基于多模态神经影像学散发性肌萎缩侧索硬化患者脑结构和功能特点的研究

发布时间：2018-08-28 12:07

【摘要】：背景目前国内外越来越多的研究结果显示肌萎缩侧索硬化(amyotrophic lateral sclerosis, ALS)是一种以运动系统受累为主,同时累及多个系统的复杂疾病。其中约10%为家族性,称家族性肌萎缩侧索硬化(familial ALS,fALS),其余为散发性肌萎缩侧索硬化(sporadic ALS, sALS)。约有50%的患者存在认知及行为改变,并且临床表现与额颞叶变性相似。该病目前尚无特效治疗措施,并且临床诊断具有明显的滞后性。本研究主要聚焦于神经影像学技术在ALS患者中的应用,联合多模态神经影像技术研究sALS患者脑结构和功能的特点,并且通过探讨与疾病进展、严重程度和认知功能评分等临床指标的相关性,研究该病的发病机制,寻找可以辅助疾病早期诊断的潜在影像学标记物。全文共包括两部分内容：第一部分散发性肌萎缩侧索硬化患者脑结构特点研究目的探索散发性肌萎缩侧索硬化患者脑结构特点,并研究sALS患者脑结构特点与临床数据的相关性。方法连续录入2013年12月～2014年6月在我院神经内科住院的散发性ALS患者22例,以及年龄、性别及受教育年限相匹配的健康对照组22例。采集患者临床资料,完善认知量表评估,并进行3D-T1结构像和DTI扫描,并将所得差异性脑区的结构核磁数据与临床资料进行相关性分析。结果 (1)认知评估：sALS患者MoCA总分及语言、抽象、延迟回忆分项得分,FAB得分及Stroop任务耗时显著低于对照组；(2)与对照组相比,sALS患者：1)灰质密度明显降低的区域包括双侧中央前回；2)皮层厚度明显变薄的区域包括：(左侧)颞上回、中央前回、缘上回；(右侧)额上回、岛叶和中央前回；3)双侧胼胝体压部/体部、皮质脊髓束、内襄后肢、上纵柬以及放射冠上部FA值显著下降；双侧内囊后肢、皮质脊髓柬、放射冠后部/上部、下纵束、下额枕束、上纵束、胼胝体膝部/体部/压部、丘脑前辐射及丘脑后辐射MD值显著升高；(3)相关性分析1) VBM:sALS患者双侧中央前回的灰质密度减少与,临床资料无明显相关性；2) SBM:右侧中央前回皮层厚度与UMN评分呈负相关(r=-0.506,p=0.023),与ALS FRS-R评分呈正相关(r=0.534,p=0.015)；左侧缘上回皮层厚度与SCWT测验耗时干扰量(C耗时-B耗时)呈负相关(r=-0.538,p=0.014)；3)DTI：异常脑白质纤维平均FA值与MoCA量表视空间/执行功能分项得分呈正相关(r=0.662,p=0.002)。异常脑白质纤维平均MD值与疾病进展速率呈负相关(r=-0.551.p=0.01)。结论 sALS患者存在认知及行为损害,并伴随着广泛的脑结构异常。右侧中央前回皮层厚度可以作为反映疾病严重程度的潜力指标,特别是UMN受累的程度;sALS患者左侧缘上回皮层变薄可以反映临床执行功能受损；全脑白质纤维平均MD值在预测疾病进展速度方面具有潜力。第二部分散发性肌萎缩侧索硬化患者脑功能特点研究目的探索散发性肌萎缩侧索硬化患者脑功能的特点,并研究sALS患者脑功能特点与临床数据的相关性。方法研究对象同第一部分,对所有被试完善静息态功能磁共振扫描,使用低频振幅算法,并将所得差异性脑区的低频振幅值(ALFF)与临床资料进行相关性分析。结果(1)与对照组相比,sALS组右侧海马旁回、左侧颞下回、左侧扣带回前部、右侧额上回及左侧枕中回ALFF值较对照组明显升高。(2)sALS患者右侧海马旁回的ALFF值与疾病进展速率呈正相关(r=0.473,p=0.026)；右侧海马旁回(r=0.514,p=0.014)、左侧颞下回(r=0.469,p=0.028)以及右侧额上回(r=0.506,p=0.016)ALFF值分别与血清肌酐呈正相关；sALS患者左侧扣带回前部ALFF值与MoCA量表中视空间/执行功能分项得分呈负相关(r=-0.454,p=0.044)；左侧颞下回ALFF值与SCWT-B部分耗时呈正相关(r=0.459,p=0.032)。结论sALS患者右侧海马旁回ALFF值可以作为预测疾病进展速度的潜力指标；左侧扣带回前部ALFF值可以反映执行功能受累；血清肌酐水平较高的sALS患者脑功能代偿性越强。
[Abstract]:BACKGROUND More and more research results at home and abroad show that amyotrophic lateral sclerosis (ALS) is a complex disease involving multiple systems as well as the motor system. About 10% of them are familial, and the rest are sporadic amyotrophic lateral sclerosis (fALS). About 50% of patients with sporadic ALS have cognitive and behavioral changes, and the clinical manifestations are similar to those of frontotemporal lobe degeneration. There is no specific treatment for this disease, and the clinical diagnosis is obviously lagging behind. To study the characteristics of brain structure and function in patients with sALS, and to study the pathogenesis of sALS by exploring the correlation with clinical indexes such as disease progression, severity and cognitive function score, and to search for potential imaging markers for early diagnosis of sALS. Objective To explore the characteristics of brain structure in patients with sporadic amyotrophic lateral sclerosis and to study the correlation between brain structure and clinical data in patients with sALS. Results (1) Cognitive assessment: MoCA score and language, abstract, delayed recall score, FAB score in sALS patients. The scores and Stroop task time were significantly lower than those in the control group. (2) Compared with the control group, sALS patients had significantly decreased gray matter density in areas including bilateral anterior central gyrus; (2) areas with significantly thinner cortex included: (left) superior