Serum lipid levels during carbamazepine therapy in epileptic children

The aim of the study was to evaluate serum lipid levels during carbamazepine therapy in epileptic children. Thirty epileptic children (18 male, 12 female; age range, 30 months to 14 years) with idiopathic or cryptogenic partial or generalized tonic-clonic seizures (13 CPS, 17 GTC) were evaluated for serum lipids at the onset and the third month of carbamazepine therapy. Carbamazepine was started at 10 mg/kg/day. Mean total cholesterol, low-density lipoprotein, very low density lipoprotein, and triglyceride levels significantly increased during treatment (P < 0.05), but mean high-density lipoprotein levels were not statistically significant throughout the study. Carbamazepine treatment alters the serum lipid profile of children in such a way that it could potentially facilitate the development of atherosclerosis.     

Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy

To assess whether epileptic children have abnormal values of serum copper (Cu), zinc (Zn), selenium (Se), glutathione peroxidase (GSH-PX) and superoxide dismutase (CuZn-SOD), and to evaluate the effect of long-term therapy with sodium valproate (VPA) and carbamazepine (CBZ) on these parameters, we studied 36 epileptic patients before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Before the beginning of therapy, there were no differences in levels of all parameters studied between controls and epileptics. After 1 year of therapy, patients treated with VPA and CBZ continued to show normal values. In conclusion our study demonstrates that epilepsy per se and treatment with VPA and CBZ do not affect levels of Cu, Zn, Se, GSH-PX and CuZn-SOD concentrations.     

Serum levels of zinc and copper in patients with Parkinson's disease.

Several recent studies have shown decreased copper and increased zinc concentrations in the substantia nigra and increased copper concentrations in the cerebrospinal fluid of Parkinson's disease patients. To elucidate whether changes in serum levels of these trace elements may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of zinc and copper by flame atomic absorption spectrophotometry, and albumin and ceruloplasmin, in 32 (Zn) and 39 PD patients (Cu), respectively, with their spouses as the control group. Serum zinc, albumin, copper and ceruloplasmin levels and the zinc/albumin and copper/ceruloplasmin ratios, did not differ significantly between the two groups and were not influenced by antiparkinsonian therapy in the PD patients. Serum zinc/albumin ratio (r = 0.43), ceruloplasmin (r = -0.36) and copper/ceruloplasmin ratio (r = 0.36) correlated significantly with age, but not with age of onset, duration of the disease, scores of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging in PD patients. These values did not correlate with age in the control group. These results suggest that serum levels of zinc and copper do not play any role as risk factors for PD.     

Psychologic and behavioral disturbance among epileptic children treated with barbiturate anticonvulsants

From their studies of epileptic children, the authors found that barbiturate anticonvulsants have several unexpected psychologic and behavioral effects. They suggest that clinicians dealing with depression in epileptic patients consider the possibility that barbiturate anticonvulsants may be a contributing factor.     

Serum serotonin levels in patients with epileptic seizures

Profound cardiovascular and/or respiratory dysfunction is part of the terminal cascade in sudden unexpected death in epilepsy (SUDEP). Central control of ventilation is mediated by brainstem rhythm generators, which are influenced by a variety of inputs, many of which use the modulatory neurotransmitter serotonin to mediate important inputs for breathing. The aim of this study was to investigate epileptic seizure–induced changes in serum serotonin levels and whether there are potential implications for SUDEP. Forty‐one epileptic patients were pooled into 2 groups based on seizure type as (1) generalized tonic–clonic seizures (GTCS) of genetic generalized epilepsy and focal to bilateral tonic–clonic seizures (FBTCS; n = 19) and (2) focal seizures (n = 26) based on clinical signs using surface video‐electroencephalography. Postictal serotonin levels were statistically significantly higher after GTCS and FBTCS compared to interictal levels (P = .002) but not focal seizures (P = .941). The change in serotonin (postictal‐interictal) was inversely associated with a shorter duration of tonic phase of generalized seizures. The interictal serotonin level was inversely associated with a shorter period of postictal generalized electroencephalographic suppression. These data suggest that peripheral serum serotonin levels may play a role in seizure features and earlier postseizure recovery; these findings merit further study.     

Serum insulin, leptin, and neuropeptide y levels in epileptic children treated with valproate

Weight gain is a common side effect of valproate treatment. The potential mechanisms of valproate-associated weight gain are not yet clear. Decreased blood glucose level, impairment of beta-oxidation of fatty acids, and increased insulin levels are some of the possible mechanisms. The aim of the present study is to evaluate the role of insulin, leptin, and neuropeptide Y in valproate-related weight gain in epileptic children. In 20 epileptic children treated with valproate before treatment and after a follow-up period of 3 and 6 months, body mass index and fasting insulin glucose ratio were calculated and serum glucose, insulin, cortisol, leptin, and neuropeptide Y levels were measured. At the end of 3 months, the mean body mass index values and the mean serum insulin, fasting insulin glucose ratio, and neuropeptide Y levels increased, whereas the serum glucose levels decreased. After 6 months of treatment, the mean serum cortisol and leptin levels were high, in addition to the body mass index, neuropeptide Y, and fasting insulin glucose ratio. These results suggest that weight gain during valproate treatment might be related to low glucose and high insulin, cortisol, leptin, and neuropeptide Y levels.     

Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine

In experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66 +/- 2.11 micromol/l and 69.35 +/- 23.20 micromol/l, 1.89 +/- 1.01 micromol/l and 49.39 +/- 10.61 micromol/l in the carbamazepine group, and 1.22 +/- 0.55 micromol/l, 29.53 +/- 10.05 micromol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P < 0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P < 0.01), however, there was no statistically significant difference in the levels of nitrite (P > 0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide.     

Serum lipids,vitamin B12 and folic acid levels in children receiving long-term valproate therapy

In this study, serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in children with epilepsy who had been receiving long-term valproate (VPA) therapy. Our purpose was to determine that whether or not there was any affect of VPA therapy on serum lipids, vitamin B12 and folic acid levels. The study includes 26 patients (13 males, 13 females) with epilepsy who had been receiving long-term VPA therapy and in 28 healthy children (14 males, 14 females). The age ranged from 14 months-12 years (8.22 +/- 3.64 years) and 9 months-18 years (8.97 +/- 4.85 years) in the study and control group, respectively. Because serum lipid ranges may be changed according to the age groups in childhood, the children were divided into three groups as follows; younger than < 5 years, between 5-10 years, and older than > 10 years. The duration of VPA use was between 10 months and 7 years (1.83 +/- 1.80 years). Serum VPA level changed between 42-108 micrograms/ml (75.09 +/- 21.42 micrograms/ml). When comparing the results we did not find any significant difference in all parameters including lipid profiles, vitamin B12 and folic acid levels between the groups (P > 0.05). Additionally, we did not find any correlation between lipid profile and age at start of therapy, duration of therapy, serum VPA level (P > 0.05). In conclusion, our findings showed that VPA therapy did not change serum lipids, vitamin B12 and folic acid concentrations; therefore, we suggest that VPA may be safely used with regard to lipid composition, vitamin B12 and folic acid levels in childhood epilepsy.     

Serum lipid changes during anticonvulsive treatment serum lipids in epileptic children

Serum lipid profile changes were investigated in 53 children receiving phenobarbital (n = 14), carbamazepine (n = 21), and valproic acid (n = 18) for their newly diagnosed seizure disorder. The patients were followed prospectively. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations increased after 3 months of treatment with carbamazepine and remained high after one year. Serum total cholesterol levels increased after 3 months of treatment with phenobarbital and remained high after one year. Serum lipid concentrations did not change during valproic acid therapy. Serum lipid profiles should be carefully monitored in children receiving enzyme inducing antiepileptic drugs.     

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     

Serum valproate concentrations in epileptic children with favourable responses

The lower limits of the "therapeutic range" for serum levels of sodium valproate (VPA) were evaluated in epileptic children showing a benign clinical course. Twenty-five outpatients, aged 5 to 16 years, whose seizures were well controlled over three years with VPA alone, were studied. Venous blood was taken 1.1 to 5 hrs after the morning dose. Serum VPA concentrations at steady-state after receiving the maintenance doses to control seizures were determined by enzyme immunoassay. The patients were divided into three groups according to the seizure type and the age at onset; A and B: patients with tonic and/or clonic seizures, aged below 3 yrs (n = 11) and 3 to 11 yrs (n = 6), respectively, C: those with absence seizures, aged 4 to 11 yrs (n = 8). The serum concentrations in A (47.8 +/- 21.6 micrograms/ml, mean +/- SD) were significantly (p less than 0.02) lower than those in groups B and C (85.2 +/- 14.0 and 73.0 +/- 17.4 micrograms/ml, respectively). VPA concentrations below 50 micrograms/ml were seen in 6 patients (55%) in group A. It was concluded that many epileptic children, whose ages at onset were below 3 yrs, with tonic and/or clonic seizures could be controlled even with low initial serum concentrations below the "therapeutic range".     

Serum carnitine levels during oxcarbazepine and carbamazepine monotherapies in children with epilepsy

Prolonged antiepilepsy drug treatment can result in secondary carnitine deficiency. The effect of oxcarbazepine on carnitine metabolism has not been reported previously. In this study, serum concentrations of total and free carnitine were measured in 20 children with epilepsy treated with oxcarbazepine monotherapy and were compared with 20 children with epilepsy who were taking carbamazepine as monotherapy. The assays were performed between 3 and 6 months of anticonvulsant treatment. The mean values of serum total and free carnitine levels in patients receiving carbamazepine monotherapy were 63.0 +/- 20.7 micromol/L and 49.1 +/- 16.7 micromol/L, respectively. The mean values of serum total and free carnitine levels in patients receiving oxcarbazepine monotherapy were 64.2 +/- 17.4 micromol/L and 50.3 +/- 13.7 micromol/L, respectively. The values were all between normal ranges. No significant difference was observed in the level of total and free carnitine levels between the two groups. Our results suggest that neither oxcarbazepine nor carbamazepine as monotherapy causes carnitine deficiency in otherwise healthy children with primary idiopathic epilepsy.     

The investigation of EEG specificity in epileptic children during Depakine therapy

Background: Antiepileptic drug (AED) therapy in epileptic children can be optimized via an anticipation of AED efficacy during early stages of therapy. We hypothesize that the comprehensive electroencephalography (EEG) evaluation can determine AED efficacy in epileptic children. Thus, this study aimed to investigate the alteration of characteristics of interictal EEG during the AED therapy. Methods: Forty-three children aged 3–9 were investigated. EEGs were recorded three times: prior to valproic acid-Depakine (Dep) monotherapy and twice under the Dep therapy (at three and six/eight months). Baseline EEG was analyzed for quantitative characteristics of interictal EEG, such as absolute values of the power (AVP) spectra and EEG topography/brain mapping. The study involved epileptiform EEG and clinical condition assessments. Results: Dep decreased AVP spectra in a low-frequency range, suppressed spontaneous epileptic discharge, and spike-wave complex 3/s. Dep partially decreased spikes-polyspikes, sharp waves, and generalized paroxysmal bursts during functional trials. Dep did not diminish rhythmic monomorphic theta-waves (RMT) of tempo-parietal localization observed by brain mapping. The presence of RMT correlated with the reocurrence of seizures if Dep was withdrawn. Conclusions: The findings of this study suggest that the presence of RMT with tempo-parietal localization on the interictal EEG can anticipate reocurrence of seizures if Dep dose will be reduced or withdrawn. The efficacy of the AED therapy can be revealed via reduction of low-frequency waves and suppression of epileptiform EEG elements parallel to clinical improvement. Thus, optimal treatment strategies can be tailored based on the evaluation of background EEG characteristics using spectral analysis, EEG mapping, and the quantitative EEG approach.     

