• J. Neurol. Neurosurg. Psychiatr. · Oct 2015

    NMDA receptor binding in focal epilepsies.

    • C J McGinnity, M J Koepp, A Hammers, D A Riaño Barros, R M Pressler, S Luthra, P A Jones, W Trigg, C Micallef, M R Symms, D J Brooks, and J S Duncan.
    • 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.
    • J. Neurol. Neurosurg. Psychiatr. 2015 Oct 1;86(10):1150-7.

    ObjectiveTo 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.MethodsEleven 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.ResultsIndividual 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.ConclusionsIn 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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