Moderate hyperhomocysteinemia in patients treated for epilepsy

Area of Science:

• Neuroscience
• Clinical Neurology
• Medical Biochemistry

Background:

• Homocysteine (Hcy) is a neuroexcitatory substance and potential neurotoxin, linked to NMDA glutamate receptors.
• Hyperhomocysteinemia (HHcy) is often a marker for vascular damage and studied in patients on antiepileptic drugs (AE).
• The neuroexcitatory impact of mild HHcy (<30 micromol/l) remains underexplored.

Purpose of the Study:

• To investigate the neuroexcitatory influence of moderate to severe HHcy in adult patients on long-term antiepileptic drugs.
• To analyze the clinical and EEG features of patients with HHcy and their correlation with genetic and vitamin status.
• To explore the potential neurotoxic effects of Hcy in the context of epilepsy.

Main Methods:

• Retrospective analysis of 8 adult patients with moderate to severe HHcy (30.7-109.0 micromol/l) on conventional AE.
• Evaluation of patients 2-5 years after HHcy normalization.
• Assessment of cytochrome P450-inducing AE use, MTHFR gene C677 T mutation status, and vitamin B12, folate, and B6 levels.

Main Results:

• All 8 patients experienced partial and/or generalized seizures with neuropsychological impairment.
• Patients concurrently used cytochrome P450-inducing AE, possessed MTHFR C677 T mutations (7 homozygous, 1 heterozygous), and had vitamin deficiencies or marginal vitamin levels (folate, B6, B12).
• HHcy was normalized in all patients during the follow-up period.

Conclusions:

• Moderate to severe HHcy may exert a neuroexcitatory influence contributing to seizures and neurological impairment in patients on specific antiepileptic drugs.
• Concurrence of MTHFR gene mutations and vitamin deficiencies may predispose individuals to HHcy and its neurological consequences.
• Further research is warranted to elucidate the pathogenetic role of Hcy in epilepsy.