【作者】 王涛；

【导师】 章军建；

【作者基本信息】 武汉大学 ， 神经病学（专业学位）， 2017， 博士

【摘要】 背景:无短暂性脑缺血发作或卒中的颈动脉狭窄临床上被称为无症状性颈动脉狭窄。然而,最近的研究证明,这些“无症状”颈动脉狭窄患者在执行功能、记忆和精神运动速度等一系列认知功能领域均较正常对照人群显著下降,提示所谓的“无症状”性并非真正的无症状。但目前“无症状”性颈动脉狭窄患者认知功能受损的病理生理机制在很大程度上仍然是未知的。此外,虽然颈动脉支架成形术已被证明可以减少缺血性脑血管病事件的发生,然而现有关于颈动脉支架植入术对认知功能影响的研究结论却存在很大的分歧:有的研究认为颈动脉支架植入术可以改善认知功能,有的认为其对认知功能的影响不明显,有的认为其反而会使认知功能恶化。究其原因,除了在研究方法、量表选择、随访时间上存在很大的差异外,关键在于缺乏对颈动脉支架成形术后认知功能改变机制的深入探讨。因此,目前还没有充分证据来判断认知功能的改变在评估颈动脉支架成形术时,能否作为权衡利弊的因素之一,国内外最新的相关治疗指南也均没有涉及到这些方面的内容。近年来,脉冲式动脉自旋标记磁共振灌注成像(arterial spin labeling,ASL)、磁共振波谱成像(magnetic resonance spectroscopy,MRS)和静息态功能磁共振成像(Resting-state functional MRI,R-fMRI)已被广泛用于认知功能障碍的研究。ASL具有安全无创和检查可重复性强等诸多优点,还有望实现对脑血流的绝对定量。MRS通过检测N-乙酰天门冬氨酸(N-acetylaspartal,NAA)、胆碱复合物(Choline,Cho)和肌酸(Creatine,Cr)等脑组织内的各种代谢物的浓度来研究人体的病理生理改变。静息态功能磁共振能从能量的角度反映大脑内不同体素自发活动水平的高低以及不同脑区之间活动的同步性。本课题采用上述多模态功能磁共振和多维度神经心理量表检测无症状性颈动脉狭窄患者认知功能的受损,以及颈动脉支架成形术对认知功能的影响,为进一步探索无症状性颈动脉狭窄患者认知功能损害及颈动脉支架成形术对其的影响提供神经影像学的标记。方法:将19例“无症状”、严重(≥70%)单侧颈内动脉狭窄患者与24例健康对照进行多维度神经精神测试(包括MMSE、MoCA北京版、数字符号测试、Rey听觉言语学习测试和言语记忆测试)和多模态磁共振检查(包括脉冲式动脉自旋标记磁共振灌注成像、磁共振波谱成像和静息态功能磁共振成像)。比较两组间不同认知功能量表得分的差异及灌注、波谱、低频振幅和功能连接等功能磁共振的差异,最后分析量表得分的差异和功能磁共振指标差异之间的相关性。另外对其中16例顺利植入颈动脉支架的患者,于术后3个月时再次进行多维度神经精神量表测试和多模态磁共振检查,进一步分析颈动脉支架植入术后各认知功能量表得分的变化及各项功能磁共振指标的变化,最后分析量表得分的变化和功能磁共振指标变化之间的相关性。结果:无症状性颈动脉狭窄患者在MMSE、MoCA、数字广度测试、听觉词语记忆测试和数字符号转换测试等量表上的得分较正常对照组均显著降低。通过多模态磁共振我们还发现无症状性颈动脉狭窄患者左侧额下回等区域存在明显的低灌注,左侧海马N-乙酰天门冬氨酸/肌酸水平较正常对照降低,双侧额中上回低频振幅降低及右侧额中上回和后扣带回的功能连接降低等。颈动脉支架植入术后3个月与术前比较,无症状性颈动脉狭窄患者MMSE、数字广度测试及延迟记忆有明显提高,MoCA、即时记忆和符号数字转换测试无明显改变。和术前相比,患者在术后3个月时左侧额叶、前扣带回、枕叶和小脑等区域均出现灌注量的增加,右侧楔前叶出现低频振幅的增高及右侧额上回与后扣带回的功能连接增强。然而,对各量表得分和功能磁共振指标进行相关性分析,未能发现两两之间的相关性。结论:优势半球额叶的低灌注和海马神经元的丢失或活性降低、默认网络前部低频振幅以及和后扣带回功能连接的降低可能是导致无症状性颈动脉狭窄患者认知功能下降的原因之一。颈动脉支架植入术可部分改善无症状性颈动脉狭窄患者的认知功能,其改善的机制可能得益于全脑灌注的增加和默认网络活性的增高。更多还原

【Abstract】 Background Carotid artery stenosis without transient ischemic attack(TIA)or stroke is considered as "asymptomatic".However,recent studies have demonstrated that these"asymptomatic" carotid artery stenosis(aCAS)patients had cognitive impairment in executive function,memory and psychomotor speed.However,the pathophysiological changes underlying these impairments largely remain unknown.Although carotid artery stenting(CAS)have been proven can reduce future strokes,the effect of carotid artery stenting on cognition are conflicting.In recent years,pulsed arterial spin labeling(pASL)MRI,Proton MR Spectroscopy(MRS)and Resting-state functional MRI(R-fMRI)have been employed to study cognition impairment This study aimed to evaluate the cognitive impairment in severe aCAS patients and the impact of carotid artery stenting by utilizing an integrated MRI including pASL MRI,MRS and R-fMRI.Methods In part one,19 asymptomatic,severe(≥70%)and unilateral internal carotid artery(ICA)stenosis patients were compared with 24 healthy controls on 5 neuropsychiatric tests(including the MMSE,the MoCA Beijing Version,the Digit Symbol Test,the Rey Auditory Verbal Learning Test and the Verbal Memory Test)and an integrated MRI(including pASL MRI,MRS and R-fMRI).In part two,we prospectively enrolled 16 asymptomatic,severe(≥70%),unilateral internal carotid artery stenosis patients,who are going to perform carotid artery stenting.Cognition assessment and integrated MRI were administered 7 days before and 3 months after carotid artery stenting.Results aCAS patients showed significantly lower scores in all cognitive tests.Utilizing this integrated MRI,we also found aCAS patients suffered from decreased cerebral blood flow in the Left Frontal Lobe,had lower NAA/Cr ratio in the left hippocampus and decreased connectivity to the posterior cingulate cortex(PCC)in the anterior part of default mode network(DMN).After carotid artery stenting,significant improvement in the scores on the MMSE,the Verbal Memory test and the delayed recall were found.After stenting,patients showed increased perfusion in the Left Frontal Gyrus,increased amplitude of low-frequency fluctuation(ALFF)in the Right Precentral Gyrus and increased connectivity to the PCC in the Right Supra Frontal Gyrus.However,no significant correlation was found between these imaging changes and cognition scores.Conclusion Hypoperfusion in the Left Frontal Lobe,lower NAA/Cr ratio in the left hippocampus and decreased connectivity to the PCC in the anterior part of DMN might be partly responsible for the cognition impairment in aCAS patients.Successful carotid artery stenting can partly improve cognition in aCAS patients.This improvement may be partly attributed to the increased perfusion in the Left Frontal Gyrus,increased ALFF in the Right Precentral Gyrus and increased connectivity to the PCC in the Right Supra Frontal Gyrus.更多还原