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1.
We studied the cognitive effects of antiepileptic drugs (AED), by investigating epileptic children who were seizure-free for at least 2 years and who had undergone fixed monotherapy. Seventy consecutive epileptic children (25 with carbamazepine (CBZ), 22 with phenobarbital (PB), and 23 with valproate (VPA)) were examined by Wechsler Intelligence Scale for Children-Revised (WISC-R) and auditory event-related potentials (P(300)) at three sessions: before AED reduction, then 1 and 7 months after complete withdrawal of treatment. There were no significant differences in IQ and subtests scores of WISC-R in any group at any of the three sessions. P(300) latencies were significantly increased in the children receiving PB but not in children receiving CBZ or VPA. P(300) amplitudes were increased but not significantly different among the three groups. These findings suggest that PB may affect cognitive function on children, but the changes of P(300) latencies may improve after discontinuation.  相似文献   

2.
Summary:  Purpose: A retrospective study was carried out on 53 cases with childhood epilepsy to evaluate the validity of the initial selection of antiepileptic drug (AED).
Methods: We investigated the AEDs selected at the beginning of the treatment from the medical records of 53 untreated cases. A follow-up study was undertaken to evaluate the effects of the AEDs. In the second study, we investigated the AEDs of 10 cases with atypical benign partial epilepsy (ABPE), to clarify whether the initial AEDs selected for rolandic epilepsy were related to the appearance of ABPE.
Results: The AEDs used at the initial stage consisted of carbamazepine (CBZ), valproic acid (VPA), phenobarbital (PB), and vitamin B6. The main AEDs were CBZ and VPA for localization-related epilepsy, and VPA for generalized epilepsy. The initial selection of AEDs in 41 (85.4%) of 48 cases treated with AEDs were considered to be correct from the results of follow-up. We could not specify any AEDs that related to the appearance of ABPE.
Conclusions: The selection of AED in this series was considered to be most appropriate. We proposed a criterion to determine whether to begin the AED treatment immediately at the initial seizure.  相似文献   

3.
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.  相似文献   

4.
The aim of the present study was to assess the effect of long-term carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PB) treatment on serum lipids and apolipoproteins in epileptic children. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) were measured and the LDL-C/HDL-C and TC/HDL-C ratios were calculated in 320 children and adolescents (129 receiving CBZ, 127 receiving VPA and 64 receiving PB) suffering from various types of epilepsy. Additionally, in a subgroup of 181 children (68 CBZ; 78 VPA; 35 PB) apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), HDL2-C and HDL3-C were measured and apoA-I/apoB and HDL2-C/HDL3-C ratios were calculated. Results of the measurements were compared with those of 169 age-and sex-matched healthy controls. None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. TC and LDL-C serum levels were high in children receiving CBZ or PB and low in those treated with VPA. Serum LDL-C level exceeded 130 mg/dl in 27.9% of CBZ-group, 31.8% of the subjects receiving PB, but only in 7% of those receiving VPA and in 11.8% of control group subjects. CBZ-treated children also showed high HDL-C and HDL3-C values. In the group receiving VPA, HDL2-C, HDL2-C/HDL3-C ratio and apo B were significantly lower than in the control group. Mean apoA-I levels were low in all treated groups: by contrast, in neither group did TGs, VLDL-C levels and TC/HDL-C or LDL-C/HDL-C ratios differ significantly from the corresponding control group. Our results suggest that the effects of long-term AED therapy on lipid profile and, particularly, on apolipoprotein serum levels increase risk of atherosclerosis-related disease. Moreover, these results confirm our previously reported increased risk in CBZ and PB-treated patients.  相似文献   

5.
Summary: Purpose : We wished to determine the oral pharmacokinetics of lamotrigine LTG and to assess possible interactions with other AEDs in an unselected population of children. Concentration data in plasma and in CSF for lamotrigine as well as for the other AEDs are presented.
Methods : Thirty-one children, children and young adults aged > 2 years with intractable generalized epilepsy despite adequate duration and dose of at least three conventional AEDs were studied.
Results : There was a linear relation between the dose administered and the maximal plasma concentration, indicating that saturation of absorption or elimination mechanisms did not occur in the dose range studied. The median elimination half-life (t1/2) in patients receiving concomitant valproate (VPA) was 43.3 h; in patients receiving carbamazepine (CBZ) and/or phenobarbital (PB), it was 14.1 h; and in patients receiving both VPA and CBZI PB or other antiepileptic drugs (AEDs), it was 28.9 h. No clinically important changes in the plasma levels of CBZ, VPA, valproate, ethosuximide, or PB were observed in the follow-up period (2–12 months). No dose adjustments of concomitant AEDs were necessary. The plasma concentration of clonazepam (CZP) was reduced when LTG was introduced.
Conclusions : The complex interaction between LTG and other AEDs in children with intractable epilepsy makes therapeutic drug monitoring (TDM) desirable.  相似文献   

6.
《Epilepsia》2006,47(S3):68-69
1 A. Pelliccia , 2 S. Frediani , and 2 T. Frediani , 2 S. Lucarelli (   1 Department of Pediatrics, Faculty of Medicine II, La Sapienza University of Rome, Italy ,   2 Department of Pediatrics, Faculty of Medicine I, La Sapienza University of Rome, Italy )
Purpose: Rolandic epilepsy is the best known form of idiopathic partial epilepsy and unquestionably the one with the best prognosis. When such treatment does prove necessary, sodium valproate (VPA) or carbamazapine (CBZ) are nearly always used. In view of previous experiences showing the efficacy of an elimination diet for cow milk in cases of partial idiopathic epilepsy, a study was carried out on children with rolandic epilepsy to compare the results of treatment with VPA or CBZ and an elimination diet for proteins of cow milk.
Method: All the patients were subjected to a diagnostic procedure to ascertain allergy to this foodstuff. The diagnosis was confirmed by means of an elimination/ provocation test with the foodstuff in question. The subjects were divided into 3 random groups: group A (17 cases) treated with VPA, group B (17) treated with CBZ, and group C (20) treated with an allergen-free diet.
Results: The children of group A displayed complete remission in 14 cases out of 17 (82.3%). In group B only 6 cases out of 17 (30%) displayed complete remission. The allergen-free made it possible to obtain complete clinical remission in all the children of group C as well as the normalisation of EEG.
Conclusion: The study suggests that while CBZ and VPA are effective drugs with comparatively few undesired effects, an allergen-free diet makes it possible to obtain complete clinical and electroencephalographic remission with no side effects as well as a behavioural improvement in cases where there is valid evidence of hypersensitivity.  相似文献   

7.
Summary: The anticonvulsant effects of felbamate (FBM) alone or in combination with phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), or phenobarbital (PB) were investigated against maximal electroshock (MES) seizures in mice. Nonprotective doses of the prototype antiepileptic drugs (AEDs) enhanced the protective effects of FBM against electrically induced seizures, as shown by significant reduction of FBM ED50 values. Toxicity as determined by rotorod test was not significantly potentiated, however, and the protective index (PI = TD50/ED50) of FBM was increased by >100% for each AED interaction. The increase in anticonvulsant potency of FBM after its combination with nonprotective doses of AEDs could not be accounted for by a pharmacokinetic mechanism.  相似文献   

8.
Summary: The protective efficacy of phenobarbital (PB, 120 min before testing) and valproate (VPA, 30 min before testing) alone or combined with aminophylline (a single dose of 50 mg/kg, 3-day or 14-day administration twice daily 50 mg/kg at 8.00 a.m. and 8.00 p.m.) was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were given intraperitoneally (i.p.), and the protection provided by PB and VPA was evaluated as the respective ED50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electro-convulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED50 values from 22 to 31 mg/kg (p < 0.001) for PB and from 247 to 281 mg/kg (p < 0.001) for VPA. After administration of aminophylline for 3 days (electroshock was performed 30 min after the last aminophylline injection), the respective ED50 values for PB and VPA were 29.5 (p < 0.01) and 269 mg/kg (p < 0.01 vs. saline-treated animals). Chronic treatment with aminophylline (14 days) resulted in further impairment of the protective activity of PB and VPA. Specifically, the ED50 value of PB was 39 mg/kg (p < 0.05 vs. PB + single injection of aminophylline) and that of VPA was 318 mg/kg (p < 0.01 vs VPA + single injection of aminophylline). Plasma levels of both PB and VPA were not affected by chronic aminophylline; moreover, the plasma level of theophylline was even lower after chronic aminophylline as compared with single aminophylline administration. The results of the present study provide evidence that no tolerance exists to aminophylline-induced impairment of antiepileptic drug efficacy; moreover, this phenomenon may even be increased with chronic aminophylline administration.  相似文献   

