Abstracts

Rationale: Overexpression of the ATP-binding cassette transporter P-glycoprotein (Pgp) at the blood-brain barrier (BBB) may contribute to pharmacoresistance in epilepsy by impeding access of antiepileptic drugs to their target sites inside the brain by active efflux transport. Positron emission tomography (PET) in combination with the radiolabelled Pgp substrate (R)-[11C]verapamil (VPM) can be used to assess Pgp activity at the BBB in vivo (1).Methods: Seven patients with drug-resistant unilateral temporal lobe epilepsy, 2 female and 5 male with a mean age SD of 41 8 years, were enrolled into the study. Subjects underwent VPM PET scans and arterial blood sampling, including analysis of radiolabelled metabolites of VPM, before and after temporal lobe resection. Four patients underwent selective amygdalahippocampectomy and three patients anteromesial temporal lobe resection. Different brain regions of interest were defined by using a frequency-based anatomical atlas (2). Kinetic analysis of PET data from 0-10 min after radiotracer injection was performed by using a one-tissue-two-rate constant compartment model to estimate the influx rate constant K1 from plasma into brain as a surrogate parameter of Pgp activity.Results: After epilepsy surgery the antiepileptic drug load was reduced in all patients. Surgery outcome was classified according to Wieser s classification (3) (table 1). Five patients were completely seizure free after operation (class 1a), one patient had recurrent auras (class 2) and one patient had maximally 3 seizure days a year (class 3). Mean PET scan times before and after surgery were 14 12 and 35 12 months, respectively. VPM metabolism did not differ between the pre- and the postoperative PET scan (paired t-test of VPM area under the curve, p= 0.24). Regional K1 values and percent changes in K1 values in the postoperative relative to the preoperative scan are shown in table 1. Conclusions: Analysis of regional VPM brain kinetics in patients before and after epilepsy surgery suggested that patients with good surgery outcome had higher K1 increases in the postsurgery scan than patients with poor outcome, pointing to diminished Pgp activity in patients with good outcome, which might have been caused by reduced seizure frequency. (1) Langer O et al., Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate (R)-[11C]verapamil. Epilepsia. 2007 Sep;48(9):1774-84. (2) Hammers A et al., Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003 Aug;19(4):224-47. (3) Wieser HG, et al. ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia. Feb 2001;42(2):282-6. The research leading to these results has received funding from the European Community s 7th Framework Program under grant agreement no. 201380 (Euripides) and from the Austrian Science Fund (FWF) project Transmembrane Transporters in Health and Disease (SFB F35).