Hyperhomocysteinemia in patients with epilepsy: does it play a role in the pathogenesis of brain atrophy? A preliminary report.

PURPOSE: Brain atrophy (BA) is observed in 20-50% of patients with epilepsy. Hyper-total-homocysteinemia (hyper-tHcy), which occurs in 10-40% of patients, is considered to be a risk factor for cardiovascular diseases and BA. The present study was aimed at investigating the possible association of hyper-tHcy with BA in a population of patients with epilepsy.

METHODS

Fifty-eight patients (33 M/25 F, 43.5 +/- 13.1 years of age) chronically treated with antiepileptic drugs (AEDs) and 60 controls matched for age and sex were enrolled. All participants underwent determination of plasma tHcy, folate, vitamin B(12), and C677T methylene-tetrahydrofolate-reductase (MTHFR) polymorphism genotyping, and brain magnetic resonance imaging (MRI).

RESULTS

Patients exhibited significantly higher tHcy and lower folate levels than controls; hyper-tHcy was significantly associated with the variables group (patients vs. controls), MTHFR genotype, and their interaction terms. BA was observed in 30.1% of patients and was significantly associated with hyper-tHcy (beta = 0.45, p = 0.003) and polytherapy (beta = 0.31, p < 0.001).

DISCUSSION: Our investigation suggests that hyper-tHcy plays a role in the development of BA in patients with epilepsy. Although the real origin of this phenomenon is not yet fully elucidated, experimental data support the hypothesis of a link of the neuronal Hcy-mediated damage with oxidative stress and excitotoxicity.