Prolactin levels during long-term risperidone treatment in children and adolescents

BACKGROUND: This analysis was designed to investigate prolactin levels in children and adolescents on long-term risperidone treatment and explore any relationship with side effects hypothetically attributable to prolactin (SHAP). METHOD: Data from 5 clinical trials (total N = 700) were pooled for this post hoc analysis. Children and adolescents aged 5 to 15 years with subaverage intelligence quotients and conduct or other disruptive behavior disorders received risperidone treatment (0.02-0.06 mg/kg/day) for up to 55 weeks. Outcome measures analyzed included serum prolactin levels, reported adverse events, and the conduct problem subscore of the Nisonger Child Behavior Rating Form. RESULTS: Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 (N = 358) and 13.0 ng/mL at weeks 52 to 55 (N = 42). There was no relationship between pro-lactin levels and age. Females returned to a mean value within the normal range (相似文献   

癫痫患者血清神经元特异性烯醇酶的测定

目的探讨癫痫持续状态（ＳＥ）和单次癫痫发作对癫痫患者大脑神经元的损伤。方法对４１例癫痫、７例假性发作患者（ＰＳＧ）和１４名正常人的血清神经元特异性烯醇酶（ＮＳＥ）含量进行测定。癫痫组和ＰＳＧ组在发作间歇期、发作后当日、次日和第３日各抽血５ｍｌ,测定ＮＳＥ含量,取峰值与发作间期结果和对照组比较。结果４１例癫痫患者发作间歇期血清ＮＳＥ均值为（５９±０．７）μｇ／Ｌ,对照组为（６３±１４）μｇ／Ｌ,两组比较差异无显著意义。癫痫组２６例单次发作后血清ＮＳＥ峰值为（９２±１．６）μｇ／Ｌ,６例ＳＥ患者血清ＮＳＥ峰值为（１９５±１３２）μｇ／Ｌ,与发作前基线比较差异有显著意义。７例ＰＳＧ间歇期与发作后血清ＮＳＥ含量比较差异无显著意义。结论癫痫发作可导致血清ＮＳＥ水平升高,提示单次癫痫发作亦有神经元损伤,ＳＥ时神经元损伤更重。     

Clobazam as add-on therapy in children with epileptic encephalopathy

RATIONALE: Clobazam has been used successfully in adults and children with partial epilepsy. The purpose of this study was to evaluate the safety and efficacy of clobazam as add-on therapy in children with epileptic encephalopathy. METHODS: This was a retrospective study conducted at the pediatric epilepsy clinic of our university hospital. Children less than 18-years of age with epileptic encephalopathy were included in the study. Clobazam was introduced as add-on therapy, starting with 5 mg/Kg/day and increased in minimally effective doses, up to the maximum tolerated dose. Data were obtained from clinical files and follow-up visits. RESULTS: Ninety-seven patients were included in the study (39 girls), aged between 1 and 17-years-old (mean = 9.9). Twenty-six patients had Lennox-Gastaut syndrome, seven had myoclonic astatic epilepsy, nine had West syndrome and, in 57 patients, the type of epileptic encephalopathy could not be determined. Clobazam dosage ranged from 5 to 60 mg/day (mean = 37.5 mg/day). Forty (41%) patients presented with adverse events, most of which were mild and transitory, and clobazam needed to be withdrawn in only 11 patients. Nine (9.2%) patients were seizure-free after clobazam adjunctive therapy. In 11 (11.3%) patients seizure improvement was >75%, in 16 (16.5%) it was >50%, in 17 (17.5%) improvement was <50% and in 44 (45.5%) there was no change in seizure frequency. Three patients were lost to follow-up. In 85% of the patients with seizure improvement, the results lasted for more than one year. CONCLUSION: Clobazam is safe and effective in the treatment of epileptic encephalopathies of childhood.     

Plasma zinc,copper, and amino acid levels in the blood of autistic children

Plasma zinc, copper, and amino acid levels have been measured in a group of autistic children. All three variables were found to be normal. These findings are in disagreement with the previously reported results of some other workers but if confirmed would indicate that autism cannot simply be attributed to a disorder of zinc metabolism.     

癫(癎)患者血清、脑脊液神经元特异性烯醇化酶的测定及意义

目的探讨癫癎患者癎性发作后对神经元和血脑屏障的损伤。方法采用酶联免疫法测定癫癎患者在癎性发作后2d内血清和脑脊液(CSF)中神经元特异性烯醇化酶(NSE)的含量,与非神经系统疾病的神经症对照组对比分析。结果患者组CSF中NSE较对照组升高,差异有统计学意义;但血清中NSE含量与对照组差异无统计学意义。结论癫癎患者癫癎发作后脑脊液中NSE升高,提示癎性发作对中枢神经的神经元有损伤;而血中NSE正常,提示血脑屏障正常。