丙戊酸快速静脉给药治疗2岁以下婴幼儿频繁癫(疒间)发作的疗效及安全性观察

目的　探讨丙戊酸快速静脉给药治疗 2岁以下婴幼儿频繁癫疒间 发作的疗效及安全性。方法　对 2 0例频繁癫疒间发作的 2岁以下婴幼儿 ,应用丙戊酸负荷量 (2 0mg/kg ,5min静脉推入 ,静注速度为 2 4～ 6 0mg/min) ,维持量 [5mg/ (kg·h)用 5h],巩固量 [1mg/ (kg·h)用 5～ 10h],进行快速静脉给药治疗 ,用药前后监测患儿生命体征、肝功能、丙戊酸血浓度及血氨 ,综合判定疗效及安全性。结果　治疗有效率 85 % ,给药期间生命体征基本平稳 ,个别患儿负荷量后出现心率增快、血压上升 ;肝功能、血氨均在正常范围 ;丙戊酸血浓度波动在每毫升 (97 8±2 8)～ (10 1 5± 2 5 ) μg之间。 结论　应用所制定的丙戊酸负荷量 维持量 巩固量快速静脉给药法可以较为安全有效地控制 2岁以下婴幼儿的频繁癫疒间发作。     

负荷量卡马西平治疗儿童癫痫持续状态和癫痫连续发作68例疗效分析

目的：探讨儿童癫痫持续状态和癫痫连续发作治疗的方法和新途径。方法：采用卡马西平首日剂量为30～40 mg/kg口服或鼻饲,24 h后减至每日15～30 mg/kg维持治疗。结果：治疗儿童癫痫持续状态和癫痫连续发作68例,24 h内控制发作44例,48 h内控制发作16例,总有效率88.2%,有效率的标准误(SP)：3.906%,有效率的95%可信区间为80.58%～95.90%。用药前,用药后1周、1月作血常规和肝功能检查无异常,无1例有中毒症状。结论：负荷量卡马西平治疗儿童癫痫持续状态和癫痫连续发作安全有效。     

Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review北大核心CSCD

目的 总结SYNGAP1基因相关常染色体显性智力障碍5型患儿临床表型及遗传学特点。方法 回顾性分析中南大学湘雅医院儿科诊治的8例SYNGAP1基因相关智力障碍患儿的临床资料。结果 8例患儿的平均起病年龄为9月龄,均伴有中重度发育迟缓(语言落后为著),其中7例患儿伴癫痫发作。8例患儿中7例为新发杂合变异(3例移码变异、2例无义变异和2例错义变异),1例为6p21.3微缺失。目前已报道的中国SYNGAP1基因变异相关智力障碍患儿(包括该研究)有48例,其中40例伴癫痫发作,癫痫发作平均起病年龄为31.4月龄,多为移码变异(15/48,31%)和无义变异(19/48,40%)。治疗上,有癫痫用药史记录的33例患儿中,丙戊酸抗癫痫发作治疗对多数患儿有效(85%,28/33),其中48%(16/33)患儿丙戊酸单药或联合用药治疗达到发作完全控制。结论 SYNGAP1基因相关常染色体显性智力障碍5型患儿起病年龄早,多数患儿伴癫痫发作,以移码变异和无义变异为主,丙戊酸抗癫痫发作治疗对多数患儿有效。     

负荷量的鲁米那合并小剂量安定治疗儿童癫癎持续状态的疗效观察

目的　研究鲁米那的负荷量合并小剂量安定对儿童癫癎持续状态的疗效,探讨其安全剂量。方法选择癫癎持续状态患儿共46例,其中治疗组23例,首先安定0.3mg/kg静脉注射后,给予鲁米那负荷量20mg/kg在30min-1h内静脉滴注,12h后给予维持量5mg/kg,对照组23例,同样首先安定0.3mg/kg静脉注射后,将安定20mg/kg加入250ml生理盐水持续缓慢静脉滴注,将二组疗效进行对照。结果　治疗组惊厥控制时间较对照组短P<0.05,药物的负作用二组无统计学差异,P>0.05。结论　负荷量的鲁米那合并小剂量安定对儿童癫癎持续状态是安全有效的治疗方法。     

