Clinical features and outcomes of women with epilepsy who withdraw anti-seizure medications in early pregnancy / 中华神经科杂志

Objective:To explore anti-seizure medication (ASM) treatment patterns, seizures, maternal and fetal outcomes and offspring outcomes of pregnant women with epilepsy (PWWE) who withdraw ASM in the first trimester of pregnancy.Methods:A retrospective analysis was performed on the PWWE database registered in West China Hospital, Sichuan University from January 2009 to October 2022. Patients who withdrew ASM therapy in the first trimester and those who maintained ASM therapy throughout pregnancy were included. Withdrawal in the first trimester was defined as discontinuation of ASM between 0 and 3 months of pregnancy. Sixty-five PWWE (withdrawal group) who withdraw ASM in the first trimester were included, and 130 PWWE (maintained-therapy group) who took ASM throughout pregnancy in West China Hospital during the same period were matched 1∶2. Demographic characteristics, ASM, seizures, maternal and fetal outcomes within 1 year were compared between the 2 groups. In the subgroup analysis, the withdrawal group was divided into a full withdrawal group ( n=53) and a resumption group ( n=12) according to whether the ASM was resumed in the second and third trimesters of pregnancy, and the 2 groups were stratified and compared. Results:In the withdrawal group, the proportion of patients with bachelor degree below [72.3% (47/65) vs 54.6% (71/130), χ 2=5.68, P=0.017], family income less than 5 000 yuan per capita [44.6% (29/65) vs 18.5% (24/130), χ 2=14.98, P<0.001], a family history of epilepsy [12.3% (8/65) vs 3.1% (4/130), χ 2=4.90, P=0.027], and a second pregnancy [43.1% (28/65) vs 26.2% (34/130), χ 2=5.72, P=0.017] was higher than in the maintained-therapy group. The proportion of patients who received multiple ASM was lower in the withdrawal group than in the maintained-therapy group [16.9% (11/65) vs 38.5% (50/130), χ 2=9.35, P=0.002]. In the withdrawal group, the rate of seizures with tonic-clonic seizures during pregnancy [50.8% (33/65) vs 31.5% (41/130), χ 2=6.81, P=0.009] and seizure exacerbation during pregnancy [32.3% (21/65) vs 9.2% (12/130), χ 2=16.41, P<0.001] was higher. The preterm birth rate in the withdrawal group was lower than that in the maintained-therapy group [4.6% (3/65) vs 19.2% (25/130), χ 2=101.70, P<0.001]. The rate of seizure exacerbation during pregnancy was higher in the resumption group than in the full withdrawal group [7/12 vs 26.4% (14/53), χ 2=3.22, P=0.073]. Conclusions:PWWE with a family history of epilepsy and a second pregnancy were more likely to withdraw ASM during pregnancy. After withdrawal, the seizures during pregnancy were significantly worse, but the preterm birth rate of offspring was relatively reduced.

Current status of treatment and drug discovery for epilepsy / 药学学报

Epilepsy is one of the most common neurological conditions, which is characterized by recurrent unprovoked seizures. Drug treatment is still the main method for the disease. Although remarkable progress has been made in the development of antiepileptic drugs in recent years, there is still a poor curative effect on patients with refractory epilepsy. This review will focus on the current status and pathogenesis of epilepsy, as well as the antiepileptic drugs (targeting sodium channels, calcium channels, potassium channels, and the balance of γ-aminobuyric acid /glutamate system, respectively) that have been developed based on classical epileptogenic mechanisms. Further the antiepileptic drugs acting on new targets (epigenetic interferers, synaptic vesicle glycoprotein 2A modulators, mammalian target of rapamycin signal pathway blockers, carbonic anhydrase inhibitors, cannabidiol and adenosine inhibitors) have also been discussed.

Efficacy and Safety of Subcutaneous Levetiracetam Injection for Terminally-ill Cancer Patients: A Case Report

Introduction: Antiepileptic drugs were occasionally administered to manage seizures in terminally-ill cancer patients. When enteral route is no longer feasible due to dysphagia or depressed level of consciousness, subcutaneous route could be an option. We reported three cases of terminally cancer patients who received subcutaneous levetiracetam (LEV) due to an inability to administer via intravenous route. Cases: The age of 3 cases was 83, 75, 82 years, respectively. In all cases, the prognosis prediction at the start of subcutaneous LEV was about 1 month. In all cases, the route of administration of LEV was changed from intravenous to subcutaneous. No exacerbation of convulsions, or injection site reaction was confirmed after subcutaneous LEV administration. Discussion: We believe that subcutaneous LEV administration may be one of the treatment options for seizures in patients with terminal cancer for whom intravenous administration of LEV is no longer feasible.

Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

Background: Neonatal seizure management has not changed much in the last 50 years. Neuronal apoptosis in animal models and cognitive impairment in human subjects has been reported with the use of Phenobarbitone. Levetiracetam is advantageous as it is effective, well tolerated and has least drug interactions.Methods: This double blinded, randomized, parallel group, active controlled study was conducted among 66 neonates in the Neonatal intensive care unit of a tertiary care hospital for a period of 18 months. Neonates with seizures fulfilling the inclusion criteria were treated either with Phenobarbitone or Levetiracetam. Seizure control was defined as no seizure activity within 40 minutes of the administration of the first drug. Failure of first line agent was treated with Phenytoin. Neonates were observed for a period of 14 weeks for recurrence of seizure and any serious adverse effects.Results: Effective seizure control was achieved in 64.7% neonates in Levetiracetam group as compared to 31.2% in Phenobarbitone group (p <0.05). Early resumption of breast feeds within 6 hours of therapy was achieved in 73.5% neonates treated with Levetiracetam compared to 31.2% neonates treated with Phenobarbitone (p value = 0.001).Conclusions: Levetiracetam is a promising alternative as first line Anti-epileptic drug in neonates with seizures. Prolonged sedation was the adverse effect noted to Phenobarbitone that made breast feeding and neuro- assessment difficult. No serious adverse effects were seen with Levetiracetam.

Antiepileptic Drugs in Children: Current Concept

An epileptic seizure is defined as the transient occurrence of signs and/or symptoms due to abnormally excessive or synchronous neuronal activity in the brain. The type of seizure is defined by the mode of onset and termination, clinical manifestation, and by the abnormal enhanced synchrony. If seizures recur, that state is defined as epilepsy. Antiepileptic drugs (AEDs) are the mainstay of treatment. Knowledge about initiating and maintaining adequate AEDs is beneficial for the clinician who treats children with epilepsy. This article will delineate the general principles for selecting, introducing, and discontinuing AEDs and outline guidelines for monitoring adverse effects. In general, AED therapy following a first unprovoked seizure in children is not recommended. However, treatment should be considered after a second seizure. In children and adolescents, if they are seizure-free for at least 2 years, attempts to withdraw medication/s should be made, taking into account the risks vs. benefits for the individual patient. The decision on when and what AED to use should be tailored according to the patient. For optimal treatment, the selection of adequate AEDs can be achieved by considering the precise definition of the patient's seizure and epilepsy syndrome. Continuous monitoring of both therapeutic and adverse effects is critical for successful treatment with AEDs.

Antiepileptic Drugs in Children: Current Concept

An epileptic seizure is defined as the transient occurrence of signs and/or symptoms due to abnormally excessive or synchronous neuronal activity in the brain. The type of seizure is defined by the mode of onset and termination, clinical manifestation, and by the abnormal enhanced synchrony. If seizures recur, that state is defined as epilepsy. Antiepileptic drugs (AEDs) are the mainstay of treatment. Knowledge about initiating and maintaining adequate AEDs is beneficial for the clinician who treats children with epilepsy. This article will delineate the general principles for selecting, introducing, and discontinuing AEDs and outline guidelines for monitoring adverse effects. In general, AED therapy following a first unprovoked seizure in children is not recommended. However, treatment should be considered after a second seizure. In children and adolescents, if they are seizure-free for at least 2 years, attempts to withdraw medication/s should be made, taking into account the risks vs. benefits for the individual patient. The decision on when and what AED to use should be tailored according to the patient. For optimal treatment, the selection of adequate AEDs can be achieved by considering the precise definition of the patient's seizure and epilepsy syndrome. Continuous monitoring of both therapeutic and adverse effects is critical for successful treatment with AEDs.

Phenytoin toxicity presenting with acute visual loss and acute delirium, a case report

@#Phenytoin is a widely prescribed antiepileptic agent for both focal and generalized seizure. We report a case of a 20-year-old man with focal epilepsy presented with acute bilateral visual loss, and delirium. His random phenytoin serum concentration on admission was 43.6 mg/L, well above the recommended therapeutic range of 10-20 mg/L. Extensive investigations have ruled out other vascular or demyelinating causes. His visual symptoms completely resolved after discontinuing phenytoin for 84 hours. This case shows that acute phenytoin toxicity can result in reversible visual failure.

Adverse Events During Perampanel Adjunctive Therapy in Intractable Epilepsy

BACKGROUND AND PURPOSE: Perampanel is the first α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist developed to treat epilepsy. The effects of either rapid or slow dose titration on adverse events remain to be elucidated. METHODS: Eighty-five patients received perampanel between March 2016 and August 2016. Patients were divided into two groups according to their dosing schedule: rapid dose titration (2-mg increments at intervals of 1 to 2 weeks) and slow dose titration (2-mg increments at intervals of at least 3 weeks). Seizure frequency and adverse events were analyzed over 3 months. RESULTS: Adverse events were reported by 47 (58%) of the 81 patients analyzed, with 12 (15%) patients discontinuing perampanel due to adverse events. Common adverse events included dizziness (n=30, 37%), aggressive mood and behavior (n=19, 24%), gait disturbance (n=16, 20%), and sleep problems (n=10, 12.4%). The overall adverse events were similar in the slow-titration group (38 of 61 patients) and the rapid-titration group (8 of 20 patients, p=0.081). However, none of the 20 patients in the slow-titration group experienced gait disturbance, compared with 16 of the 61 patients in the rapid-titration group (p=0.009), while appetite change was experienced by 4 patients in the slow-titration group but only 1 in the rapid-titration group (p=0.003). No relationship was noted between adverse events and the maximum dose of perampanel (p=0.116). Sex differences were observed, with the response to perampanel being better and the rate of adverse events being higher in females (p=0.015 and p=0.046, respectively). CONCLUSIONS: Slow titration of perampanel may reduce perampanel-related adverse events.

Lamotrigine, an antiepileptic drug, inhibits 5-HT₃ receptor currents in NCB-20 neuroblastoma cells

Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC₅₀ value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT₃-mediated currents evoked by 1 mM dopamine, a partial 5-HT₃ receptor agonist, were inhibited by lamotrigine co-application. The EC₅₀ of 5-HT for 5-HT₃ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT₃ receptor desensitization, inhibited 5-HT₃ receptor currents in a concentration-dependent manner. The deactivation of 5-HT₃ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT₃ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT₃-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

Influence of parental compliance on therapeutic effect of children with epilepsy / 中国中西医结合急救杂志

Objective To investigate the influence of parental compliance on the therapeutic effect of children with epilepsy.Methods Two hundred and sixty children with epilepsy and their parents admitted to the First People's Hospital of Wenling from December 2013 to June 2016 were enrolled,and the classical Morisky medication adherence questionnaire (MMAS-8) was applied to evaluate the compliance of parents for treatment of their children with epilepsy;after the patient taking drug for 3 days,fasting venous blood was collected in the morning,the concentration of the blood drug was tested and the influence of parent compliance on the blood drug concentration of the child with epilepsy was evaluated.Results In 260 patients,122 cases took karma form,and 138 cases took valproate orally.There were parents with good medication compliance in 130 cases (50％),medium medication compliance 80 cases (30.76％) and poor adherence to the doctor order in 50 cases (19.23％).In cases using medication irregularly,there were 26 cases sometimes without taking any drug (10.0％),17 patients' medication being interrupted (6.54％) and 10 cases having excessive medication (3.85％);no relationships were found between parental compliance and each of the following items,family role,occupation and age (all P ＞ 0.05);and the compliance was related to gender,indicating that women's good compliance level was higher than that of males';the education level was positively proportional to the compliance,and the compliance of parents with senior high school or above degree was higher than those with primary school and junior secondary school levels (83 cases vs.9 cases,38 cases,both P ＜ 0.01).Under situation of parents with poor compliance,their children had blood drug concentration higher or lower than proper range of drug level (high in 22 cases,low in 41 cases,higher than the result in good compliance 0 cases and 17 cases respectively),thus seriously affected the safety and efficacy of the treatment;the patients' frequency of irregular medication in parents' good compliance group was significantly lower than that in parents' poor compliance group [3.08％ (4/130) vs.72.0％ (36/50),P ＜ 0.05].Conclusion To improve the therapeutic effect of epileptic children,their parental good cooperation is necessary.

