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Epilepsy is a prevalent chronic neurological disorder in children, often requiring long term antiepileptic drug (AED) therapy. These medications can have cardiovascular side effects, including the development of atherosclerotic lesions. Such effects have been reported to impact the thickness of the carotid intima-media and the ejection fraction of the heart. This study aims to compare the carotid artery intima-media thickness and ejection fraction in children with epilepsy undergoing monotherapy versus polytherapy. This cross-sectional study collected primary data from pediatric epilepsy patients at the Child Neurology Outpatient and Inpatient Installation, Department of Pediatrics, RSUD Dr. Soetomo Surabaya, from June to August 2023. Patients who met the inclusion criteria and consented to participate were included through consecutive sampling. Data analysis was performed using the paired t-test, and data processing was conducted using SPSS. The study included 30 patients, predominantly male (53.3%). The mean age was 9.33 ± 5 years in the monotherapy group and 7.29 ± 4.59 years in the polytherapy group. In the polytherapy group, the mean carotid intima-media thickness was 0.073 ± 0.13 cm, compared to 0.06 ± 0.08 cm in the monotherapy group. The mean ejection fraction was 58 ± 1.76% in the polytherapy group and 71.05 ± 3.9% in the monotherapy group. The comparison of carotid intima-media thickness showed no significant difference (p > 0.05), while the ejection fraction comparison was significantly different (p < 0.05). Polytherapy in pediatric epilepsy is associated with a significantly lower ejection fraction, indicating potential cardiovascular risks, while differences in carotid intima-media thickness were not statistically significant. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a chronic neurologic disorder characterized by abnormal functioning of brain networks, making it a complex research topic. Recent advancements in neuroimaging technology offer an effective approach to unraveling the intricacies of the human brain. Within different types of epilepsy, there is growing recognition regarding ongoing changes in the default mode network (DMN). However, little is known about the shared and distinct alterations of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in DMN among epileptic subtypes, especially in children with epilepsy. Methods: Here, 110 children with epilepsy at a single center, including idiopathic generalized epilepsy (IGE), frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), and parietal lobe epilepsy (PLE), as well as 84 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scan. We investigated both sFC and dFC between groups of the DMN. Results: Decreased static and dynamic connectivity within the DMN subsystem were shared by all subtypes. In each epilepsy subtype, children with epilepsy displayed significant and distinct patterns of DMN connectivity compared to the control group: the IGE group showed reduced interhemispheric connectivity, the FLE group consistently demonstrated disturbances in frontal region connectivity, the TLE group exhibited significant disruptions in hippocampal connectivity, and the PLE group displayed a notable decrease in parietal-temporal connectivity within the DMN. Some state-specific FC disruptions (decreased dFC) were observed in each epilepsy subtype that cannot detect by sFC. To determine their uniqueness within specific subtypes, bootstrapping methods were employed and found the significant results (IGE: between PCC and bilateral precuneus, FLE: between right middle frontal gyrus and bilateral middle temporal gyrus, TLE: between left Hippocampus and right fusiform, PLE: between left angular and cingulate cortex). Furthermore, only children with IGE exhibited dynamic features associated with clinical variables. Conclusions: Our findings highlight both shared and distinct FC alterations within the DMN in children with different types of epilepsy. Furthermore, our work provides a novel perspective on the functional alterations in the DMN of pediatric patients, suggesting that combined sFC and dFC analysis can provide valuable insights for deepening our understanding of the neuronal mechanism underlying epilepsy in children.

Epilepsy affects nearly 50 million people worldwide. Epilepsy can affect the quality of life of both the child and the caregiver leaving them unable to function in other areas of life. This quality of life is highly dependent on treatment adherence and how individuals feel about taking their medication. In our study, we aimed to investigate the frequency of medication adherence and the quality of life of caregivers of children with epilepsy. For this purpose, we conducted a cross-sectional survey at the Abha Maternity and Children's Hospital. We enrolled 133 consecutive participants and asked them to complete a questionnaire. The results showed that 37.6% of the participants forgot to take their medications, 9.8% of the participants reported that they were sometimes careless about giving their children medications and sometimes stopped giving them when the children were feeling better, 15.8% of the participants indicated that they sometimes stopped giving the medication when they felt that their children were getting worse when they took the medication., and 26.3% of the participants agreed that they only administered the medication when the children were sick. It was also found that the quality of life of the caregivers decreased when they forgot to give their children the medication and the quality of life of the caregivers increased when they continued to take the medication. In conclusion, quality of life increases as adherence to treatment increases, indicating that more intervention programs are needed to improve the adherence of epilepsy patients.

Objective: The aim of this study was to establish a population pharmacokinetic (PPK) model of valproic acid (VPA) in pediatric patients with epilepsy in southern China, and provide guidance for individualized medication of VPA therapy.Methods: A total of 376 VPA steady-state trough concentrations were collected from 103 epileptic pediatric patients. The PPK parameter values for VPA were calculated by using the nonlinear mixed-effects modeling (NONMEM) method, and a one-compartment model with first-order absorption and elimination processes was applied. Covariates included demographic information, concomitant medications and selected gene polymorphisms. Goodness-of-fit (GOF), bootstrap analysis, and visual predictive check (VPC) were used for model evaluation. In addition, we used Monte Carlo simulations to propose dose recommendations for different subgroup patients.Results: A significant effect of the patient age and ABCB1 genotypes was observed on the VPA oral clearance (CL/F) in the final PPK model. Compared with patients with the ABCB1 rs3789243 AA genotype, CL/F in patients with GG and AG genotypes was increased by 8% and reduced by 4.7%, respectively. The GOF plots indicated the satisfactory predictive performance of the final model, and the evaluation by bootstrap and VPC showed that a stable model had been developed. A table of individualized dosing regimens involving age and ABCB1 genotype was constructed based on the final PPK model.Conclusion: This study quantitatively investigated the effects of patient age and ABCB1 rs3789243 variants on the pharmacokinetic variability of VPA. The PPK models could be beneficial to individual dose optimization in epileptic children on VPA therapy.

