丙戊酸钠和苯巴比妥对癫患儿尿β_2-微球蛋白的影响

目的研究丙戊酸钠和苯巴比妥对癫患儿肾小管功能的影响。方法观察60例癫患儿,分别予丙戊酸钠及苯巴比妥单药治疗6个月,测定服药前后尿β2-微球蛋白的变化。结果丙戊酸钠组治疗前尿β2-MG为(0.27±0.04)mg/L,治疗后为(0.31±0.06)mg/L,t=2.60,P<0.01。苯巴比妥组治疗前后相比较,差别无显著性。结论丙戊酸钠对癫患儿肾小管功能有一定程度的损伤。     

托吡酯对儿童骨代谢的影响

目的研究托吡酯(TPM)对癫患儿骨代谢的影响。方法正常对照组30例,诊断明确的癫患儿30例,于治疗前、TPM单药治疗3个月、6个月后,分别测定血清Ⅰ型前胶原羧基末端前肽(PICP)和Ⅰ型胶原氨基末端交联肽(NTX)浓度。结果 (1)TPM组治疗前的血清PICP浓度和血清NTX浓度与正常对照组无明显差异。(2)治疗6个月后,TPM组的血清PICP浓度低于正常对照组(P<0.01)。(3)TPM组治疗6月后的血清PICP浓度低于治疗前、治疗3月后(P<0.05),治疗前后的血清NTX浓度无统计学意义(P>0.05)。结论提示应用TPM治疗癫可抑制骨形成,对于长期服用TPM的癫患儿需要补充维生素D、钙剂。     

甘松治疗戊四氮致大鼠的实验性研究

目的观察甘松对戊四氮致大鼠的疗效。方法将50只Wistar大鼠随机分为5组,每组各10只,分别为正常对照组、模型组、甘松治疗组、丙戊酸钠治疗组和甘松合并丙戊酸钠治疗组;采用腹腔注射戊四氮制作建立癫模型;观察各组大鼠行为学及脑电图、NSE(神经元特异性烯醇化酶)浓度变化。结果与模型组比较,甘松治疗组、丙戊酸钠治疗组、甘松合并丙戊酸钠组可明显减轻大鼠样发作程度,减少发作频率和持续时间,改善大鼠皮层脑电图,降低脑脊液神经元特异性烯醇化酶浓度,其中以甘松合并丙戊酸钠组最为明显。结论甘松对戊四氮致大鼠具有一定的抗癫及脑保护作用,与丙戊酸钠联用有协同作用。     

不同剂型丙戊酸钠治疗儿童癫血药浓度监测及临床分析

目的探讨癫患儿使用不同剂型丙戊酸钠制剂对血药浓度的影响及临床疗效。方法采用高效液相色谱法对582例服用不同剂型丙戊酸钠患儿进行血药浓度测定,分为丙戊酸钠缓释片组261例,丙戊酸钠口服片组223例,丙戊酸钠普通片剂组98例,对3组监测结果及临床疗效对比分析。结果丙戊酸钠缓释片组血药浓度谷水平为(72.56±18.62)mg/L,口服液组为(50.23±21.88)mg/L,普通片剂组为(41.43±19.87)mg/L。缓释片组血药谷浓度最高,普通片剂组最低,3组相比差异有统计学意义(P<0.05);缓释片组与口服液组临床疗效比较差异无统计学意义(P>0.05),与普通片剂组比较差异有统计学意义(P<0.05)。结论服用丙戊酸钠缓释剂血药谷浓度相对较高,且依从性好,值得临床推广。     

丙戊酸钠和苯巴比妥对癫癎患儿尿β2-微球蛋白的影响

目的 研究丙戊酸钠和苯巴比妥对癫癎患儿肾小管功能的影响.方法 观察60例癫癎患儿,分别予丙戊酸钠及苯巴比妥单药治疗6个月,测定服药前后尿β2-微球蛋白的变化.结果 丙戊酸钠组治疗前尿β2-MG为(0.27±0.04)mg/L,治疗后为(0.31±0.06)mg/L,t=2.60.P<0.01.苯巴比妥组治疗前后相比较,差别无显著性.结论 丙戊酸钠对癫癎患儿肾小管功能有一定程度的损伤.     

