异丙酚持续静滴治疗小儿癫癎持续状态的临床观察

目的总结异丙酚持续静滴治疗小儿癫癎持续状态的疗效.方法对2001年4月至2003年10月唐山工人医院儿科8例继发性癫癎持续状态患儿的治疗进行分析,本组8例均为常规抗癫癎药物不能控制的继发性癫癎所致癫癎持续状态.在使用常规止惊药物失败后开始异丙酚静滴.结果8例患儿全部抽搐停止.结论癫癎持续状态是儿科急症之一,如何在短时间内控制癫癎持续状态是治疗成败的关键,在正确常规治疗无逆转时,应用异丙酚持续静滴可以有效控制癫癎持续状态且未见严重不良反应.     

儿童癫(癎)持续状态治疗进展

癫(癎)持续状态(status epilepticus,SE)是小儿时期最常见的危急重症之一.近年来,对于其定义、易忽视的发作形式、药物治疗及脑电图监测的作用不断有新的认识.本文着重对于SE定义、诊断、治疗等方面的新进展进行综述,并介绍国外难治性SE的最新治疗方案.     

Emergency management of the paediatric patient with generalized convulsive status epilepticus

The present guideline paper addresses the emergency management of generalized convulsive status epilepticus (CSE) in children and infants older than one month of age. It replaces the previous statement from 1996, and includes a new treatment algorithm and table of recommended medications, reflecting new evidence and the evolution of clinical practice over the past 15 years. The document focuses on the acute pharmacological management of CSE, but some issues regarding supportive care, diagnostic approach and treatment of refractory CSE are discussed.     

Diagnostic evaluation and management of seizures and status epilepticus in children with known epilepsy or new-onset seizures: A retrospective and comparative analysis

ObjectivesThe purpose of this study was to describe and compare the initial management, including clinical/biological investigation and treatment, of new-onset seizures and status epilepticus (SE) in children versus seizures and SE in those with known epilepsy.MethodsThis was a retrospective, single-center, observational study conducted in an urban pediatric hospital in Paris. All patients, aged from 1 month to 18 years, admitted to the pediatric intensive care unit, the high-dependency care unit, and those who required hospitalization in the short-term unit of the emergency department between January 1 and December 31, 2014 for seizures and/or SE were included.ResultsWe analyzed the data of 190 children: new-onset seizures (N = 118; group A) versus those with known epilepsy (N = 72; group B). At least one diagnostic test was performed on 156 patients (82.1%) (group A, N = 104, 88.1%; group B, N = 52, 72.2%; P = 0.05). In group B, blood levels of antiepileptic drugs were measured in 14 of the 38 patients with SE, of whom six were under dosed. Treatments were: first line, diazepam (group A, 80%; group B, 46%; P < 0.001); second line, diazepam (group A, 56%; group B, 34%; P = 0.02) or clonazepam (group A, 24%; group B, 46%; P = 0.001); third line, phenytoin (group A, 54%; group B, 22%; P < 0.001) or clonazepam (group A, 18%; group B, 61%; P < 0.001).ConclusionDiagnostic evaluation and treatment should be individualized for children with known epilepsy.     

Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABAAR antibodies

Background

Febrile infection-related epilepsy syndrome (FIRES) has been described as an epileptic encephalopathy of unknown etiology affecting previously healthy children following febrile illness. Despite large investigations on autoimmune pathogenesis no membrane antibodies has been associated since now.

儿童癫痫持续状态治疗进展

癫痫持续状态（status epilepticus,SE）是小儿时期最常见的危急重症之一。近年来,对于其定义、易忽视的发作形式、药物治疗及脑电图监测的作用不断有新的认识。本文着重对于SE定义、诊断、治疗等方面的新进展进行综述,并介绍国外难治性SE的最新治疗方案。     