Epilepsy affects nearly 50 million people worldwide. Epilepsy can affect the quality of life of both the child and the caregiver leaving them unable to function in other areas of life. This quality of life is highly dependent on treatment adherence and how individuals feel about taking their medication. In our study, we aimed to investigate the frequency of medication adherence and the quality of life of caregivers of children with epilepsy. For this purpose, we conducted a cross-sectional survey at the Abha Maternity and Children's Hospital. We enrolled 133 consecutive participants and asked them to complete a questionnaire. The results showed that 37.6% of the participants forgot to take their medications, 9.8% of the participants reported that they were sometimes careless about giving their children medications and sometimes stopped giving them when the children were feeling better, 15.8% of the participants indicated that they sometimes stopped giving the medication when they felt that their children were getting worse when they took the medication., and 26.3% of the participants agreed that they only administered the medication when the children were sick. It was also found that the quality of life of the caregivers decreased when they forgot to give their children the medication and the quality of life of the caregivers increased when they continued to take the medication. In conclusion, quality of life increases as adherence to treatment increases, indicating that more intervention programs are needed to improve the adherence of epilepsy patients. [ABSTRACT FROM AUTHOR]

Objective: A number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS. Methods: Here, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed. Results: The static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time). Significance: Our findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children. [ABSTRACT FROM AUTHOR]

Nageh Shehata,1 Salah Mahmoud Saleh,1 Ahmed M Kamal,2 Omnia Kamal Awad1 1Department of Pediatrics, Faculty of Medicine, Minya University, El Minya, 61111, Egypt; 2Department of Neurology, Faculty of Medicine, Minya University, El Minya, EgyptCorrespondence: Nageh ShehataPediatric Department, Minia Children Hospital, El Minya, 61111, EgyptEmail nagehismael@yahoo.comBackground: Epilepsy, the most common neurological disorder in children, may present with many psychiatric comorbidities, the most common of which is depression.Aim of the Work: We evaluated the frequency of depressive symptoms in epileptic children, with regard to the possible association between depression and their demographic data or seizure-related variables.Patients and Methods: This cohort study was conducted on 80 children (6– 13 years old) diagnosed as idiopathic epilepsy and were regularly recruiting the pediatric neurology clinic at Minya University Children Hospital. The Structured Birleson Depression Scale Questionnaire was used for assessment of presence of depressive symptoms, and Quality Of Life in Epilepsy (QOLIE-31) score was used to assess quality of life in those patients.Results: Depressive symptoms were found in 37.5% of enrolled patients. There were statistically significant differences between the patients with depressive symptoms and the other group regarding age (p=0.001), residence (p=0.006) and past history of mood disorders (p=0.03). Sleep disturbance was the highest predictor of depression in cases with depressive symptoms, detected in 90% of cases, followed by appetite disturbance in 86.6% of cases, while delusions and hallucinations were the lowest, detected in only 10% of cases. Both duration of epilepsy and frequency of seizures were significantly higher in cases with depressive symptoms than the other group (p=0.001) for both. QOLIE score was significantly lower in cases with depressive symptoms than the other group (p= 0.01 for all).Conclusion: Depressive symptoms are common in epileptic children, and it is often challenging and underestimated. It should be screened during the management of such children. Early diagnosis and more comprehensive package of care for depression in epileptic children will enable them to have a better quality of life.Keywords: depressive symptoms, epileptic children, quality of life

Background: There is a relationship between diseases and the quality of life. Epilepsy is a disease that is unpredictable and uncontrollable and its actions are limited to scattered and brief education. Therefore, this study aimed to investigate the effect of family-centered empowerment program on the quality of life of mothers with epileptic children. Methods: This clinical trial was undertaken on 60 mothers with epileptic children. Thirty mothers with epileptic children participated in family-centered empowerment sessions and 30 mothers with epileptic children served as the control group. Personal information form and quality of life questionnaire were administered at baseline and 75 days after intervention. In order to analyze data, chi-square test, independent t-test, paired t-test, and covariance were used accordingly. Results: The quality of life between the two groups was not significantly different at the beginning of the study, but it was significantly different 75 days after the onset of the empowerment program. In other words, the family-centered empowerment program had a significantly positive impact on the quality of life of mothers with epileptic children (P = 0.03). Conclusion: According to the results of this study, the family-centered empowerment program can be considered as a potent alternative in health care system to enhance the quality of life of families with epileptic children.

Background: To observe the relationship between Tumor Necrosis Factor-alpha (TNF-α) and Neuropeptide Y (NPY) expression and neurological function score in epileptic children. Methods: Fifty-four epileptic children diagnosed and treated in Xuzhou Children's Hospital, China from Feb 2017 to Mar 2018 were collected and included in a research group (RG), while 30 healthy children who underwent physical examination at the same time were included in the control group (CG). ELISA was used to detect the expression of TNF-α and NPY in the serum of children in the two groups, and those before treatment were compared. The National Institute of Health stroke scale (NIHSS) and Hamilton Anxiety (HAMA) scores before and after treatment were observed, and Pearson correlation was used to analyze the relationship between the expression levels of TNF-α and NPY in the serum as well as NIHSS and HAMA scores. Results: The expression levels of TNF-α and NPY in the serum of children in the RG were significantly higher than those in the CG (P

Abstract Introduction Generalized tonic‐clonic seizure (GTCS) is a condition that is characterized by generalized spike‐wave discharge in bilateral cerebral hemispheres during the seizure. Although previous neuroimaging studies revealed functional abnormalities in the brain activities of children with GTCS, the topological alterations in whole‐brain networks remain poorly understood. Methods The present study used graph theory to investigate the topological organization of functional networks in 13 GTCS children and 30 age‐matched healthy controls. Results We found that both groups exhibited a small‐world topology of the functional network. However, children with GTCS showed a significant decrease in nodal local efficiency and clustering coefficient in some key nodes compared with the controls. The connections within the default mode network (DMN) were decreased significantly, and the internetwork connections were increased significantly. The altered topological properties may be an effect of chronic epilepsy. As a result, the optimal topological organization of the functional network was disrupted in the patient group. Notably, clustering coefficient and nodal local efficiency in the bilateral temporal pole of the middle temporal gyrus negatively correlated with the epilepsy duration. Conclusion These results suggest that the bilateral temporal pole plays an important role in reflecting the effect of chronic epilepsy on the topological properties in GTCS children. The present study demonstrated a disrupted topological organization in children with GTCS. These findings provide new insight into our understanding of this disorder.

