RESUMEN
A series of researches concerning the relationship between multidrug transporters and drug resistance in medically intractable epilepsy have been done. There is accumulating evidence demonstrating that P-glycoprotein (PGP) is a candidate to cause AEDs resistance. The effect of PGP inhibitor-verapamil on the intracellular AEDs accumulation in a MDR(multidrug resistant) K562 was investigated. The multidrug resistant (overexpression of PGP) cell line K562/Dox was established and the intracellular PHT and CBZ accumulation in multidrug resistant cell line and non- multidrug resistant cell line was observed. After PGP inhibitor-verapamil was applied to the two cell lines, the concentration change of PHT and CBZ in MDR cell was observed. The results were found: compared with non-MDR cell line K562, which IC50 was significantly increased in MDR cell line K562/Dox after PHT and CBZ was applied; verapamil could decrease significantly the level of IC50 in MDR cell line K562/Dox, and the reversal index were 2.5 and 1.5. The concentration of PHT and CBZ in MDR cell line K562/Dox was lower than that in non-MDR cell line K562, and verapamil significantly increased the concentration of PHT and CBZ in MDR cell line K562/Dox(P
RESUMEN
PURPOSE: Recently, Vagus nerve stimulation (VNS) has been reported to show promising results as an adjunctive therapy for medically intractable seizures. We report early experiences with VNS for medically intractable epilepsy in young adults and pediatric patients. METHODS: Eleven patients ages ranging from 7 years to 29 years underwent implantation of vagal nerve stimulators (Cyberonics, Houston, TX) from September 1999 to April 2003. We reviewed clinical findings in 11 patients and recorded changes of seizure frequency, quality of life (QOL), and antiepileptic drug (AED). RESULTS: The mean age of seizure onset was 4.5 years old (range:3 months-11 years). The seizure duration before VNS was mean 8.7 years (range:1.5-19 years). Seven patients had symptomatic partial epilepsies, and one had cryptogenic partial epilepsy. Unclassified patients had 2 Lennox-Gastaut syndrome and 1 reflex epilepsy. Two patients received total callosotomy for reducing drop attack, but refractory. One patient, who underwent a temporal lobectomy, failed to obtain desirable results. One implantation was performed with total callosotomy, simultaneously. All of implantations were successful, except for one wound revision due to a subcutaneously protruded anchoring device of electrode. About two weeks after the implantation, programming of the stimuli was started and increased the output current to the levels, at which patients was tolerated. The most common adverse effect was hoarseness or voice alteration (44%). Mean reduction of seizure frequency compared with baseline before VNS was 23.6% after 3 months, 33.5% after 6 months, 41.3% after 1 year, and 46.6% at latest follow-up. Three patients had no response to VNS. One patient was added 1 one new AED after VNS. Two patients were reduced 1 or 2 drugs. But there was no correlation between VNS effect and AED change. Six patients had some improvement of QOL. Mean follow-up period, which was 28 months (range:12-48 months). CONCLUSIONS: We concluded that VNS has a role of adjunctive therapy for medically intractable epilepsy and the further studies should be focused on the prediction of unresponsiveness and the adjustment of VNS parameters for maximal efficacy in patients with various backgrounds.