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J Neurol Neurosurg Psychiatry ; 86(10): 1150-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25991402

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.


Subject(s)
Drug Resistant Epilepsy/metabolism , Epilepsies, Partial/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Adult , Antidepressive Agents/adverse effects , Brain Mapping , Carbazoles , Cross-Sectional Studies , Drug Interactions , Drug Resistant Epilepsy/diagnostic imaging , Electroencephalography , Epilepsies, Partial/diagnostic imaging , Female , Humans , Male , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Receptors, N-Methyl-D-Aspartate/drug effects , Young Adult
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