Introduction: Generalized tonic‐clonic seizure (GTCS) is a condition that is characterized by generalized spike‐wave discharge in bilateral cerebral hemispheres during the seizure. Although previous neuroimaging studies revealed functional abnormalities in the brain activities of children with GTCS, the topological alterations in whole‐brain networks remain poorly understood. Methods: The present study used graph theory to investigate the topological organization of functional networks in 13 GTCS children and 30 age‐matched healthy controls. Results: We found that both groups exhibited a small‐world topology of the functional network. However, children with GTCS showed a significant decrease in nodal local efficiency and clustering coefficient in some key nodes compared with the controls. The connections within the default mode network (DMN) were decreased significantly, and the internetwork connections were increased significantly. The altered topological properties may be an effect of chronic epilepsy. As a result, the optimal topological organization of the functional network was disrupted in the patient group. Notably, clustering coefficient and nodal local efficiency in the bilateral temporal pole of the middle temporal gyrus negatively correlated with the epilepsy duration. Conclusion: These results suggest that the bilateral temporal pole plays an important role in reflecting the effect of chronic epilepsy on the topological properties in GTCS children. The present study demonstrated a disrupted topological organization in children with GTCS. These findings provide new insight into our understanding of this disorder. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurologic disorder characterized by abnormal functioning of brain networks, making it a complex research topic. Recent advancements in neuroimaging technology offer an effective approach to unraveling the intricacies of the human brain. Within different types of epilepsy, there is growing recognition regarding ongoing changes in the default mode network (DMN). However, little is known about the shared and distinct alterations of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in DMN among epileptic subtypes, especially in children with epilepsy. Here, 110 children with epilepsy at a single center, including idiopathic generalized epilepsy (IGE), frontal lobe epilepsy (FLE), temporal lobe epilepsy (TLE), and parietal lobe epilepsy (PLE), as well as 84 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scan. We investigated both sFC and dFC between groups of the DMN. Decreased static and dynamic connectivity within the DMN subsystem were shared by all subtypes. In each epilepsy subtype, children with epilepsy displayed significant and distinct patterns of DMN connectivity compared to the control group: the IGE group showed reduced interhemispheric connectivity, the FLE group consistently demonstrated disturbances in frontal region connectivity, the TLE group exhibited significant disruptions in hippocampal connectivity, and the PLE group displayed a notable decrease in parietal-temporal connectivity within the DMN. Some state-specific FC disruptions (decreased dFC) were observed in each epilepsy subtype that cannot detect by sFC. To determine their uniqueness within specific subtypes, bootstrapping methods were employed and found the significant results (IGE: between PCC and bilateral precuneus, FLE: between right middle frontal gyrus and bilateral middle temporal gyrus, TLE: between left Hippocampus and right fusiform, PLE: between left angular and cingulate cortex). Furthermore, only children with IGE exhibited dynamic features associated with clinical variables. Our findings highlight both shared and distinct FC alterations within the DMN in children with different types of epilepsy. Furthermore, our work provides a novel perspective on the functional alterations in the DMN of pediatric patients, suggesting that combined sFC and dFC analysis can provide valuable insights for deepening our understanding of the neuronal mechanism underlying epilepsy in children. • Decreased static and dynamic connectivity within the DMN subsystem were shared by all children with epilepsy • State-specific FC disruptions were observed in each patient group that were not detected by state FC • Epilepsy children in each subtype also showed unique connectivity patterns of the DMN that reflect their epilepsy types • The findings of static and dynamic functional abnormalities in DMN confirmed the essential role of DMN in children with epilepsy [ABSTRACT FROM AUTHOR]

Introduction: The relationship between autism and epilepsy is definitely reported. The prevalence of autism among epileptic children is definitely higher than non-epileptic cases. The purpose of this investigation was to diagnose autism among epileptic children earlier and comparing them with non-epileptic children as well as investigating risk factors, which increased autism among them. Methods: In this case control study, 2 questionnaires were applied; one of them was related to the features of autism and seizure, which was filled for 160 epileptic children between 4-16 years old referring to pediatric neurologic unit in Emam Reza's Clinic in Shiraz. The other questionnaire was the autism screening questionnaire, which was also filled for 160 non epileptic children referring to other pediatric units in that clinic as the control group. This questionnaire was based on DSM-IV-TR criteria and every suspicious child for autism was confirmed or refused by neurologist and psychiatrist. Result: 12 children among 160 epileptic cases were diagnosed as autistic patients. However, no autistic child was diagnosed in the control group that this difference was statistically significant. Furthermore, there was a significant correlation between the prevalence of autism and the age of seizure onset, as well as the findings of CT and MRI and the etiology of the seizure, but there were not any significant correlations with other variables of seizure. Discussion: According to this study, the prevalence of autism among epileptic children is higher than non epileptic ones. As the age of the onset of seizure is lower the prevalence of autism will be higher. Also, the prevalence of autism among epileptic children will be higher as abnormal findings of imaging and known etiologies of seizureincrease. Loss of significant correlations among prevalence of autism and some variables of seizure can be due to few numbers of autistic cases, which were diagnosed in this study comparing with previous studies.

Aim: To evaluate the quality of life of epileptic children. Methods and Material: This descriptive cross-sectional study was undertaken from 1st January 2014 to 1st May 2014 in children aged 3-16 years with epilepsy who followed up in the pediatric neurology unit of the Yaounde Gynaeco-Obstetrics and Pediatric Hospital in Yaounde in Cameroon. Parents responded to the quality of life questionnaire for children with epilepsy. Results: Eighty-six patients with a mean age of 8.8 ± 4.2 years were included in the study. Epilepsy was associated with poor quality of life in 18 (20.9%) patients and was mainly in children with non-idiopathic generalized epilepsy, behavioral disorders, and cognitive deficits. Social, behavioral, cognitive and depressive disorders were noted in 43 (50%), 17 (19.8%), 23 (26.7%) and 55 (63.9%), respectively. In 17 (19.8%) children, clinical examination was abnormal. Twenty (23%) children were not attending school. Conclusion: Epileptic children have a decline in their quality of life, and this is multifactorial, and controlling epileptic seizures alone does not appear to be a sufficient factor to improve the quality of life of these children. [ABSTRACT FROM AUTHOR]