唑尼沙胺与丙戊酸钠对癫痫患者认知功能的影响

目的评价唑尼沙胺(ZNS)作为新型抗癫痫药物与传统抗癫痫药物丙戊酸钠(VPA)对癫痫患者认知功能的影响。方法唑尼沙胺与丙戊酸钠各单药治疗30例未经治疗的癫痫患者,所有患儿在治疗前、治疗后3个月及治疗后6个月时进行WAIS-CR问卷调查,对相关数据进行统计学分析。结果唑尼沙胺组患者治疗后3个月时语言能力测定分值下降,操作及总智力测定分值无明显变化;治疗6个月后语言、操作及综合智力测定分值均下降;而丙戊酸钠组患者的语言、操作及综合智测水平在治疗后3个月时、6个月时无明显变化。结论唑尼沙胺对癫痫患者的认知功能有损害作用,以语言能力的损害最为突出;丙戊酸钠对癫痫患儿的认知功能无明显影响。     

比较奥卡西平或拉莫三嗪联合丙戊酸钠治疗脑外伤术后癫疒间复发疗效

目的探讨丙戊酸钠治疗脑外伤术后癫疒间复发后,添加奥卡西平或拉莫三嗪联合治疗外伤性癫疒间效果。方法以治疗前3个月癫疒间发作频度为对照,对治疗12个月后的疗效、不良反应及安全性进行自身对比观察。结果应用奥卡西平或拉莫三嗪联合丙戊酸钠治疗12个月后,患者发作频率均较用药前明显减少;发作频率减少≥50%的患者分别为89.2%和89.7%,用药前后差异无统计学意义(P<0.05);奥卡西平或拉莫三嗪联合丙戊酸钠两组间差无明显统计学意义(P>0.05)。奥卡西平联合丙戊酸钠不良反应的发生率为19.3%,拉莫三嗪联合丙戊酸钠不良反应的发生率为9.1%,差异显著(P<0.05)。结论奥卡西平或拉莫三嗪联合丙戊酸钠治疗外伤性癫疒间复发疗效确切,副作用拉莫三嗪组明显低于奥卡西平组。     

丙戊酸钠治疗中老年脑卒中后继发癫癎的疗效及对认知功能的影响

目的探讨丙戊酸钠治疗中老年脑卒中后继发癫癎的临床疗效及对认知功能的影响。方法选择56例脑卒中后继发癫癎中老年患者为研究对象,给予丙戊酸钠口服治疗6个月。采用简易精神状态检查表(MMSE)评估认知功能,比较患者治疗前后癫癎发作次数、血糖水平、脑水肿发生率及MMSE评分改变。结果本组患者治疗后癫癎发作次数显著少于治疗前(1.56±0.73vs 4.28±1.37,P<0.05);治疗后脑水肿发生率显著减少(8.9%vs 35.7%,P<0.05);治疗前后血糖水平差别无统计学意义(P>0.05);治疗后MMSE各项评分显著优于治疗前(P<0.05)。结论丙戊酸钠可显著减少中老年脑卒中后癫癎发作次数,改善认知功能。     

托吡酯联合丙戊酸钠治疗儿童癫痫的有效性及安全性

目的探讨托吡酯联合丙戊酸钠治疗儿童癫痫的有效性及安全性。方法选取80例癫痫患儿,随机分为对照组和联合组各40例,对照组给予托吡酯单药治疗,联合组在对照组用药基础上加用丙戊酸钠治疗。观察2组疗效及不良反应发生情况。结果治疗3个月时联合组治疗总有效率95.00%高于对照组80.00%(P0.05),治疗6个月时2组治疗总有效率分别为97.50%、87.50%,差异无统计学意义(P0.05);治疗3、6个月时2组癫痫发作月均频率明显低于治疗前(P0.01),治疗6个月癫痫发作月均频率明显低于治疗3个月(P0.01),治疗3、6个月时联合组癫痫发作月均频率明显低于对照组(P0.01);对照组不良反应发生率10.00%,联合组为15.00%,差异无统计学意义(P0.05)。结论托吡酯联合丙戊酸钠治疗儿童癫痫可在短期内减少癫痫发作频率,未明显增加不良反应发生率,耐受性较好。     

