Early Vascular Disease in Children with Epilepsy

Abstract

Background: Mortality from cardiovascular and cerebrovascular disease in patients with epilepsy is up to five times that seen in the general population. It is postulated that this elevation in cardiovascular disease is partly due to elevation of the cardiovascular risk factor Total Plasma Homocyst(e)ine (tHcy). Elevated tHcy is frequently elevated in adolescents and adults with epilepsy as a result of Antiepileptic Drug (AED) induced B-vitamin deficiencies, particularly folate, vitamin B12 and vitamin B6 that are important cofactors for homocysteine metabolism. It has been recommended by previous investigators that all children with epilepsy should receive vitamin supplementation to reduce their cardiovascular risk. Other cardiovascular risk factors, such as oxidative stress, hyperinsulinaemia and hyperlipidaemia are also frequently reported in patients with epilepsy treated with AEDs. As early cardiovascular disease, especially in children, is potentially reversible, we plan to investigate endothelial function and structure as well as biochemical cardiovascular risk factors, such as tHcy and lipid levels, in children with epilepsy treated with AED therapy. Methods: Thirty children with idiopathic or symptomatic epilepsy who had been on AED treatment for at least twelve months were recruited from paediatric outpatient clinics in Wellington, New Zealand. Thirty age, sex and BMI matched healthy controls were also recruited. Fasting tHcy, serum folate, red blood cell folate, Pyridoxal-5-Phosphate (PLP), vitamin B12, plasma glucose and lipid levels were measured in each participant. Endothelial function and structure through Flow-Mediated Dilation (FMD) and Intima-Media Thickness (IMT) of the carotid and aortic arteries were measured in subjects and controls. Results: No statistical differences in tHcy, serum folate, red blood cell folate and PLP concentrations were observed between the epilepsy and control groups. Sub group analysis of individual AED therapies also showed no differences. Vitamin B12 levels were elevated in children with epilepsy compared to controls, particularly in the Sodium Valproate (VPA) monotherapy group. Marginally significantly lower fasting glucose was apparent in children with epilepsy compared to controls. This was seen to be primarily due to VPA monotherapy. Lipid and lipoprotein concentrations in children with epilepsy were statistically comparable to controls. After analysis of individual AED treatments however elevated total cholesterol, total cholesterol/ HDL cholesterol ratio, free triglycerides and lipoprotein B levels were evident in children treated with Carbamazepine monotherapy. No statistical differences were apparent in FMD, carotid IMT and aortic IMT between children with epilepsy and controls. Conclusions: We were unable to demonstrate elevated tHcy in our children with epilepsy and so not surprisingly their endothelial function and structure was also unremarkable. Given our findings vitamin supplementation in all children with epilepsy would appear unnecessary. It is likely that our population has diets with vitamin intakes adequate to compensate for any loss of vitamins induced by AED therapy and subsequently the threshold needed to produce elevated tHcy was not reached. Therefore, vitamin supplementation may only be indicated in populations with lower nutritional intakes and adults who naturally have lower B-vitamin levels compared to children. We conclude that recommendations of diets high in B-vitamins by paediatricians and neurologists would be of benefit.