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目的探讨难治性癫癎持续状态(RSE)的临床特征,提出可能早期预测RSE的因素。方法回顾性对比分析2001-01—2004-03重庆医科大学附属儿童医院52例癫癎持续状态(SE)住院患儿的临床资料。结果(1)52例SE中,29例呈RSE。(2)23例SE中22例为强直-阵挛(GTCS)发作,1例为混合发作;29例RES中14例为GTCS发作,2例强直性发作,4例部分运动性发作,1例复杂部分性发作,8例混合性发作。(3)52例中,23例非RSE病例对安定和(或)苯巴比妥治疗有效。RSE组中,药物治疗有效19例,其中对安定和(或)苯巴比妥治疗有效15例(78·9%);安定+硫喷妥钠1例(5·3%);氯硝安定1例(5·3%);利多卡因2例(10·5%)。结论(1)在儿童SE中,RSE发生率高。(2)局限性发作、强直发作、混合性发作多提示SE可能呈RES。(3)安定静脉注射联合苯巴比妥肌注是治疗SE的首选用药。对首次使用安定不敏感的RSE,重复使用的有效率低,可尽早考虑换用二线抗癫癎药物,利多卡因不失为治疗RSE的有效方法。     

癫(癎)持续状态与脑损伤机制研究进展

癫(癎)持续状态(SE)的发病机制与脑损伤密切相关,已有试验证实钙/钙调素依赖性蛋白激酶2活性改变、氧化应激、神经免疫-内分泌网络失衡等因素不仅参与癫(癎)持续状态的机制,且能作为始动因素,参与神经元损伤.SE后脑组织急性缺血、缺氧,糖利用减少,神经元过度兴奋,N-甲基-D-天冬氨酸(NMDA)和非NMDA受体的活化,大量阳离子内流,除导致神经细胞急性坏死,同时还启动细胞凋亡相关基因的表达,引起细胞内的凋亡酶级联反应,导致细胞凋亡.目前研究发现死亡受体活化、线粒体损伤及内质网应激通路均介导SE后神经元凋亡信号的传导.

Abstract：

The pathogenesis of status epilepticus is closely associated with brain injury. Some animals experiments have proved that the activity of calcium / calmodulin-dependent protein kinase 2 ( CaM kinase Ⅱ ) ,oxidative stress, and the imbalance of nervous immune-endocrine factors are not only involved in the mechanisms of status epilepticus, but also act as the initial factor in neuronal injury. The pathophysiological changes after SE,such as acute brain ischemia, hypoxia and the reduced glucose utilization, over-excited neurons, N-methyl-Daspartate (NMDA) and non-NMDA receptor activated, a large amount of cation influx, can give rise to acute necrosis of neurons, also initiate the expression of apoptotic genes, at last leading to apoptosis by cell apoptotic enzymes cascade reaction. Studies have found that the pathway of death receptor activation, mitochondrial damage and endoplasmic reticulum stress mediated the neuronal apoptotic signal transduction after SE.     

Emergency management of the paediatric patient with convulsive status epilepticus

This guideline addresses the emergency management of convulsive status epilepticus (CSE) in children and infants older than 1 month of age. It replaces a previous position statement from 2011, and includes a new treatment algorithm and table of recommended medications based on new evidence and reflecting the evolution of clinical practice over the past several years. This statement emphasizes the importance of timely pharmacological management of CSE, and includes some guidance for diagnostic approach and supportive care.     

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??Convulsive status epilepticus ??CSE?? in severe encephalitis is one of the most common medical emergencies in children. Recently?? there has been some understanding on the management of convulsive status epilepticus. Not only have the definition and time frame of a seizure changed but many new drugs have been introduced. The aim of this review is to present the current definition of CSE and treatment options it     

