الفهرس 
Excitability arising from individual neuronsOnly 14 pages are availabe for public view
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Abstract
Epilepsy is one of the most common neurological disorders in the pediatric age group. It is also a major public health problem affecting the children worldwide. By the neurological, cognitive, psychologic and social consequences of epilepsy, it is considered to be a serious neurologic disorder that often requires lifelong treatment. Refractory epilepsy may be defined as failure of adequate trials of two tolerated and appropriately chosen and used AEDs schedules whether as monotherapies or in combination to achieve sustained seizure freedom. Epilepsy affects 4–10 per 1000 people which translates into approximately 50 million people worldwide. For most patients, treatment with anticonvulsants will be necessary over a long period, and despite optimal medical treatment up to 30% of patients will be refractory. AEDs are frequent and selection of antiepileptic drug is a challenging task. Age, sex, type of seizures, and presence of other medical conditions should be considered during choice of antiepileptic drug. The aim of epilepsy management is complete seizures cessation and maintenance of a good quality of life, which is affected not only by the epileptic attacks but also by adverse effect of the drug. Treatment with AEDs is generally chronic, if not lifelong and may be associated with various metabolic side effects as well as vascular risks and events which may arise even within the therapeutic ranges of the administered AEDs including lipid profiles, CRP, tHcy, and uric acid and also weight gain and obesity, insulin resistance, type 2 diabetes, subclinical hypothyroidism and high levels of vWF, fibrinogen, and markers of oxidative stress. Atherosclerotic risks may account for the higher mortality and morbidity arising from cerebrovascular disease or atherosclerosis-related heart disease in patients with epilepsy who received prolonged AED therapy. An elevated of tHcy concentration is a marker of low folate status and an independent risk factor for arteriosclerosis. The harmful effect of elevated homocysteine may be multifactorial, affecting both the vascular wall structure and the blood coagulation system. Plasma homocysteine can be increased by various drugs and condition that interfere with folate, vitamin B12 and vitamin B6 metabolism. It had been well documented that atherosclerotic vascular alterations may start early in life and progress with age. The first signs of hyperlipidemia can be detected in childhood and fatty streaks, which are the earliest pathologic lesions of atherogenic process, can be observed in the aorta and coronary arteries of individuals by the age of 20. Non-invasive measurement of CCA-IMT by high resolution B-mode ultrasound is widely used for early prediction of atherosclerosis. The aim of this work was to Investigate the cardiovascular risk factors and vascular endothelial function and structure in children with idiopathic refractory epilepsy treated with more than one AED for more than two years particularly VPA and CBZ, to evaluate the hypothesis that the cumulative effect of long term exposure to AEDs plays a role in the pathogenesis of atherosclerosis. Patients and methods This prospective case-controlled study was carried out at Pediatric Neurology Unit, Tanta University Hospital within the duration started from [June 2016 to June 2018].After obtaining the approval of the Ethics Committee, consents for participating in the study were signed by the parents. Fifty children with refractory idiopathic epilepsy aged five to fifteen years were enrolled in this study and were divided in two group. group I: included 30 patients [15 male &15 female] treated with polytherapy in the form of VPA, LEV, and topiramate. group II: included 20 patients [8 male &12 female] treated with polytherapy in the form of CBZ, LVE, and LTG. Fifty healthy children [22 male, 28 female] with matched age and sex served as the control group, those children had no history of cardiac, renal, hepatic or endocrinal diseases, drug intake as folic acid, or any vitamin supplements. We included in this study children with idiopathic refractory epilepsy with normal intelligence, received two or more AEDs for more than two years with good compliance to treatment, with serum AEDs levels within the therapeutic range. Family history of epilepsy in most of cases and normal brain MRI
We excluded in this study patients with symptomatic epilepsy as children with structural brain lesion, metabolic diseases. Patient with congenital or acquired Heart diseases, diabetes mellitus, hematological diseases, or endocrinal disorders. And also who taking vitamin supplementation or receiving medications that can affect lipid metabolism at time of blood sampling. All children enrolled in the study had subjected to the following: Complete physical and neurological examination with clinical record of the patients had been reviewed and the age of the onset of seizure, type of seizure, frequency per month during the last year, etiology of seizure, duration of AEDs therapy, and the type of the current AEDs . Patient investigated by MRI to rule out any structural brain lesion. EEG to confirm type of epilepsy Laboratory investigations of all studied patients to analysis of the circulating biochemical markers which include serum levels of triglycerides. Total cholesterol, HDL-C, LDL-C, blood sugar, serum folic acid and serum homocysteine levels to determined vascular risk factor. Non-invasive measurement of Common carotid artery intima media thickness (CCA-IMT) by high resolution B-mode ultrasound is widely used for early prediction of atherosclerosis in preclinical cases. Results: There was a significant difference between the studied groups as regards serum homocysteine levels and serum folic acid levels. Significant difference between the studied groups as regards serum cholesterol level and serum LDL-C levels show that there were significantly higher in group II compared to group I and control group In the contrary, serum HDL-C and triglycerides levels and fasting blood sugar levels showed no significance difference between the studied groups There was a significant difference between the studied groups as regards CCA-IMT with significantly higher in group I and group II compared to control group. We found a significant positive correlation between the duration of the treatment in months and serum homocysteine and CCA-IMT in both groups I&II .and significant negative correlation between the duration of the treatment in months and serum folic acid There was significant negative correlation between serum homocysteine and serum folic acid. Also significant positive correlation between serum homocysteine and CCA-IMT in both groups I&II.