Department of Child Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
J Neuroinflammation. 2021 Jan 6;18(1):8. doi: 10.1186/s12974-020-02055-1.
Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy.
Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [C] DPA713. The PET image of [C] DPA713 was co-registered to individual's magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed.
Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [C] DPA713 uptake. The SUVr of [C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [C] DPA713 uptake was associated with microglial activation.
This study indicates that [C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.
神经炎症与各种慢性神经疾病有关，包括癫痫；然而，用于可视化神经炎症的神经影像学方法尚未在临床常规中使用。在这项研究中，我们使用[C] DPA713 正电子发射断层扫描（PET）来研究儿童起病局灶性癫痫患者致痫区的神经炎症。
在大阪大学癫痫中心招募了难治性局灶性癫痫患者；排除正在服用任何免疫抑制剂或类固醇的患者。静脉注射[C] DPA713 后 60 分钟采集 PET 图像。[C] DPA713 的 PET 图像与个体的磁共振成像（MRI）配准，在非病变和病变区域创建感兴趣区，并使用小脑作为伪参考区计算标准化摄取值比（SUVr）。在癫痫手术的情况下，分析病变部位 SUVr 与病理发现之间的相关性。
本研究纳入了 27 名患者（平均年龄：11.3 ± 6.2 岁，男/女：17/10）。其中，85.1%的患者在局灶性癫痫病变部位出现[C] DPA713 的摄取增加。3 名患者出现癫痫痉挛，提示部分发作起始，所有 18 名 MRI 异常患者同样显示[C] DPA713 的摄取显著增加。DPA713 阳性患者的病因广泛，包括局灶性皮质发育不良、肿瘤、梗死和海马硬化。9 名 MRI 阴性患者中有 5 名出现异常[C] DPA713 摄取。[C] DPA713 在病变部位的 SUVr 明显高于非病变部位。在接受癫痫手术的 7 名患者中，[C] DPA713 摄取增加与小胶质细胞激活有关。
本研究表明，[C] DPA713 摄取在识别儿童起病局灶性癫痫的致痫灶方面具有很高的敏感性，炎症与各种病因引起的致痫灶的病理生理学有关。需要进一步研究来建立识别局灶性致痫灶的诊断工具。
