丙戊酸和托吡酯对癫(癎)患儿游离肉毒碱的影响

目的探讨丙戊酸(VPA)和托吡酯(TPM)对癫癎患儿游离肉毒碱的影响。方法35例癫癎患儿,年龄6～8岁,男20例,女15例,其中12例予VPA单药治疗,11例予TPM单药治疗,12例予VPA及TPM联合治疗6～8个月。15例健康儿童作为正常对照组。测定血浆游离肉毒碱的浓度。结果VPA组血浆游离肉毒碱的浓度明显低于对照组及TPM组,VPA-plus- TPM组与VPA组比较差异无显著性,TPM组与对照组比较差异无显著性。结论VPA可降低癫癎患儿血浆游离肉毒碱水平,而TPM对血浆游离肉毒碱无明显影响。     

丙戊酸钠治疗难治性癫(癎)持续状态疗效观察

目的 探讨丙戊酸钠治疗难治性癫(癎)持续状态的疗效.方法 我院2008-03-2011-03收治难治性癫(癎)持续状态患者29例,应用丙戊酸钠注射液治疗.结果 26例于1 h 内完全控制,控制率89.65%,本组起效时间5～15 min,平均(6±7)min,发作控制时间25～52 min,平均(38.56±10.85) min.结论 丙戊酸钠注射液治疗难治性癫(癎)持续状态具有起效快、应用安全,临床疗效确切等优点,适于临床应用.     

单纯地西泮与地西泮联合丙戊酸治疗癫(癎)持续状态的疗效比较

目的 比较单纯地西泮和地西泮联合丙戊酸钠治疗癫(癎)持续状态(SE)的疗效.方法 选择成人SE患者35例,分成地西泮组(给予地西泮静脉治疗)和地西泮联合丙戊酸钠组(地西泮联合丙戊酸钠静脉治疗)两组,观察两组的疗效.结果 两组治疗的有效率差异无统计学意义,地西泮联合丙戊酸钠组72 h内复发率低于地西泮组(P＜0.05).结论 地西泮联合丙戊酸钠治疗可降低SE患者的复发.     

丙戊酸钠对癫(癎)患儿血淀粉酶和脂肪酶的影响

目的研究丙戊酸钠对癫癎患儿血淀粉酶和脂肪酶的影响。方法观察22例癫癎患儿,男12例,女10例,年龄1·5～11岁,均丙戊酸钠单药治疗,治疗前及治疗6月后测定血淀粉酶和脂肪酶浓度。结果血淀粉酶浓度治疗前为(61·14±12·96)IU/L,治疗后为(69·09±9·22)IU/L,二者相比较,t=2·24,P=0·036。血脂肪酶浓度治疗前为(62·50±11·88)IU/L,治疗后为(71·14±14·59)IU/L,二者相比较t=2·46,P=0·023。结论丙戊酸钠可升高癫癎患儿血淀粉酶和脂肪酶浓度。     

醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果观察

目的:探讨醒脑静注射液配合丙戊酸钠治疗癫(癎)持续状态的疗效.方法:选择我院2013年8月～2016年1月收治的癫(癎)持续状态患者74例为研究对象,以随机数字表法分组,观察组37例,对照组37例,对照组单用丙戊酸钠治疗,观察组采取醒脑静注射液辅助静脉用丙戊酸钠治疗,对两组患者疗效进行观察.结果:观察组总有效率为92％,对照组为81％,两组比较差异有统计学意义(P＜0.05);观察组起效时间及完全控制时间均较对照组短,两组比较差异有统计学意义(P＜0.05);观察组复发率与不良反应发生率分别为8％和11％,对照组分别为11％和21％,两组比较差异均有统计学意义(P＜0.05).结论:醒脑静注射液辅助静脉用丙戊酸钠治疗癫(癎)持续状态效果显著,此两药具有相互协同作用,可快速起效,安全性高,利于远期预后.     