拉莫三嗪对成年癫患者血清中瘦素、抵抗素和脂联素水平的影响

目的探讨抗癫新药拉莫三嗪对成年癫患者血清瘦素、抵抗素、脂联素水平的影响。方法对30名女性健康查体人员和60例首发癫全面性强直-阵挛发作女性患者随机分为拉莫三嗪组和丙戊酸钠组,在治疗前和治疗后分别进行血清瘦素、抵抗素和脂联素水平测定,并测量腰臀比(帆)、体重指数(BMI)。结果拉莫三嗪治疗后、对照组BMI、WHR及血清瘦素、抵抗素、脂联素水平间均无明显差异,而丙戊酸钠治疗后血清瘦素、抵抗素水平明显升高,脂联素水平明显降低(P<0.01)。结论拉莫三嗪治疗不引起癫患者体重增加,瘦素、脂联素、抵抗素水平可能是肥胖发生的预测指标。     

Evaluation of subclinical hypothyroidism in ambulatory children with controlled epilepsy on valproate monotherapy

There are conflicting reports in the literature about the influence of valproate on thyroid function. A cross-sectional study was performed to determine the prevalence of subclinical hypothyroidism in ambulatory children aged 3 to 15 years with controlled epilepsy receiving valproate monotherapy for at least 6 months. Fifty-seven consecutive children with controlled epilepsy on valproate monotherapy and 52 healthy age- and sex-matched control children were studied. Thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, and serum valproic acid levels were measured. There was a significantly high (P = .012) prevalence of subclinical hypothyroidism (26%) in those receiving valproate monotherapy compared with healthy controls (7.7%). Median duration of valproate therapy was significantly higher (P = .039) in the subclinical hypothyroidism group (21 months, range 6-36) compared with those without subclinical hypothyroidism (14 months, range 6-25). Results of the present study suggest higher prevalence of subclinical hypothyroidism in children with controlled epilepsy on long-term valproate monotherapy.     

托吡酯联合丙戊酸钠治疗小儿癫痫临床观察

目的分析托吡酯联合丙戊酸钠治疗小儿癫痫的临床效果及对血清细胞因子水平的影响。方法选取2014-03—2016-11在解放军第152中心医院接受治疗的癫痫患儿180例,随机分为观察组(n=90)与对照组(n=90)。2组均给予托吡酯治疗,观察组同时联合丙戊酸钠治疗。结果观察组有效率92.22%,对照组为82.22%。观察组有效率明显高于对照组(P0.05)。2组治疗后NSE、Hcy、IGF-1水平均有显著改善,观察组改善更加明显,差异有统计学意义(P0.05)。2组治疗后IL-2、IL-6、TNF?α水平均有显著改善,观察组改善更加明显,差异有统计学意义(P0.05)。结论托吡酯联合丙戊酸钠治疗小儿癫痫的临床效果显著,安全性高,且有利于改善血清细胞因子水平。     

The effect of carbamazepine and sodium valproate on the blood and serum values of children from a third-world environment

In third-world countries many children with epilepsy also suffer from malnutrition, anemia, liver disease, and immunosuppression. Doctors might have reservations about the use of anticonvulsants that could aggravate these disorders. The purpose of this study was to establish the prevalence of abnormal blood and serum values in children receiving carbamazepine or sodium valproate as monotherapy who attended a child neurology clinic serving a third-world community in Cape Town, South Africa Blood samples were taken at routine follow-up visits from 104 children who had been on carbamazepine or sodium valproate monotherapy for at least 6 months. Hematology, serum chemistry, immunoglobulins, and anticonvulsant levels were measured by standard laboratory procedures. Very few subjects had any values outside accepted normal ranges. When clinically indicated and available, carbamazepine and sodium valproate can be prescribed for children from a third-world environment. Frequent blood and serum testing is not necessary in asymptomatic individuals.     

丙戊酸钠联合左乙拉西坦治疗小儿癫痫的疗效

目的探讨丙戊酸钠联合左乙拉西坦治疗小儿癫痫的临床疗效。方法将92例小儿癫痫患者随机分为对照组和实验组,在丙戊酸钠治疗基础上,对照组联合托吡酯治疗;实验组联合左乙拉西坦治疗。结果实验组总有效率93.5%高于对照组78.3%,治疗前,2组患者血钙和血磷水平无显著差异(P0.05);但治疗后实验组血钙水平(2.39±0.36)mmol/L、血磷水平(1.45±0.36)mmol/L均低于对照组(2.07±0.18)mmol/L、(1.21±0.15)mmol/L(均P0.05)。结论丙戊酸钠、左乙拉西坦联合用药治疗小儿癫痫疗效显著,且对钙、磷代谢影响较小,安全性高,临床值得应用。     

Characterization of glucose homeostasis and lipid profile in adult,seizure‐free,epileptic patients in Asian population

Background and purpose: The most common prescribed antiepileptic drugs (AEDs), phenytoin and valproate, are potent enzyme inducers and inhibitors of the cytochrome P450 system, which interfere with lipid profile and glucose homeostasis. Studies on this topic have suffered from inadequate assessment of confounders and have rarely included glucose homeostasis and lipid profile as well as both enzyme inducers and inhibitors in the same study. We sought to determine whether these drugs had an effect on lipid profile and glucose homeostasis in Thai epileptic patients. Methods: We recruited 98 patients with epilepsy (45 taking phenytoin, 27 taking valproate, and 26 not taking any AED). Fasting blood samples were obtained to measure serum lipid, and glucose homeostasis was evaluated via the oral glucose tolerance test. We calculated the homeostasis model assessment index for each patient. Results: Our study revealed that CYP450 was induced by AEDs, and that patients on phenytoin had an increased mean value of serum total cholesterol, serum total triglycerides, and serum LDL cholesterol when compared with patients with epilepsy taking valproate and those taking no AEDs. No statistical significant difference was observed between patients taking valproate and patients taking no AEDs. In addition, patients with epilepsy taking phenytoin had higher fasting plasma glucose levels at fasting state than both those taking valproate and those taking no AEDs. Thirty percent of the patients taking phenytoin exhibited insulin resistance. We have found a negative correlation between log insulin sensitivity and log TG, but not high‐density lipoprotein (HDL). Conclusion: CYP450‐induced phenytoin produces significant amelioration in several serologic markers of atherosclerosis. These findings suggest that phenytoin may substantially increase the risk of vascular events.     

Transient decrease in serum albumin concentrations in epileptic children treated with sodium valproate monotherapy

OBJECTIVE: Hypoalbuminemia has been reported in patients with severe disability and epilepsy and in patients with epilepsy treated with short-term sodium valproate (VPA) therapy; however, serum albumin concentrations have not previously been determined in otherwise healthy patients with epilepsy and receiving long-term VPA monotherapy. METHODS: Serum albumin concentrations were determined in 26 ambulatory children with epilepsy before and at 6, 12, and 24 months of VPA monotherapy. Serum total protein concentrations and serum concentrations of other biochemical markers of liver and renal function such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and creatinine concentration were also measured in the study participants before and at 6, 12, and 24 months of treatment. RESULTS: Serum albumin concentrations were reduced at 6 months of treatment (P = 0.007). Serum alanine aminotransferase concentrations were significantly increased at 6 (P = 0.034) and 12 months of treatment (P = 0.046), whereas serum aspartate aminotransferase concentrations were significantly increased at 6 (P = 0.002) and 12 months of treatment (P = 0.002). There were no significant correlations between serum albumin and the other parameters at 6 months of treatment. CONCLUSIONS: Ambulatory children who receive VPA monotherapy may have early but transient decrease in serum albumin concentrations. Further studies are needed to address this issue and to determine the possible clinical implications and the mechanisms involved in VPA-mediated decrease in serum albumin concentrations.     

An observational study of first-line valproate monotherapy in focal epilepsy

The objective of this multinational open-label, prospective study was to collect, under naturalistic conditions, data on the effectiveness and tolerability of first-line monotherapy with valproate in subjects newly or recently diagnosed with focal onset epilepsy. Patients were treated with sustained release sodium valproate. Seizure control and occurrence of adverse events were assessed after 6 months. Around 1192 adults and 792 children were included. The mean daily valproate dose was 683 mg in children and 987 mg in adults. The retention rate at 6 months was 90.0%. At this time, 77% of subjects were seizure free (83.7% of children and 72.7% of adults). Adverse events possibly related to treatment were observed in 10.2% of subjects, leading to treatment modification for 1.7%. The most common adverse events were weight gain, gastro-intestinal, neurological and skin disorders. Sustained release sodium valproate is effective and shows acceptable tolerability as first-line monotherapy in focal onset epilepsy.     

Monitoring sodium valproate treatment of epilepsy in the development years

The levels of sodium valproate were determined in the blood and saliva of children treated for epilepsy. The determination of drug in saliva may be a simple test checking whether the patient is taking the drugs systematically, and makes possible determination of the approximate level in the serum without blood sampling. In doubtful cases poorly responding to treatment serial monitoring of valproic acid should be undertaken.     

The longer term outcome of children born to mothers with epilepsy

OBJECTIVES: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME MEASURES: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.