Abstracts

Rationale: The efflux drug transporter P-glycoprotein, physiologically expressed in cerebral capillary endothelium, has been found to be over-expressed in epileptogenic brain tissues removed from patients with pharmacoresistant epilepsy. We investigated the hypothesis that increased expression levels of P-glycoprotein in the epileptogenic temporal neocortex would correlate with a greater likelihood of ongoing pharmacoresistent epilepsy post-surgery. Methods: Sixty-nine adult patients (38% male) who had standard anterior temporal lobectomy and hippocampectomy, performed by a single surgeon, for pharmacoresistant mesial temporal lobe epilepsy (MTLE) were recruited. Histopathology sections were reviewed by two neuropathologists blinded to clinical outcome independently. Hippocampal sclerosis was confirmed in all cases. P-glycoprotein was stained by JSB-1 monoclonal antibody in the resected temporal neocortex at a standardised anatomical position. Level of P-glycoprotein in the temporal lobe sections was rated by an expression index (number of capillaries stained x intensity of staining). Surgical outcome was classified as good (Engel Class I) or poor (Engel Classes II, III or IV). Results: Mean follow up duration was 5.1 (SD 2.3) years. Surgical outcome was good with long-term seizure control in 51 patients and poor with ongoing pharmacoresistant seizures in 18. There was no significant difference in sex, age at operation, duration of epilepsy or duration of follow up between patients with good and poor outcomes. Mean P-glycoprotein levels in capillaries were 27% higher in cortex (p=0.027) and 21% higher in white matter (p=0.037) in temporal neocortex of patients with poor outcome compared to those with good outcome. Novel staining of P-glycoprotein in cortical neurons showed a trend to be present in a higher proportion of patients with good outcome than poor outcome (35.3% vs. 16.7%, p=0.23). Conclusions: Higher P-glycoprotein level in capillaries of the temporal neocortex may be a marker for ongoing pharmacoresistance in patients undergoing surgery for MTLE. Greater likelihood of novel expression of P-glycoprotein in neurons in patients with good outcome suggests the protein might play different roles in the different cell types.