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探寻预测急性卒中事件后发生癫痫的生物标记物

血液生物标记物在卒中后癫痫中的作用尚未得到广泛研究。本研究旨在研究急性卒中的临床因素和生物标记物，并经过较长时间的观察分析它们与卒中癫痫发生的关系。对缺血性和出血性卒中的患者进行 14 个血液生物标记物的检测。用 Z-scores 对生物标记物进行规范化和标准化。同时还评估了卒中和癫痫相关变量：卒中严重程度（依据美国国立卫生研究院卒中量表 NIHSS 评分）、卒中类型和病因、从卒中到迟发性癫痫发作的时间以及癫痫发作类型。使用多因素 Cox 回归分析来确定与癫痫相关的独立的临床变量和生物标记物。从 1 115 例患者队列中纳入 895 例。平均年龄为（72.0±13.1）岁，其中有 57.8% 的患者为男性。51 例患者（5.7%）发展为迟发性癫痫，中位时间为 232 天［四分位数间距 IQR（86～491）］。NIHSS 分数≥8［P<0.001，HR=4.013，95%CI（2.123，7.586）］和早发性癫痫发作的病史［P<0.001，HR=4.038，95%CI（1.802，9.045）］是与癫痫发展风险相关的独立因素。预测癫痫的独立生物标记物有：高水平的内皮抑素>1.203［P=0.046，HR=4.300，95%CI（1.028，17.996）］、低水平的 70 kDa 热休克蛋白 8（Hsc70）<2.496［P=0.006，HR=3.795，95%CI（1.476，9.760）］和 S100B<1.364［P=0.001，HR=2.955，95%CI（1.534，5.491）］。当这些生物标记物共同存在时，癫痫风险上升至 17%。临床变量和血液生物标记物联合使用时，预测模型中受试者工作特性（ROC）曲线下的面积比单独一个存在时［68.9%，95%CI（60.3%，77.6%）］的面积大，为［74.3%，95%CI（65.2%，83.3%）］。S100B 和 Hsc70 的下降及内皮抑制素的升高可能有助于预测卒中后癫痫，这为临床危险因素提供了额外信息。此外，这些数据为癫痫发生假说过程提供了一定依据。

表现为局灶性癫痫发作的糖尿病合并脑脓肿一例

从病例看“自身免疫（相关）性癫痫” 在临床诊治中的挑战

通过回顾性分析3例代表性临床病例的诊断、治疗及后期随访资料，以揭示目前有关“自身免疫（相关）性癫痫”在诊断和治疗方面存在的挑战和问题，并通过文献复习来探讨合理的应对策略。3例患者中，2例因反复癫痫发作就诊，在临床未明显提示免疫病因的情况下，多次送检相关抗体或启动免疫治疗。另1例患者临床除了癫痫发作，还有其他脑病表现，结合病史和影像所见高度提示免疫病因，最终经抗体检测阳性结果证实。3例患者的诊治经过提示，目前对“自身免疫（相关）性癫痫”诊断和治疗存在一定程度“过度化”情况。“自身免疫”和“癫痫”的关系较为复杂。自身免疫性脑炎中的癫痫发作和慢性自身免疫（相关）性癫痫之间的界限仍不清晰，缺乏可用于实际操作的标准（如生物标记物）是造成后者混乱临床诊疗现状的重要原因。现阶段，理清诸如“急性症状性发作”和“癫痫”等基本概念，仔细全面评估患者，尽早识别出自身免疫性脑炎中已经确定的、具有一定表型特征的综合征，以及使用可指导临床送检抗体或启动免疫治疗的相关评测量表，可帮助临床医生更加合理、有效地诊疗。

Clinical analysis of phase Ⅰ total corpus callosotomy in adults with intractable epilepsy

ObjectiveTo investigate the efficacy and safety of the phase Ⅰ corpus callosotomy in the treatment of adult refractory epilepsy. MethodsWe conducted a retrospective analysis of 56 adults with intractable epilepsy in Tangdu Hospital from January 2011 to July 2016.All patients were treated for the phase Ⅰ total corpus callosotomy, followed up 1~5 years after surgery. Results14 cases (25.0%) patients achieved complete seizure free after surgery, 19 cases (33.9%) whose seizures reduced more than 90%, 10 cases (17.9%) reduced between 50%~90%, 7 cases (12.5%) between 30%~50%, 6 cases (10.7%) decreased below 30%; Drop attacks of 47 cases (83.9%) patients disappeared. Postoperative complications occurred in 13 cases(23.2%), and most of them recovered well. 5 cases(8.9%) had long-term sensory disassociation, no serious complications and death. The percentage of patients reporting improvement in quality of life was 67.9%. ConclusionsFor patients with intractable epilepsy who can not undergo focal resection, Ⅰ phase total corpus callosotomy has a certain effect on reducing seizure frequency, eliminating drop attacks, and improving the quality of life.

