Elsevier

Epilepsy Research

Volume 41, Issue 3, 2 October 2000, Pages 253-257
Epilepsy Research

Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine

https://doi.org/10.1016/S0920-1211(00)00150-9Get rights and content

Abstract

Objective: To evaluate plasma homocysteine (Hcy) concentrations in children receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and dosage and plasma concentrations of the antiepileptic drugs. Methods: We measured levels of fasting and post-methionine Hcy, plasma pyridoxal 5′-phosphate (PLP, active vitamin B6), serum folate, erythrocyte folate and serum vitamin B12 in 60 epileptic patients (29 females, 31 males), aged from 14.2 to 17.9 years, subdivided into two groups according to their therapy. Sixty-three healthy sex- and age-matched children served as controls. These measurements have been performed before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Results: Before the beginning of therapy, there were no significant differences in fasting and post-methionine Hcy, plasma PLP, serum folate, erythrocyte folate and serum vitamin B12 values between the control group and the two groups of epileptic children. After 1 year of therapy, patients treated with VPA and CBZ showed a significant increase of the plasma concentrations of Hcy when compared to baseline data and controls values. Moreover, was observed a significant decrease of serum folate and plasma PLP. On the contrary, serum vitamin B12 and erythrocyte folate levels remained in the normal range. Conclusions: Our study demonstrates that prolonged treatment with VPA and CBZ increases plasma concentrations of Hcy.

Introduction

Homocysteine (Hcy) is a thiol-containing amino acid formed by demethylation of methionine. Once synthesized, Hcy may undergo remethylation to methionine in a reaction that uses 5-methyltetrahydrofolate as a methyl donor and vitamin B12 as a cofactor. Alternatively, Hcy may conjugate with serine to form cystathionine in a reaction which requires pyridoxal 5′-phosphate, the biologically active form of vitamin B6, as a cofactor (Ueland and Refsum, 1989, Selhub et al., 1993).

More recent data suggest that deficiency of vitamin cofactors required for Hcy metabolism (vitamin B6, folate and vitamin B12) is associated with increased plasma concentrations of Hcy (Ubbink et al., 1993, Ubbink et al., 1996). Some authors have suggested that a deficiency of these vitamins can be present during treatment with antiepileptic drugs (AEDs) (Ubbink et al., 1993, Fröscher et al., 1995; Ubbink et al., 1996). On the other hand, it has been suggested that AEDs treatment increases plasma concentrations of Hcy, a potential convulsant and vascular risk factor (Fröscher et al., 1995). The data in the literature are very few and conflicting and there is no study that has evaluated the Hcy levels in patients before and after the beginning of AEDs, monotherapy. Moreover, there is no study carried out in adolescents with epilepsy.

The aims of our study were to evaluate whether differences exist in Hcy plasma concentrations in children receiving different AEDs, monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and AEDs dosage and their serum concentrations.

Section snippets

Patients and methods

We studied 60 adolescents (29 females, 31 males), aged from 14.2 to 17.9 years, suffering from various types of epilepsy who received different AEDs, monotherapy; the patients were subdivided into two groups according to their therapy: Group A, 32 patients (15 females, 17 males) treated with sodium valproate (VPA) and Group B, 28 subjects (14 females, 14 males) treated with carbamazepine (CBZ). Gender and sex ratio were similar in the two groups.

Patients were recruited from the Department of

Baseline evaluation

At the beginning of the study, there were no significant differences in fasting and post-methionine Hcy, plasma PLP, serum folate, erythrocyte folate and serum vitamin B12 values between the control group and the two groups of epileptic children.

After 1 year of treatment

Group-A patients showed a significant increase of the plasma concentrations of Hcy when compared to baseline data and controls values (see Table 1). Also plasma concentrations of post-methionine Hcy persisted significantly higher than controls.

Discussion

The present study demonstrates that epileptic patients taking AEDs have increased plasma levels of Hcy. The increase of Hcy in these patients is demonstrable on both fasting and post-methionine loading.

Our data are in agreement with a previous report on Hcy concentrations in patients with epilepsy, although this study lacked a stringent control group (Ono et al., 1997). More recently Schwaninger et al. (1988) found an increase of Hcy with concomitant reduction of vitamin B6 and folate in adult

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