BACKGROUND & AIMS: PURPOSE:Sodium valproate (VPA) is a broad-spectrum anti-epileptic drug usually well tolerated. We conducted a pilot study to assess the feasibility, efficacy and side-effects of VPA in the treatment of convulsive epilepsy in primary care settings in rural China as an alternative to phenobarbital. METHODS:People with convulsive epilepsy were identified at primary health care level and provided with VPA monotherapy. Local trained physicians identified participants, managed treatment, and carried out the follow-up, whilst diagnoses were confirmed by a neurologist. Participants were followed for 12 months. Efficacy was assessed from the percentage reduction in seizure frequency and by retention of treatment. Tolerability was assessed by reports of treatment-emergent effects. RESULTS:Of 532 people enrolled, 512 completed the assessment. Most (431 people, 84%) had a decrease in seizure frequency of at least 50% and 218 became seizure-free. Treatment retention was 96% at one year. VPA was well tolerated and only 47 people reported adverse events which were mostly mild. Only two people discontinued VPA due to side-effects. CONCLUSION:In this 12-month assessment, VPA had favourable efficacy, few side effects and overall good acceptability. It was also relatively cheap. VPA is, therefore, a suitable alternative to phenobarbital as treatment of convulsive epilepsy in rural areas of China.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. METHODS:In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075. FINDINGS:Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. INTERPRETATION:Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. FUNDING:National Institute of Neurological Disorders and Stroke, National Institutes of Health.

背景与目标：

BACKGROUND & AIMS: :Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.

背景与目标： : 丙戊酸盐主要在躁郁症的躁狂方面有效。丙戊酸的耐受性比对照者更有利，常见的不利影响是胃肠道紊乱和体重增加。总胆固醇和低密度脂蛋白被丙戊酸盐降低。丙戊酸与锂或抗精神病药物合用有效且耐受性良好。丙戊酸盐在混合和喜快躁狂症中有效。在维持与安慰剂和活性比较者的研究中，与全样本分析相比，最初接受双丙戊酸钠治疗躁狂症的患者具有更强大的长期益处。在维持治疗中，丙戊酸盐血清水平在75至99 microg/ml之间的患者由于任何原因或新的情绪发作而停药的时间比接受安慰剂的患者更长。双相情感障碍的实用性主要是针对躁狂症状的核心特征 (例如，冲动，多动和易怒)，几乎没有证据表明对焦虑或精神病有益。丙戊酸盐似乎在其他具有行为维度的疾病中有用，包括在双相情感障碍 (例如精神分裂症) 中丙戊酸盐有益的领域。

BACKGROUND & AIMS: BACKGROUND:This is an updated version of the Cochrane Review previously published in 2019. Absence seizures (AS) are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with AS. OBJECTIVES:To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures (AS), when compared with placebo or each other. SEARCH METHODS:For the latest update we searched the Cochrane Register of Studies (CRS Web, 22 September 2020) and MEDLINE (Ovid, 1946 to September 21, 2020). CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively. SELECTION CRITERIA:Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with AS: ethosuximide, sodium valproate, lamotrigine, or placebo. DATA COLLECTION AND ANALYSIS:Outcome measures were: 1. proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; 2. individuals with a 50% or greater reduction in seizure frequency; 3. normalisation of EEG and/or negative hyperventilation test; and 4. adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). We used GRADE quality assessment criteria to evaluate the certainty of evidence for the outcomes derived from all included studies. MAIN RESULTS:On the basis of our selection criteria, we included no new studies in the present review. Eight small trials (total number of participants: 691) were included from the earlier review. Six of them were of poor methodological quality (unclear or high risk of bias) and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from randomised controlled trials (RCTs) to support a specific effect on AS for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, seizure freedom was higher in patients taking ethosuximide (70/154, 45%) than in patients taking lamotrigine (31/146, 21%; P < 0.001), with no difference between valproate (64/146, 44%) and ethosuximide (70/154, 45%; P > 0.05). In this study, the frequency of treatment failures due to intolerable adverse events was significantly different among the treatment groups, with the largest proportion of adverse events in the valproic acid group (48/146, 33%) compared to the ethosuximide (38/154, 25%) and the lamotrigine (29/146, 20%) groups (P < 0.037). Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. This study provided high certainty of the evidence for outcomes for which data were available. However, the certainty of the evidence provided by the other included studies was low, primarily due to risk of bias and imprecise results because of the small sample sizes. Hence, conclusions regarding the efficacy of ethosuximide, valproic acid and lamotrigine derive mostly from this single study. AUTHORS' CONCLUSIONS:Since the last version of this review was published, we have found no new studies. Hence, the conclusions remain the same as the previous update. With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with AS. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.