广西农村部分地区癫(癎)及丙戊酸钠疗效的初步调查

目的 了解广西农村部分地区癫(癎)的发病情况、治疗缺口以及丙戊酸钠的疗效.方法 利用统一的调查表对广西田东、田阳、平果、天等县已确定或怀疑癫(癎)的患者进行调查,再经神经科医生复查后确诊,并对适合使用丙戊酸钠的病例进行疗效观察.结果 共诊断癫(癎)患者303例,未经治疗46.2%,西药治疗45.5%,仅中药、偏方治疗6.3%,治疗不详2.0%,其中活动性癫(癎)人数295例,治疗缺口达81.0%.295例患者进入丙戊酸钠治疗的随访研究,显效率为58.6%,总有效率为75.2%.结论 广西农村地区癫(癎)的治疗缺口较全国其他农村地区高,经丙戊酸钠治疗后,约75%患者发作可得到有效控制,但是不正规治疗可影响患者的预后,故应重视癫(癎)患者的正规治疗.     

广西农村地区癫(癎)发病情况及丙戊酸钠疗效的初步研究

目的 观察广西部分农村地区癫(癎)发病情况,并通过治疗有效率和保留率评价丙戊酸钠单药治疗疗效.方法 由经过培训的全科医师采用统一调查表的方式对广西部分农村地区已明确诊断或可疑癫(癎)的部分人群进行筛查,再由神经科医师复查确诊人组.采用治疗有效率和治疗保留率评价丙戊酸钠单药治疗效果.结果 癫(癎)患者309例,病因明确者86例(27.83%);随访>6个月者134例,显效76例(56.72%),有效34例(25.37%),无效20例(14.93%),恶化4例(2.99%).其中,全面性强直-阵挛发作治疗总有效率为83.51%(81/97),部分继发性全面性发作87.50%(14/16),单纯部分性发作71.43%(5/7),复杂部分性发作60%(6/10),失神发作100%(3/3),其他类型100%(1/1);治疗第6、12及18个月时,治疗保留率分别为97.73%(302/309)、97.09%(300/309)和83.50%(258/309).共30例患者出现不良反应.依次为乏力、嗜睡、记忆力减退、肝功能异常、头晕、体质量增加、食欲亢进、头痛、震颤、脱发、步态不稳及食欲不振;不良反应总发生率为9.71%.结论 广西农村地区癫(癎)患者发病年龄及性别分布与全国其他农村地区相似.治疗保留率作为评价抗癫(癎)药物长期治疗效果的指标,与治疗有效率联合应用能够综合反映丙戊酸钠的治疗效果,丙戊酸钠具有向广西更多农村及条件相似地区临床推广应用的价值.     

丙戊酸钠个体化治疗108例婴幼儿癫癎的疗效和安全性分析

婴幼儿是癫癎发病的第一个高峰期,发病率0.15%～0.34%。抗癫癎药物是首选的治疗方法,抗癫癎药物应用个体差异较大且不良反应多,临床选药方案较多,目前主张单药治疗[1]。我院2005—2011年应用丙戊酸钠口服溶液治疗婴幼儿癫癎疗效满意,且不良反应发生率较低,现报告如下。     

脑电图检查对癫(癎)病人致(癎)灶的定位价值

1 临床资料 1.1 一般资料 经临床、影像学及脑电图(EEG)检查,明确诊断为癫(癎)并接受手术者共计96例,其中男60例,女36例,年龄8～49岁,平均28.5岁.发作类型(按1985年中华医学会第一届全国癫(癎)会议确定的标准)为简单部分性发作6例,复杂部分性发作18例,复杂部分性发作伴精神症状6例,全身强直阵孪性发作66例.     

