Abstracts

^99mTC Sestamibi (MIBI) is a substrate of P-glycoprotein (P-gp), a product of the MDR1 gene. As has been previously reported elsewhere, accelerated ^99mTC- MIBI- liver-clearance has been observed in patients with drug-resistant epilepsy, suggesting over expression of P-gp on the luminal surface of biliary hepatocytes (Epilepsia 45: 120, 2004). Two patients were treated with nimodipine, a calcium channel blocker which inhibits P-gp transport efflux. The excretion mean time (T[frac12]) (time to reach the 50% of maximun liver uptake) of ^99m Tc MIBI-liver-clearance was studied in two drug-resistant epilepsy patients who underwent epilepsy surgery for unilateral mesial temporal sclerosis (MTS). One patient had had previous surgery for an AVM during chilhood. The other presented refractory epilepsy and MTS syndrome. In both cases, seizure rates had been reduced by at least 50% after surgery. Immunohistochemical studies conducted on patient brain tissue samples showed increased P-gp expression in both neurons and glia of MTS-affected regions, but not in the lateral temporal neocortex. Both patients were under double or triple AED regimens. Kinetic studies were performed before and after nimodipine treatment (1-2 mg/Kg). The initial T[frac12] of ^99mTC MIBI-liver-clearence values were: 1636 sec in one patient and 1583 sec in the other (normal controls T[frac12] was 7789 [plusmn] 3739 sec). After 2 months on nimodipine, T[frac12] increased to 2134 sec and 2565 sec respectively. One year later, both patients showed significant clinical improvement and sustained the kinetic changes and the 50% drop in the rate of seizures. One patient was entirely free of seizures for four months. Accelerated ^99mTC MIBI-liver-clearance was confirmed in both patients, suggesting the presence of P-gp over expression on the canalicular biliary cell surface. Inhibitors of this efflux pump, in this instance nimodipine, improved the clinical and kinetic phenotypes. It might represents a novel target treatment strategy in drug-resistant epilepsy patients with over expression of P-gp.