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 B₁₂, 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 (β = 0.45, p = 0.003) and polytherapy (β = 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.