不同丙戊酸负荷量对癫痫持续状态的治疗效果分析

目的了解不同丙戊酸负荷量对癫痫持续状态患儿的治疗效果。方法收集2013年1月1日至2017年12月31日在浙江大学医学院附属儿童医院重症监护室住院治疗的癫痫持续状态患儿的病例资料,根据丙戊酸负荷量进行分组,了解各组患儿癫痫持续状态的控制情况。结果(1)66例癫痫持续状态患儿,包括癫痫36例(54.5%),颅内感染16例(24.2%),缺氧窒息3例(4.5%),颅内肿瘤2例(3.0%),脑发育异常2例(3.0%),颅内出血2例(3.0%),病因不明确5例(7.6%)。(2)所有癫痫持续状态患儿根据不同的丙戊酸负荷量(0 mg/kg,10~15 mg/kg,16~39 mg/kg,40 mg/kg)分为4组,各组间的性别、年龄差异无统计学意义,癫痫持续状态控制时间和癫痫控制情况差异无统计学意义(P=0.402、0.340)。(3)所有患儿予丙戊酸钠应用后都有监测肝功能,无一例患儿出现肝功能损害的表现。结论不同丙戊酸负荷量对于癫痫持续状态患儿的治疗效果无明显差异,并且接受负荷量为40 mg/kg治疗的癫痫持续状态患儿未出现相关不良反应。     

Ketogenic diet in 3 cases of childhood refractory status epilepticus

IntroductionRefractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution.ResultsA 3-year-old girl with RSE due to Hemiconvulsion-Hemiplegia Epilepsy syndrome. KD was instigated on day 6. Seizures stopped with ketosis on day 7.A 10-year-old boy rapidly developing RSE. After months a mitochondrial disorder was discovered. KD was tried twice with severe side-effects but no seizure control.11-year-old healthy boy with RSE as FIRES. On KD seizures stopped for 24 h one day after reaching ketosis. He improved over 3–4 weeks.DiscussionKD was efficient in two of three cases of RSE. The non-responder had severe side-effects and proved to have a mitochondrial disorder which is arguably a contraindication for KD.More studies are needed to prove efficacy of KD in RSE, to define optimal timing of KD and possible contraindications for KD in RSE.     

儿童癫痫持续状态的研究进展

癫痫持续状态(status epilepticus,SE)是一种在儿科常见的威胁生命的神经系统急症,如不及时控制,常导致脑及多器官缺氧缺血性损害,造成继发性永久性脑损伤甚至死亡.积极、迅速、有效控制癫痫发作是挽救患者生命、改善其预后的关键,在儿科领域尤为重要.SE目前最被认可的定义为:每次癫痫发作持续5min以上,或2次以上发作,发作间期神经系统功能未恢复至正常基线.2015年国际抗癫痫联盟(international league against epilepsy,ILAE)更新了SE最新定义,重新确定了各发作类型符合SE诊断及持续发作造成损伤的发作时间,使临床治疗更积极主动,减少合并症及后遗症的产生.该文从目前国内外的研究现状出发,总结了儿童SE的定义及更新、病因、分类、治疗、处置及预后,同时回顾最近几年国内外相关文献,为临床早期识别诊断和临床规范治疗儿童SE提供参考.     

营养不良对幼鼠癫癎持续状态后海马神经发生影响的研究

目的　探讨发育期营养不良伴发癫持续状态对海马神经发生的影响。方法　采用5 溴脱氧尿苷 (BrdU)标记新生细胞 ,β微管蛋白Ⅲ ( βⅢtubulin ,TuJ1)和胶质原纤维酸性蛋白(glialfibrillaryacidicprotein ,GFAP)分别标记早期神经元和胶质细胞的单、双标免疫组织化学染色 ,观察幼鼠海马的神经发生。结果　营养良好 (N)组和营养不良 (M)组幼鼠癫发作的潜伏时间差异无显著性 [( 12 4± 2 6)min与 ( 11 9± 2 9)min ,P >0 0 5 ]。组织学染色示各组幼鼠海马部位均无明显的神经元丢失。各组幼鼠齿状回BrdU阳性细胞数 ,营养不良 +惊厥组 (MS组 ,3 74± 18)和营养良好 +惊厥组 (NS组 ,3 12± 2 4)分别明显高于营养不良组 (M组 ,3 0 3± 2 0 )和营养良好组 (N组 ,2 69± 18) (P均 <0 0 1) ,而M组和MS组分别明显高于N组和NS组 (P均 <0 0 1)。BrdU阳性细胞中 ,约有 60 %的BrdU阳性细胞同时表达神经元特异性标记物TuJ1,5 %～ 10 %的BrdU阳性细胞同时表达神经胶质特异性标记物GFAP。结论　早期营养不良没有改变幼鼠在海藻酸致过程中惊厥的易感性和行为表现。营养不良和癫持续状态均可促进幼鼠海马齿状回新生细胞的增殖 ,营养不良伴发癫持续状态时这种增殖将进一步加强 ,而且大多数新生细胞分化为早期     

