评估儿科癫痫患者病情及认知功能的PET分子影像临床应用

发布时间：2017-12-28 08:29

本文关键词：评估儿科癫痫患者病情及认知功能的PET分子影像临床应用　出处：《浙江大学》2017年博士论文　论文类型：学位论文

【摘要】：癫痫是最常见的神经系统疾病之一,并且在儿童和青少年中的发病率最高。癫痫发作给患者造成的巨大生理、心理痛苦,严重影响患者及其家庭的生活质量。在接受合理、规范的抗癫痫药物治疗后,仍有30%的患者为难治性癫痫。对难治性癫痫患者的早期鉴别有利于及时进行手术治疗,从而避免长期反复的癫痫发作和不必要的抗癫痫药物对脑功能的损害。18氟-脱氧葡萄糖正电子发射计算机断层显像(~(18)F-fluorodeoxyglucose positron emission tomography,~(18)F-FDG PET)能够检测癫痫活动引起的脑葡萄糖代谢异常,作为神经影像学检查手段已常规应用于癫痫的术前评估。然而对于非手术患者,特别是其中的儿科癫痫患者,~(18)F-FDG PET在评价病情及预后中的诊断价值尚不明确。认知功能损害是抗癫痫药物最常见的副作用之一,而且在联合用药时风险可进一步增加。儿童患者大脑仍处于发育之中,对抗癫痫物药损害认知功能的副作用尤为敏感。对该项副作用的早期评估将有利于治疗方案的及时调整和患儿长期治疗的依从性。认知功能损害与多种神经递质系统组成的复杂神经功能网络的异常有关。其中单胺能神经递质系统(包括多巴胺和5-羟色胺)不仅参与癫痫的发生,也与认知功能相关的多个脑区存在广泛的联系。因此我们推测单胺能神经递质系统的异常在抗癫痫药物所致认知功能损害中具有重要作用。本研究将评价统计参数图(statistical parametric mapping,SPM)软件和PET/MRI融合技术在儿科癫痫患者影像诊断中的价值;并进一步探索性分析儿科癫痫的脑代谢异常特点,以及脑代谢异常程度与病情严重程度、预后之间的关系。此外,我们采用11碳-氮-甲基螺哌酮(11C-N-methylspiperone,11C-NMSP)PET显像评价儿科癫痫患者抗癫痫药物所致认知功能损害相关的单胺受体功能改变。第一部分联合视觉分析及SPM软件评价儿科癫痫患者脑葡萄糖代谢特点我们回顾性的纳入100例已完成~(18)F-FDG PET/CT、磁共振及脑电图检查的儿科癫痫患者。另外15例年龄匹配的儿童作为SPM分析的对照组。联合视觉分析及SPM软件综合评价~(18)F-FDGPET图像。对异常代谢脑区进一步行半定量的不对称指数(|AI|)分析,并与患者的病情严重程度和预后进行相关性分析。结果显示:与单独视觉分析相比,联合视觉分析及SPM软件评价~(18)F-FDGPET图像能够提高脑葡萄糖代谢异常的检出率。在具有脑代谢异常的患者中,|AI|值与癫痫发作频率呈显著正相关(P0.01),而与发作后间隔时间呈显著负相关(P0.01)。多因素线性回归分析结果表明:在低代谢和高代谢患者中(均P0.01),发作后间隔时间均是唯一对|AI|值具有显著作用的因素。通过随访发现,难治性癫痫患者的|AII|值较病情缓解的患者在低代谢人群中明显增高(P0.01),而在高代谢人群中有增高的趋势(P = 0.209)。复查PET较初次PET图像|AI|值降低的程度在临床症状明显改善的患者中较其它患者更为显著(P0.01)。我们的研究表明联合视觉分析及SPM软件评价~(18)F-FDG PET图像可提高癫痫患儿脑葡萄糖代谢异常的检出率。通过|AI|分析能够评价癫痫患儿的临床病情严重程度及预后情况。严格掌握临床癫痫发作后的PET扫描时间窗可增加~(18)F-FDGPET的临床诊断价值。第二部分儿科癫痫患者抗癫痫药物所致认知功能损害的单胺受体功能研究我们对25名儿科癫痫患者分别进行了 11C-NMSP的单胺受体显像和~(18)F-FDG的葡萄糖代谢显像。每位患儿进一步接受智商水平测试。结果显示:单药治疗组患者的言语、操作和全量表智商得分均显著高于联合用药组(均P0.01)。与单药治疗组相比,联合用药组患者在尾状核、前额叶皮层、背侧前扣带回皮层和杏仁核部位的单胺类受体结合水平显著降低(均P0.05)。我们的研究表明癫痫的治疗方案应尽可能采用单一抗癫痫药物;PET单胺受体显像技术有望成为在体评估抗癫痫药物所致认知功能损害的影像学指标。
[Abstract]:Epilepsy is one of the most common diseases of the nervous system and the highest incidence in children and adolescents. The severe physical and psychological pain caused by epileptic seizures seriously affects the quality of life of the patients and their families. After a reasonable and standardized antiepileptic drug treatment, 30% of the patients were still treated for intractable epilepsy. Early identification of refractory epilepsy is conducive to timely surgical treatment, so as to avoid long-term recurrent seizures and unnecessary antiepileptic drugs on brain damage. 18 fluorodeoxyglucose positron emission tomography (~ (18) F-fluorodeoxyglucose positron emission tomography, ~ (18) F-FDG PET) to cerebral glucose metabolism caused by detection of epileptic activities as abnormal neuroimaging methods have been routinely used in presurgical assessment. However, the diagnostic value of ~ (18) F-FDG PET in evaluating the condition and prognosis of non operative patients, especially in the pediatric epileptic patients, is not clear. Cognitive impairment is one of the most common side effects of antiepileptic drugs, and the risk can be further increased in combination with drug use. The brain is still in development in children, and it is particularly sensitive to the side effects of the cognitive function of antiepileptic drug damage. Early assessment of the side effects will be beneficial to the timely adjustment of the treatment plan and the compliance of the children with long-term treatment. Cognitive impairment is associated with the abnormality of a complex neural network of neurotransmitter systems. Monoaminergic neurotransmitter system, including dopamine and 5- serotonin, is not only involved in the occurrence of epilepsy, but also widely associated with cognitive function related brain regions. Therefore, we speculate that the abnormality of monoamine neurotransmitter system plays an important role in the cognitive impairment induced by antiepileptic drugs. This study will evaluate the statistical parametric