Background: There is a relationship between diseases and the quality of life. Epilepsy is a disease that is unpredictable and uncontrollable and its actions are limited to scattered and brief education. Therefore, this study aimed to investigate the effect of family-centered empowerment program on the quality of life of mothers with epileptic children. Methods: This clinical trial was undertaken on 60 mothers with epileptic children. Thirty mothers with epileptic children participated in family-centered empowerment sessions and 30 mothers with epileptic children served as the control group. Personal information form and quality of life questionnaire were administered at baseline and 75 days after intervention. In order to analyze data, chi-square test, independent t-test, paired t-test, and covariance were used accordingly. Results: The quality of life between the two groups was not significantly different at the beginning of the study, but it was significantly different 75 days after the onset of the empowerment program. In other words, the family-centered empowerment program had a significantly positive impact on the quality of life of mothers with epileptic children (P = 0.03). Conclusion: According to the results of this study, the family-centered empowerment program can be considered as a potent alternative in health care system to enhance the quality of life of families with epileptic children. [ABSTRACT FROM AUTHOR]

Background Long-term anticonvulsant therapy, especially with enzyme inducers, has been associated with low 25-hydroxyvitamin D [25(OH)D] levels and high prevalence of vitamin D deficiency. However, there have been inconsistent results in studies on the effect of long-term, non-enzyme inducer anticonvulsant use on vitamin D levels. Objective To compare 25(OH)D levels in epileptic children on long-term anticonvulsant therapy and non-epileptic children. We also assessed for factors potentially associated with vitamin D deficiency/insufficiency in epileptic children. Methods This cross-sectional study was conducted at two pediatric neurology outpatient clinics in Jakarta, from March to June 2013. Subjects in the case group were epileptic children, aged 6-11 years who had used valproic acid, carbamazepine, phenobarbital, phenytoin, or oxcarbazepine, as a single or combination therapy, for at least 1 year. Control subjects were non-epileptic, had not consumed anticonvulsants, and were matched for age and gender to the case group. All subjects’ 25(OH)D levels were measured by enzyme immunoassay. Results There were 31 epileptic children and 31 non-epileptic control children. Their mean age was 9.1 (SD 1.8) years. Most subjects in the case group were treated with valproic acid (25/31), administered as a monotherapy (21/31). The mean duration of anticonvulsant consumption was 41.9 (SD 20) months. The mean 25(OH)D level of the epileptic group was 41.1 (SD 16) ng/mL, lower than the control group with a mean difference of 9.7 (95%CI 1.6 to 17.9) ng/mL. No vitamin D deficiency was found in this study. The prevalence of vitamin D insufficiency in the epileptic group was higher than in the control group (12/31 vs. 4/31; P=0.020). No identified risk factors were associated with low 25(OH)D levels in epileptic children. Conclusion Vitamin D levels in epileptic children with long-term anticonvulsant therapy are lower than that of non-epileptic children, but none had vitamin D deficiency.

Highlights • The manuscript "High frequency of persistent subtherapeutic levels of more common AEDs in epileptic children under polytherapy" by Czornyj L et al., describe a retrospective evaluation of 21,040 plasma values recorded from 3279, from both ambulatory and inpatient controls epileptic patients, and the frequency of their subtherpaeutic plasma levels of AEDs, developed at the main Children´s Hospital of Argentina, Juan P. Garrahan of Buenos Aires, Argentina. • The main highlight is to describe the similar high frequency of persistent low levels of AEDs observed in both ambulatory and inpatients, and particularly in cases under long period of hospitalization. • These results should be interpreted as particular therapeutic behavior phenotype that could be related with the "pharmacokinetics hypothesis" for pharmacoresistance to AEDs in epileptic children with refractory epilepsy. Abstract Background Low levels of AEDs can be secondary drug–drug interactions or related to irregular intake due to poor treatment adherence. This latter behavior is highly suspected in ambulatory pediatric epileptic patients when controls of AEDs are subtherapeutic. However, it cannot be considered for inpatients during long periods of hospitalization. A few isolated case reports have documented persistent low levels (PLL) of AEDs in hospitalized epileptic children, but no population study has currently been reported. Objective The aim of this study was to document the incidence of PLL of the most common AEDs – phenytoin (PHT), phenobarbital (PHB), valproic acid (VA), and carbamazepine (CBZ) – in pediatric epileptic in- and outpatients (PEP). Methods 21,040 plasma levels of the aforementioned AEDs from 3279 PEP were retrospectively analyzed. Plasma levels of AEDs were measured by an automated method using trademarked commercial kits with their corresponding quality control programs. Randomized samples were also controlled by HPLC methods. Only cases with more than 3 controls were included in the study. Results A high rate of PLL of PHT was detected in in- (71.7%) and outpatients (74.1%), while PLL of PHB, VA, and CBZ were detected in a lower proportion. Rates of PLL of PHT were similar in in- and outpatients. PLL of PHB was more commonly observed in outpatients while PLL of VA and CBZ were more frequently seen in inpatients. In some hospitalized patients receiving polytherapy, PLL of at least one AED were documented during a long time. Discussion Treatment non-adherence could be present in part of the outpatients, but cannot explain the PLL observed in a group of inpatients as described here. The recently described "pharmacokinetic hypothesis" of pharmaco-resistant epilepsy should be addressed in cases with AEDs-PLL, particularly in hospitalized cases. Perhaps, instead of stopping the subtherapeutic medication, the increasing doses of this AED and/or administration of inhibitors of CYP and P-glycoprotein, could help to achieve its therapeutic range, allowing a better pharmacologic effect and avoiding the development of more severe complications, such as status epilepticus or SUDEP. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a first-line anti-epileptic drug that is used in the treatment of generalized and partial seizures. Gene variants had been proved to influence the pharmacokinetics (PK) of VPA and contribute to its inter-individual variability (IIV). The aim of this study was to systematically investigate the effects of candidate gene variants ( CYP s, UGT s, ABC transporters, and nuclear receptors) on VPA PK in Chinese children with epilepsy. A total of 1065 VPA serum trough concentrations at steady state were collected from 264 epileptic pediatric patients aged 3 months to 16 years. The population pharmacokinetic (PPK) model was developed using a nonlinear mixed effects modelling (NONMEM) approach. For the final PPK model, the oral clearance (CL/F) of VPA was estimated to be 0.259 L/h with IIV of 13.3%. The estimates generated by NONMEM indicated that the VPA CL/F was significantly influenced by patient body weight (increased by an exponent of 0.662), co-administration with carbamazepine (increased CL/F by 22%), and daily dose of VPA (increased by an exponent of 0.22). CL/F in patients with the LEPR rs1137101 variant (668 AG and GG genotypes) was much lower than in patients with the AA genotype (17.8% and 22.6% lower, respectively). However, none of the CYP s or UGT s gene variants was found to influence the PK of VPA in this study. Evaluation by bootstrap and normalized prediction distribution error (NPDE) showed that the final model was stable. The predictive performance was evaluated by goodness-of-fit (GOF) plots and visual predictive checks (VPC), and the results indicated satisfactory precision. Our model suggests a correlation between VPA CL/F and LEPR rs1137101 variants, which might be beneficial in the context of individual dose optimization. [ABSTRACT FROM AUTHOR]

Increasing literature has shown the usefulness of a dimensional approach to mental disorders, particularly when exploring subjects exposed to traumatic experiences such as a severe illness in one's child. Recent evidence suggests an increased vulnerability in subjects with autism spectrum symptoms to develop post-traumatic stress symptoms. The aim of the present study was to evaluate the presence of adult autism subthreshold spectrum in a sample of parents of children with epilepsy and its impact on post-traumatic stress spectrum symptoms in the same study sample. Results revealed noteworthy correlations between post-traumatic stress symptoms and adult autism subthreshold spectrum (AdAS Spectrum) only in the subgroup of the fathers. In particular, were evidenced correlations between AdAS Spectrum domain of rumination and narrow interests and some TALS-SR nuclear domains: reaction to traumatic events, reexperiencing and arousal. These findings corroborate the hypothesis that subthreshold autistic features may influence the possible psychopathological reaction to trauma. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the needs and identify factors that predict those needs of caregivers who look after epileptic children. Material and Method: This study was a survey of a selected purposive sample of 130 caregivers of epileptic children who attended the out patient Pediatric Neurology Clinic at Songklanagarind Hospital for case follow-up. Results: This study showed that the overall mean score of caregivers’ needs when caring for epileptic children was at a moderate level and the mean scores of caregivers’ needs of each section were in the moderate to high level range. The range of need score levels from high to low was information, physical, psychological, spiritual, household management and financial. Caregivers’ characteristics show that education level was positively correlated with information needs but family income had a negative correlation with financial needs. Duration of caring, was negative correlated with both information and household management needs. The sense of severity of the disease and frequency of seizures were found to be positively correlated with financial needs. Complications of the patient were positively correlated with both the physical and financial needs. However, caregivers’ age and experience of caring were unable to predict caregivers’ needs. Conclusion: The highest score of caregivers needs is that for information. The health team, especially doctors and nurses, should respond to the needs of caregivers and give them confidence to effectively take care of their epileptic children.

OBJECTIVE: Epilepsy is a chronic neurological disease. Evidence has indicated that epilepsy has an impact on mental and physical health of children. The present study aimed to determine the effectiveness of attribution retraining on health enhancement of epileptic children. MATERIALS & METHODS: This was an experimental study with a pre-test and a post-test design with a control group. Thirty students with epilepsy (11 female and 19 male students) were selected in convenience from Iranian Epilepsy Association. They were assigned to experimental and control groups and their mothers completed Child Health Questionnaire (CHQ-PF.28) before and after the intervention. The experimental group attended to eleven sessions (each session 45 minutes; twice a week). Subjects were trained by attribution retraining program, but control group was not. Multivariate analysis of covariance (MANCOVA) was used for analyzing the data. RESULTS: Health (both psychosocial and physical) of experimental group enhanced significantly after the intervention sessions compared to control group. CONCLUSION: Attribution retraining is an effective intervention to enhance the psychosocial and physical health of epileptic children. [ABSTRACT FROM AUTHOR]

Objective Approximately one third of epileptic children are resistant to anticonvulsant drugs. This study evaluates the effectiveness, safety, and tolerability of pregabalin as adjunctive therapy in epileptic children relative to Zonisamide. Materials & Methods From April 2012 to November 2012,121 children were referred to Mofid Children's Hospital with intractable epilepsy and enrolled in the study. The patients were divided into two groups (A and B) randomly. Group A was treated with Zonisamide and group B was treated with Pregabalin in addition to prior medication. We assessed seizure frequency and severity during a 4-week interval from the beginning of the drug treatment and compared the ef fi cacy of each in these two groups. Results Group A consists of 61 patients, 26 (42.6%) girls, and35 (57.4%) boys with an age range from 1.5 months-14 years (mean, 73.9± 44.04 months). Group B consists of 60 patients, 31(51.7%) girls, 29 (48.3%) boys with an age range from 6 months-16 years (mean, 71±42.9 months). Age, gender, seizure onset, seizure frequency, seizure type, and previous antiepileptic medications showed that there was no significant difference between the groups (P>0.05). Zonisamide and pregabalin reduced more than 50% of seizure intensity in 40.2%; 45.8% of patients also had a seizure frequency decline between35.8-44.4%, respectively and there was no significant superiority between these two novel anticonvulsants (P>0.05). Conclusion In this survey both pregabalin and Zonisamide were impressive for seizure control in children with intractable epilepsy and well sustained with mild complications that were completely reversible. [ABSTRACT FROM AUTHOR]