癫痫发作期相关生物标志物的研究进展

癫痫是一种由多种病因引起的慢性脑部疾病，以脑神经元过度放电导致反复性、发作性和短暂性的中枢神经系统功能失常为特征。临床上癫痫致病的原因及机制较为复杂，癫痫的诊断需要症状学及脑电图的支持。但是由于癫痫发作早期症状学较为隐匿且容易与其他发作性疾病相混淆，脑电图也可能表现为正常，因此，癫痫的早期诊断一般较为困难。回顾既往的研究报道，以癫痫发作期是否存在诊断性生物标志物为出发点，阐述与发作相关的血清学及脑脊液标记物，本综述主要关注癫痫发作期相关的蛋白、激素及炎症因子等方面，目的在于筛选出具有代表性的癫痫发作期相关生物标记物，为癫痫的早期诊断提供新的思路。

炎症、癫痫发作和癫痫发生：对人类疾病的探索

癫痫在历史上被认为是一种神经元信号异常传导的疾病，表现为癫痫发作。随着大量自身抗体的发现和对自身免疫性脑炎认识的不断加深，人们越来越重视先天性和适应性免疫系统在癫痫发作和癫痫发生中的作用。在不同的癫痫发作相关的神经炎症和自身免疫疾病中，不同程度观察到了致病性抗体、补体激活、CD8+细胞毒性T细胞和小胶质细胞激活。这些异常的免疫反应被认为会导致神经元信号传导破坏，产生急性症状性癫痫发作，并且在某些情况下，还会发展为长期的自身免疫性癫痫。虽然早期使用免疫调节疗法可以改善自身免疫性脑炎和自身免疫性癫痫的预后，但患者的识别和治疗方法的选择并不总是明确。本篇综述讨论了免疫系统的不同成分在各种形式的癫痫发作中的作用，包括自身免疫性脑炎、自身免疫性癫痫、Rasmussen脑炎、热性感染相关性癫痫综合征和新发难治性癫痫持续状态。尤其是讨论了在这些疾病中观察到的病理生理学和独特的细胞因子谱，及其与诊断、预后和治疗决策的联系。

儿童癫痫的 50 年随访研究：医疗结局、发病率和药物治疗

描述儿童癫痫的长期预后，尤其侧重于癫痫发作缓解、复发、药物治疗、相关神经系统功能障碍、死亡率和死亡原因。针对 1962 年—1964 年间基于人群总数为 195 例癫痫发作儿童队列的一项前瞻性纵向研究。数据均通过医疗记录和调查问卷收集。来自最初队列 94% 的随访数据显示，无智力或神经功能障碍的患儿，无癫痫发作的长期预后最好。这些患儿发病较晚，癫痫发作的持续时间较短，且通常不使用药物。他们中仅少数曾复发。全面性而非局灶性癫痫，通常较少复发，持续用药更短。 “真正发病”组，即在 1962 年—1964 年间纳入的发病患儿，无癫痫发作的长期预后最好，90% 在 50 年后癫痫无发作。尽管该组中仅 10% 在随访时仍有发作，但 22% 仍使用抗惊厥药物，且常使用传统药物—苯巴比妥或苯妥英钠作为抗癫痫药物之一。整个组的标准化死亡率（Standardized mortality ratio，SMR）为 2.61，且在有无其他神经系统缺陷的患者之间无差异。年轻的死亡患者部分有神经系统损伤，部分死于癫痫相关的情况，而年龄较大的患者死亡通常由非癫痫相关疾病导致。发病组中无患者死于癫痫猝死（Sudden unexpected death in epilepsy，SUDEP）。我们 12 年的随访和以往的报道相比，儿童癫痫患者的 50 年长期随访总体显示出更好的癫痫无发作结局。文章报道了癫痫发作较低的复发率，癫痫发作的缓解并不意味着药物治疗的终止，SUDEP 相关的死亡率也低于以往的报道。

