儿童生长激素缺乏症患者认知功能与多模态脑核磁共振研究

发布时间：2018-06-13 20:07

本文选题：儿童生长激素缺乏症 + 智商　；参考：《北京协和医学院》2015年博士论文

【摘要】：目的：儿童生长激素缺乏症是由于垂体前叶合成分泌生长激素过少引起的身材矮小、生长速度减慢的内分泌疾病。针对该患者群体可能存在的认知能力受损的热点问题,本文通过多模态脑核磁共振成像技术研究其脑结构及功能的改变,分析脑结构、功能与其认知能力和生长激素/胰岛素样生长因子-1之间的相关关系。方法：北京协和医院内分泌科矮小门诊自2013年至今招募学龄期诊断为完全性生长激素缺乏症患者作为病例组,骨龄偏小同时生长激素/胰岛素样生长因子-1及生长速度正常的儿童作为对照组,使用韦氏儿童智力量表评估智力,采集脑核磁共振T1加权像、弥散张量成像及静息态脑功能像数据,结合激素水平进行统计分析。结果：病例组(n=11)与对照组(n=10)儿童年龄(10.36±0.61岁vs 9.21±0.54岁)、性别(男性被试百分比81.8%vs 70.0%)及父母经济受教育情况相匹配。患儿在智商总分、语言理解、知觉推理、工作记忆及加工速度分测试方面均显著低于对照组(p0.05)。病例组在双侧皮质脊髓束的平均弥散率较对照组显著升高(p0.01)。相关分析(检验水平p0.05)发现,血清IGF-1水平与智商、工作记忆及加工速度指数存在显著正相关；IGF-1水平与左侧丘脑、苍白球,右侧壳核体积呈显著正相关,与包括非优势半球枕中回、枕下回、楔叶等多个脑区皮层厚度呈负相关；与位于右侧皮质脊髓束、上纵束脑区的各向异性分数呈负相关；与左侧海马、海马旁回脑区局部一致性,双侧中央前回、中央后回及中央旁小叶脑区低频振幅及局部一致性呈显著负相关,其中后者脑区的低频振幅水平完全介导了血清IGF-1水平与工作记忆指数的相关关系。结论：儿童生长激素缺乏症患者在言语理解、知觉推理、工作记忆和加工速度维度的认知能力均存在轻微降低,其中智商总分、工作记忆和加工速度指数与IGF-1水平呈正相关。丘脑等皮质下核团,枕叶中下回等皮质厚度,皮质脊髓束的弥散特性,海马、海马旁回、中央前回、中央后回、中央旁小叶等脑区的脑活动异常可能是儿童GHD患者的脑部表现。上述发现对于GH/IGF-1的作用部位和疾病认知异常的可能机制提供了实验依据。
[Abstract]:Objective: growth hormone deficiency in children is an endocrine disease of short stature and slow growth caused by low synthesis and secretion of growth hormone in anterior pituitary. In view of the hot issues of cognitive impairment in this patient group, the changes of brain structure and function were studied by multimodal MRI, and the brain structure was analyzed. The correlation between function and cognitive ability and growth hormone / insulin-like growth factor-1. Methods: school age patients with complete growth hormone deficiency were recruited from the dwarf outpatient department of Endocrinology Department of Peking Union Hospital from 2013 to present as case group. Children with small bone age and normal growth rate of growth hormone / insulin-like growth factor 1 were used as control group. Intelligence was assessed by Wechsler Intelligence scale and brain MRI T 1 weighted images were collected. Diffusion Zhang Liang imaging and resting brain function imaging data were analyzed with hormone level. Results: the age of the children in the case group was 10.36 卤0.61 years old vs 9.21 卤0.54 years old. The sex (the percentage of male subjects 81.8%vs 70.0) and the economic education of parents were matched with those of the control group (10. 36 卤0. 61 years old vs 9. 21 卤0. 54 years old). The scores of intelligence quotient, language understanding, perceptual reasoning, working memory and processing speed were significantly lower than those of the control group (P 0.05). The average diffusion rate of bilateral cortical spinal tract in the case group was significantly higher than that in the control group (P 0.01). Correlation analysis (p0.05) showed that there was a significant positive correlation between serum IGF-1 level and intelligence quotient (IQ), working memory and processing speed index. The level of IGF-1 was positively correlated with the volume of left thalamus, globus pallidus and right putamen nucleus. There was a negative correlation between the cortical thickness of the middle occipital gyrus, the inferior occipital gyrus and the wedge lobe, the anisotropy fraction of the upper longitudinal tract and the left hippocampus. The low frequency amplitude and local consistency of bilateral precentral gyrus, posterior central gyrus and paracentral lobular area were negatively correlated. The low frequency amplitude level of the latter completely mediates the correlation between the serum IGF-1 level and the working memory index. Conclusion: the cognitive ability of children with growth hormone deficiency in speech comprehension, perceptual reasoning, working memory and processing speed was slightly decreased. The total IQ score, working memory and processing speed index were positively correlated with IGF-1 level. The abnormal brain activity in hypocortical nucleus of thalamus, inferior middle occipital gyrus, diffusion characteristic of corticospinal tract, parahippocampal gyrus, precentral gyrus, posterior central gyrus and paracentral lobules may be the brain manifestations of children with GHD. These findings provide experimental evidence for the site of GHP IGF-1 and the possible mechanisms of disease cognitive abnormalities.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R725.8

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