TY - JOUR T1 - NMDA receptor binding in focal epilepsies JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1150 LP - 1157 DO - 10.1136/jnnp-2014-309897 VL - 86 IS - 10 AU - C J McGinnity AU - M J Koepp AU - A Hammers AU - D A Riaño Barros AU - R M Pressler AU - S Luthra AU - P A Jones AU - W Trigg AU - C Micallef AU - M R Symms AU - D J Brooks AU - J S Duncan Y1 - 2015/10/01 UR - http://jnnp.bmj.com/content/86/10/1150.abstract N2 - Objective To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [18F]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 [18F]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 [18F]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 [18F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [18F]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 [18F]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. [18F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy. ER -