Updates on the relationship between vitamin D and epilepsy / 国际儿科学杂志

Vitamin D adjusts the body′s absorption and utilization of calciumand phosphorus. Vitamin D deficiency is closely related to incidence of many disease. Several disorders,both systemic and those of the nerv-ous system,have been linked with vitamin D deficiency. Neurological disorders with a vitamin D link include but are not limited to multiple sclerosis,Alzheimer and Parkinson disease,as well as cerebrovascular disorders. In re-cent years,studies have found that the vitamin D may play a critical role in the pathogenesis of epilepsy and pos-sess certain anticonvulsant effects. This article summarized the role of vitamin D in the nervous system and epi-lepsy,the level of serum vitamin D and the correlation of the polymorphism of its receptor genes with epilepsy. The review also summarizes the interaction between antiepileptic drugs and vitamin D.

Systemic Family Therapy of Comorbidity of Anxiety and Depression with Epilepsy in Adolescents

OBJECTIVE: The aim of this study was to find if systemic family therapy (SFT) does work in anxiety and depression with epilepsy in adolescents (ADAE). METHODS: 104 adolescents with epilepsy, aged 13-20 years old, were included from December 2009 to December 2010, the enrolled patients were with anxiety [Hamilton Anxiety Scale (HAMA) score ≥14 points] or depression [Hamilton Depression Scale (HAMD) score ≥20 points]. The patients were randomly divided into the control group (n=52) treated with antiepileptic drugs (AED) and the intervention group (n=52) undergone Systemic Family Therapy (SFT) as well as AED. The AED improvements, anxiety and depression scores, Social Support Rating Scale (SSRS), Family Assessment Device (FAD) and scale of systemic family dynamics (SSFD) were observed after 3-month treatment. RESULTS: The frequencies of epileptic seizures in intervention group was decreased much more significantly than the control group (4.22±3.54 times/month vs. 6.20±5.86 times/month, p=0.04); and the scores of anxiety (9.52±6.28 points vs. 13.48±8.47 points, p=0.01) and depression (13.86±9.17 points vs. 18.89±8.73 points, p=0.02) were significantly decreased than the control group; meanwhile, the family dynamics and family functions were significantly improved, and the social support was also increased (p<0.05). CONCLUSION: SFT combined with AEDs had better efficacies than AEDs alone, not only the frequency of epileptic seizures was decreased, but also the patients' anxiety and depression were improved, and the family dynamics, family functions and social support were improved.

Effects of Prophylactic Antiepileptic Drugs on Clinical Outcomes in Patients with a Good Clinical Grade Suffering from Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE: Routine use of prophylactic antiepileptic drugs (AED) has been debated. We retrospectively evaluated the effects of prophylactic AED on clinical outcomes in patients with a good clinical grade suffering from aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between September 2012 and December 2014, 84 patients who met the following criteria were included: (1) presence of a ruptured aneurysm; (2) Hunt-Hess grade 1, 2, or 3; and (3) without seizure presentation. Patients were divided into two groups; the AED group (n = 44) and the no AED group (n = 40). Clinical data and outcomes were compared between the two groups. RESULTS: Prophylactic AEDs were used more frequently in patients who underwent microsurgery (84.1%) compared to those who underwent endovascular surgery (15.9%, p < 0.001). Regardless of prophylactic AED use, seizure episodes were not observed during the six-month follow-up period. No statistical difference in clinical outcomes at discharge (p = 0.607) and after six months of follow-up (p = 0.178) were between the two groups. After six months, however, favorable outcomes in the no AED group tended to increase and poor outcomes tended to decrease. CONCLUSION: No difference in the clinical outcomes and systemic complications at discharge and after six months of follow-up was observed between the two groups. However, favorable outcomes in the no AED group showed a slight increase after six months. These findings suggest that discontinuation of the current practice of using prophylactic AED might be recommended in patients with a good clinical grade.

Effects of Prophylactic Antiepileptic Drugs on Clinical Outcomes in Patients with a Good Clinical Grade Suffering from Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE: Routine use of prophylactic antiepileptic drugs (AED) has been debated. We retrospectively evaluated the effects of prophylactic AED on clinical outcomes in patients with a good clinical grade suffering from aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between September 2012 and December 2014, 84 patients who met the following criteria were included: (1) presence of a ruptured aneurysm; (2) Hunt-Hess grade 1, 2, or 3; and (3) without seizure presentation. Patients were divided into two groups; the AED group (n = 44) and the no AED group (n = 40). Clinical data and outcomes were compared between the two groups. RESULTS: Prophylactic AEDs were used more frequently in patients who underwent microsurgery (84.1%) compared to those who underwent endovascular surgery (15.9%, p < 0.001). Regardless of prophylactic AED use, seizure episodes were not observed during the six-month follow-up period. No statistical difference in clinical outcomes at discharge (p = 0.607) and after six months of follow-up (p = 0.178) were between the two groups. After six months, however, favorable outcomes in the no AED group tended to increase and poor outcomes tended to decrease. CONCLUSION: No difference in the clinical outcomes and systemic complications at discharge and after six months of follow-up was observed between the two groups. However, favorable outcomes in the no AED group showed a slight increase after six months. These findings suggest that discontinuation of the current practice of using prophylactic AED might be recommended in patients with a good clinical grade.

Estado epiléptico convulsivo en adultos atendidos en el Instituto Nacional de Ciencias Neurológicas de Lima, Perú 2011-2013. / Convulsive status epilepticus in adults attending the Instituto Nacional de Ciencias Neurológicas in Lima, Perú 2011-2013.

Objetivos: describir las características clínicas y la evolución del estado epiléptico convulsivo (EEC) en pacientes adultos admitidos en el Servicio de Emergencia del Instituto Nacional de Ciencias Neurológicas de Lima, Perú entre los años 2011 y 2013. Métodos: Se realizó un estudio prospectivo de serie de casos. Resultados: Se incluyeron 28 pacientes mayores de 17 años, la mediana de edad fue 31 años. El 57% fueron hombres y el 89% tenían antecedentes de epilepsia. La principal causa del EEC fue el incumplimiento de la medicación antiepiléptica (54%). El diazepam seguido de la fenitoína fue el tratamiento antiepiléptico más empleado (75%) y la frecuencia de EEC refractario fue del 4%. Conclusiones: los pacientes fueron mayoritariamente varones, adultos jóvenes, con antecedentes de epilepsia que presentaron un EEC debido el incumplimiento de la medicación antiepiléptica y respondieron favorablemente al tratamiento con diazepam seguido de fenitoína.

Objectives: to describe the characteristics features and outcome of convulsive status epilepticus (CSE) in adult patients admitted to the Emergency Department at the Instituto Nacional de Ciencias Neurológicas in Lima, Peru between 2011 and 2013. Methods: a prospective study was conducted. Results: twenty-eight patients older than 17 years were included, the median age was 31 years old. 57% were male and 89% had a history of epilepsy. Main cause of CSE was antiepileptic medication noncompliance (54%). Diazepam followed by phenytoin was the most used therapeutic regimen (75%) and the frequency of refractory CSE was 4%. Conclusion: patients were mostly male, young adults with a history of epilepsy who presented a CSE caused by the antiepileptic medication noncompliance and the response to treatment based on diazepam followed by phenytoin was positive.

Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy.

Background: Epilepsy is a chronic neurological condition which may require long-term treatment with antiepileptic drugs (AEDs). The challenge in AED management is to attain freedom from seizures, without side-effects and with good quality-of-life. However, AEDs are reported to induce potential adverse effects, which can remain unnoticed over long time. In this regard, earlier studies report inconsistent results in hematological and biochemical toxicity of AEDs. The objective of the present study was to evaluate the effects of AED monotherapy and polytherapy on hematological and biochemical parameters. Methods: This was a cross-sectional, observational study carried out among patients with epilepsy (PWE) receiving AEDs. The data on baseline demographic characteristics, treatment, adverse drug reactions, hematological, and biochemical investigations were collected. Statistical analysis was performed using the SPSS version 18 and descriptive statistics such as mean and median were used to summarize the data and inferential tests like Chi-square was used to compare categorical variables between groups. Results: There were 255 PWE in mean age range of 28.68±9.29 years, with 56.54% males. A total of 78.04% had focal, 18.04% had generalized seizures and remaining 3.92% were unclassified. Majority of (55.69%) PWE received polytherapy with AEDs. Females had significantly lower levels of hemoglobin (Hb) when compared with males (p=0.000), and patients on AED polytherapy showed significant difference in low Hb (p=0.006) and high alkaline phosphatase (ALP) levels (p=0.001). Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy.

Toxic epidermal necrolysis induced by lamotrigine treatment in a child / 소아과

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.