癫(癎)患儿月服用丙戊酸镁缓释片治疗前后认知功能的变化

目的观察丙戊酸镁缓释剂治疗癫的疗效及其对癫患儿认知功能的影响。方法对38例患儿予丙戊酸镁缓释剂治疗,并密切观察其发作控制的程度、服药期间的不良反应,定期复查肝功能和血常规,治疗前、治疗后6个月分别予患儿智商、P300测定,与正常对照组40例比较。结果完全控制18例(47.4%),显效11例(28.9%),有效6例(15.8%),无效3例(7.9%),总有效率92.1%;治疗前、治疗后6个月癫组智商与正常对照组相比,差异均有显著性(P均<0.01);治疗后6个月癫患儿的P300潜伏期、波幅治疗6个月后较治疗前有所改变,但均无显著性差异(P均>0.05)。结论丙戊酸镁缓释剂治疗儿童癫疗效显著,使用方便,无明确的不良反应,且对儿童认知功能的影响不明显。     

丙戊酸钠缓释片与丙戊酸镁治疗儿童癫痫疗效比较

为了解丙戊酸钠缓释片(Oepakin Chrono, Sustained-release sodium Valproata-VPA-Na.SR)在治疗儿童癫痫的疗效、血药浓度及其副作用,现对原用丙戊酸镁(VPA-Mg)单药治疗的15例癫痫患儿改用VPA-Na.SR,进行自身比较,结果报道如下。 资料与方法 一、临床资料 15例为原用(VPA-Mg)单药治疗的患儿,家长及患儿能接受VPA-Na.SR治疗及采血标本检查,无其他系统疾病,采血前1个月内未服用其他药物,肝功能均正常者。其中男性8例,     

左乙拉西坦改善发作控制的癫痫患儿异常脑电图的疗效

目的 探讨左乙拉西坦对临床发作缓解而脑电图明显异常的癫痫患儿的脑电图的影响.方法 将就诊于我院神经专科门诊临床发作得到控制1年以上而脑电图依然明显异常的39例卡马西平单药治疗中的部分性或复杂部分性发作的癫痫患儿按来诊顺序交叉分为对照组、丙戊酸钠组及左乙拉西坦组,各13例.入组前半个月内均行脑电图检查,入组后分别予以维持原药治疗、加用丙戊酸钠口服及加用左乙拉西坦口服.观察时间6个月,6个月后复查脑电图,分析其疗效.结果 3组患儿脑电图改善率(控制+显效+有效/总例数-失访人数)分别为9.1％、23.1％和66.7％;3组患儿脑电图改善率比较差异有统计学意义(P＜0.01),丙戊酸钠组与对照组比较差异无统计学意义(P＞0.0125),左乙拉西坦组与对照组比较差异有统计学意义(P＜0.012 5).结论 添加左乙拉西坦可以有效减少癫痫患儿发作间期脑电图异常放电频率.     

负荷量苯巴比妥静脉注射治疗癫持续状态15例

目的探讨负荷量苯巴比妥静脉注射治疗小儿癫持续状态(SE)的效果。方法SE患儿15例予10~20 mg/kg负荷量苯巴比妥针,以不超过25 mg/min速度静脉推注。发作控制后12 h开始给维持量5 mg/(kg.d),分两次静脉推注或口服,12h/次,连用5 d。结果10 min内控制发作9例,10~15 min控制发作6例。6例意识障碍者在6~12 h全部恢复,未发现严重不良反应。结论负荷剂量苯巴比妥静脉推注是有效控制SE的方法之一。     

