Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells

Purpose:   To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells.
Methods:   Fifty-six female prepubertal Wistar rats (21–24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques.
Results:   In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 ± 1.32 in controls, and significantly increased to 29.60 ± 1.58, 34.20 ± 2.53, and 54.80 ± 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group.
Conclusion:   VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.     

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。     

奥卡西平治疗儿童部分性发作的临床疗效及安全性观察

目的观察及评价奥卡西平（OXC）对儿童部分性发作的临床疗效和安全性。方法2006年3月-2007年5月经门诊诊断的PS／CPS或sGTCS儿童患者81例，其中27例采用奥卡西平添加治疗，54例单药治疗，经4～6周加量期和12周稳定期观察后进行评价。结果OXC添加治疗组及单药治疗组总有效率分别为81．5％和83．3％，完全控制率分别为37．0％和40．7％，且不良反应较轻，耐受性良好。结论奥卡西平治疗儿童部分性发作有效且安全，可用于儿童部分性发作的单药治疗和添加治疗。     

奥卡西平治疗癫(癎)的临床研究

目的观察奥卡西平(OXC)治疗癫癎的疗效、耐受性和安全性。方法294例患者,120例加用OXC治疗,174例单用OXC治疗。通过逐步加量的方法达到目标剂量。结果本组总有效率为86.05%,完全控制为39.8%;其中单药治疗组控制率45.98%,总有效率为89.08%,添加治疗组控制率为30.83%,总有效率为81.67%。单药治疗组不良反应总发生率为15.52%,添加组不良反应发生率为26.67%,2组比较,添加治疗组出现的反应相对多于单药治疗组。结论奥卡西平治疗癫癎有效、安全、稳定。     

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures

OBJECTIVE: To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures. METHODS: A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence. RESULTS: Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. CONCLUSION: Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.     

Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication

Summary: Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment. Methods: Forty‐one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age‐matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean follow‐up of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation. Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T₄), 70.2; SD, 10.9 nM; and free thyroxine (FT₄), 11.5; SD, 1.8 pM] or OXC (T₄, 74.9; SD, 16.4 nM; and FT₄, 11.3; SD, 1.8 pM) than in the control girls (T₄, 96.6; SD, 15.1 nM, and FT₄, 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty‐three% of the girls taking CBZ and 67% of the girls taking OXC had serum T₄ and/or FT₄ levels below the lower limit of the reference range. The VPA‐treated girls with epilepsy had normal serum T₄ and FT₄ concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication. Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication.     

Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function in women with epilepsy

PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously. METHODS: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.     

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.     

The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate

PURPOSE: The aim of this study was to evaluate the effects of short-term oxcarbazepine (OXC) and valproate (VPA) monotherapy on thyroid functions in children. METHODS: Fifty-five newly diagnosed epileptic children with normal thyroid functions (confirmed with the thyrotropin releasing hormone stimulation test) participated in this study. VPA treatment was started in 30 patients and OXC in 25 patients. Serum thyroxine (T(4)), free thyroxine (fT(4)), triiodothyronine (T(3)), free triiodothyronine (fT(3)), reverse T3 (rT(3)), thyroid peroxidase antibodies (TPO-ab), and urine iodine levels were evaluated at baseline and at the third and sixth months of therapy. RESULTS: In the OXC group, serum T(4), fT(4), T(3), fT(3), and rT(3) levels were found to be decreased at the third and sixth months, the differences were significant compared to the baseline values except for fT(3) levels at the third month and fT(4) and rT(3) levels at the sixth month (p < 0.05). At the sixth month, serum T(4) level dropped below the normal reference value in 8 (32%), fT(4) in 5 (20%), T(3) in 4 (16%), and fT(3) in 3 (12%) patients. In the VPA group, mean T(4), fT(4), T(3), fT(3), and rT(3) levels at 3 and 6 months remained similar compared to the baseline values (p > 0.05). Mean serum thyroid stimulating hormone levels increased significantly at the sixth month compared to the baseline values in the VPA group (p < 0.05) while it remained unchanged in the OXC group (p > 0.05). There was no effect of either drug on urinary iodine excretion and serum TPO-ab levels remained in normal ranges throughout the study. CONCLUSIONS: In this prospective study, it is documented that children under short-term OXC or VPA therapy showed altered thyroid functions similar to the changes observed after long-term treatment. Although, the clinical significance of these results need to be evaluated with future studies, this observation of altered thyroid functions points out that thyroid functions may need to be monitored closely in children receiving antiepileptic treatment, even in the short-time interval.     

Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism

PURPOSE: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). METHODS: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L. RESULTS: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism. CONCLUSIONS: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.     

槲皮素对大鼠卵巢发育和卵巢寿命的影响

背景：研究发现一些植物雌激素可改变生殖系统发育,并可能最终影响生殖衰老的年龄。槲皮素是一种黄酮类物质,具有微弱的雌激素效应,但对卵巢卵泡发育和卵巢衰老进程究竟有无影响还不清楚。 目的：观察槲皮素对大鼠卵巢卵泡发育和卵巢寿命的影响。 方法：健康成年SD 大鼠30只雌雄按2∶1合笼所生的新生雌鼠,分为3组：母鼠灌胃组,对孕10.5 d母鼠槲皮素灌胃,1次/d,直至分娩,取1,2,4 d新生雌鼠;腹腔注射组,对正常出生后12 h内新生雌鼠槲皮素腹腔注射,1次/d,取2,4 d新生雌鼠;空白对照组：不进行任何干预的1,2,4 d新生雌鼠;观察新生鼠卵巢发育情况。另取12月龄雌性大鼠22只,以数字表法随机分为实验组和对照组：实验组用槲皮素灌胃4个月,1次/d;对照组灌胃给予生理盐水。对灌胃前和灌胃期间12月龄雌性大鼠行阴道涂片,观察大鼠动情周期模式;灌胃结束后,计算卵巢和子宫系数,苏木精-伊红染色观察各期卵泡发育情况和卵泡总数变化。 结果与结论：用槲皮素干预1,2 d龄新生大鼠未装配的卵泡均减少,而发育更晚期阶段的卵泡即原始卵泡或发育卵泡有所增加。灌胃前大部分大鼠动情周期已经不规则,用药后,随着大鼠年龄的增长,实验组与对照组显示了相似的动情周期变化：规则的动情逐渐消失,周期变得延长或不规则,灌胃结束时均以不规则动情为主。灌胃4个月后,实验组大鼠卵巢大部分由闭锁卵泡组成,另外可见少许原始卵泡、发育卵泡以及窦状卵泡和黄体,实验组窦状卵泡较对照组增加(P < 0.05),两组卵巢和子宫系数及体质量增加无差异。 提示槲皮素可能具有一定促进卵巢卵泡发育和成熟的作用,但不影响卵巢寿命。     

我国农村地区607例癫痫患者应用丙戊酸钠治疗效果评价

目的 观察基层医生使用国产丙戊酸钠(VPA)治疗癫痫的可行性、疗效及其不良反应.方法 癫痫患者来自湖北省天门市和广西田东县农村地区.由县、乡级医生按规定的入选标准筛选病例,并使用VPA治疗和随访.疗效评估以发作频率与治疗前的变化为标准,其中无发作、显效和有效三者之和为总有效率.结果 入组607例癫痫患者接受治疗随访,男性395例,女性212例,其中579例随访满12个月.患者中全面强直-阵挛性发作517例(85.2%),失神发作20例(3.3%),其余70例(11.5%)为部分性发作、单纯强直、阵挛、肌阵挛或失张力发作.服药满3个月、6个月、12个月时癫痫发作完全控制的患者分别有270例(45.5%)、249例(42.3%)和238例(41.1%),总有效率三个时段分别为65.2%、75.4%和85.5%.治疗随访期间共有58例出现困倦、嗜睡、疲乏、头晕等不良反应.治疗随访期间有19例(3.1%)先后脱组.结论 VPA是一种疗效较好、严重不良反应少、基层医生比较容易掌握的广谱抗癫痫药,同苯巴比妥一样适合在我国农村地区推广应用.

Abstract：

Objective To observe the efficacy and the side-effects of sodium valproate (VPA) in patients with epilepsy in rural China. Methods Epilepsy patients were selected from rural areas of Tianmen in Hubei province and Tiandong county in Guangxi province according to the inclusion and exclusion criteria.Efficacy evaluation standard depending on the change of seizure frequency compared with the situation prior to entering the treatment group. Among the treated patients, no seizures, seizure reduced ＞ 75%, seizure reduced 50%-75% sums for the total effective rate. Results All 607 patients with epilepsy were treated and followed up, the male were 395 (65. 1% ) female 212 (34. 9% ), and 579 patients were treated for 12 months. Patients with generalized tonic-clonic seizures were 517 (85.2%), absence seizures 20 (3. 3% )and the other types of seizures 70 (11.5% ) including simple partial seizures, tonic, clonic, myoclonic or atonic seizures etc. The completed control of seizures ( without any seizures) during the period after taking 3 months, 6 months, 12 months were 270 (45.5%), 249 (42. 3% ) and 238 (41.1%) respectively. The total effective rates in the three periods were 65.2% , 75.4% and 85.5% respectively. The 58 patients in the total group showed side-effects during the follow-up period, mainly including drowsiness, lethargy,fatigue, dizziness, headache and tremor. Nineteen patients (3. 1% ) quitted the treatment group.Conclusions The VPA is an effective antiepileptic drug and no more severe side-effects. It is the same as Phenobarbital and suitable to be used in rural areas of China.     

丙戊酸钠合并碳酸锂治疗反复躁狂发作的长期疗效及安全性

目的 探讨丙戊酸钠合并碳酸锂治疗反复躁狂发作的长期疗效及安全性.方法 收集各类双相躁狂发作患者105例,分为碳酸锂组、丙戊酸钠组和碳酸锂+丙戊酸钠组(以下简称合并治疗组),每组各35例.急性期治疗6周后随访5年以上.随访者不干预患者治疗.基线及疗效采用倍克-拉范森躁狂量表(BRMS)评定.随访内容包括复发次数、药物剂量、长期疗效及安全性.结果 完成随访105例.急性期治疗后BRMS减分率:碳酸锂组(43±29)%;丙戊酸钠组(42±27)%;合并治疗组(58±25)%,三组间的差异有统计学意义(F=3.579,P=0.031).5年内躁狂复发次数:碳酸锂组(3.5±1.8)次,丙戊酸钠组(3.5±2.2)次,合并治疗组(2.0±1.5)次,三组间的差异有统计学意义(F=7.387,P=0.001);抑郁复发次数:碳酸锂组(2.1±2.4)次,丙戊酸钠组(2.1±2.6)次,合并治疗组(1.4±1.7)次,三组间的差异无统计学意义(F=1.313,P=0.273).合并治疗组与其他两组疗效的差异主要在快速循环型(F=4.120,P=0.033).合并治疗组的碳酸锂及丙戊酸钠剂量均分别明显低于其他两组(P＜0.01;P＜0.001).三组总体不良反应的差异无统计学意义.结论 丙戊酸钠合并碳酸锂用于双相情感障碍的维持治疗能减少躁狂的复发率,安全性较高.     

Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy

The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs.     

Plasma concentrations of risperidone and olanzapine during coadministration with oxcarbazepine

PURPOSE: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. METHODS: OXC, at a dosage of 900-1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. RESULTS: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 +/- 3.6 ng/ml at baseline to 4.8 +/- 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 +/- 7.5 to 24.7 +/- 7.4 ng/ml), and olanzapine (from 26.5 +/- 5.7 ng/ml at baseline to 27.8 +/- 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. CONCLUSIONS: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes.     

Quantitative EEG effects of carbamazepine, oxcarbazepine, valproate, lamotrigine, and possible clinical relevance of the findings

Quantitative EEG (QEEG) effects of therapeutic doses of carbamazepine (CBZ), oxcarbazepine (OXC), valproate (VA) and lamotrigine (LA) monotherapy were investigated in patients with beginning epilepsy. Baseline waking EEG (EEG1) was recorded in the untreated state, the second EEG (EEG2) was done after 8 weeks of reaching the therapeutic dose. Left occipital data were used for analysis. QEEG target parameters were absolute band-power (delta: AD, theta: AT, alpha: AA, beta: AB), and alpha mean frequency (AMF). Group effects (untreated versus treated condition in the CBZ, VA, OXC, LA groups) were computed for each target parameter. One group with benign rolandic epilepsy remained untreated for clinical reasons and served to estimate the QEEG test–retest differences. In addition, the individual QEEG response to each drug was calculated as (EEG2 − EEG1). Results: statistically significant (p < 0.05) group differences indicated the QEEG domain systematically affected by the drugs. CBZ caused AT increase and AMF decrease. OXC caused AMF decrease. VA and LA did not decrease AMF (LA even increased it), but reduced broad-band power. Individual power and AMF changes showed considerable variability in each group. >0.5 Hz AMF decrease (that was reported to predict cognitive impairment in prior studies) occurred in 10/41 patients in the CBZ group but never in the OXC, VA, LA groups. The results may be utilized in planning further studies addressing the relationship between antiepileptic drugs and their CNS effects. In addition, the relationship of AED-related cognitive impairment and AMF changes was discussed.     

海人酸颞叶癫痫模型及丙戊酸钠治疗作用的观察

目的 建立海人酸癫痫动物模型并给予丙戊酸钠治疗，探讨其治疗作用。方法 42只Wistar大鼠置于立体定向仪上，于右侧海马注射海人酸制备大鼠癫痫模型。根据癫痫发作病程，随机分为急性期、静止期、慢性期等实验组；另设丙戊酸钠治疗组，分别于海人酸注射后24h和自发性癫痫出现后给予丙戊酸钠治疗。在实验过程中以视频录像监测大鼠症状的改变，深部脑电图观察癫痫的病理过程及丙戊酸钠治疗前后脑电活动的改变。组织切片经Nissl和Timm染色观察海马神经元数目、苔藓状纤维发芽。结果 (1)电生理学改变：海人酸注射后数分钟大鼠即出现癫痫发作并呈现急性期、静止期和慢性期等病变过程。脑电图于急性期和慢性期均表现为典型的癫痫发作电活动及发作间期表现。(2)病理学改变：海马神经元死亡主要出现在急性期，以实验侧CA3、CA4区最为明显，齿状回无明显神经元缺失。Timm染色显示从静止期开始出现苔藓状纤维发芽并进行性增加。(3)丙戊酸钠治疗前后症状的改变：早期应用丙戊酸钠治疗可抑制癫痫发作及其症状的发展；出现自发性癫痫后丙戊酸钠的治疗效果欠佳，停药后症状再次出现。结论 海人酸模型是模拟人类颞叶癫痫较为理想的动物模型。早期丙戊酸钠治疗效果较好，否则不能有效控制癫痫。     

奥卡西平辅助治疗精神分裂症及分裂样精神病兴奋躁动的比较研究

目的评估奥卡西平治疗兴奋躁动精神分裂症、分裂样精神病辅助疗效和安全性。方法将符合中国精神障碍分类与诊断标准第3版中精神分裂症、分裂样精神病诊断标准,并以兴奋躁动为主要表现的80例患者随机分为研究组(n=39)和对照组(n=41),研究组应用抗精神病药物(氯氮平、奥氮平、利培酮、喹硫平、阿立哌唑或齐拉西酮其中之一)联合奥卡西平,对照组单一使用抗精神病药物,观察6周。采用简明精神病量表(BPRS)和阳性和阴性综合征量表(PANSS)兴奋因子,不良反应量表(TESS)在治疗前及治疗后第1,2,4,6周分别评估疗效和安全性。结果治疗6周后,研究组有效28例(71.8%),对照组有效26例(65.0%),2组有效率差异有统计学意义(χ2=6.02,P=0.028)。研究组与对照组患者分别脱落2例和4例。研究组的主要不良反应为镇静(11例)、便秘(10例)、头晕(7例)、心动过速(7例)等,对照组的主要不良反应为便秘(14例)、口干(12例)、心动过速(12例)、锥体外系不良反应(7例)等。结论奥卡西平能有效辅助治疗精神分裂症、分裂样精神病的兴奋状态。     

Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy

PURPOSE: To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures. METHODS: The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated. RESULTS: Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups. CONCLUSIONS: KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control.     

Transplacental passage of oxcarbazepine and its metabolites in vivo

PURPOSE: The purpose of this study was to investigate human fetal exposure to oxcarbazepine (OCBZ) in vivo. METHODS: Transplacental passage and placental tissue concentrations of OCBZ and its metabolites were determined. Maternal venous blood, cord blood, and placental tissue samples from 12 mothers using OCBZ during pregnancy alone or in combination with other antiepileptic drugs were collected. Samples were analyzed with high-performance liquid chromatography. RESULTS: Maternal venous concentrations of OCBZ and its major metabolites were at same range as cord blood concentrations (OCBZ in maternal serum, 0.19 +/- 0.16 microg/ml, and in cord serum, 0.21 +/- 0.19 microg/ml; 10-hydroxy-10,11-dihydrocarbamazepine (10-OH-CBZ) in maternal serum, 5.69 +/- 2.49 microg/ml, and in cord serum, 5.23 +/- 1.44 microg/ml; 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine (10,11-D) in maternal serum, 0.29 +/- 0.22 microg/ml, and in cord serum, 0.28 +/- 0.14 microg/ml). OCBZ (0.17 +/- 0.16 microg/g placental tissue), 10-OH-CBZ (3.49 +/- 1.34 microg/g placental tissue) and 10,11-D (0.25 +/- 0.11 microg/g placental tissue) were detected in the placental tissue. The amount of OCBZ detected from placental tissue was 0.01% of the daily dose. CONCLUSIONS: OCBZ, like other antiepileptic drugs, is transferred significantly through the placenta in humans.