Impact of Mono-therapy Antiepileptic Drugs on lipid profile of epileptic children

Background: Epilepsy is one of the most common neurological disorders, which required long term therapy or lifelong treatment in some cases. Chronic use of antiepileptic drugs (AEDs) therapy might modify some vascular risk factors, Since atherosclerotic vascular alterations may start early in life, this study focuses on dyslipidemia which is a major atherogenic risk factor among epileptic children. The aim of this study: to evaluate different effects of mono-therapy antiepileptic drugs (AEDs) on lipid profile of children with idiopathic epilepsy. Methods: this study was carried out on 80 children , their age rage (716) divided into group I included 20 healthy children their age and sex matched served as a control ,group II included 20 newly diagnosed epileptic children ( according to ILAE2014 diagnostic criteria of epilepsy ) they didn't receive medication till the time of study and and lastly group III included epileptic children receiving monotherapy AEDs n=40 ,where the duration of treatment were not less than 2 months ; groupIII divided into four subgroup according to the type of AEDs . Measurement received for all participant include detailed history, clinical examination ,neurological examination and serum fasting lipid profile, while the analysis of seizure (onset ,type, frequency and classification of epilepsy according to (ILAE2017)) , inter-ictal EEG ,history of AEDs administration; daily dose and compliance to medication were for epileptic patient only. Result: serum TC, LDL were significantly higher in epileptic children receiving AEDs than control groups or group of newly diagnosed epileptic children , TG and VLDL were higher in epileptic children treated with old AEDs than other groups ,while newly diagnosed epileptic children have higher LDL than control group, on the other hand there is a significant higher HDL in epileptic children treated with new antiepileptic drugs than newly diagnosed epileptic children and epileptic children treated with old antiepileptic drugs. Conclusion: epilepsy and antiepileptic drugs especially old generation antiepileptic drugs are considered risk factors of dyslipidemias& atherosclerosis. We recommend routine monitoring of the serum lipid profile in epileptic children especially they treated with old generation AEDs (VAP and CBZ namely). Keyword: epilepsy antiepileptic drugs AEDs serum lipid profile old AEDs new AEDs Introduction Epilepsy is one of the most prevalent chronic neurologic disorders (World Health Organization, 2015). Many people with epilepsy receive lifelong prescription treatment. Older antiepileptic drugs (AEDs), mainly enzyme inducers (EIAEDs), may be associated with more adverse effects than newer AEDs. For example, they alter lipid profile, increasing serum cholesterol levels (Mintzer et al., 2009). However, there is a lack of information about the prevalence of dyslipidemia related to the use of AEDs, which would facilitate appropriate management to reduce the risk of vascular diseases. Another AED that has been related to vascular risk factors is valproic acid (VPA), which has been associated with metabolic syndrome (Kim and Lee, 2007). For these reasons, some authors have suggested starting new AEDs in newly diagnosed patients or changing EIAEDs if patients MJMR, Vol. 30, No. 4, 2019, pages (168-174). Soliman et al., 169 Impact of Mono-therapy Antiepileptic Drugs on lipid profile of epileptic children experience metabolism-related effects (Brodie et al., 2013) However, limited data are available especially in children to determine the effects of AEDs on lipid profile as a vascular risk factor for atherosclerosis. Objectives To compare the effect of different AEDs (carbamazepine, valproic acid, levetiracetam & oxacarbama-zepine) on lipid profile Materials and Methods This study was a hospital based crosssectional study was conducted in Minia university hospital, This study carried out on 80 children above the age of 7 years with age range (7-16), selected subjects divided into 3 groups: the group I included control (n=20), Group II included newly diagnosed epileptic children before starting treatment with AEDs (n=20), group III (n=40) included epileptic children receive mono-therapy antiepileptic drugs for period not less than 2 months; the last group is further subdivided into 4 groups according to the type of AEDs were received (14 patients on valproic acid (VPA), 6 patients on carbamazepine (CBZ),12 patients on levetiracetam (LEV), 8 patients on ooxacarbamazepine (OXC)) . All participant were evaluated for all measurement including demographic & clinical data, serum lipid profile, complete clinical examination, anthropometric measures: (weight, height and BMI) and complete neurological examination except the analysis of seizure, and EEG for diseased patients only. Measurement for epileptic patients includes Analysis of seizures; duration of epilepsy careful history taking from patients or near relative to determine type of epilepsy according to (ILAE2017) (2) and history of Antiepileptic drugs administration: as regards type, dose and compliance. Digital electro-encephalogram for all epileptic patients in the study: All patients were submitted to Nihon Koden digital EEG, the EEG was carried out on 16 channels. (the patient hair was washed with water and soaps), crocodile electrodes were applied according to 10-20 mm international system of electrodes placement recording was made using 35 & 50 mv calibration, with eye of the patient closed, provocation with hyperventilation and photic stimulation was performed in every record. EEG was reported by double blind separation technique by 2 professional neurophysiologists and discussed with colleagues in the department of clinical neurophysiology to estimate EEG finding in diseased patient. Specimen Collection Sample was collected from study all participant. 5ml of venous blood was collected by trained lab technician under sterile conditions using a disposable syringe between 9.00 to 10.00 a.m. after fasting at least (8-10h) and the sample was tested for TC, HDL-C, LDL-C and TG. The blood was allowed to clot at room temperature, and centrifuged at 3000rpm for 10min to separate serum. It was then kept frozen at 20°C to be analyzed later on. TC was calculated by enzymatic method and expressed in mg/dl. HDL-C was calculated using polyanion precipitation and expressed as mg/dl. LDL-C was calculated using Friedewald’s equation and expressed in mg/dl. Triacylglycerol in serum was converted to glycerol and then estimated using glycerol kinase enzyme based kinetic method and expressed in mg/dl. Ethical Permission Ethical permission to conduct the hospital based study was obtained as written & verbal consent from all participants. Exclusion criteria 1. Patients with secondary epilepsy, 2. Patients with other neurological or psychiatric disorder, MJMR, Vol. 30, No. 4, 2019, pages (168-174). Soliman et al., 170 Impact of Mono-therapy Antiepileptic Drugs on lipid profile of epileptic children 3. Patients with other genetic or medical disorder, 4. Patients with serious illness, malignancy or other complications, 5. Patients on more than one antiepileptic drug. Statistical Analysis Data obtained from patients with epilepsy and control cases were fed into computer soft were package (SPSSS, version 20) through which, descriptive statistics were calculated descriptive statistics, i.e. . mean ± Standard deviation (SD), Range, median and inter quartile range (IQR). One-way ANOVA test for parametric quantitative data between the four groups followed by post Hoc Tukey’s analysis between each two groups, Kruskal Wallis test for non-parametric quantitative data between the four groups followed by Mann Whitney test between each two groups Chi square test (if expected values within cell > 5) and Fisher’s exact test (if expected value within cell < 5) for qualitative data between the groups Superscripts with same small letter indicate insignificant difference between each two groups, otherwise there was significant difference between each two groups Results The results of this study were summarized and illustrated in the following tables and figures Table (1): demographic of all studied groups: Group I Group II Group III P value N=20 N=20 N=40 Age Range Mean ± SD (7-16) a