O presente estudo relata os problemas e dificuldades percebidas por mães e professores de crianças portadoras de epilepsia, que foram atendidas na área de Neurologia, no Ambulatório Regional de Especialidades de uma cidade de porte médio do Estado de São Paulo. Teve como objetivos: 1. Caracterizar problemas e necessidades percebidas por pais e professores de crianças epilépticas em situação de crise convulsiva. 2. Caracterizar o atendimento que pais e professores vêm dando para atender as necessidades específicas de crianças epilépticas. 3. Propor alternativas que possam auxiliar mães e professores, particularmente, na situação de crise convulsiva. À amostra deste estudo constituiu-se de mães e professores de 10 crianças portadoras de epilepsia, de ambos os sexos, na faixa etária de 7 a 14 anos.El presente estudio relata los problemas y dificultades percibidos por madres y profesores de niños portadores de epilepsia que fueron atendidas en el área de neurología en un Centro Regional de Especialidades, en una ciudad de porte medio del Estado de São Paulo. Tuvo como objetivos: 1 - Caracterizar problemas y necessidades percibidas por padres y profesores de niños en situación de crisis convulsiva. 2 - Caracterizar la atención que padres y profesores vienen dando para atender necesidades específicas de niños epilépticos. 3 - Proponer alternativas que puedan auxiliar a las madres y profesores, particularmente en situación de crisis convulsiva. La muestra de este estudio fue formado por madres y profesores de 10 niños portadores de epilepsia de ambos sexos y en la faja etarea de 7 a 14 años.This study reports the problerms and difficulties perceived by parents and teachers of epileptic children, who have been attended in the Neurological ward of a hospital located in a medium - size cite of the state of São Paulo, Brazil. The goals of this work are: 1. To characterize problems and needs detected by parents and teachers of epileptic children under convulsive crises. 2. To caracterize the assistance that parents and teachers have been giving in order to meet the specific needs of epileptic children. 3. To propose alternatives that can help mothers and teachers, particularly in the situation of convulsive crises. The sample of this study was formed by mothers and teachers of 10 epileptic children, male or female from 7 to 14 years old.

Generalized tonic-clonic seizures (GTCS) is a group of epileptic disorders characterized by widespread generalized spike-and-waves discharges along with unresponsiveness and convulsions. Abnormal connectivity in the DMN is the common findings in children with generalized epilepsy. However, the neural mechanisms underlying the altered brain connectivity of DMN in children with GTCS remain unclear. The aim of the current study was to explore the temporal properties of functional connectivity states by dynamic functional connectivity (dFC) within the DMN of GTCS children. We collected resting-state functional MRI data from 22 GTCS children and 29 age-matched healthy controls. Sliding window approach and k-mean clustering analysis were applied to analyze the dFC and identify transient states of the DMN. Furthermore, the relationship between the dynamic properties and clinical features was assessed. The dFC analyses identified two reoccurring states: a more frequent and weak connected state (State 1) and a less frequent and strong connected state (State 2). Relative to the normal control, GTCS children spent more time in State 1 showing weak connections and spent less time in State 2 showing strong connections. Dynamic functional network connectivity strength within the DMN showed both increase and decrease in patient group. In addition, the changes of dynamic metric were found to be correlated with epilepsy duration. Our findings imply abnormal interactions and the state dynamics in DMN of the children with GTCS. These disruptions of temporal dynamic in DMN may provide significance for understanding the neural mechanism underlying the GTCS in children and suggest that dFC method can be considered as a valuable tool in children with epilepsy. ● GTCS children spent more time in the state with more frequent and weak connection within DMN. ● Abnormal interactions and the state dynamics in DMN correlated with epilepsy duration. [ABSTRACT FROM AUTHOR]

Objectives: The numerous antiepileptic drug (AED) withdrawal studies published in the last 40 years have relied mainly on heterogeneous study groups. There is still no general agreement on the criteria to predict safe discontinuation. The goal of this study was to assess the outcome of AED withdrawal in epileptic children. Materials and Methods: Three hundred and eight children with epilepsy were enrolled, and these patients followed at least 1 year after drug withdrawal. Time to seizure relapse and predictive factors were analyzed by survival methods. Results: Among the 308 patients, 179 (58.1%) were boys and 129 (41.9%) were girls and the mean age at the seizure onset was 60.41 ± 36.54 months (2-144 months). The recurrence occurred in 73 (23.7%) patients. Mental retardation, history of febrile seizure, etiological of epilepsy, abnormal first electroencephalogram (EEG), abnormal neuroimaging findings, and total number of AED before remission were significantly associated with relapse risk according to univariate analysis. In the multivariate analysis, abnormal first EEG and number of AED before remission (polytherapy) were the risk factors influencing seizure recurrence. Conclusions: In our study, recurrence rate was 23.7% in children and most occurred during the 1st year. The potential risk factors of recurrence are history of febrile seizure, mental retardation, etiological of epilepsy, abnormal first EEG, abnormal neuroimaging findings, and total number of AED before remission. However, we found abnormal first EEG and polytherapy as risk factors of recurrence in multivariate analysis. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to establish a population pharmacokinetic (PPK) model of valproic acid (VPA) in pediatric patients with epilepsy in southern China, and provide guidance for individualized medication of VPA therapy. Methods: A total of 376 VPA steady-state trough concentrations were collected from 103 epileptic pediatric patients. The PPK parameter values for VPA were calculated by using the nonlinear mixed-effects modeling (NONMEM) method, and a one-compartment model with first-order absorption and elimination processes was applied. Covariates included demographic information, concomitant medications and selected gene polymorphisms. Goodness-of-fit (GOF), bootstrap analysis, and visual predictive check (VPC) were used for model evaluation. In addition, we used Monte Carlo simulations to propose dose recommendations for different subgroup patients. Results: A significant effect of the patient age and ABCB1 genotypes was observed on the VPA oral clearance (CL/F) in the final PPK model. Compared with patients with the ABCB1 rs3789243 AA genotype, CL/F in patients with GG and AG genotypes was increased by 8% and reduced by 4.7%, respectively. The GOF plots indicated the satisfactory predictive performance of the final model, and the evaluation by bootstrap and VPC showed that a stable model had been developed. A table of individualized dosing regimens involving age and ABCB1 genotype was constructed based on the final PPK model. Conclusion: This study quantitatively investigated the effects of patient age and ABCB1 rs3789243 variants on the pharmacokinetic variability of VPA. The PPK models could be beneficial to individual dose optimization in epileptic children on VPA therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Chen, Lu, Chen, Li, Zhu, He, Guo, Xu and Fan.)

