颅内动脉狭窄的微栓塞与血流动力学研究

【作者】 陈洁；

【导师】 崔丽英； 高山；

【作者基本信息】 北京协和医学院 ， 神经病学， 2014， 博士

【摘要】 第一部分烟雾病患者微栓子信号预测未来脑缺血事件研究背景：烟雾病患者脑梗死一直被认为是由于血管狭窄引起的低灌注所致。然而,最近有研究显示,在烟雾病患者可以检测到微栓子信号(microembolic signals, MES)。这表明在烟雾病中有动脉到动脉的微栓塞发生。但是,MES在烟雾病患者脑梗死中的作用尚不明确。目的：探索MES在预测烟雾病患者未来脑缺血事件中的作用。方法：连续入组54例烟雾病患者。应用经颅多普勒超声(transcranial Doppler, TCD)监测入组患者双侧大脑中动脉30分钟。随访1年,记录主要终点事件：缺血性卒中及短暂性脑缺血发作(transient ischemic attack, TIA)的情况。结果：共有11(20.4%)例烟雾病患者患者监测到MES,占烟雾病半球数的10.2%。Logistic回归分析发现MES与烟雾病患者3个月内脑缺血症状有关(OR=4.41,95%CI1.11-17.59)。在中位时间384天的随访期间,共有14(13.0%)个半球发生脑缺血事件(7例缺血性卒中、7例TIA)。Cox生存分析显示,在调整了年龄、性别、缺血性卒中及TIA史、铃木分期以及血管重建术后,MES阳性半球发生缺血性卒中及TIA的风险是MES阴性半球的6.84倍(95%CI1.82-25.66),缺血性卒中的风险是阴性半球的10.61倍(95%CI1.66-67.70),结论：烟雾病患者MES与近期脑缺血症状相关,而且MES是烟雾病患者未来脑缺血事件的独立预测因子。对烟雾病患者进行TCD微栓子监测或将有利于对患者更好的临床管理,亟待进一步研究。第二部分烟雾病脑血流自动调节机能研究背景：既往研究表明烟雾病患者的脑血流自动调节机能受损,有可能会增加其脑组织缺血及出血的风险。然而在烟雾病逐渐进展的过程中,我们尚不清楚自动调节这种重要的脑保护机制从何时开始受损,以及如何随疾病的进展而变化。目的：应用无创的新型方法研究烟雾病患者动态脑血流自动调节机能与烟雾病血管分期之间的关系。方法：连续入组13例经数字减影血管造影诊断为双侧烟雾病的患者及10例健康对照。应用改良铃木分期对入组的26个烟雾病半球进行血管分级。应用传递函数的算法分析大脑中动脉血流速度及动脉血压的自然波动以分析脑血流自动调节机能。结果：工期烟雾病的脑血流自动调节参数-恢复率及相位与对照相比即显著降低(恢复率22.70±4.93%/s VS.40.78±20.92%/s, p<0.05:相位35.20±12.29°VS.60.01±18.96°,p<0.05)°而增益及相关函数自Ⅱ期开始也出现显著变化(增益0.40±0.16VS.0.86±0.50,p<0.05:相关函数0.64±0.11VS.0.42±0.16,p<0.05)。恢复率(r=-0.478,p<0.05)、增益(r=-0.507,p<0.001)及相位(r=-0.619,p<0.001)均同狭窄程度显著相关。结论：烟雾病早期患者脑血流自动调节机能即显著受损,且自动调节参数与烟雾病血管分期显著负相关,表明调节机能受损程度随疾病的进展而加剧。第三部分大脑中动脉狭窄脑血流自动调节及脑血管反应性研究背景：既往研究表明,颈内动脉狭窄后脑血流自动调节及脑血管反应性会受损,且受损患者未来罹患缺血性卒中的风险显著增加。而颅内动脉尤其是大脑中动脉(middle cerebral artery,MCA)粥样硬化性狭窄在中国人群高发,且是缺血性卒中的主要病因。然而,目前有关大脑中动脉狭窄后脑血流自动调节及脑血管反应性的研究非常少。目的：研究大脑中动脉狭窄患者脑血流自动调节机能及脑血管反应性是否受损,以及二者同狭窄程度之间的关系。方法：入组21例经磁共振血管成像诊断为MCA狭窄的患者及15例健康对照。应用传递函数的算法分析MCA血流速度及动脉血压的自然波动以分析脑血流自动调节机能。应用自呼吸的方法测量脑血管反应性。结果：MCA中度狭窄侧的脑血流自动调节参数(恢复率、相位)及脑血管反应性参数与对照相比均显著降低(恢复率17.76±8.21%/s VS.39.62±27.99%/s, p<O.05:相位26.93±15.67. VS.55.66±22.10., p<0.05:脑血管反应性1.53±0.84%/mmHg VS.2.18±0.80%/舳Hg, p<0.05)..恢复率(r=-0.698,p<0.001)、相位(r=-0.738,p<0.001)及脑血管反应性(r=-0.690, p<0.001)均同狭窄程度显著相关。结论：MCA狭窄超过50%的患者同侧脑血流自动调节及脑血管反应性受损,且受损程度随狭窄的程度增加而加剧。更多还原