咪达唑仑持续静脉泵入治疗儿童癫(癎)持续状态的疗效观察

目的 观察咪达唑仑治疗儿童癫(癎)持续状态的疗效及不良反应.方法 将癫(癎)持续状态患儿按随机分配原则分为2组:研究组给予咪达唑仑0.3 mg/kg静注,15 min后若发作未能控制,以1～2 μg/(kg·min)持续静脉泵入,每15min增加1 μg/(kg·min),最大量20 μg/(kg·min).对照组给予安定0.3mg/kg静注,15 min后若发作未能控制,以5 μg(kg·min)持续静脉泵入.每15分钟增加.5 μg/(kg·min),最大量50 μg/(kg·min).结果 咪达唑仑组7例癫(癎)发作完全控制,1例在药量达20 μg/(kg·min)癫(癎)发作仍未控制,本组患儿控制癎痴持续状态的有效率为87.5%.安定组6例癫(癎)发作完全控制,1例在药量达50 μg/(kg·min)癫(癎)发作未控制,本组患儿控制癫(癎)持续状态的有效率为83.3%.两组控制惊厥疗效及控制惊厥药物起效时间的比较无显著性.安定组1例肌张力减低和1例呼吸抑制.咪达唑仑组未发现血压、心率、血氧饱和度和呼吸状态的变化.结论 咪达唑仑治疗癫(癎)持续状态起效快,效果好,不良反应小,可用于治疗癫(癎)持续状态.     

丙戊酸相关脑病1 例报告及文献复习

目的探讨儿童丙戊酸相关性高血氨脑病(VHE)的临床特点和诊治。方法回顾分析1例丙戊酸钠治疗Dravet综合征后并发VHE患儿的临床资料。结果女性患儿,6岁2个月。10月龄诊断Dravet综合征,长期口服丙戊酸钠及托吡酯治疗。因抽搐发作就诊,意识障碍,血氨明显升高,肝功能异常,脑功能受损严重;脑电图示低电压明显,头颅磁共振示大脑半球弥漫性水肿,双侧基底节信号异常。患儿经停用丙戊酸钠及降血氨治疗后,血氨下降,意识状态较前好转。结论对使用丙戊酸钠的癫痫患儿,特别是联合托吡酯治疗时,需警惕高氨血症及VHE,及时治疗可改善预后。     

Rescue therapy with high-dose oral phenobarbitone loading for refractory status epilepticus

Aim:   Parenteral phenobarbitone was unavailable in South Africa from 2005 to 2006. This study aimed to establish the effectiveness of enteral phenobarbitone in the management of childhood status epilepticus.
Method:   Patients in status epilepticus (December 2005–June 2006) received 20 mg/kg phenobarbitone via nasogastric tube in addition to standard status interventions (benzodiazepine boluses, phenytoin infusion). Phenobarbitone concentrations were taken post loading. Phenobarbitone population pharmacokinetics was analysed using non-linear mixed effects modelling.
Results:   Sixteen patients (7 female, 9 male) were assessed, median age 5 months (range 9 days–168 months). Nine patients received 20 mg/kg; the maximum total dosage administered was 80 mg/kg with a concentration of 283 µmol/L. The typical population value of the volume of distribution was 1.2 (95% confidence interval (CI): 0.8–1.6) L/kg with interindividual variability (as coefficient of variation) of 53% (95% CI, 9–74%). Seizure control was documented within 1 h ( n = 8), 1¹/₂ h ( n = 1), 3 h ( n = 1) and 4 h ( n = 5) following enteral phenobarbitone loading. No adverse effects were apparent from the enteral phenobarbitone administration.
Conclusion:   Patients tolerated enteral loading with phenobarbitone. A single enteral loading dose resulted in adequate phenobarbitone exposure. This practice was a safe intervention for centres lacking parenteral phenobarbitone. Therapeutic concentrations and seizure control after enteral loading suggested a role for enteral phenobarbitone in the management of acute status epilepticus as well as prophylaxis against seizure recurrence.     

