title: In vivo P-glycoprotein function before and after epilepsy surgery.
abstract: OBJECTIVE
  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)-[(11)C]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 Pgp-positive 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.
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bauer
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Karch
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Joan
authors.initials: J
authors.lastname: Liu
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Asselin
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Pataraia
authors.affiliation: From the Departments of Clinical Pharmacology (M.B., M.Z., M. Müller, O.L.) and Neurology (E.P.), Center for Medical Statistics, Informatics, and Intelligent Systems (R.K.), Institute of Neurology (J.A.H.), and Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine (W.W., M. Mitterhauser), Medical University of Vienna, Austria; Department of Clinical and Experimental Epilepsy (J.L., M.J.K., S.M.S.), UCL Institute of Neurology, London; Epilepsy Society (M.J.K., S.M.S.), Chalfont St Peter, Buckinghamshire; Institute for Population Health Wolfson Molecular Imaging Centre (M.-C.A.), University of Manchester, MAHSC, UK; and Health and Environment Department (O.L.), AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria. oliver.langer@meduniwien.ac.at.
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000927:Anticonvulsants; D002250:Carbon Radioisotopes; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011184:Postoperative Period; D057234:Preoperative Period; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D014700:Verapamil
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D002250:Carbon Radioisotopes; D014700:Verapamil