Young people aged between 10 and 20 years will account for nearly 23% of the UK's total population by the end of 2012. This fact, coupled with an increasing number of children with chronic illness surviving into adulthood, means that the transition of children with chronic illness into adult care is becoming an increasingly important issue. Epilepsies are pervasive disorders that consist not only of recurrent epileptic seizures that can change over time, but also of evolving behavioural, academic and social difficulties. Many of these young individuals feel 'dumped' or 'left in the dark' once they are 'transferred' to adult care. Conclusion Therefore, it is essential to acknowledge that 'transition of care' in children with epilepsies is not a 'step' but a 'process'. It is a very challenging time with increased stress and anxiety, for both the individual and their families. This article will discuss the various factors associated with the complex topic and aim to establish a framework for the successful transition of children with epilepsy into adult care. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is one of the most serious and most common chronic diseases of children with a prevalence of 5.7 percent. This research was conducted to evaluate the effect of coping-therapy on coping ways of mothers with epileptic children in Qom, Iran. Method: In a correlative study in selected neurology centers of Qom, 34 mothers of children with grandmal epilepsy (2-11 years old) were selected at convenience and divided to two groups. During pretest, both groups completed Folkman-Lazaros Coping Style Questionnaire. In the next stage, the control group received 8 sessions of intervention to modify their coping styles. After this course, both groups filled the questionnaire again. Data were analyzed using ANCOVA. Results: The results showed that coping-therapy decreased distancing and escape-avoidance and increased self-controlling, seeking social support and positive reprisal. Conclusion: The results of this study suggest coping therapy be used for all mothers with epileptic children to improve coping. [ABSTRACT FROM AUTHOR]

Objective: A number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS., Methods: Here, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed., Results: The static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time)., Significance: Our findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Wang, Chen, Qin and Chen.)

Background: Antiepileptic drugs (AED) adverse effects are frequently encountered, careful monitoring for evaluation of adverse effects during AED administration should done as a routine in epilepsy practice. Objective: To determine the changes in thyroid function tests in male children who were under antiepileptic therapy. Methods: This study was carried out in cohort fashion on 42 male children with new onset epilepsy who had not been previously treated with antiepileptic medication. Plasma level of TSH, T3 FT3, T4 & FT4 hormones were measured and compared at baseline and 3 and 6 months after treatment. Results: A total of 42 patients were studied over a period of 6 months. These patients divided into three groups, 15 patients treated with carbamazepine, 15 patients treated with sodium valproate and 12 patients treated with phenobarbital. The results of our study suggested that the increase in the plasma level of TSH was significant only in the sodium valproate group the plasma level of T3 significantly decrease 3 and 6 months after treatment in the Phenobarbital group while the plasma level of FT3 significantly decreased only in the sodium valproate group. The decrease in T4 plasma level was significant in all groups (Carbamazepine, sodium valproate and Phenobarbital group) 3 and 6 months after the onset of treatment but the decreasing in FT4 plasma level was only significant in the carbamazepine group 6 months after onset of treatment. Conclusion: Phenobarbital had the least effect on thyroid hormones considering the effect such medications on thyroid function test, it necessary to check & test the plasma levels of thyroid hormones periodically after beginning the treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Valproate (VPA) is a simple fatty acid and a substrate for the fatty acid β-oxidation pathway. Previous data suggested that the toxicity of VPA may be provoked by carnitine deficiency and the inhibition of mitochondrial β-oxidation. Objective: The aim of the present study was to elucidate the effect of VPA treatment on carnitine and isomer-differentiated acylcarnitine disposition, and determined the relationships between acylcarnitines and blood VPA levels in long-term treated patients with VPA and/or other antiepileptic drugs. Methods: Serum samples were obtained from children aged 1–15years old treated for at least 6months with VPA alone (n =28) or VPA combined with other anticonvulsants (n =23) and untreated controls (n =23). Serum acylcarnitines were separated from their isomers and quantified using high-performance liquid chromatography–tandem mass spectrometry. Results: We found higher 3-hydroxyisovalerylcarnitine levels and trace amounts of valproylcarnitine in both VPA monotherapy and polytherapy patients. Other acylcarnitines, hexanoylcarnitine, C12, C14:1-carnitines and the ratio of long-chain acylcarnitine to free carnitine were also higher in VPA polytherapy individuals than in controls. VPA monotherapy does not result in decreases in free carnitine or in the accumulation of long-chain acylcarnitines. Blood VPA concentrations correlated positively with hexanoylcarnitine, C12, C14:1, C16:1, C18:1-carnitines in all VPA-treated children (n =51). Conclusion: Long-term VPA treatment in pediatric patients could affect some specific acylcarnitines, which is enhanced by the concomitant use of other anticonvulsants, and the formation of valproylcarnitine alone seems insufficient to develop severe carnitine deficiency at therapeutic doses of VPA. [Copyright &y& Elsevier]

In this study, we investigated the changes of the serum levels of thyroid hormones including Thyroxine (T4), Triiodothyronine (T3), T3 resin uptake and Thyroid stimulating hormone (TSH) in epileptic children during treatment with anti-epileptic drugs (AEDs) including carbamazepine (CBZ), primidone (PRM), phenobarbital and valproic acid (VPA). Materials and Methods This study consisted of four case-series comparisons, was conducted on 115 epileptic children (37 girls and 78 boys with an age range between 2 months and 15 years, mean: 62.06 ± 44.97 months). These children were divided into 4 groups who took either phenobarbital (n=29), PRM (n=28), CBZ (n=29), or VPA (n=29) for 3 months. Thyroid hormone levels (T3, T3 resin uptake, T4 and TSH) were measured at the beginning and three months after starting the study. Results At first, all patients were euthyroid and there were no clinical or laboratory findings suggestive of hypothyroidism. Regarding thyroid hormones before and after the administration of phenobarbital, carbamazepine, valproic acid and primidone, there were no significant changes in serum T3, T4, T3 resin uptake and TSH levels. Conclusion Our findings showed that short term therapy with phenobarbital, carbamazepine, valproic acid and primidone had no effect on thyroid function tests. [ABSTRACT FROM AUTHOR]

Abstract: To investigate by a prospective, self-controlled method, whether early treatment with sodium valproate (VPA) monotherapy has some effect on serum total amylase and particularly on its pancreatic isoenzyme and lipase activities in epileptic children. Serum total amylase, pancreatic amylase and lipase activities have been evaluated in 23 epileptic children, before and at 6 and 12 months of VPA monotherapy. All children remained without clinical symptoms of pancreatitis during the period of study. Serum pancreatic amylase activities were significantly decreased at 6 and 12 months of treatment with VPA, whereas serum total amylase and lipase activities did not show any significant changes at 6 or 12 months of treatment. Non-pancreatic isoenzyme activities of amylase were significantly higher at 6 and 12 months of treatment. Three patients (13%) had slightly elevated serum total amylase levels at 6 and 12 months of treatment. There was no significant correlation of serum pancreatic amylase levels or non-pancreatic isoenzyme levels of amylase with serum VPA levels at 6 and 12 months of treatment. Non-pancreatic amylase activities, probably derived from salivary glands, may be increased in children treated with VPA monotherapy. Measurement of serum pancreatic amylase and/or serum lipase activities is indicated in patients with increased serum total amylase levels but without clinical symptoms of pancreatitis and, furthermore, in patients with symptoms suggesting dysfunction of pancreas, in order to avoid unnecessary discontinuing of VPA. [Copyright &y& Elsevier]

Abstract: Purpose: Hyperuricemia has been shown to be related to cardiovascular morbidity and mortality. There is controversial data about the effect of sodium valproate (VPA) monotherapy on serum uric acid concentrations. The purpose of this study was to investigate by a long-term, prospective method, whether treatment with VPA monotherapy may alter serum uric acid concentrations and liver function tests in ambulatory epileptic children. Material and methods: Serum uric acid concentrations were determined in 28 ambulatory epileptic children before and at 6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical markers of liver and renal function, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (γ-GT) and creatinine (Cr) were also measured before and at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained within the therapeutic range (50–100mg/L) during the period of study. Results: No statistically significant changes in serum uric acid concentrations were found at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months of treatment and LDH concentrations at 12 months of treatment. Conclusions: VPA monotherapy does not have a significant effect on serum uric acid concentrations in ambulatory epileptic children. Further studies are needed to definitively address whether it would be useful for physicians to routinely check for elevated serum uric acid levels in children treated with VPA. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study was to investigate by a prospective, self-controlled method, whether treatment with carbamazepine (CBZ) and sodium valproate (VPA) monotherapy may alter serum lipoprotein (a) [Lp(a)] concentrations in epileptic children. Methods: Serum Lp(a) concentrations have been determined in 18 epileptic children before and at 6, 12 and 24 months of treatment with CBZ monotherapy and in 30 epileptic children before and at 6, 12 and 24 months of treatment with VPA monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B concentrations and serum concentrations of biochemical markers of liver and renal function were also measured in the study participants. Results: Serum Lp(a) concentrations were significantly increased at 6, 12 and 24 months of CBZ and VPA monotherapy. There were no significant correlations between serum Lp(a) and serum lipids, lipoproteins, apolipoproteins, concentrations of biochemical markers of liver and renal function or antiepileptic-drugs concentrations. Conclusions: Children who receive CBZ or VPA monotherapy may have significant and persistent increase in serum lipoprotein (a) concentrations, occuring early in the course of therapy. It may be useful to measure serum Lp(a) concentrations routinely in epileptic children taking these antiepileptic drugs, especially in those that are already at higher atherosclerotic risk. [Copyright &y& Elsevier]

The intra-individual variation in plasma concentration of phenytoin was studied in ten clinically well controlled children on monotherapy. The drug concentration was determined in routine pre-dose samples taken on three to five different mornings. On two of these occasions, plasma phenytoin was also determined at 0.5, 1, 2, 3, 5 and 7 h after the dose. The difference between the highest and lowest morning concentrations in a patient varied between 7.5 and 40 μmol/l (mean 20.1 μmol/l). Half of all morning concentration values were lower than 40 μmol/l. This often-recommended lower limit for good seizure control should therefore be reconsidered. The two concentration versus time curves in each patient during 7 h after administration differed considerably in shape, and the first curve could not be used for prediction of the second curve. The ratio between unbound and total drug was very stable and amounted to 9.4, SD 0.94% ( n = 168). It is concluded that the conventional single morning sample is satisfactory for routine monitoring in well-controlled children on monotherapy with phenytoin. In problem patients, and during combination therapy, however, more extensive investigation will be necessary, including repeated morning samples as well as determination of dose-interval curves and protein binding. [ABSTRACT FROM AUTHOR]

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The developmental change of dopamine β-hydroxylase (DBH) activity in cerebrospinal fluid (CSF) of epileptic children was studied. Non-epileptic children showed lower DBH activity in CSF than adult, and its activity increased with age. In contrast, epileptic children showed no increase in DBH activity with age. DBH in CSF may be a good index of noradrenergic function in child brain. The results on developmental change in DBH in CSF suggest that refractory epilepsy with long term medication has decreased activity in central noradrenergic neurons. [ABSTRACT FROM AUTHOR]

• SCN2A rs2304016 AG genotype more prevalent in the VPA-resistant group in Chinese children with epilepsy. • In subgroup of focal seizure, SCN1A rs2298771 AG carriers showed lower incidence of VPA resistance than AA carriers. • SCN2A rs2304016 and SCN1A rs2298771 polymorphisms might be associated with the VPA response in epileptic children. This study was conducted to explore the influence of genetic variations on responsiveness to valproic acid (VPA) monotherapy among Chinese children with epilepsy. One hundred and forty epileptic children taking VPA as monotherapy were enrolled, and at least one-year follow-up was obtained to assess the therapeutic outcome. Twenty-seven single nucleotide polymorphisms (SNPs) within twelve candidate genes correlated with the metabolic enzymes, transporters and targets of VPA were genotyped. The effects of selected polymorphisms on VPA efficacy were identified by binary logistic regression analysis adjusting for potential confounders. SCN2A rs2304016 (A > G) AG genotype was more common among the VPA-resistant patients in comparison with the VPA-responsive patients (OR = 3.18, 95 % CI = 1.10−9.14, P = 0.032), and in subgroup of focal seizure, lower frequency of VPA resistance was found in epileptic children with SCN1A rs2298771 AG genotype than those with AA genotype (OR = 0.11, 95 % CI = 0.01−0.91, P = 0.040). Our study indicated that SCN2A rs2304016 and SCN1A rs2298771 polymorphisms might be associated with the response to VPA monotherapy in Chinese epileptic children. Further and larger researches are required to validate these results. [ABSTRACT FROM AUTHOR]