McGinnity C J, Koepp M J, Hammers A, Riaño Barros D A, Pressler R M, Luthra S, Jones P A, Trigg W, Micallef C, Symms M R, Brooks D J, Duncan J S
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.
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK.
J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1150-7. doi: 10.1136/jnnp-2014-309897. Epub 2015 May 19.
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.
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.
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.
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.
使用正电子发射断层扫描（PET）和[(18)F]GE - 179来证明局灶性癫痫患者中N - 甲基 - D - 天冬氨酸（NMDA）受体可用性的改变，[(18)F]GE - 179是一种选择性结合开放NMDA受体离子通道的配体，该通道在癫痫中被认为过度活跃。
在一项横断面研究中，11例已知频繁发作间期癫痫样放电的患者（中位年龄33岁，6例男性）进行了[(18)F]GE - 179 PET扫描。MRI显示2例有局灶性病变但脑电图变化不一致，2例无定位意义且有多灶性脑电图异常，其余7例MRI正常但均有多灶性脑电图变化。使用统计参数映射将个体患者的[(18)F]GE - 179分布容积（VT）图像与一组10名健康对照者（47岁，7例男性）进行比较。
个体分析显示4例患者有单个局灶性VT增加簇；1例有单个病灶，1例有多灶性MRI病变，2例MRI正常。事后分析显示，相对于对照组，未服用抗抑郁药患者的[(18)F]GE - 179 VT总体增加（+28%；p<0.002），而3例服用抗抑郁药的患者[(18)F]GE - 179 VT总体降低（-29%；p<0.002）。癫痫组没有共同的局灶性异常。
在局灶性癫痫患者中，我们主要检测到[(18)F]GE - 179 VT总体增加，这与NMDA通道激活增加一致，但服用抗抑郁药的患者可用性降低，这与这类药物可能的作用方式一致。[(18)F]GE - 179 PET显示11例患者中有4例NMDA结合有局灶性增强，这些患者患有难以定位和治疗的局灶性癫痫。
