title: NMDA receptor binding in focal epilepsies.
abstract: OBJECTIVE
  To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [(18)F]GE-179, a ligand that selectively binds to the open NMDA receptor ion channel, which is thought to be overactive in epilepsy.
  
  
  METHODS
  Eleven patients (median age 33 years, 6 males) with known frequent interictal epileptiform discharges had an [(18)F]GE-179 PET scan, in a cross-sectional study. MRI showed a focal lesion but discordant EEG changes in two, was non-localising with multifocal EEG abnormalities in two, and was normal in the remaining seven patients who all had multifocal EEG changes. Individual patient [(18)F]GE-179 volume-of-distribution (VT) images were compared between individual patients and a group of 10 healthy controls (47 years, 7 males) using Statistical Parametric Mapping.
  
  
  RESULTS
  Individual analyses revealed a single cluster of focal VT increase in four patients; one with a single and one with multifocal MRI lesions, and two with normal MRIs. Post hoc analysis revealed that, relative to controls, patients not taking antidepressants had globally increased [(18)F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [(18)F]GE-179 VT (-29%; p<0.002). There were no focal abnormalities common to the epilepsy group.
  
  
  CONCLUSIONS
  In patients with focal epilepsies, we detected primarily global increases of [(18)F]GE-179 VT consistent with increased NMDA channel activation, but reduced availability in those taking antidepressant drugs, consistent with a possible mode of action of this class of drugs. [(18)F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.
authors.affiliation: Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK Division of Imaging Sciences & Biomedical Engineering, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: C J
authors.identifier: http://orcid.org/0000-0002-2692-918X
authors.initials: CJ
authors.lastname: McGinnity
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Koepp
authors.affiliation: Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK Division of Imaging Sciences & Biomedical Engineering, Faculty of Life Sciences & Medicine, King's College London, London, UK Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK The Neurodis Foundation, CERMEP Imagerie du Vivant, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Hammers
authors.affiliation: Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Riaño Barros
authors.affiliation: Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Pressler
authors.affiliation: GE Healthcare plc, The Grove Centre, Amersham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Luthra
authors.affiliation: GE Healthcare plc, The Grove Centre, Amersham, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Jones
authors.affiliation: GE Healthcare plc, The Grove Centre, Amersham, UK.
authors.forename: W
authors.initials: W
authors.lastname: Trigg
authors.affiliation: National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Micallef
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Symms
authors.affiliation: Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Duncan
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects; D001931:Brain Mapping; D002227:Carbazoles; D003430:Cross-Sectional Studies; D004347:Drug Interactions; D000069279:Drug Resistant Epilepsy / Q000000981:diagnostic imaging / Q000378:metabolism*; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D002227:Carbazoles; C571664:GE-180; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate
keywords: DEPRESSION; EPILEPSY; NMDA; PET