TY - JOUR
T1 - In vivo P-glycoprotein function before and after epilepsy surgery
AU - Bauer, Martin
AU - Karch, Rudolf
AU - Zeitlinger, Markus
AU - Liu, Joan
AU - Koepp, Matthias J.
AU - Asselin, Marie Claude
AU - Sisodiya, Sanjay M.
AU - Hainfellner, Johannes A.
AU - Wadsak, Wolfgang
AU - Mitterhauser, Markus
AU - Müller, Markus
AU - Pataraia, Ekaterina
AU - Langer, Oliver
N1 - Publisher Copyright:
© 2014 American Academy of Neurology.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Objectives: To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[11C]verapamil (VPM)- PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Methods: Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- And postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Results: Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgppositive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. Conclusions: The data from our pilot study suggest that Pgp overactivity in epilepsy is dynamic, and complete seizure control and elimination of antiepileptic medication is associated with reversal of overactivity, although these findings will require confirmation in a larger patient cohort.
AB - Objectives: To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[11C]verapamil (VPM)- PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Methods: Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- And postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Results: Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgppositive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. Conclusions: The data from our pilot study suggest that Pgp overactivity in epilepsy is dynamic, and complete seizure control and elimination of antiepileptic medication is associated with reversal of overactivity, although these findings will require confirmation in a larger patient cohort.
UR - https://www.scopus.com/pages/publications/84921966208
U2 - 10.1212/WNL.0000000000000858
DO - 10.1212/WNL.0000000000000858
M3 - Article
C2 - 25186858
AN - SCOPUS:84921966208
SN - 0028-3878
VL - 83
SP - 1326
EP - 1331
JO - Neurology
JF - Neurology
IS - 15
ER -