temporal gyrus, anterior central gyrus, superior marginal gyrus; (right) superior frontal gyrus, insular lobe and anterior central gyrus; and (3) bilateral corpus callosum pressure. FA values in the posterior limbs of bilateral internal capsule, corticospinal cord, posterior/upper part of radiation corona, inferior longitudinal tract, lower frontal-occipital tract, superior longitudinal tract, genu/body/compression of corpus callosum, anterior thalamic radiation and posterior thalamic radiation increased significantly; (3) Correlation analysis 1) Patients with VBM:sALS The decrease of gray matter density in bilateral anterior central gyrus was not significantly correlated with clinical data; 2) SBM: the thickness of right anterior central gyrus was negatively correlated with UMN score (r = - 0.506, P = 0.023), and positively correlated with ALS FRS-R score (r = 0.534, P = 0.015); the thickness of left superior central gyrus was negatively correlated with time-consuming interference (C time-consuming-B) in SCWT test (r = - 0.538). DTI: Average FA of abnormal white matter fibers was positively correlated with MoCA visual spatial/executive function score (r = 0.662, P = 0.002). Average MD of abnormal white matter fibers was negatively correlated with disease progression rate (r = - 0.551.p = 0.01). Conclusion There were cognitive and behavioral impairments in patients with sALS, accompanied by extensive brain structural abnormalities. Cortical thickness of the lateral anterior central gyrus can be used as a potential indicator of disease severity, especially the extent of UMN involvement; thinning of the left superior marginal gyrus in patients with sALS can reflect impaired clinical executive function; and the average MD value of the whole brain white matter fibers has potential in predicting disease progression. Part II Sporadic amyotrophic lateral sclerosis Objective To explore the characteristics of brain function in patients with sporadic amyotrophic lateral sclerosis and to study the correlation between brain function and clinical data in patients with sALS. Results (1) Compared with the control group, the ALFF values of right parahippocampal gyrus, left infratemporal gyrus, left anterior cingulate gyrus, right superior frontal gyrus and left middle occipital gyrus in sALS group were significantly higher than those in the control group. (2) The ALFF values of right parahippocampal gyrus in sALS patients were positively correlated with the disease progression rate (r = 0.47). 3, P = 0.026; right parahippocampal gyrus (r = 0.514, P = 0.014), left infratemporal gyrus (r = 0.469, P = 0.028) and right superior frontal gyrus (r = 0.506, P = 0.016) were positively correlated with serum creatinine, respectively; left anterior cingulate gyrus ALFF was negatively correlated with MoCA visual space / executive function score (r = - 0.454, P = 0.04A). Conclusion The ALFF value of right parahippocampal gyrus in patients with sALS can be used as a potential predictor of disease progression rate; the ALFF value of left anterior cingulate gyrus can reflect executive function involvement; the higher serum creatinine level, the more compensatory brain function in patients with sALS.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R744.8

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