What is new: Talk about status epilepticus in the neonatal period

Nowadays, no general consensus was achieved regarding neonatal status epilepticus and its definition. Indeed, different criteria (mainly based on seizure duration) were used. Whereas a recent proposal has been developed to define status epilepticus in older ages, it seems that the peculiar characteristics of neonatal seizures and of the immature brain make difficult to find a tailored definition for this period of life. Achieving a consensus on this entity would mean to make the first step toward a targeted therapeutic strategy of intervention.     

MicroRNA-132拮抗剂对匹罗卡品诱导的幼年大鼠癫癎持续状态的影响

目的 探讨microRNA-132 拮抗剂对氯化锂-匹罗卡品诱导的幼年Sprague-Dawley（SD）大鼠癫癎持续状态（SE）的影响。方法 将3 周龄SD 大鼠分为癫癎模型组、microRNA-132 拮抗剂组和microRNA-132拮抗剂阴性对照组,每组15 只。MicroRNA-132 拮抗剂及其阴性对照预处理在造模前24 h 进行,利用氯化锂-匹罗卡品建立幼年SD 大鼠SE 模型。通过行为学观察各组大鼠SE 发作潜伏期及SE 诱导成功率;Lado 幼鼠癫癎评分观察各组大鼠抽搐发作的严重程度;脑电图监测各组大鼠癫癎样放电的频率及波幅,并统计各组死亡率。结果 在实验各组中,SE 诱导成功率差异无统计学意义（P > 0.05）;与microRNA-132 拮抗剂阴性对照组和癫癎模型组比较,microRNA-132 拮抗剂组大鼠造模以后达到SE 的潜伏期明显延长（P P P 结论 microRNA-132拮抗剂预处理对氯化锂-匹罗卡品诱导的幼年SD 大鼠SE 发生和发展具有抑制作用,抑制microRNA-132 有可能成为SE 药物治疗的潜在靶点和新方向。     

重症病毒性脑炎患儿非惊厥性癫痫持续状态9例临床分析

目的 通过分析重症病毒性脑炎患儿非惊厥性癫痫持续状态（NCSE）的临床特征、诊断和治疗,提高对NCSE的认识。方法 回顾性分析2012年6月至2014年9月广州市妇女儿童医疗中心神经内科诊断为重症病毒性脑炎NCSE的病例。结果 ①9例重症病毒性脑炎NCSE连续病例进入本文分析,男5例。脑炎起病年龄（7.2±3.9）岁;Glasgow评分（8.6±1.9）分;脑炎起始与NCSE起始间隔4~70（19.4±20.9）d;昏迷中癫痫持续状态（SEC）4例,复杂部分发作持续状态4例,不典型失神发作持续状态1例。②病因包括病毒性脑炎8例,病毒性脑炎抗癫痫药物调整1例;9例前驱均有惊厥,其中3例伴惊厥性癫痫持续状态。③9例临床发现主要有口面部或肢体微小抽动、认知障碍、孤独症样行为等。④VEEG发作期主要以背景活动变慢,伴δ、θ、β、棘节律,或棘慢波持续发放为特征。⑤4例SEC患儿予麻醉药联合多种抗癫痫药物治疗,发作平均持续42.8 d;5例非SEC患儿予多种抗癫痫药物治疗,其中3例发作平均持续9 d,1例抗癫痫药物调整所致NSEC发作持续4个月。⑥1例自动出院失访,1例死亡,余7例随访3个月至2.5年;6例VEEG均有不同程度的发作期或发作间期脑电异常,1例正常;1例神经学功能正常,5例有不同程度认知下降伴继发性癫痫,1例持续植物状态伴继发性癫痫。结论 口面部或肢体运动现象、认知及行为改变为重症病毒性脑炎患儿NCSE临床特征;发作期脑电波形变异大,棘节律可能是重症病毒性脑炎患儿NCSE的独特形式;抗癫痫治疗及起效时间与NCSE类型相关。     

