Haginoya Kazuhiro, Togashi Noriko, Kaneta Tomohiro, Hino-Fukuyo Naomi, Ishitobi Mamiko, Kakisaka Yosuke, Uematsu Mitsugu, Inui Takehiko, Okubo Yukimune, Sato Ryo, Miyabayashi Takuya, Arai Akira, Ogiwara Ikuo, Mazaki Emi, Yamakawa Kazuhiro, Iinuma Kazuhie, Kure Shigeo
Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan; Department of Pediatric Neurology, Miyagi Children's Hospital, Sendai 989-3126, Japan.
Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-8574, Japan; Department of Pediatric Neurology, Miyagi Children's Hospital, Sendai 989-3126, Japan.
Epilepsy Res. 2018 Nov;147:9-14. doi: 10.1016/j.eplepsyres.2018.08.008. Epub 2018 Aug 27.
To understand cerebral brain dysfunction in patients with Dravet syndrome (DS), we conducted a [F]fluorodeoxyglucose-positron emission tomography (FDG-PET) study in patients with DS whose SCN1A gene variant was confirmed.
FDG-PET was performed on eight patients with DS. A SCN1A mutation analysis revealed missense variants in four patients and truncation variants in four patients. The patients' ages at the time of the PET study were 2, 2, 2, 3, 6, 13, 20, and 29 years old, respectively. The patients' developmental/intelligence quotient at the time of the PET study were 62, 52, 64, 35, 30, 15, and <25, respectively. The mean standardized uptake value (SUV) was calculated in four segments (frontal, temporal, parietal, and occipital) for the semi-quantitative analysis of F-FDG uptake. This value represents the average of the regions of interest in each lobe and was divided by the average SUV of the cerebellar hemisphere of each patient and compared between the patients with DS and the diseased controls.
Glucose uptake in patients with DS decreased significantly, particularly in those ≥6 years old. Importantly, a comparison between the younger and older patients with DS revealed that glucose uptake was normal in patients who were ≤3 years (2, 2, 2, and 3 years), whereas a profound reduction in glucose uptake in the fronto-temporo-parietal-occipital cortices was observed in patients ≥ 6 years (6, 13, 20, and 29 years). Magnetic resonance imaging revealed no detectable atrophic legions or other changes in the cerebral cortices of patients ≥ 6 years of age.
The present study showed a remarkable reduction in cerebral glucose metabolism in multiple lobes for the first time, which became obvious after the late infantile period. These findings may indicate a functional neuroimaging aspect of epileptic encephalopathy of DS or a feature of the SCN1A variant itself.
为了解德拉韦综合征（DS）患者的脑功能障碍，我们对SCN1A基因变异得到确认的DS患者进行了一项[F]氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）研究。
对8例DS患者进行了FDG-PET检查。SCN1A突变分析显示，4例患者存在错义变异，4例患者存在截短变异。PET研究时患者的年龄分别为2岁、2岁、2岁、3岁、6岁、13岁、20岁和29岁。PET研究时患者的发育/智商分别为62、52、64、35、30、15和<25。计算四个脑区（额叶、颞叶、顶叶和枕叶）的平均标准化摄取值（SUV），用于对F-FDG摄取进行半定量分析。该值代表每个脑叶感兴趣区域的平均值，并除以每位患者小脑半球的平均SUV，然后在DS患者和患病对照之间进行比较。
DS患者的葡萄糖摄取显著降低，尤其是6岁及以上的患者。重要的是，对年龄较小和较大的DS患者进行比较发现，3岁及以下（2岁、2岁、2岁和3岁）的患者葡萄糖摄取正常，而6岁及以上（6岁、13岁、20岁和29岁）的患者额颞顶枕叶皮质的葡萄糖摄取则显著降低。磁共振成像显示，6岁及以上患者的大脑皮质未检测到萎缩性病变或其他变化。
本研究首次显示多个脑叶的脑葡萄糖代谢显著降低，这在婴儿晚期后变得明显。这些发现可能表明DS癫痫性脑病的功能性神经影像学特征或SCN1A变异本身的特征。