Management of Acute Seizure and Status Epilepticus in Pediatric Emergency

Acute seizure and status epilepticus constitute one of the major medical emergencies in children. Among children, the incidence ranges from 4-38/100,000 children per year respectively. The incidence in developing countries is somewhat higher because of infections. Although, the definition of status epilepticus is based on duration of seizures, the operational definition is to treat any child who is brought seizing to the emergency room, as status epilepticus. An urgent time bound approach is of paramount importance when managing a child in status epilepticus. Benzodiazepines remain the first line antiepileptic drugs in the emergency room; a long acting drug (Lorazepam) is preferred when available. This is followed by Phenytoin (20 mg/kg) loading. In patients refractory to above drugs, valproate (30 mg/kg) loading is commonly used and if effective, followed by an infusion (5 mg/kg/h) for seizure free period of 6 h. In non-responders, a trial of Levetiracetam (40 mg/kg infused at 5 mg/kg/min) can be used before starting benzodiazepine or thiopental coma (3–4 mg/kg loading dose, followed by 2 mg/kg/min infusion). When pharmacological coma is initiated, the child needs to be shifted to pediatric intensive care unit for proper monitoring and titration of medications.     

不同维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的前瞻性随机对照研究

目的分析不同维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的疗效及安全性。方法将2016年1月至2018年1月收治的诊断为原发性呼吸暂停的极低出生体重早产儿78例随机分为高剂量咖啡因组（n=38）及低剂量咖啡因组（n=40）。两组均采取相同的枸橼酸咖啡因负荷量20 mg/kg治疗，24 h后分别给予每日10 mg/kg及5 mg/kg的维持剂量，观察比较两组患儿治疗的有效率及不良反应的发生率。结果高剂量咖啡因组治疗有效率（71%）高于低剂量咖啡因组（48%）（P < 0.05）；呼吸暂停持续时间、咖啡因治疗时间均较低剂量咖啡因组明显缩短（P < 0.05）。两组住院时间、心动过速及喂养不耐受发生率，以及支气管肺发育不良、坏死性小肠结肠炎及颅内出血的发生率比较差异无统计学意义（P > 0.05）。两组间病死率比较差异无统计学意义（P > 0.05）。结论高维持剂量枸橼酸咖啡因治疗极低出生体重早产儿呼吸暂停的效果优于低维持剂量咖啡因，而且未增加相关药物不良反应和早产儿严重并发症的发生率。     

多药耐药基因在慢性癫癎大鼠中的表达及托吡酯对其表达的影响

目的探讨多药耐药基因（mdr）在慢性大鼠中的表达及托吡酯（TPM）对其表达的影响。方法将生后28d的SD大鼠给予海人酸致,对照组给予相同的方法注射生理盐水。待自发性形成后,将癫痫组分为持续状态并发自发性（简称SE）组、持续状态并发自发性治疗（简称SE＋TPM）组、非癫痫持续状态并发自发性癫痫（简称N—SE）组和非持续状态并发自发性治疗（简称N—SE＋TPM）组;将生理盐水对照组分为正常生理盐水对照组和正常生理盐水对照治疗（对照＋TPM）组。治疗组均给予TPM治疗,治疗6周后,将所有大鼠断头取海马,RT—PCR检测mdr1α和mdr1b mRNA的表达。结果SE组、SE＋TPM组和N—SE＋TPM组的mdr1α和mdr1b mRNA表达均比对照组高（P〈0．001或〈0．05）,SE＋TPM组的mdr1α和mdr1b mRNA表达也比SE组高（P〈0．001）,其他治疗组（N—SE＋TPM,对照＋TPM）mdr1α和mdr1b mRNA表达较相对应的未治疗（N—SE,对照）组相比高,但无统计学意义（P〉0．05）。结论反复癫痫发作,特别是持续状态可使大鼠海马中mdr1α和mdr1b mRNA表达增加,颞叶的耐药可能与mdr1α和mdr1b mRNA高表达有关。TPM可增加大鼠海马中mdr1α和mdr1b mRNA的表达,尤其mdr1α mRNA的表达更明显。mdr1α 和mdr1b mRNA高表达可能与癫痫和TPM均有关。     

Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study

OBJECTIVE: To compare the antipyretic benefit of acetaminophen or ibuprofen monotherapy with an alternating regimen of both drugs in young children aged 6 to 36 months. DESIGN: Randomized, double-blind, parallel-group trial. SETTING: Three primary pediatric community ambulatory centers in central Israel. PARTICIPANTS: A total of 464 children aged 6 to 36 months with fever. INTERVENTION: Infants were assigned to receive either acetaminophen (12.5 mg/kg per dose every 6 hours) (n = 154) or ibuprofen (5 mg/kg per dose every 8 hours) (n = 155) or to receive alternating acetaminophen and ibuprofen (every 4 hours) (n = 155) for 3 days after a loading dose. MAIN OUTCOME MEASURES: Temperature, stress score, amount of antipyretic received, total days that the infant or caregiver was absent from day care or work, respectively, at the 3-day time point, recurrence of fever, and number of emergency department visits. RESULTS: The group given the alternating regimen was characterized by a lower mean temperature, more rapid reduction of fever, receiving less antipyretic medication, less stress, and less absenteeism from day care as compared with the other groups; all of the differences were statistically significant (P< .001). None of the regimens were associated with a significantly higher number of emergency department visits (P = .65) or serious long-term complications (P = .66). The drug used for initial loading had no effect on outcome in any of the groups. CONCLUSIONS: An alternating treatment regimen of acetaminophen (12.5 mg/kg per dose) and ibuprofen (5 mg/kg per dose) every 4 hours for 3 days, regardless of the initial loading medication, is more effective than monotherapy in lowering fever in infants and children.     

Optimal dose of acetaminophen in children

Acetaminophen is an antipyretic and analgesic drug frequently prescribed in children. Unlike aspirin, the recommended doses for acetaminophen are different in France (20-30 mg/kg/24 h) and in the USA (65 mg/kg/24 h). The authors reviewed literature data, looking for the scientific basis of these recommendations in children. The antipyretic effect of a 7-20 mg/kg single oral dose was demonstrated versus placebo. A dose-effect relationship was established: 20 mg/kg as a single oral dose was more effective than 10 mg/kg while 5 mg/kg had little antipyretic effect. More than 10 mg/kg were required to keep on average the temperature 1.5 degrees C below the starting point for 6 hours. There was no significant difference regarding the antipyretic effects of a single 10-15 mg/kg dose using suppositories or oral suspension, although there was a greater consistency of response with the oral suspension. There was no significant difference concerning the antipyretic effect between a 10-15 mg/kg acetaminophen oral dose and the same dose of aspirin. The analgesic effect of a single 10-15 mg/kg oral dose was also demonstrated versus placebo in children. Plasma concentrations between 4 and 18 mg/l seem appropriate to obtain an antipyretic effect. Half-life is 1-3.5 h. Based on these data different dose regimens including an initial loading dose have been proposed. The simplest one is as follows: 25 mg/kg loading dose and 12.5 mg/kg every 6 h as maintenance dose.     

Endocrine effects of valproic acid therapy in girls with epilepsy: A prospective study