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BACKGROUND & AIMS: :Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.

背景与目标： : 46例难治性癫痫患儿 (12例症状性全身性癫痫，14例症状性部分性癫痫，20例未确定癫痫) 接受大剂量 (血清水平高于100微克/毫升) 丙戊酸钠 (VPA) 治疗。单药治疗34例，两种药物12例。血清VPA浓度范围为105.1至198.4微克/毫升。在血清水平达到适当水平后，对治疗的初始反应的评估显示，46例患者中有15例 (32.6% 例) 的癫痫发作得到完全控制，而12例 (26.1% 例) (50% 例或以上) 的癫痫发作得到改善。初始反应时间后超过6个月的随访显示14例 (30.4%) 癫痫发作得到控制，11例 (23.9%) 改善。对EEG的最初影响是46例患者中有3例 (6.5% 例) 癫痫放电消失，而15例 (32.6% 例) 明显改善。随访显示7例 (15.2% 例) 癫痫放电消失，9例 (19.6% 例) 明显改善。大剂量VPA治疗对West综合征和慢波睡眠期间持续尖峰波的癫痫特别有效。非典型缺勤和肌阵挛发作的控制相对较好。有时会遇到低纤维蛋白原血症和血小板减少症，但随着剂量的减少，这些副作用是可逆的。

BACKGROUND & AIMS: -2

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BACKGROUND & AIMS: Previous work in this laboratory has suggested that the nonlinear disposition of valproic acid (VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1-2 mmol/L) was incubated with isolated rat hepatocytes in vitro. Uptake of [(3)H]-VPA was linear from 10 to 50 seconds, with minimal (<7 percent) biotransformation. The initial velocity of VPA uptake varied in proportion with the extracellular concentration and was temperature independent, suggesting that VPA traverses the hepatocyte membrane predominantly by passive diffusion. In separate studies, the hepatobiliary disposition of VPA (20mg) was examined in the isolated perfused rat liver (IPL). A pharmacokinetic model was developed to describe the influence of phenobarbital on the hepatobiliary disposition of VPA and valproate glucuronide (V-G) in the IPL; all processes governing VPA and V-G disposition appeared to be linear. Acute administration of phenobarbital to the liver (1.12 mg) decreased the rate constant for canalicular egress of V-G (0.0489 +/- 0.0266 vs. 0.164 +/- 0.075 min(-1)). In vivo pretreatment with phenobarbital (75 mg/kg/d x 5 d) before liver isolation decreased the biliary excretion of both VPA (1.06E-04 +/- 0.27E-04 vs. 2.76E-04 +/- 0.45E-04 min(-1)) and V-G (5.63E- 03 +/- 1.98E-03 vs. 1.74E-02 +/- 0.5E-02 min(-1)), and increased the apparent volume of distribution of VPA (84.6 +/- 2.2 vs. 72.3 +/- 2.1 mL). In vivo phenobarbital pretreatment a changed V-G excretion from a formation to an elimination rate-limited process. These results are consistent with phenobarbital-associated impairment of canalicular egress of some organic anions. This work further supports the utility of pharmacokinetic modeling in(1) determining the rate-limiting steps in hepatobiliary drug disposition and (2) identifying sites of drug interactions within the hepatobiliary system that may not be evident based on conventional mass-balance analysis.

背景与目标： 该实验室先前的工作表明，丙戊酸 (VPA) 在大鼠中的非线性分布可能是由于VPA在肝脏中的非线性分布所致。本研究旨在进一步阐明VPA的肝胆分布。将VPA (0.1-2 mmol/L) 与分离的大鼠肝细胞体外孵育。[(3)H]-VPA的摄取在10至50秒之间是线性的，具有最小 (<7%) 的生物转化。VPA摄取的初始速度与细胞外浓度成比例变化，并且与温度无关，这表明VPA主要通过被动扩散穿过肝细胞膜。在单独的研究中，在分离的灌注大鼠肝脏 (IPL) 中检查了VPA (20mg) 的肝胆分布。建立了药代动力学模型来描述苯巴比妥对IPL中VPA和丙戊酸葡糖醛酸苷 (v-g) 的肝胆分布的影响; 控制VPA和v-g处置的所有过程似乎都是线性的。向肝脏急性施用苯巴比妥 (1.12 mg) 降低了V-G小管流出的速率常数 (0.0489/- 0.0266 vs. 0.164/- 0.075分钟 (-1))。肝隔离前用苯巴比妥 (75 mg/kg/d x 5 d) 进行体内预处理可降低VPA的胆汁排泄 (1.06E-04/-0.27e-04与2.76e-04/-0.45e-04 min(-1)) 和V-G (5.63E- 03 +/-1.98e-03对1.74e-02 +/-0.5e-02 min(-1))，并增加VPA的表观分布体积 (84.6 +/- 2.2对72.3 +/- 2.1 mL)。体内苯巴比妥预处理将v-g排泄从形成改变为消除速率受限的过程。这些结果与苯巴比妥相关的某些有机阴离子的小管出口受损是一致的。这项工作进一步支持药代动力学模型在以下方面的实用性 :( 1) 确定肝胆药物处置中的限速步骤，以及 (2) 根据常规的质量平衡分析确定肝胆系统内药物相互作用的位点。

BACKGROUND & AIMS: OBJECTIVES:To review signs and symptoms of valproate-induced hyperammonaemic encephalopathy without hepatotoxicity in the psychiatric setting, explore its mechanisms, and give recommendations for prevention and treatment. METHODS:Medline search with keywords valproate, ammonia, hyperammonaemia, encephalopathy, and then cross-references to articles obtained through this search. Only cases with indication of valproate for psychiatric condition were included. RESULTS:Fourteen cases published in the psychiatric setting are reviewed. Valproate-induced hyperammonaemic encephalopathy is a rare adverse event, occurring almost equally in men and women, with a large age range, and reported in two patients with mental retardation. Symptoms appeared either a few days after initiation of valproate therapy, or after several months or years. The main symptoms were fluctuations in consciousness and disorientation. Clinical severity was not related to blood ammonia levels. All patients recovered after valproate-induced hyperammonaemic encephalopathy diagnosis and treatment, usually involving discontinuation of valproate. CONCLUSIONS:Valproate-induced hyperammonaemic encephalopathy is rare and usually reversible in patients without urea cycle disorders when valproate is discontinued. Therapy with carnitine is recommended. Special caution should be used in patients with mental retardation. Psychiatrists should suspect valproate-induced hyperammonaemic encephalopathy when consciousness deteriorates.

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BACKGROUND & AIMS: WHAT IS KNOWN AND OBJECTIVE:Hydralazine is an inhibitor of DNA methyltransferases, whereas valproate interferes with histone deacetylation. In combination, they show a marked synergism in reducing tumour growth as well as development of metastasis and inducing cell differentiation. Hydralazine is metabolized by the highly polymorphic N-acetyltransferase 2. The current pilot study was performed to analyse the pharmacokinetic parameters of a single dose of hydralazine in 24 h (one tablet with 83 mg for slow acetylators and one tablet with 182 mg for fast acetylators) and three fixed doses of valproate (one tablet of controlled liberation with 700 mg every 8 h) in healthy genetically selected volunteers. Selection was performed based on their NAT2 activity as deduced from their genotype. METHODS:An open label non-randomized single arm study was conducted in two groups of six healthy volunteers of both genders aged 20-45 years with a body mass index 22·2-26·9 which were classified as fast or slow acetylators after genotyping 3 SNPs that cover 99·9% of the NAT2 variants in the Mexican population. Blood samples were collected predose and serially post-dose in an interval of 48 h. Hydralazine and valproate concentrations were determined by ultra-high performance liquid chromatography (UPLC) coupled to tandem mass spectroscopy (MS/MS). RESULTS AND DISCUSSION:The AUC0-48 h and Cmax of hydralazine were almost identical (1410 ± 560 vs. 1446 ± 509 ng h/mL and 93·4 ± 16·7 vs. 112·5 ± 42·1 ng/mL) in both groups with NAT2 genotype-adjusted doses, whereas the multidose parameters of valproate were not significantly affected neither by the selection of the NAT2 genotype (AUC0-48 h 2064 ± 455 vs. 1896 ± 185 μg h/mL; Cmax 96·4 ± 21·1 vs. 88·8 ± 7·2 μg/mL, for the fast and slow acetylators, respectively) nor the co-administration of 83 or 182 mg of hydralazine. WHAT IS NEW AND CONCLUSION:Comparable hydralazine exposures (differences in AUC0-inf of only 7%) were observed in this study with genetic selection of volunteers and concomitant dose adjustment. However, the conclusions have yet to be confirmed with a full-powered 2 × 2 crossover study.

