Effects of long-term antiepileptic therapy on carotid artery intima-media thickness

Abstract

A BSTRACT Background: Common first-line antiepileptic drugs (AEDs) used in children are valproate, phenytoin, and levetiracetam. Many side effects for these AEDs are reported including obesity, atherosclerosis, and metabolic syndrome. The aim of our study was to evaluate changes in carotid artery intima-media thickness (CIMT) in epileptic children and to correlate with lipid profile of those who are on long-term antiepileptic therapy. Materials and Methods: This case–control study was done over 18 months in department of pediatrics. Sample size was 84 with equal number of cases and controls. Epileptic children between 1 and 18 years of age receiving monotherapy with valproate, phenytoin, or levetiracetam for at least 6 months were included in the study. Measurement of CIMT was done by B mode ultrasonography. Lipid profile was analyzed. Statistical analysis was performed using one-way analysis of variance (ANOVA) test and Pearson correlation. Results: Among 42 cases of epilepsy, 30 were on valproate, 9 on phenytoin, and 3 on levetiracetam monotherapy. No significant difference was noted in body mass index (BMI) among children receiving AED compared with that of controls ( P = 0.82). Mean value for CIMT was significantly higher among valproate (0.43 ± 0.04, P ≤ 0.001), phenytoin (0.44 ± 0.04, P ≤ 0.001), and levetiracetam group (0.43 ± 0.03, P = 0.01) compared to controls (0.39 ± 0.01). Significant correlation was noted between CIMT and total cholesterol ( P = 0.034), triglyceride ( P = 0.011), low-density lipoprotein ( P = 0.008), and very low-density lipoprotein ( P = 0.011). Conclusion: Children on long-term monotherapy with valproate, phenytoin, and levetiracetam have significantly abnormal CIMT. This might be associated with atherosclerotic changes, and these children may require close follow-up to prevent cardiovascular and cerebrovascular risks.

The Study of Carotid Artery Intima-Media Thickness in Children With Epilepsy on Anti-Epileptic Drugs

“…57,58 Karatoprak et al, 2020, and Kolekar et al, 2021, concluded that non-obese children with epilepsy who receive monotherapy of valproic acid or levetiracetam may be at higher risk of developing subclinical atherosclerosis despite a normal lipid profile. 27,59 In our study, we found significant positive correlations between CIMT and TC, triglyceride, and LDL. Also, we found a significant negative correlations between CIMT and HDL.These findings are comparable to Kolekar et al, who reported similar correlations between CIMT and individual lipid profiles.…”

“…Our results were consistent with other studies. 26,27,32 Also, we observed that with increasing age, the values of CIMT increased as well. However, no significant difference in the mean CIMT between males and females as reported in other studies.…”

“…They reported significant abnormalities in CIMT with these AEDs. 27 We found that CIMT abnormalities were significantly prominent in children on valproate than those on carbamazepine and levetiracetam.…”

“…26 However, similar to our findings, Kolekar et al, did not report significant findings between BMI and AEDs monotherapy. 27 In a study of 114 children with epilepsy treated with valproate monotherapy over 24 months, obesity and metabolic syndrome were significantly reported in 46 and 20 children during the study period. 28 In present study, the mean values of CIMT in the controls were 0.38 ± 0.03, and most of our patients (71.7%) showed CIMT above normal reference value.…”

Influence of Different Antiseizure Medications on Vascular Risk Factors in Children with Epilepsy

“…Both Karatoprak et al, 2020, and Kolekar et al, 2021, concluded that non-obese children with epilepsy who receive monotherapy of valproic acid or levetiracetam alone may be at higher risk of developing subclinical atherosclerosis despite a normal lipid profile [ 28 , 29 ]. This might be linked to atherosclerotic alterations, and these children will need to be closely monitored to avoid cardiovascular and cerebrovascular risks [ 29 ].…”