丙戊酸钠治疗对血清瘦素、体重指数的影响

目的服用丙戊酸钠(VPA)抗癫痫治疗的患者,15%～70%的成人可发生体重增加[1-2],而瘦素在体重和能量平衡的调节中起重要影响,近年来许多研究表明VPA引起的体重改变可能与瘦素有关。探讨丙戊酸钠抗癫痫治疗对血清瘦素的影响,该影响与患者体重改变的相关性,以及瘦素的可能机制。方法以丙戊酸钠治疗超过3个月的33例癫痫患者为治疗组,20例未经丙戊酸钠治疗癫痫患者作为对照组来比较,检测患者体重、身高、血清瘦素水平,比较两组的体重指数(BMI)、血清瘦素水平。结果丙戊酸钠治疗组的血清瘦素(8.8503±4.7924)ug/ml与对照组(2.8490±1.3962)ug/ml比较有增高,治疗组BMI(23.7202±2.5182)高于对照组(20.8468±1.6815)。结论丙戊酸钠治疗可能引起血清瘦素、体重指数增高,很可能通过诱导导致瘦素抵抗的机制之一,从而导致患者体重增加。     

丙戊酸钠合并氯丙嗪治疗精神分裂症的对照研究

目的观察丙戊酸钠合用氯丙嗪治疗精神分裂症的疗效与不良反应。方法符合CCMD-3诊断标准的精神分裂症住院患者,丙戊酸钠合用氯丙嗪组(研究组)35例,单用氯丙嗪组(对照组)31例。以PANSS、CGI、TESS量表评定观察12周。结果研究组总体疗效自第2周起明显优于对照组(P<0.05),其中研究组兴奋症状分及攻击因子分自第4周起缓解明显优于对照组(P<0.05)。研究组较对照组副反应较少且程度较轻(P<0.05)。结论丙戊酸钠合并氯丙嗪治疗精神分裂症疗效肯定,安全性与耐受性较好。     

Juvenile Myoclonic Epilepsy: Factors of Error Involved in the Diagnosis and Treatment

Juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, has a distinct clinical and electroencephalographic profile. Often JME is not recognized, with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis even in an epilepsy clinic. Of 70 JME patients, 66 (91.4%) were not diagnosed on referral and 22 (33%) were not initially recognized in the epilepsy clinic. The correct diagnosis was established after a mean of 8.3 +/- 5.5 years from disease onset and an interval of 17.7 +/- 10.4 months from first evaluation in the epilepsy clinic. Myoclonic jerks, the hallmark of the disease, were not usually reported by patients. Similarly, relevant questioning may not be included in the history. Absence seizures antedating jerks by many years, myoclonic jerks reported as unilateral, generalized tonic-clonic seizures occurring during sleep and focal EEG abnormalities are other factors contributing to not recognizing JME. Our study reemphasizes the need to have not only a correct seizure diagnosis but also a correct epilepsy-disease diagnosis.     

丙戊酸钠治疗对血清胰岛素、体重指数的影响

目的探讨丙戊酸钠抗癫痫治疗对血清胰岛素、体重指数的影响,血清胰岛素的改变与患者的体重指数的改变的相关性,以及胰岛素抵抗的可能机制。方法以丙戊酸钠治疗超过3个月的25例癫痫患者为治疗组,15例未经丙戊酸钠治疗癫痫患者作为对照组来比较,检测患者体重、身高、血糖、胰岛素水平,比较两组的体重指数(BMI)、稳态模式评估指数(HOMA)和胰岛素水平。结果丙戊酸钠治疗组的HOMA指数(1．6811±0．6492)与对照组(1．1053±0．6129)比较有增高,治疗组BMI(23．634±2．5304)高于对照组(21．8573±2．2458),治疗组血清胰岛素(7．2080±2．5521)MU/L高于对照组(4．5413±1．1767)MU/L。结论丙戊酸钠治疗可能引起血清胰岛素增高并通过诱导导致胰岛素抵抗,从而导致患者体重增加。     

Rearrangement of Valproate Glucuronide in a Patient with Drug-Associated Hepatobiliary and Renal Dysfunction

Formation of beta-glucuronidase-resistant "glucuronides" of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to beta-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such beta-glucuronidase-resistant conjugated VPA in vivo are largely unknown.     

Discontinuation of Phenytoin, Carbamazepine, and Valproate in Patients with Active Epilepsy

The effects of discontinuing individual antiepileptic drugs (AEDs) in patients with active epilepsy who are receiving combination therapy have not been studied systematically. We report a double-blind, prospective study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 70 patients with chronic active epilepsy. Each drug discontinuation was randomized to one of two relatively fast rates of reduction, and a control group of 25 patients continued with stable therapy. Patients who had CBZ removed had a significant increase in seizures that was maintained for 4 weeks after the end of drug reduction, and 10 of these 23 patients had to restart therapy with CBZ. There was no significant change in seizure numbers in the other groups. Two patients discontinued from VPA had to restart the drug; none had to restart PHT. The optimal rates of reduction of CBZ remain uncertain. There was no evidence for a clinically or temporally distinct burst of "discontinuation seizures" in any group. Any marked increase in seizures always resolved on reintroduction of the discontinued drug.     

Effects of chronic treatment with valproate on serotonin-1A receptor binding and function

Valproate is effective in treating bipolar disorder characterized by rapid cycling or acute mania, although the mechanism of action is unclear. In contrast to other treatments for depression, 21 days of treatment in rats with valproate (100, 200 or 400 mg/kg) did not significantly alter the hypothermia induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors. Treatment with valproate also had no effect on radioligand binding to serotonin-1A, serotonin-2 or -adrenergic receptors. Based on these animal studies in frontal cortex and hippocampus, the therapeutic benefit of valproate in mood disorders does not appear to involve adaptive changes in serotonin-1A, serotonin-2 or -adrenergic receptor number.     

Plasma concentrations of valproate during maintenance therapy in epileptic children

Summary A total of 20 children with various types of epilepsy were treated with valproate, 11 with monotherapy and 9 with valproate in combination with phenobarbitone, phenytoin, or carbamazepine. Valproate was given either every 8 or 12 h. At least two different dose levels were tried in each patient. The pharmacokinetics of valproate during the interval between doses was determined using a gas chromatographic technique. The clinical effect of the treatment was assessed by interviewing the parents.The plasma concentrations showed considerable fluctuation during the intervals between doses. The mean increase from pre-administration to peak level was 82% when the dose interval was 12 h, and 62% when it was 8 h. The mean plasma half-life of valproate, using a one-compartment model, was 10.9±1.3 h (mean±SD). The plasma half-life of valproate was decreased when the drug was combined with the other anti-epileptics. The calculated area under the concentration versus time curve was linearly related to dose, both in a single patient on four dose levels and when different patients were compared. The clinical effect of valproate monotherapy was best in patients with absences, usually good in myoclonus and less favourable in other types of epilepsy. For children with absences, the optimal dose range of valproate was between 20 and 40 mg/kg/24 h. In comparison, the myoclonic types of epilepsy needed a slightly higher dose level, between 30 and 60 mg/kg/24 h. In the latter group a therapeutic window seems to exist, since patients below and above the suggested dose levels were not well-controlled. Therapeutic monitoring of valproate does not appear meaningful when the drug is used as monotherapy. However, in combination therapy, determination of the plasma levels of all anti-convulsants used may be helpful. The large fluctuations of valproate during a dose interval must be taken into consideration when the clinical effects are analysed.Supported by the Swedish Medical Research Council (Project No. 522), Stiftelsen Margarethahemmet, and Sällskapet Barnavård     

拉莫三嗪治疗癫痫的剂量及血药浓度

目的:研究拉莫三嗪治疗癫痫的有效血药浓度、剂量与疗效三者之间关系以及和/或丙戊酸等其它抗癫痫药合用时的相互影响。方法:83例患者分为3组,即拉莫三嗪组、拉莫三嗪+丙戊酸组及拉莫三嗪+丙戊酸+其它抗癫痫药组。拉莫三嗪的起始剂量拉莫三嗪组为2mg/(kg·d),联合用药组为0.2mg/(kg·d),丙戊酸成人起始剂量为负荷量。结果:联合用药组中的部分病例拉莫三嗪剂量高于国外推荐剂量。当拉莫三嗪剂量在2～7mg/kg、血药浓度在1～6mg/L,丙戊酸的剂量在4～28.19mg/kg、血药浓度在37.46～113.79mg/L时,癫痫有效控制率在67.6％～86.4％之间。结论:国外推荐的拉莫三嗪有效血药浓度及与其它抗癫痫药合用时的剂量可能偏低。     

Treatment of refractory complex-partial status epilepticus with propofol: case report

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.