Background/aimIt is controversial whether the endocrine dysfunction in epilepsy patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We prospectively evaluated the long-term impact of valproic acid monotherapy compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal, and ultrasonographic parameters in girls with epilepsy.MethodsFifty-seven female patients with epilepsy who had started therapy at mean age of 11.5 ± 3.3 years, 42 with valproic acid (mean dose 13.1 ± 7.0 mg/kg/day and 15 with other anti-epileptic agents were followed for a mean of 3.2 years (range 1.0–8.5 years) in our center. Clinical, hormonal and transabdominal pelvic ultrasound data were collected at 3 time points: before and 6–12 months after onset of anti-epileptic drug treatment; and at the last visit while patients were still taking anti-epileptic drugs.ResultsThere were no significant between-group differences regarding changes in height, body mass index standard deviation score, levels of glucose and insulin, or lipid and endocrine profile from first to last visits. Mean thyroid-stimulating hormone level increased significantly between first and last visit only in the valproic acid group (p < 0.001), with no significant difference in free T4 level over time or between groups. The rate of clinical polycystic ovary syndrome for the valproic acid group (11%) was comparable to that reported in healthy controls (5–10%).ConclusionsAdministration of valproic acid had no adverse effect on body weight, metabolic status or endocrine function over an average follow-up of 3.2 years. Valproic acid appears to be safe for use in girls with epilepsy.     

Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection

BACKGROUND: Respiratory syncytial virus (RSV) infection represents a major cause of pediatric respiratory hospitalizations. Limited treatment options exist. Palivizumab is a humanized monoclonal IgG1 antibody to the fusion protein of RSV that is highly active against RSV A and B strains. METHODS: A phase I/II, multicenter, randomized, double-blind, placebo-controlled, escalating dose clinical trial to describe the safety, tolerance, pharmacokinetics and clinical outcome of a single intravenous dose of palivizumab in previously healthy children hospitalized with acute RSV infection. RESULTS: Fifty-nine children < or =2 years of age received study drug. Sixteen children received 5 mg/kg of palivizumab (n = 8) or placebo (n = 8); 43 received 15 mg/kg of palivizumab (n = 22) or placebo (n = 21). Adverse events judged to be related to study drug were seen in one 5-mg/kg palivizumab patient and one 15-mg/kg palivizumab patient. These events were transient or consistent with progression of RSV disease. No discontinuations of study drug infusion because of adverse events occurred. Mean serum concentrations of palivizumab in the 5- and 15-mg/kg groups, respectively, were 61.2 and 303.4 microg/mL at 60 min and 11.2 and 38.4 microg/mL after 30 days. There were no significant differences in clinical outcomes between placebo and palivizumab groups for either dose. CONCLUSIONS: Intravenous palivizumab was safe and well-tolerated in children hospitalized with RSV disease. A single 15-mg/kg dose achieved serum palivizumab concentrations above the 25- to 30-microg/mL concentration associated with 2-log reduction of pulmonary RSV titer in the cotton rat model.     

Lorazepam versus diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial

BackgroundConvulsive status epilepticus demands urgent and appropriate management with anticonvulsants. Intravenous diazepam is an established drug in the management of convulsive status epilepticus in adults as well as in children. The efficacy of intravenous lorazepam has not been well established in children.ObjectiveTo determine whether intravenous lorazepam is as efficacious as diazepam–phenytoin combination in the treatment of convulsive status epilepticus in children.Study designRandomized controlled trial.MethodsA total of 178 children were enrolled in the study; 90 in the lorazepam group and 88 in the diazepam–phenytoin combination group. Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus, presenting in pediatric emergency of a tertiary care hospital. They were randomized to receive either intravenous lorazepam (0.1 mg/kg) or intravenous diazepam (0.2 mg/kg)–phenytoin (18 mg/kg) combination at admission and were followed up for subsequent 18 h.ResultsThe overall success rate of therapy was 100% in both the groups. There was no statistically significant difference in the two groups (lorazepam versus diazepam–phenytoin combination) in the median time taken to stop the seizure [20 s in both groups], the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(6.7%) versus diazepam–phenytoin combination: 14 (15.9%); adjusted RR (95% CI) = 0.377 (0.377, 1.046); P = 0.061] and the number (%) of patients having respiratory depression [lorazepam 4(4.4%) versus diazepam–phenytoin combination 5 (5.6%)]. None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure. No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimen.ConclusionLorazepam is as efficacious and safe as diazepam–phenytoin combination. We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam–phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus.