期刊
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
卷 86, 期 10, 页码 1150-1157出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jnnp-2014-309897
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资金
- Medical Research Council (MRC) Clinical Sciences Centre
- GE Healthcare plc.
- Medical Research Council [MR/L013215/1, G108/585] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10161] Funding Source: researchfish
- MRC [G108/585, MR/L013215/1] Funding Source: UKRI
Objective To demonstrate altered N-methyl-D-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [F-18] 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 [F-18] 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 [F-18] 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 [F-18] GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [F-18] 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 [F-18] 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. [F-18] GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.
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