintenance period. Patients completing Part I could enter two open-label extension periods (Part II, 1 year; Part III, ≥2 years), during which all received ESL (400-1600 mg QD). Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs). Efficacy assessments included responder and seizure freedom rates. The safety population included 125, 92, and 23 Asian patients in Parts I, II, and III, respectively. Incidence of ESL-related TEAEs was 61.3%, 45.7%, and 17.4% during Parts I, II, and III, respectively. ESL-related TEAEs (most commonly, dizziness, somnolence, and headache) were consistent with ESL\'s known safety profile. During Part I, responder rates were higher with ESL 800 (41.7%) and 1200 mg QD (44.4%) versus placebo (32.6%), although not statistically significant. Seizure freedom rates with ESL 800 (5.5%) and 1200 mg QD (11.1%) were also higher versus placebo (0%) (p < 0.05 for ESL 1200 mg QD versus placebo). At the end of Part II, responder and seizure freedom rates were 60.3% and 14.7%, respectively. In summary, adult Asian patients with refractory focal seizures were responsive to treatment with ESL as adjunctive therapy and generally showed treatment tolerance well for up to 3 years. No new/unexpected safety findings were observed.
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