9.
BACKGROUND: Epilepsy is a frequent condition in persons with intellectual disability and is more often difficult to treat than in the average population. Seizure freedom is the primary therapeutic goal which has important implications for the patient's quality of life. The aim of this study was to find out which antiepileptic therapy regimens (monotherapy or combination therapy) are effective in achieving this goal in intellectually disabled epilepsy patients. We were especially interested in the impact of the new antiepileptic drugs (AEDs) which were introduced during the past decade. METHOD: We investigated retrospectively the antiepileptic regimens on which the resident patients of a large epilepsy centre (as a rule with additional intellectual disabilities of different degrees) were seizure free in 2002. Information on antiepileptic medication and seizure frequency was taken out of the individual case documentation. It was also determined whether seizure free patients had already been seizure free in 1992. RESULTS: Two hundred and forty out of 675 patients (35,6%) with epilepsy were seizure free. The proportion of seizure freedom was 43,7% in patients with borderline intelligence, 39,2% in mild, 33,2% in moderate, 31,9% in severe, and 21,9% in profound intellectual disability. One hundred and twenty-two (50,8%) seizure free patients were on monotherapy; 53 of them were on CBZ (PB: 34, VPA: 25, PHT: 7, LTG: 3). Ninety-three patients (38,7%) were on duotherapies, CBZ/PB (27 patients), PB/PHT (17), and LTG/VPA (14) being the commonest. Of 18 (7,5%) triple therapies, LTG/PB/VPA (4 patients) was the commonest. Taken together, the five most frequent therapeutic regimens were CBZ monotherapy, PB monotherapy, CBZ/PB, VPA monotherapy and PB/PHT (a clear preponderance of classic AEDs). A distinction was made between "old seizure free" (seizure free already in 1992) and "new seizure free" (in 1992 still seizures) patients. In the 132 old seizure free patients the classic AEDs prevailed again, monotherapies with CBZ, PB and VPA being the most frequent regimens. In comparison, in the 78 new seizure free patients the novel combination LTG/VPA was the third most frequent, after the classic regimens CBZ/PB and CBZ; PB monotherapies were rare. CONCLUSION:In a majority of intellectually disabled patients with epilepsy (including those who became seizure free since 1992), complete seizure control has been achieved by monotherapy or duotherapy with classic AEDs. Of the new AEDs LTG in combination with VPA appears to be an important innovation.  相似文献   

10.
Maternal use of antiepileptic drugs (AEDs) during pregnancy has been associated with an increased risk of congenital abnormalities in the fetus. This is partly attributable to AEDs. We aimed to analyse seizure frequency and the rate and type of any congenital malformation related to pregnancies in women with epilepsy in this prospective study. Eighty four pregnant women with epilepsy on AEDs were followed for congenital malformations. Z test was used for statistical analysis. Pregnancy did not influence the seizure frequency in 64 (76.2%) pregnancies. The seizure frequency increased in 16 (19.04%) pregnancies. In 4 (4.76%) pregnancies the number of seizures decreased during pregnancy. Overall percentage of congenital malformations in infants of mothers with epilepsy treated with AEDs was 10%, versus 3.65% in the general Turkish population. Percentages of malformations in children of pregnancies in women with epilepsy on antiepileptic drugs (AEDs) were; 6.52% (3/46) for carbamazepine (CBZ), 14.28% (2/14) for phenytoin (PHT), 13.33% (2/15)for valproic acid (VPA) and 20% (1/5) for phenobarbital (PB). This comfirms previous reports that all four AEDs (CBZ, PHT VPA, PB) are associated with an increased risk of congenital malformations, although CBZ seems to be the the safest agent in monotherapy.  相似文献   

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