丙戊酸钠对成人癫痫患者认知功能的影响

目的了解丙戊酸钠对成人癫痫患者认知功能的影响。方法采用简易精神状态评定量表,分别于治疗前及治疗6个月、1年、2年、3年对74例接受丙戊酸钠治疗的成人癫痫患者认知功能进行评价,并选同期健康体检者85例作为对照组。结果癫痫组丙戊酸钠血药浓度均在正常浓度范围。简易精神状态评定量表评分：在干预前,癫痫组11项得分均低于对照组（P〈0.01）;在干预后6个月、1年、2年、3年,癫痫组11项得分均低于对照组（P〈0.05）;癫痫组自身与治疗前比较,11项得分均增高（P〈0.05）,但随时间延长无进一步改善趋势（P〉0.05）;癫痫组治疗前后原发性和继发性癫痫患者间比较无差异（P〉0.05）。结论成人癫痫患者存在认知功能下降,丙戊酸钠具有改善癫痫患者认知功能的作用。     

丙戊酸钠对男性癫痫患者生殖功能的影响

目的 探讨丙戊酸钠(VPA)对男性癫痫患者生殖功能的影响.方法 对32例应用VPA单药治疗≥6个月的男性癫痫患者(VPA组)及30名健康对照者(正常对照组)的血液性激素水平、精液质量进行检测;采用国际勃起功能指数量表简化版问卷(IIEF-5)评估两组已婚者的性功能评估,并进行比较.结果 与正常对照组比较,VPA组的生育率显著降低(P＜0.05),血液中黄体生成素、卵泡刺激素水平显著降低,泌乳素水平及生物活性雄激素/黄体生成素显著升高(均P＜0.01).两组间睾酮、雌二醇水平、生物活性雄激素/生物活性雌激素及精液浓度差异无统计学意义;VPA组总精子畸形率及头部、体部尾部精子畸形率显著高于正常对照组,总精子活动率、A级精子＜25％及A+B级精子＜50％的比率均显著低于正常对照组(均P ＜0.01);IIEF-5总分及问题l、2、3得分显著低于正常对照组(均P＜0.01).结论 VPA可损害男性癫痫患者的生殖功能.     

丙戊酸钠的应用进展

本文对丙戊酸钠的抗痫机制及用量进行了综述,详述了丙戊酸钠的临床应用,与卡马西平、苯妥英钠的相互作用及不良反应。     

老年癫痫患者合用阿司匹林对丙戊酸钠血药浓度的影响

目的 观察老年癫痫患者合并使用阿司匹林(ASA)对丙戊酸钠(VPA)血药浓度的影响.方法 选择门诊随访的单用VPA治疗的癫痫患者,65岁以上者为观察组,65岁以下者为对照组,测定VPA的血药浓度.对观察组,再根据有无使用ASA,比较血药浓度及肝肾功能情况.结果 观察组的VPA血药浓度明显高于对照组,服用ASA与未服ASA者的血药浓度及肝肾功能无明显区别.结论老年人在临床应用VPA时,应减少剂量.老年患者使用ASA不会对VPA血药浓度产生影响.     

苯妥因钠,丙戊酸钠,卡马西平对癫痫患者智力的影响

抗癫痫药物造成认知功能的损害及损害程度至今仍无明确结果。为此，我们对４６例全身性强直一阵挛发作的癫痫患儿进行了服药前后的智力测验，并以１６例健康同龄人对照，以检测苯妥历钠，丙戊酸钠，卡马西平对智力的影响。     

丙戊酸钠和卡马西平对脑电图的影响

目的：探讨丙戊酸钠（ＶＰＡ）和卡以西平（ＣＢＺ）对脑电图的影响。方法：对３９例单独应用ＶＰＡ和３５例单独应用ＣＢＺ，临床发作已被控制的两组病例进行脑电图描记和分析。结果：ＶＰＡ治疗治疗组，７２％的病例发作间歇期痫样放电消失或明显减少，而ＣＢＺ治疗后，仅４９％消失或明显减少。结论：ＣＢＺ可使临床发作控制，但却有２０％的病例痫放电增加，但在ＶＰＡ治疗者则未见此现象。ＶＰＡ对脑电背景活动影响不明显，而Ｃ     

丙戊酸钠负荷疗法治疗中风后癫痫的临床观察

脑中风后并发癫痫不仅能加重脑损伤，而且引起全身多系统病理异常，具有更大的危险性。为探求一种快速控制中风后癫痫的治疗办法，作者采用丙戊酸钠负荷疗法治疗中风后各型癫痫２４例。即于首次癫痫发作后立即给予负荷量１５ｍｇ／ｋｇ，维持量为负荷量的１／３，每８小时１次口服维持９次后改为２００ｍｇ，每日３次治疗。对照组首剂量及维持量均为负荷量的１／３，治疗方法同治疗组。两组治疗１个月，观察癫痫控制情况及药物副作用     

丙戊酸钠致多囊卵巢综合征1例报告

丙戊酸钠(VPA)致女性癫疒间患者发生多囊卵巢综合征(PCOS)临床少见,现报告1例如下。1病例女,24岁。因发作性意识障碍22年于2003年12月10日来我院就诊。患者出生2个月时有高热惊厥,2岁后出现数次发作性意识丧失,数秒钟自行缓解;当时头颅CT检查正常,脑电图(EEG)检查结果不详,诊断     

卡马西平联合丙戊酸钠治疗早期癫痫的效果观察

目的观察卡马西平联合丙戊酸钠治疗早期癫痫的临床效果。方法选取我院神经内科2010-01—2012-06收治的早期癫痫患者90例,随机分成3组,每组30例,分别采取卡马西平单药治疗,丙戊酸钠单药治疗以及卡马西平联合丙戊酸钠治疗;对所有患者在治疗开始后随访半年,比较3组有效率及不良反应。结果卡马西平组总有效率66.67%,丙戊酸钠组60.67%,联合用药组93.33%,联合用药组较其他2组整体有效率均明显增高(P0.05)。3组并发症发生率比较差异无统计学意义(P0.05)。结论与单药卡马西平或者丙戊酸钠用药治疗相比,卡马西平联合丙戊酸钠治疗癫痫具有很好的效果,且不良反应发生率与单药治疗无明显差别,可作为癫痫临床治疗的常规方案。     

癫痫病人丙戊酸钠血浓度监测及其临床应用

本文报告丙戊酸钠治疗各型癫痫122例,丙戊酸钠治疗各型癫痫的有效率为83％。多数患者的有效血浓度范围为30～120μg/ml,有效剂量为10～60mg/kg·d,对癫痫患者,应据其临床发作情况,有无药物不良反应,参考丙戊酸钠血浓度调整剂量。     

Endocrine effects of valproate in adolescent girls with epilepsy

Summary:  Purpose: To investigate the effect of epilepsy and/or valproate (VPA) monotherapy on physical growth, weight gain, pubertal development, and hormonal status in adolescent girls with epilepsy.
Methods: The study group included 88 consecutive female patients with epilepsy aged 6–20 years (28 premenarche, 60 postmenarche) attending an endocrinology institute of a major tertiary center. Forty-five patients were under treatment with VPA, and 43 were before treatment initiation. The groups were compared for the relevant biochemical, anthropometric, ultrasonographic, and endocrine parameters.
Results: No statistically significant differences were found in any of the parameters studied between the groups, as a whole or by menarche status. The treated postmenarcheal subgroup had a higher mean testosterone level than the untreated postmenarcheal controls (1.83 ± 0.65 vs. 0.88 ± 0.24, p = 0.006). Body mass index–standard deviation score (BMI-SDS) was 0.75 in the treated group and 0.63 in the untreated group; rates of obesity were 16.3% and 15.5%, respectively. No between-group differences were found in menses irregularities, hirsutism, or acne. No correlation was found between duration or dosage of treatment and BMI-SDS, height–SDS, or androgen level. The treated group had higher levels of thyroid-stimulating hormone and lower levels of free thyroxine than did the untreated group, although still within normal range.
Conclusions: Long-term treatment with VPA in girls with epilepsy is associated with increased testosterone levels after menarche, without clinical hyperandrogenism, polycystic ovary syndrome, or an increase in BMI-SDS. VPA is a good treatment option in this age group but should be accompanied by careful endocrine observation.     

Successful initiation of combined therapy with valproate sodium injection and divalproex sodium extended-release tablets in the epilepsy monitoring unit

Summary: Purpose: Patients in epilepsy monitoring units (EMUs) often require aggressive initiation or reinitiation of therapy before discharge. We developed a simple dosing scheme using valproate sodium injection (VPA‐IV) and divalproex sodium extended‐release (VPA‐ER) tablets to minimize the time required for initiation of therapy, without increasing the likelihood of seizures and adverse effects. Methods: We identified 42 patients in the EMU, naïve to VPA‐IV and VPA‐ER, for whom one of the discharge AEDs included divalproex sodium. On the day of discharge, patients were loaded with 20 mg/kg VPA‐IV at 6 mg/kg/min, followed by ～20 mg/kg VPA‐ER within 1 h. The discharge daily dose of VPA‐ER was identical to the dose given after the IV load. We assessed tolerability and seizure occurrence during infusion, at 1 h, 4 h, and 1 week after discharge. Results: All patients tolerated the VPA‐IV dose followed by VPA‐ER. Four patients reported mild nausea, and two patients reported mild dizziness within 4 h. No seizures or significant changes in heart rate or blood pressure occurred within 4 h, and all patients were discharged the same day. All patients denied systemic complaints at 1 week, and five had seizures during the week after discharge. All patients had improved seizure frequencies at the end of the first week. Conclusions: VPA‐IV is well tolerated and convenient for rapid loading in the EMU. When promptly followed by VPA‐ER, seizure control remains excellent.     

Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: A prospective randomized study

Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia and hyperandrogenism in women. Few prospective data are available. We evaluated the reproductive endocrine and insulin-related metabolic parameters in men and women with untreated epilepsy randomized to valproate (n = 44) or lamotrigine (n = 37) monotherapy for 12 months. On treatment, there was no significant difference in fasting serum insulin concentrations between the two groups. In women (n = 40), there was no significant difference between the two groups in change from baseline in serum total testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, or follicle-stimulating hormone. In men (n = 41), follicle-stimulating hormone concentration significantly decreased in patients taking valproate compared with those on lamotrigine as early as 3 months after treatment. Greater attention should be paid to investigate the potential impact of valproate on reproductive function in men.     

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。     

小剂量拉莫三嗪与丙戊酸合用治疗成人癫痫临床观察

目的 研究小剂量拉莫三嗪与丙戊酸合用治疗成年人各种类型癫痫的有效件和安全性.方法 对100例成年癫痫患者采用逐步增量的方法给予拉莫三嗪至每目100 mg,加约期4周,并继续服用原剂量的丙戊酸治疗,连续观察6月,记录患者发作的情况及不良反应.结果 小剂量拉其三嗪与丙戊酸合用总有效率为77.2%,完全控制50.O%,各种类型发作之间疗效比较差异无显著性(χ2=1.37,P>0.05);各型癫痫在人组4～6个月后较入组前3个月发作频率均减少,差异有显著性(P<0.05).不良反应发生率23.7%,与入组前后小良反应发牛率相比无显著变化(χ2=0.21,P>0.05).结论 小剂量托莫二三嗪与丙戊酸合用治疗成年人各种类犁癫痫均取得良好疗效,不良反应无增加.     

Effect of sodium valproate on mania

Summary A possible antimanic property of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind placebo-controlled ABA design in 5 acutely ill manic patients. In 4 cases a marked improvement was observed after valproate medication whereas one patient showed no response. Seven further patients with frequently recurrent episodes of a manic or maniform schizoaffective psychosis, irresponsive to lithium prophylaxis, were chronically treated with valproate in combination with low doses of lithium (one case only with valproate). Over an observation period of 1 1/2–3 years none of the patients exhibited a relapse. It is proposed that, in general, GABA-ergic anticonvulsants possess antimanic properties and that the specific antimanic effect of lithium is due to a GABA-ergic mode of action. The possible role of GABA-systems in affective disorders and in organic types of psychoses (e.g., porphyria-psychosis, delirium tremens) is discussed on the basis of pharmacopsychiatric considerations.Supported by the Heisenberg-grant of the Deutsche Forschungsgemeinschaft     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

养血清脑颗粒和丙戊酸联用对戊四氮点燃癫痫大鼠的影响

目的 探讨养血清脑颗粒(YXQNG)联用丙戊酸(VPA)对戊四氮(PTZ)慢性点燃模型大鼠癫痫发作、EEG、认知功能及颞叶、海马T型Ca2+通道蛋白(Cav3.2)表达的影响. 方法 成年雄性SD大鼠40只按随机数字表法分为PTZ组、VPA组、VPA+YXQNG组、NS组,每组10只.前3组大鼠腹腔注射PTZ溶液制作慢性点燃模型,VPA组大鼠在注射PTZ前1 h给予VPA灌胃;VPA+YXQNG组除给予VPA外,注射PTZ前1.5 h给予YXQNG灌胃;NS组腹腔注射生理盐水,每天一次.8周后观察各组大鼠的行为学变化、Y型电迷宫检查大鼠的正确反应率、捕记EEG并应用免疫组化染色检测颞叶和海马Cav3.2的表达. 结果 给药8周后PTZ组大鼠全部达到完全点燃(连续3 d出现Ⅳ级发作或达到Ⅴ级发作),VPA组和VPA+YXQNG组大鼠仅出现0～Ⅱ级发作;Y型电迷宫检查结果显示VPA+YXQNG组大鼠正确反应率高于PTZ组,差异有统计学意义(P＜0.05);EEG结果显示PTZ组大鼠癫痫发作时EEG有明显异常放电,总功率高于用药前,差异有统计学意义(P＜0.05).VPA组、VPA+YXQNG组大鼠用药前后EEG总功率的差值均高于PTZ组,差异有统计学意义(P＜0.05);免疫组化染色结果显示VPA组、VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于PTZ组,VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于VPA组,差异均有统计学意义(P＜0.05). 结论 YXQNG和VPA联用能降低癫痫大鼠发作级别、改善认知功能、减少脑部异常放电并降低脑组织Cav3.2水平,有抗癫痫和脑保护作用.

Abstract：

Objective To explore the effet of Yangxue Qingnao granule (YXQNG) on seizures and cognition function of pentylenetetrazole (PTZ)-kindled chronic epileptic rats models, expression of Cav3.2 in the hippocampus and the temporal lobe of these rats, and EEG features of the rats. Methods Forty healthy adult male SD rats were equally divided into 4 groups at random: PTZ group, VPA treatment group, VPA+YXQNG treatment group, normal saline (NS)-control group (n=10). PTZ solution was intraperitoneally injected for 8 weeks to induce the kindling model in the above 3 groups except the NS-control group. VPA by intragastric administration was given to the rats in the VPA treatment group 1 h before PTZ injection; YXQNG and VPA by intragastric administration were given to the rats in the VPA+YXQNG treatment group 1.5 h before PTZ injection. Behavioral changes of the rats were observed 8 weeks after PTZ injection; accuracy rate of response of the rats were examined by electric maze test;EEG was performed; and the expression ofT-type Ca2+ channel protein (Cav3.2) in the temporal lobe and hippocampus was detected by immunohistochemical staining. Results Rats in the PTZ group appeared grade Ⅳ or Ⅴ seizures for 3 consecutive d, and rats in the VPA treatment group, VPA+YXQNG treatment group appeared grade 0-Ⅱ seizures. The accuracy rate of response of the rats in the VPA+YXQNG treatment group was significantly higher than that in the PTZ group (P＜0.05). EEG indicated that paradoxical discharge was noted in rats of PTZ group when seizures appeared, and the total power at the time was obviously higher than that before PTZ injection (P＜0.05). The D-value of total power of EEG in rats of the VPA treatment group and VPA+YXQNG treatment group before and after treatment was significantly higher than that in the PTZ group (P＜0.05). And the level of Cav3.2 in the temporal and hippocampus in rats of the VPA treatment group and VPA+YXQNG treatment group was significantly lower than that in the PTZ group (P＜0.05); as compared with that in the VPA treatment group, the expression of Cav3.2 in the temporal and hippocampus in rats of the VPA+YXQNG treatment group was significantly reduced (P＜0.05). Conclusion The combination use of YXQNG and VPA can decrease the seizure stage, the paradoxical discharge of the brain and the level of Cav3.2 in brain tissue,and improve the cognitive function of the PTZ-kindled rats, indicating that using VAP and YXQNG simultaneously can treat epileptic seizure and protect the neurons.     

发育期大鼠内侧颞叶癫痫模型丙戊酸治疗前后的蛋白质组学研究

目的 研究丙戊酸(VPA)对发育期大鼠内侧颞叶癫痫(MTLE)模型海马蛋白质表达谱的影响,寻求与VPA抗癫痫作用相关的蛋白质以及探讨VPA在MTLE发病早期发挥抗癫痫作用的机制.方法 建立氯化锂-匹罗卡品诱导的发育期大鼠MTLE模型,采用二维凝胶电泳(2-DE)技术分离海马总蛋白,PDQuest软件识别差异表达蛋白质,基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)进行鉴定.结果 建立了VPA治疗前后的MTLE模型大鼠海马蛋白质的2-DE图谱.质谱鉴定出9个差异表达的蛋白质,其中4个在VPA治疗后表达上调;5个下调.结论 本实验成功建立了发育期大鼠MTLE模型VPA处理前后的海马蛋白质2-DE图谱;β-synuclein、Neurogranin等差异表达蛋白可能与VPA在MTLE发病早期发挥抗癫痫作用的机制相关.