Preliminary investigation on inducing factors of epileptic seizures

ObjectiveTo explore and clarify the relationship between epileptic seizure and inducing factors. Avoid inducing factors and reduce epileptic seizure, so as to improve the quality of life in patients with epilepsy.MethodsClinical data of 604 patients diagnosed with epilepsy in Xijing Hospital of Air Force Military Medical University from January 2018 to January 2019 were collected. The clinical data of patients with epilepsy were followed up 6 months.ResultsAmong the 604 patients, 318 (52.6%) were seizure-free in the last 6 months, 286 (47.4%) had seizures. 169 (59.1%) had seizures with at least one inducing factor. Common inducing factors: 123 cases of sleep disorder (72.8%), 114 cases of emotion changes (67.5%), 87 cases of irregular medication (51.5%), 97 cases of diet related (57.4%), 33 cases of menstruation and pregnancy (19.5%), etc. Using the χ2 test, seizures with age, gender differences had no statistical significance (P > 0.05), but seizure type was statistically different between inducing factors. In generalized seizures, tonic-clonic seizures associated with sleep deprivation (χ2= 0.189), absence seizures and anger (χ2= 0.237), pressure (χ2= 0.203), irregular life (χ2= 0.214). In the focal seizures, focal motor seizures was correlated with coffee consumption (χ2=0.145), focal sensory seizures with cold (χ2=0.235), electronic equipment use (χ2 =0.153), satiety (χ2 =0.257). Complex partial seizures was correlated with anger (χ2 =0.229), stress (χ2 =0.187), and cold (χ2 =0.198). The secondarily generalized seizures was correlated with drug missing (χ2 =0.231), sleep deprivation (χ2 =0.158), stress (χ2 =0.161), cold (χ2 =0.263), satiety (χ2 =0.182). Among the inducing factors, sleep deprivation was correlated with anger (χ2 =0.167), fatigue (χ2 =0.283), and stress (χ2 =0.230).ConclusionsEpileptic seizure were usually induced by a variety of factors. Generalized seizures were associated with sleep disorders, emotional changes, stress, irregular life, etc. While focal seizures were associated with stress, emotional changes, sleep disorders, cold, satiety, etc. An analysis of the triggers found that sleep deprivation was associated with anger, fatigue, and stress. Therefore, to clarify the inducing factors of epileptic seizure, avoid the inducing factors as much as possible, reduce the harm caused by seizures, and improve the quality of life of patients.

抗体介导的自身免疫性脑炎患者的癫痫特点

越来越多的自身免疫性脑炎（Autoimmune encephalitis，AE）患者的资料显示，其临床表现和结局的特异性依赖于患者脑脊液、血清中特定抗原的抗体。这些特异性包括了癫痫相关的临床表现及对抗癫痫药物的反应。虽然学者们对这一类疾病的研究热情不断增加，且发现了新的抗体和相关的临床综合征，但仍有一些问题需要进一步解答。首先，鉴于每一种自身免疫性抗体介导的综合征的严重程度、患者特点、治疗时间不尽相同，治疗需要个体化；其次，缺乏随机对照试验是形成适当的免疫治疗策略的重大障碍。文章就一些已阐明的 AE 患者的癫痫诊断和治疗方面的新进展和挑战作一综述，并阐述在这一新兴领域中合理应用精确药物的原则。

Research progress on the influence and mechanism of SARS-CoV-2 infection on seizure

At present, there are few studies on patients with epilepsy (PWE) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the results of many studies are inconsistent. SARS-CoV-2 may cause new seizures through a variety of mechanisms, and the susceptibility and mortality of PWE to SARS-CoV-2 remains controversial. During the SARS-CoV-2 pandemic, anxiety, depression and other psychological problems were common among epileptic patients. Clinicians providing telemedicine, telephone chat and video call can effectively reduce the risk of psychological disorders in PWE patients. At the same time, there are many interactions between antiepileptic drugs and various antiviral drugs, which should be carefully considered when using. Considering that the research results are few and many studies contradict each other, PWE and SARS-CoV-2 deserve further exploration in future studies.