mapping (statistical parametric mapping SPM) software and PET/MRI fusion technique in the diagnosis of pediatric patients with epilepsy in value; and further exploratory analysis of brain metabolic features of pediatric epilepsy, and the relationship between the degree of abnormal brain metabolism and disease severity and prognosis. In addition, we evaluated the monoamine receptor function changes in pediatric epilepsy patients with cognitive impairment induced by antiepileptic drugs by using 11 carbon nitrogen methylspiramidone (11C-N-methylspiperone, 11C-NMSP) PET imaging. The first part is joint visual analysis and SPM software to evaluate the characteristics of cerebral glucose metabolism in children with epilepsy. We retrospectively reviewed 100 cases of pediatric epilepsy who had completed ~ (18) F-FDG PET/CT, magnetic resonance imaging and electroencephalogram examination. The other 15 age matched children were used as the control group of SPM analysis. Combined visual analysis and SPM software comprehensive evaluation of ~ (18) F-FDGPET images. The abnormal metabolic brain region was further analyzed by semi quantitative asymmetric index (|AI|), and the severity and prognosis of the patients were analyzed. The results showed that compared with the single visual analysis, the combined visual analysis and SPM software evaluation of ~ (18) F-FDGPET images could improve the detection rate of abnormal brain glucose metabolism. In patients with abnormal brain metabolism, the |AI| value was significantly positively correlated with the frequency of epileptic seizures (P0.01), and had a significant negative correlation with the interval of post seizures (P0.01). Multivariate linear regression analysis showed that in patients with low metabolism and high metabolism (all P0.01), the interval between episodes was the only factor that had a significant effect on |AI| value. Follow up showed that the |AII| value of patients with intractable epilepsy was significantly higher than that of the patients in the low metabolism group (P0.01), but increased in the high metabolic population (P = 0.209). The degree of the decrease in the |AI| value of the PET in the first PET image was more significant than that of the other patients (P0.01) in the patients with significantly improved clinical symptoms. Our study shows that combined visual analysis and SPM software evaluation of ~ (18) F-FDG PET images can improve the detection rate of glucose metabolism abnormalities in the brain of children with epilepsy. |AI| analysis can be used to evaluate the clinical severity and prognosis of children with epilepsy. The clinical diagnostic value of ~ (18) F-FDGPET can be increased by strict mastery of the PET scanning time window after clinical seizures. The second part is the monoamine receptor function of pediatric epilepsy patients with cognitive impairment induced by antiepileptic drugs. We studied the monoamine receptor imaging and ~ (18) F-FDG glucose metabolism imaging of 11C-NMSP in 25 pediatric epilepsy patients. Each child was further tested for the IQ level. The results showed that the scores of speech, operation and full scale IQ in the single drug treatment group were significantly higher than those in the combination group (P0.01). Compared with the monotherapy group, the level of monoamine receptor binding in the caudate nucleus, prefrontal cortex, dorsal anterior cingulate cortex and amygdala was significantly decreased in the combination group (all P0.05). Our research shows that the treatment plan of epilepsy should use single antiepileptic drugs as far as possible. PET monoamine receptor imaging technology is expected to be an imaging index for evaluating the cognitive impairment induced by antiepileptic drugs in vivo.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R742.1;R817.4

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