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BACKGROUND & AIMS: BACKGROUND:Previous studies have shown a high prevalence of aggressive behavior in abstinent heroin users who are on methadone maintenance therapy (MMT) compared with healthy controls. Some studies suggest that olanzapine and valproate may be effective in managing aggressive behavior and preventing a relapse of substance misuse in patients on methadone regime. AIM:The aim of the present study was to evaluate and compare the effectiveness of these medications in the management of aggressive behavior and prevention of relapse in patients maintained on methadone. PATIENTS AND METHODS:Two hundred and one patients on MMT were randomized into two treatment groups of olanzapine (2.5-15 mg) and sodium valproate (600-1000 mg). Both groups were treated for 12 weeks. Patients visited the clinic twice weekly to receive medication. Patients' urine samples were screened for trace of any illicit substances on each visit. Upon each consultation, the clinicians, using overt aggression scale-modified version (OAS-M), assessed the degree and frequency of aggressiveness in each patient. RESULTS:Fifty three patients completed the trial. Both medications significantly reduced the overt aggression and subscales of irritability, aggression and suicidality. Improvement was more pronounced in the group treated with olanzapine. The mean percentages of positive urine samples for morphine, cannabis and methamphetamine abuse for the 12 weeks period of the study were not significantly different between the two groups. CONCLUSIONS:Both olanzapine and sodium valproate are useful as an adjunctive agent in reducing aggressive behavior in heroin dependent individuals who are on MMT, but the beneficial effect of olanzapine was greater than sodium valproate in this respect.  

背景与目标：

BACKGROUND & AIMS: :Valproic acid (VPA) has been reported as inhibitor of histone deacetylases (HDACs). Several reports indicated that HDACs play a crucial role in the pathogenesis of fibrosis and hepatic stellate cell (HSC) activation. The present study was aimed to evaluate the anti-fibrotic effect of VPA against thioacetamide (TAA)-induced hepatic fibrosis and activation of the HSC in rat. VPA and TAA were administrated intraperitoneally at the dose of 400 and 200 mg/kg each at 2 days interval, respectively for a period of 6 weeks. Administration of TAA significantly increased the absolute and relative liver weight, aspartate aminotransferase and alanine aminotransferase levels, which were significantly decreased by VPA treatment as compared to TAA control. VPA treatment prevents the TAA-induced activation of HSC and decreases collagen deposition and infiltration of inflammatory cells as revealed by Sirius red and H&E staining. Interestingly, VPA co-treatment led to significantly increase the DNA damage and apoptosis in the activated HSC as compared to TAA control. Further, TAA decreased the expression of matrix metalloproteinase-2 (MMP-2), while VPA co-treatment significantly increased the expression of MMP-2 as compared to respective control. The present study clearly demonstrated that VPA treatment significantly alleviates TAA-induced activation of HSC and subsequent hepatic fibrosis.

背景与目标： TCP connection reset by peer

BACKGROUND & AIMS: :Two epileptic patients treated with anticonvulsants of valproic acid, phenobarbital, nitrazepam, and diphenylhydantoin developed anorexia, convulsions, and unconsciousness. The liver biopsy samples showed degenerated hepatocytes containing enlarged mitochondria with a distorted matrix. The matrix granules in the mitochondria were enlarged in size as compared with those of chronic hepatitis (Po = 0.0009). X-ray microanalysis has revealed the presence of calcium in large mitochondrial matrix granules. Both patients were thought to have valproic acid intoxication because they recovered quickly after the withdrawal of valproic acid.

背景与目标： : 两名接受丙戊酸，苯巴比妥，硝西泮和二苯乙内酰脲抗惊厥药治疗的癫痫患者出现厌食，抽搐和意识丧失。肝活检样本显示退化的肝细胞，其中线粒体扩大，基质扭曲。与慢性肝炎相比，线粒体中的基质颗粒尺寸增大 (Po = 0.0009)。X射线显微分析显示，大线粒体基质颗粒中存在钙。两名患者都被认为患有丙戊酸中毒，因为他们在停用丙戊酸后迅速康复。