Lacosamide in children with refractory status epilepticus. A multicenter Italian experience

ObjectiveStatus epilepticus (SE) is considered a life-threatening medical emergency. First-line treatment with antiepileptic drugs (AEDs) consists of intravenous benzodiazepines followed by phenytoin. SE is considered refractory (RSE) when unresponsive to standard doses of the first two AEDs. Scarce evidence is available to support specific guidelines for the management of RSE in either adults or children. This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in children affected by RSE.MethodChildren with RSE who were treated with ivLCM were included in the study. Efficacy was defined as the cessation of seizures after administration of ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following standard protocols before ivLCM was administered.ResultsEleven children entered the study (mean age: 9.4 years). Etiology was symptomatic in 7 patients (63%). RSE was convulsive (focal or generalized) in 6 patients and nonconvulsive in 5. The mean initial bolus dose of LCM was 8.6 mg/kg. The drug, which was used as a fourth or later option, was effective in stopping RSE in 45% of patients, with seizures terminating within 12 h in three children. No serious adverse events attributable to LCM were reported.ConclusionsLCM might be an effective and well-tolerated AED in children with RSE.     

环氧化酶-2选择性抑制剂塞来昔布对癫癎持续状态大鼠脑内主穹隆蛋白表达的影响

目的 观察环氧化酶-2选择性抑制剂塞来昔布对癫癎持续状态大鼠脑内主穹隆蛋白(MVP)表达的影响,探讨其在治疗难治性癫癎中的作用及可能机制,为难治性癫癎的新药治疗提供理论依据。方法 健康成年雄性Sprague-Dawley大鼠60只,随机分为空白对照组(n=16)、癫癎模型组(n=22)和塞来昔布干预组(n=22),氯化锂-匹鲁卡品诱发大鼠癫癎持续状态模型成功后,各组均有16只大鼠纳入实验。采用免疫组化法和Westernblot法检测各组大鼠额叶皮质区及海马区MVP的表达情况。结果 癫癎模型组大鼠脑内MVP的表达水平较空白对照组显著增高(PP结论 塞来昔布可降低MVP在癫癎持续状态大鼠脑组织中的高表达,有望为治疗难治性癫癎提供新方法 。     

Lidocaine treatment in pediatric convulsive status epilepticus.

BACKGROUND: Convulsive status epilepticus (CSE) may end fatally or leave serious sequelae. CSE treatment, invariably an emergency case, is based upon i.v. benzodiazepines as well as phenytoin, barbiturates or both. The present paper reports efficiency of lidocaine in CSE. METHODS: The effects of lidocaine on patients with CSE due to infectious and non-infectious reasons were compared. Lidocaine was given in 29 episodes of CSE to 49 patients having failed to respond to first-line anticonvulsive drugs, such as diazepam, phenobarbital and phenytoin therapy. Lidocaine was given in doses of 2 mg/kg bolus i.v., and then in 4 mg/kg per h infusion. RESULTS: Mean duration of lidocaine infusion was 14.6 +/- 7.8 h. Effectiveness of lidocaine in patients with CSE was found to be 44.4%. Also, 11 patients responded to a single dose of lidocaine (37.9%), while another two (6.9%) required another dose to suppress their seizures. Patients with seizures attributable to infections were observed to have responded favorably to lidocaine when compared to those with seizures due to epilepsy (37.9% vs 6.8%; P < 0.05). Subsequent epilepsy was found to occur more frequently in patients with a poor response to lidocaine than in patients with a good response (P < 0.05). Adverse reactions to lidocaine were observed in three patients (10.3%), two of them having ventricular arrhythmia. As for the other patient, the focal seizure developed into a generalized one. CONCLUSIONS: Lidocaine seems to be useful for the management of CSE as a rapid-acting anticonvulsant, particularly in patients with CSE due to infections. But further studies with larger number of patients are needed.