Effect of lamotrigine on cerebral blood flow in patients with idiopathic generalised epilepsy

The purpose of this study was to investigate the effects of the new anti-epileptic drug, lamotrigine, on cerebral blood flow by performing (99m)Tc-ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) before and after medication in patients with drug-naive idiopathic generalised epilepsy.

Interictal (99m)Tc-ECD brain SPECT was performed before drug treatment started and then repeated after lamotrigine medication for 4-5 months in 30 patients with generalised epilepsy (M/F=14/16, 19.3+/-3.4 years). Seizure types were generalised tonic-clonic seizure in 23 patients and myoclonic seizures in seven. The mean lamotrigine dose used was 214.1+/-29.1 mg/day. For SPM analysis, all SPECT images were spatially normalised to the standard SPECT template and then smoothed using a 12-mm full-width at half-maximum Gaussian kernel. The paired t test was used to compare pre- and post-lamotrigine SPECT images.

SPM analysis of pre- and post-lamotrigine brain SPECT images showed decreased perfusion in bilateral dorsomedial nuclei of thalami, bilateral uncus, right amygdala, left subcallosal gyrus, right superior and inferior frontal gyri, right precentral gyrus, bilateral superior and inferior temporal gyri and brainstem (pons, medulla) after lamotrigine medication at a false discovery rate-corrected p<0.05. No brain region showed increased perfusion after lamotrigine administration.

Our study demonstrates for the first time the effect of lamotrigine on interictal cerebral perfusion in drug-naive idiopathic generalised epilepsy patients. In summary, lamotrigine medication was found to reduce perfusion in cortico-thalamo-limbic areas, the orbitofrontal cortex, and brainstem.