Effect of Phenobarbital on Bcl-2 and Bax expressions in brain tissue of young rats / 中华实用儿科临床杂志

Objective To study the effect of Phenobarbital (PB) on experimental rats,observe the histological changes of immature brain and the expressions of apoptosis-related proteins Bcl-2 and Bax in neurons detected by immunohistochemistry,and to explore the influence and mechanism of PB on brain damage at therapeutic levels to immature brain maturation of rat in order to provide the theoretical and experimental base for clinic.Methods A total of 40 healthy 18-day-old Sprague-Dawley(SD) rats (male or female) were randomly assigned into 2 groups:normal saline (NS) treated as control group(20 cases),PB group(20 cases).Each group was further randomly divided into longterm(4 weeks) treated group and short-term(2 weeks) treated group(10 rats in each group).The rats in PB group received intragastricadministration with PB (30 mg/kg).The rats in control group were handled by injection of NS into stomach and abdomen according to 4 mL/kg.All performances were undertaken for twice every day.At the end of the therapeutic period,body and brain weight were measured when the rats were sacrificed.Histological studies on the tissues of frontal lobes and hippocampus were performed by Hematoxylin-Eosin(HE) staining and Nissl staining.Expressions of apoptosis-related proteins Bcl-2 and Bax in neurons were detected by immunohistochemistry.Results There were no significant differences in body and brain weights or histological studies index among control group as well as PB group before and after treatment for short term(P ＞0.05).Remarkable reduction of brain weight was only observed in immature rats exposed to PB compared to control group for long period,and significant neurodegeneration,neuronal necrosis were observed in immature rats exposed to PB compared to control group(all P ＜ 0.01).The expression of Bax protein in the frontal lobe increased significantly in immature rats receiving PB for long period comparing with control (P＜0.01).In contrast,expression of Bcl-2 protein did not change at therapeutic level.The ratio of Bax/Bcl-2 was obviously increased.Conclusions Chronic treatment with PB will result in significant neuronal apoptosis and necrosis and persistent cognitive impairment and brain damage to immature rates.Brain damage of PB at therapeutic level to immature brain may be irreversible.The significant expression of Bax protein in the frontal lobe and the high rate of Bax/Bcl-2 are probably the main reasons which cause brain weight decreasing and brain damage by PB in immature brain tissue.

Long-term anti-epileptic drug therapy and metabolic bone disase in children / 国际儿科学杂志

Epilepsy is a common chronic brain dysfunction in children.Studies have showed that antiepileptic drugs (AED) affect the hydroxylation of vitamin D in liver and kidney and inhibit the calcification of bone,mainly by up-regulating cytochrome oxidase P450 and promoting the resolution of vitamin D,and then increasing serum parathyroid hormone compensatory.Long-term use can cause children metabolic bone disease occurrence,clinical manifestations include bone pain,short stature,rickets,teeth agenesis,fracture,etc.AED firstly affect the hormones related to bone metabolism in vivo,so that the present researches focus on biochemical tests and measurement of sclerotin and bone density.In the children's long-term use of antiepileptic drug treatment at the same time,the application of Vitamin D,calcium and exercise can prevent the occurrence of metabolic bone disease.

A Survey of the Use of Antiepileptic Drugs in Stroke Patients

BACKGROUND: Seizures occur in 2-20% of stroke patients. Recent studies have reported that post-stroke seizures are associated with poorer functional outcomesand higher mortality. However there are no official guidelines on how to use antiepileptic drugs (AEDs) in stroke-related seizures. In this study we surveyed neurologists and neurosurgeons and compared the responses of subgroups categorized by department, specialty and workplace discrimination using a questionnaire containing questions concerning the present tendency to use AEDs in stroke patients. METHODS: 256 neurologists and neurosurgeons participated in the survey. The research instrument was a questionnaire comprising 9 parts and 30 questions. The questions concerned stroke mechanism, the prophylactic use of AEDs, and the choice of AED in early and late onset post-stroke seizures. RESULTS: Tendencies to use prophylactic AEDs in stroke differed depending on specialty and workplace(neurologist vs. neurosurgeon; 17.8% vs. 83.1%, p<0.001, hospital vs. university staff; 46.2% vs. 28.4%, p=0.05). The most commonly used prophylactic AEDs were valproic acid (75%) and levetiracetam (60%). Carbamazepine was the most commonly used AED and phenytoin and phenobarbital were still used in all subgroups to treat post-stroke seizures. CONCLUSIONS: There are significant differences between neurologists (17.8%) and neurosurgeons (83.1%) in the use of prophylactic AEDs after stroke. Valproic acid and levetiracetam are considered first-line prophylactic AEDs by neurosurgeon. Phenytoin and phenobarbital are still used in post-stroke seizure although they have been reported to have an adverse influence on motor recovery. We suggest that proper guidelines should be established for the use of AEDs in stroke-related seizures.