丙戊酸单药治疗与癫痫患者血浆同型半胱氨酸水平间关系的Meta分析

目的分析癫痫患者血浆同型半胱氨酸水平变化与丙戊酸单药治疗间的关系。方法选择epileDsv、valproate、homocysteine和epilep。为检索词,计算机检索1990年1月-2013年8月美国国立医学图书馆、科学引文索引数据库、荷兰医学文摘等数据库,获得丙戊酸单药治疗与癫痫患者血浆同型半胱氨酸水平间关系的相关英文文献,均为丙戊酸单药治疗的癫痫患者与正常对照受试者血浆同型半胱氨酸水平比较的病例．对照临床研究。通过Newcastle—Ottawa量表独立进行文献质量评价和数据提取,Stata12．0统计软件行Meta分析。结果共纳入符合条件的英文文献8篇,包括266例行丙戊酸单药治疗的癫痼患者和489例正常对照受试者,所有纳入文献质量评分均〉6分。Meta分析显示,丙戊酸单药治疗组患者血浆同型半胱氨酸水平显著高于正常对照组[标准化均数差（SMD）：0．620,95％CI：0．320-0．920;P=0．000];经异质性检验存在显著异质性（I^2=65．600％,P=0．005）,根据不同地区和受试者年龄差异行进一步亚组分析,结果显示西亚组癫痫患者异质性风险（I^2=47．400％,P=0．107）较整体（I^2=65．600％,P=0．005）降低。采用敏感性分析评价Meta分析之稳定性,当任何一项研究被剔除后,相应的SMD值均不发生变化,表明分析结果稳定性良好。结论丙戊酸单药治疗可显著增加癫痫患者血浆同型半胱氨酸水平,后者是否受种族因素的影响尚待进一步研究。     

The metabolic syndrome in overweight epileptic patients treated with valproic acid

Purpose: To evaluate the presence of metabolic syndrome (MS) in children and adolescents treated with valproate (VPA). Methods: One hundred fourteen patients (54 male and 60 female) were studied. These patients were followed from the beginning of therapy for at least 24 months; at the end of follow‐up, 46 patients (40.4%) had a considerable increase in body weight, whereas the other patients (59.6%) remained with the same weight. The MS was defined as having at least three of the following: abdominal obesity, dyslipidemia, glucose intolerance, and hypertension. Results: Forty‐six patients developed obesity; 20 (43.5%) of 46 patients developed MS. Abnormal glucose homeostasis was identified in 45% of patients. High total serum cholesterol concentrations were noted in 10 (50%), high serum triglyceride concentrations in 7 (35%), and low high‐density lipoprotein (HDL) in 15 (75%) of the 20 subjects with MS. However, there were no significant differences in the features of MS between boys and girls with MS. Conclusions: Patients who gain weight during VPA therapy can develop MS with a possible risk of cardiovascular disease.     

Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treated with valproic acid

The aim of this study is to evaluate the carotid artery intima media thickness and serum lipids in pediatric patients with epilepsy treated with valproic acid. The study included 44 pediatric epileptic and 40 healthy children. Intima media thickness of left common carotid artery and fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) were assessed. Although we did not observe any differences regarding serum lipid profiles, intima media thickness of common carotid artery was significantly higher in epileptic patients treated with valproic acid. We suggest that this increase in intima media thickness of common carotid artery may be due to epilepsy and/or valproic acid treatment.     

Concentration of metabolites of valproic acid in plasma of epileptic patients

With the help of synthetic reference substances, five metabolites of valproic acid (VPA) could be quantitated by gas chromatography in the plasma of 26 epileptic patients undergoing chronic therapy with sodium valproate. The products of beta-oxidation, i.e., 2-en-VPA, 3-hydroxy-VPA, and 3-keto-VPA were found to be the major metabolites of VPA in plasma, whereas the intermediates of omega-oxidation, 4-hydroxy-VPA and 5-hydroxy-VPA, were present only in markedly lower concentrations. It was thus confirmed that in addition to the excretion of VPA as the glucuronide, beta-oxidation is the preferred metabolic pathway of VPA in man. However, taking the anticonvulsant activity of the metabolites as derived from animal experiments into consideration, none of the metabolites found in human plasma seems to contribute markedly to the therapeutic effect of VPA. Thus, in most patients, VPA seems responsible for more than 90% of the antiepileptic activity during continued medication in man.     

Hyperaminoacidemia in epileptic children treated with valproic acid

Serum amino acids were determined in 22 epileptic children treated with valproic acid. This treatment caused hypocarnitinemia in all, and hyperammonemia in 16. Regardless of the blood ammonia levels, values for glutamic acid, arginine, glycine, serine and alanine were higher than those of normal controls, while aspartic acid and ornithine were lower. These findings suggest that valproate causes intramitochondrial dysfunction of the urea cycle.     

Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency

A 47-year-old man suffering from a bipolar disorder and intermittent myoglobinuria presented with acute rhabdomyolysis with renal failure after starting therapy with valproic acid. On morphological examination, skeletal muscle revealed increased lipid storage. Biochemically, decreased enzyme activity of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the lower limit was found. Genetic analysis detected the common Ser113Leu substitution on one allele of the CPT2 gene. We conclude that valproic acid should be avoided in patients with CPT type II deficiency.     

Effects of valproic acid on sleep in children with epilepsy

Purpose:   Parents frequently report increased sleep duration in their children during treatment with valproic acid (VPA). We assessed sleep duration and sleep behavior before and after tapering VPA in children treated for more than 6 months.
Methods:   Sleep variables were assessed by questionnaire, diary, and actigraphy (for 7 consecutive days and nights) before and 8–12 weeks after termination of VPA.
Results:   Forty-six children (age range 1.7–17.4 years) completed the study. The questionnaire data showed no significant difference in bed and wake time, duration of sleep, and time to fall asleep before and after ending VPA treatment, although some qualitative measures on daytime sleepiness improved after tapering VPA. The actigraphy data revealed that the average sleep amount without VPA was reduced in 33 children (9 of them >30 min) and longer in 13 children (1 of them >30 min). The mean Assumed Sleep Time per Day decreased by 15.2 min or 9.5 min when the physiologic decrease of sleep duration within 0.3 years was considered. Also mean Actual Sleep Time per Day was significantly reduced after VPA termination (−15.2min; after correction −10.7 min). The reduction was only significant in children older than age 6 years.
Discussion:   Termination of VPA after long-term treatment leads to a significant reduction of sleep duration in children older than 6 years of age. The change was small in the majority, but considerable in a subgroup of children.     

Effects of acute valproic acid administration on carnitine plasma concentrations in epileptic patients

Serial plasma samples collected after an acute administration of valproic acid, (VPA, 15 mg/kg as oral solution) in epileptic patients were selected for this study. The plasma samples were selected from three different groups of patients; patients on phenobarbital and phenytoin with clinical VPA intolerance (group A); patients on phenobarbital and phenytoin without clinical VPA toxicity (group B); and patients without phenobarbital and phenytoin and without clinical VPA toxicity (group C). Plasma samples from 6 patients per group were analyzed for carnitines and ammonia. Ammonia levels during acute study increased significantly (P less than 0.05) in patients who experienced VPA intolerance, while no changes were found in the other patients. After acute VPA administration, total carnitine was unchanged but free carnitine was decreased (P less than 0.05) and carnitine esters were increased (P less than 0.05) in all groups of patients studied. No difference in carnitine profiles was seen between patients with or without evidence of VPA administration has an important effect on carnitine metabolism. However, unlike the acute effect on ammonia metabolism, this acute effect does not seem to be correlated with any associated antiepileptic therapy, nor does it predict clinical VPA intolerance.     

The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients

Objectives

To investigate influences of the functional polymorphisms of Cytochrome P450 isozymes 2A6 (CYP2A6), 2B6 (CYP2B6), and 2C9 (CYP2C9) on pharmacokinetics of VPA in vivo.

Patients and methods

In the study, we analyzed the genotypes of CYP2A6, CYP2B6, and CYP2C9 and their contribution to the steady-state standardized plasma VPA concentrations in 179 subjects with epilepsy of a Northern Han Chinese population. The genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The subjects with one or two variant CYP2A6*4 alleles showed higher mean plasma VPA concentrations compared with non-*4 alleles [(3.4 ± 0.4) μg kg ml⁻¹ mg⁻¹ vs. (3.6 ± 0.4) μg kg ml⁻¹ mg⁻¹, p = 0.0055]. A significant difference [one-way ANOVA (p = 0.0203)] was also found between mean plasma VPA concentrations and the CYP2B6 genotypes. In addition, subjects with the heterozygous genotype CYP2C9*3 had higher mean plasma VPA concentrations than did those subjects with the wild-type genotype [(3.9 ± 0.4) μg kg ml⁻¹ mg⁻¹ vs. (3.4 ± 0.4) μg kg ml⁻¹ mg⁻¹, p = 0.0001].

Conclusion

The presently evaluated variant alleles in the CYP2A6, CYP2B6, and CYP2C9 genes may explain part of the substantial variability in VPA pharmacokinetics between different subjects.