BACKGROUND & AIMS: OBJECTIVE:To compare the efficacy of phenytoin, valproate, and levetiracetam in the management of pediatric convulsive status epilepticus. DESIGN:Randomized double-blind controlled clinical trial. SETTING:Pediatric critical care division in a tertiary care institute from June, 2016 to December, 2018. PARTICIPANTS:110 children aged three month to 12 year with convulsive status epilepticus. INTERVENTION:Patients not responding to 0.1 mg/kg intravenous lorazepam were randomly assigned (1:1:1) to receive 20 mg/kg of phenytoin (n=35) or valproate (n=35) or levetiracetam (n=32) over 20 minutes. Patients with nonconvulsive status epilepticus, recent hemorrhage, platelet count less than 50,000 or International normalized ratio (INR) more than 2, head injury or neurosurgery in the past one-month, liver or kidney disease, suspected or known neurometabolic or mitochondrial disorders or structural malformations, and allergy to study drugs; and those who were already on any one of the study drugs for more than one month or had received one of the study drugs for current episode, were excluded. OUTCOME MEASURE:The primary outcome was the proportion of patients that achieved control of convulsive status epilepticus at the end of 15 minutes after completion of the study drug infusion. Secondary outcomes were time to control of seizure, rate of adverse events, and the requirement of additional drugs to control seizure, length of ventilation, hospital stay, and functional status after three months (Glasgow Outcome Scale). RESULTS:The study was stopped after the planned mid-interim analysis for futility. Intention to treat analysis was done. There was no difference in primary outcome in phenytoin (31/35, 89%), valproate (29/35, 83%), and levetiracetam (30/32, 94%) (P=0.38) groups. There were no differences between the groups for secondary outcomes. One patient in the phenytoin group had a fluid-responsive shock, and one patient in the valproate group died due to encephalopathy and refractory shock. CONCLUSIONS:Phenytoin, valproate, and levetiracetam were equally effective in controlling pediatric convulsive status epilepticus.

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BACKGROUND & AIMS: PURPOSE:To compare the incidence and magnitude of weight gain associated with valproic acid (VPA) monotherapy in male and female epilepsy patients and to determine possible gender-specific differences in frequency of carbohydrate craving, body-composition, glucose homeostasis and lipid metabolism. METHODS:Epilepsy patients on VPA monotherapy were consecutively recruited at the outpatient clinic of the Department of Neurology, Innsbruck Medical University. Weight gain during VPA-therapy, frequency of carbohydrate craving and physical exercise, sociopsychological problems and family history for diabetes were obtained from all patients. Clinical data also comprised body-impedance analysis, body mass index and waist-to-hip ratio. Morning fasting blood samples were drawn to determine serum leptin, glucose and lipid concentrations, as well as insulin, C-reactive protein and TNF-alpha. RESULTS:One hundred and six patients (55 women) were enrolled in the study. Significant weight gain was seen during VPA-therapy in both genders (each p<0.001) with women experiencing increment of weight more frequently and more pronounced than did men. Analyses of patients who gained weight during VPA-therapy revealed significantly higher serum leptin concentrations in women than in men (p<0.001). Women also revealed significantly higher high-density lipoprotein-cholesterol and lower triglyceride concentrations than men (p=0.004 and 0.014, respectively). Frequency of carbohydrate craving was 25.8% in women and 14.3% in men. More women tried to lose or control weight through diet than did men (22.6% versus 7.1%). Moreover, weight gain as a sociopsychological problem was more numorous in women than in men. CONCLUSION:Women are more prone to gain weight during VPA therapy though higher frequency of diet and sociopsychological burden than men, which might possibly be related to leptin-resitance and a higher frequency of carbohydrate craving.

背景与目标：

BACKGROUND & AIMS: Thirty-eight patients (median age 77 years; range 62-88 years) with elderly-onset seizures were entered into a single-blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects.

背景与目标： 38例老年发作癫痫患者 (中位年龄77岁; 范围62-88岁) 进入了一项单盲，随机研究，旨在比较苯妥英 (PHT) 和丙戊酸钠 (VPA) 对认知功能的影响。分层最小化程序在年龄，性别和癫痫发作类型方面与两组匹配。在治疗前 (以最大程度地减少实践效果)，6周和 (对于仍在研究中的患者) 在3个月，6个月和1岁时对注意力，注意力，精神运动速度和记忆力进行了两次评估。大量的心理测试。认知功能的变化很小，有些趋于改善。与预期相反，PHT和VPA对认知功能的影响几乎没有差异。报告了频繁的非认知不良反应。因此，我们没有复制以前文献的发现。我们得出的结论是，我们试验中使用的抗癫痫药物 (AED) 单药治疗不会产生明显的不良认知作用。因此，考虑到其他不利影响，老年人对AED的选择可能会受到更大的影响。