@article {McGinnity1150, author = {C J McGinnity and M J Koepp and A Hammers and D A Ria{\~n}o Barros and R M Pressler and S Luthra and P A Jones and W Trigg and C Micallef and M R Symms and D J Brooks and J S Duncan}, title = {NMDA receptor binding in focal epilepsies}, volume = {86}, number = {10}, pages = {1150--1157}, year = {2015}, doi = {10.1136/jnnp-2014-309897}, publisher = {BMJ Publishing Group Ltd}, abstract = {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.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/86/10/1150}, eprint = {https://jnnp.bmj.com/content/86/10/1150.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }