【作者】 刘勇；

【导师】 郑健；

【作者基本信息】 第三军医大学 ， 神经病学， 2008， 博士

【摘要】 目的:(1)了解颈动脉狭窄患者认知功能损害的临床特征;(2)观察颈动脉狭窄患者的磁共振波谱(Magnetic resonance spectroscopy, MRS)、磁共振弥散张量成像(Diffusion tensor imaging, DTI)和磁共振灌注成像(Perfusion-weighted Imaging, PWI)表现;(3)探讨颈动脉狭窄患者局部脑血流和脑代谢改变与认知功能损害的关系,为探索颈动脉狭窄患者认知功能损害的病理生理机制提供线索,促进颈动脉狭窄患者认知功能损害临床诊治水平的提高。方法:(1)采用威斯康星卡片分类测验(Wisconsin card sorting test, WCST)、词语流畅性测验(Verbal fluency test, VFT)、连线测验(Trail making test, TMT)、符号-数字模式测验(Symbol digit modalities test, SDMT)、简易精神状况检查法(Mini-mental state examination, MMSE)、美国国立卫生院神经功能缺损评分量表(National institute of health stroke scale, NIHSS)和工具性日常生活活动能力(Instrumental activity of daily living, IADL)等神经心理学量表对经全脑血管造影证实的31例症状性颈动脉狭窄或闭塞患者(狭窄组)和14例无颈动脉狭窄患者(无狭窄组)进行认知功能评价;(2)对22例狭窄组患者和12例无狭窄组患者双侧额叶白质和顶枕联合区进行MRS扫描,同时对两组患者进行DTI和PWI扫描,获得额叶、半卵圆区和后分水岭区的部分各向异性(Fractional anisotropy, FA)、表观弥散系数(Apparent diffusion coefficient, ADC)、相对峰值时间(Time to peak, TTP)、相对平均通过时间(Mean transit time, MTT)、相对局部脑血流量(Cerebral blood flow, CBF)、相对局部脑血流容积(Cerebral blood volume, CBV)等参数,计算狭窄侧与对侧、右侧与左侧(无狭窄组)的血流动力学参数比值;(3)对神经心理学量表测评得分和功能磁共振检测结果进行相关性分析。结果:(1)汇总本研究采纳的多种神经心理学量表测评结果,发现所有颈动脉狭窄患者均存在一定程度认知损害;VFT测评判定96.8%(30例/31例)的颈动脉狭窄患者存在认知损害;WCST的持续反应数(Preservative responses, Rp)测评判定67.7%(21例/31例)的颈动脉狭窄患者存在认知损害;而MMSE测评仅发现26.3%(5例/31例)的颈动脉狭窄患者存在认知损害。(2)狭窄组和无狭窄组Rp、VFT和SDMT测评结果存在显著性差异(p<0.05);颈动脉中度狭窄与重度狭窄患者Rp、VFT、NIHSS和IADL测评结果存在显著性差异(p<0.05);左侧和右侧颈动脉狭窄的患者各项神经心理学量表检测未发现显著性差异(p>0.05);VFT测定结果与SDMT测定结果成正相关(r=0.3642, P=0.0139),与Rp测定结果成负相关(r=-0.3316, P=0.0261);(3)颈动脉狭窄患者狭窄侧额叶白质NAA/cr值明显下降(p<0.05);额叶白质Cho/cr和mI/cr,顶枕联合区NAA/cr、Cho/cr和mI/cr改变不明显(p>0.05);(4)狭窄组患者狭窄侧额叶和半卵圆中心FA值较无狭窄组相应区域两侧平均值明显下降(p<0.05);两组患者相应区域ADC改变不明显(p>0.05);(5)50.00%(11例/22例)颈动脉狭窄患者存在额叶、半卵圆中心或后分水岭区灌注不足表现,而中度狭窄组,重度狭窄组和无狭窄组额叶、半卵圆区和后分水岭区CBF、CBV、MTT、TTP比值之间并无显著性差异(p>0.05);(6)颈动脉狭窄患者狭窄侧额叶NAA/Cr与额叶CBF比值成正相关(r=0.4899, P=0.0081),FA值与NAA/Cr和CBF比值相关性不显著(p>0.05);狭窄侧额叶NAA/Cr值与VFT(r=0.5335, P=0.0060)和MMSE(r=0.4094, P=0.0421)分值成正相关,与NIHSS(r=-0.6500, P=0.0004)、Rp(r=-0.4594, P=0.0209)和TMT(r=-0.4015, P=0.0467)分值成负相关;狭窄侧半卵圆FA值与VFT(r=0.4455, P=0.0154)和SDMT(r=0.3892, P=0.0369)分值成正相关,与TMT(r=-0.4228, P=0.0223)分值成负相关。结论:(1)颈动脉狭窄患者存在认知损害,以认知转换、执行功能和注意功能损害表现突出, VFT是检测颈动脉狭窄患者认知损害的敏感工具,WCST可在确证时使用;(2)颈动脉狭窄患者额叶白质脑血流灌注的损害及其引起的代谢改变可能是其认知损害的主要原因。(3)颈动脉狭窄患者狭窄侧的额叶白质区NAA/cr和FA值下降可能主要不是由于神经元的减少或缺失导致,而是由于神经轴突和髓鞘破坏引起;(4)临床进行颈动脉狭窄患者的认知功能损害评价时,选择部分磁共振脑功能成像指标,包括NAA/Cr和FA,能对其损害的病理生理基础或严重程度作出相对客观的判断;(5)探讨动脉狭窄患者认知损害的病理生理机制时,应重视额叶-皮质下神经环路的结构和功能评价。更多还原

【Abstract】 Objective: (1) To investigate the clinical features of cognitive impairment in patients with carotid artery stenosis; (2) To evaluate the characteristics of magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) of the patients with carotid artery stenosis; (3) To make an approach to the relationship between the cognitive impairments and changes of regional cerebral blood flow and metabolism in patients with carotid artery stenosis, offer clues to better understand the pathophysiological mechanisms of cognitive impairments and promote the clinical diagnosis and treatment of cognitive impairment in patients with carotid artery stenosis.Methods: (1) Thirty–one patients with symptomatic carotid artery stenosis or occlusion (stenosis) and 14 patients without carotid and intracranial vascular stenosis or occlusion (no-stenosis) identified by cerebral angiography were tested with a set of neuropsychological scales, including Wisconsin Card Sorting Test (WCST), Verbal Fluency Test (VFT), Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT), Mini-Mental State Examination(MMSE), National Institute of Health Stroke Scale(NIHSS), and Instrumental Activity of Daily Living (IADL). (2) Single voex 1H-MRS was operated on 22 stenosis patients and the 12 no-stenosis patients in non-infarcted bilateral frontal white matter and occipio-parietal gray matter, simultaneously DTI and PWI were also performed in all patients to obtain parameters of fractional anisotropy (FA), apparent diffusion coefficient (ADC), relative time to peak (rTTP), relative mean transit time (rMTT), relative regional cerebral blood flow (rrCBF) and relative regional cerebral blood volume (rrCBV) in frontal white matter, centrum semiovale and posterior cortical watershed. The rMTT, rTTP , rrCBV and rrCBF ratio were calculated as stenosis side against contralateral side or right side against left side. (3) Correlation analysis was performed between the scores of neuropsychological scaling and the measurements of functional magnetic resonance imaging . Results: (1) Cognitive impairments with various degrees were found in all patients with stenosis after analyzing the results of all the neuropsychological scaling adopted. Thirty patients(96.8%) were diagnosed as cognitive impairment depending on the score of VFT. Twenty-one patients(67.7 %) were presumed cognitive impairment depending on the score of preservative responses(Rp) in WCST. But only 5 patients (26.3%) were considered as cognitive impairment depending on the score of MMSE. (2) They both have significant differences in the scores of Rp, SDMT and VFT between the stenosis and no-stenosis groups and the scores of Rp, VFT, NIHSS and IADL between the moderate stenosis and severe stenosis patients(p<0.05).No significant difference of the scores of the neurop -sychological tests was found between the patients with left and the patients with right carotid artery stenosis(p>0.05).The VFT scores correlated with SDMT(r=0.3642, P=0.0139) and Rp(r=-0.3316, P=0.0261). (3) N-acetyl aspartate/creatine (NAA/Cr) in the frontal white matter on the side of carotid artery stenosis obviously decreased(p<0.05),yet choline-related compounds/creatine ( Cho/cr) and myo-inositol/ creatine( mI/cr) in frontal white matter, NAA/cr, Cho/cr and mI/cr in occipio-parietal gray matter changed a little(p>0.05). (4) FA in frontal and centrum semiovale white matter on the side of carotid artery stenosis decreased significantly by comparison with the average FA in both sides in the corresponding regions of no-stenosis group(p<0.05), ADC values had no significant differences between stenosis and no-stenosis groups(p>0.05). (5) Eleven patients(50%) with stenosis had inadequate perfusion in the frontal lobe, centrum semiovale or posterior cortical watershed. No significant difference of the ratio for rrCBF、rrCBV、rMTT、rTTP was found among the patients with severe carotid stenosis, the patients with moderate carotid stenosis, and the no-stenosis patients(p>0.05). (6) A positive correlation was formed between the NAA/Cr of frontal white matter on the stenosis side and the rrCBF ratio(r=0.4899, P=0.0081) of frontal lobe,while no significant dependability was formed between the value of FA, NAA/Cr and rrCBF ratio(p>0.05). The NAA/Cr of frontal white matter on the stenosis side positively correlated with scores of MMSE(r=0.4094, P=0.0421) and VFT(r=0.5335, P=0.0060), while negatively correlated with scores of NIHSS(r= -0.6500, P=0.0004), Rp(r=-0.4594, P=0.0209) and TMT(r=-0.4015, P=0.0467). The FA value of centrum semiovale on the stenosis side positively correlated with scores of VFT(r=0.4455, P=0.0154) and SDMT(r=0.3892, P=0.0369), while negatively correlated with scores of TMT(r=-0.4228, P=0.0223).Conclusion: (1) Patients with carotid artery stenosis have definite cognitive impairment, prominently in cognitive conversion, executive function, and attention.The VFT is a very sensitive test to detect cognitive impairment in patients with carotid artery stenosis. Cognitive impairment in patients with carotid artery stenosis can be definitely identified by WCST. (2) The reduction of cerebral blood flow and consequently the change of regional metabolism in the frontal white matter are the main reasons leading to cognitive impairment in the patients with carotid artery stenosis. (3) The NAA/cr and FA of frontal white matter on the stenosis side may drop mainly not because of the neuron loss, but mainly because of nerve axons and myelin damage in patients with carotid artery stenosis . (4) The functional magnetic resonance imaging, especially the NAA/Cr and the FA, might be as the diagnostic tools to detect the basis of pathological damage while managing the cognitive impairment patients with carotid artery stenosis . (5) The evaluation of the structure and function integrity of the frontal lobe-subcortex neural circuits should be attached more importance while making an approach to the pathophysiological mechanisms of cognitive impairment in patients with carotid artery stenosis.更多还原