Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs

Vincenzo Belcastro, Pasquale Striano, Gaetano Gorgone, Cinzia Costa, Clotilde Ciampa, Daniela Caccamo, Laura R. Pisani, Giancarla Oteri, Maria G. Marciani, Umberto Aguglia, Salvatore Striano, Riccardo Ientile, Paolo Calabresi, Francesco Pisani

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Methods: Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B 12, and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Results: Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were signifi-cantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 μM; physiologic range 5-13 μM] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nM; normal > 6.8 nM) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) μM, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) μM]. Discussion: Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

Original languageEnglish
Pages (from-to)274-279
Number of pages6
JournalEpilepsia
Volume51
Issue number2
DOIs
Publication statusPublished - 2010

Keywords

  • Folate deficiency
  • Hepatic enzyme induction
  • Hyperhomocysteinemia
  • Oxcarbazepine
  • Topiramate

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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