【Abstract】 Part1Microembolic Signals Predict Cerebral Ischemic Events in Patients with Moyamoya DiseaseBackground:Recent studies found that microembolic signals (MES) could be detected by transcranial Doppler in patients with moyamoya disease. However the clinical significance of MES in moyamoya disease remains unclear.Objective:We aimed to investigate whether the MES could predict cerebral ischemic events in patients with moyamoya disease.Methods:Fifty-four consecutive patients with moyamoya disease were recruited. MES were monitored by transcranial Doppler for30minutes in bilateral middle cerebral arteries of each patient on admission. Patients were followed up for1year. The primary endpoint was cerebral ischemic events including stroke and transient ischemic attack (TIA).Results:MES were detected in11(20.4%) patients, with a frequency of11(10.2%) in108hemispheres. Logistic regression analysis revealed that previous ischemic events within3months was associated with the presence of MES (OR=4.41,95%CI1.11-17.59). During median follow-up of384days,14(13.0%) hemispheres had ischemic events (7strokes and7TIAs). Cox regression showed that the hazard ratio for the risk of new ischemic stroke and TIA in the hemispheres with MES was6.84(95%CI1.82-25.66) compared with those without, and10.61(95%CI1.66-67.70) for ischemic stroke alone, after controlling for age, sex, presence of ischemic events at baseline, Suzuki stages and revascularization surgery.Conclusions:In patients with moyamoya disease, the presence of MES is associated with recent ischemic symptoms, and independently predict cerebral ischemic events. MES detection may be of potential clinical value in the management of patients with MMD. Part2Impaired Dynamic Cerebral Autoregulation in Moyamoya DiseaseBackground:Moyamoya disease (MMD) can lead to deficit of cerebral autoregulation, thus may increases the risk of cerebral ischemia and hemorrhage. It is desirable to know when this protective mechanism begins to impair and how it changes as MMD progress.Purpose:We applied a non-invasive method to investigate the status of autoregulation at different stages of MMD.Methods:This study investigated26hemispheres with MMD amongl3patients and20hemispheres without stenosis amonglO controls. Degree of distal carotid artery stenosis was classified according to modified Suzuki stage. Cerebral autoregulation was assessed by transfer function analysis from spontaneous oscillations of cerebral blood flow velocity and blood pressure.Results:Three autoregulatory parameters, the rate of recovery (RoRc), phase shift, and gain were derived from transfer function. RoRc and phase shift estimated from the first stage are significantly different from controls (RoRc22.70±4.93%/s VS.40.78±20.92%/s, p<0.05; phase35.20±12.29°VS.60.01±18.96°, p<0.05).Gain and coherence becomes significantly different when MMD develops to stage II(gain0.40±0.16VS.0.86±0.50,p<0.05; coherence0.64±0.11VS.0.42±0.16,p<0.05).RoRc (r=-0.478, p<0.05), phase (r=-0.619, p<0.001)and gain (r=-0.507, p<0.001) are all significantly correlated with the angiographic stages.Conclusions:Cerebral autoregulation starts to impair at early stage of MMD. And autoregulatory parameters are highly correlated with the stages, suggesting the dysautoregulation may tend to worsen gradually with progression of MMD. Part3Impaired Dynamic Cerebral Autoregulation and Cerebrovascular Reactivity in Middle Cerebral Artery StenosisBackground:A number of studies reported that stenosis in internal carotid artery may impair cerebral hemodynamics, including cerebral autoregulation and cerebrovascular reactivity (CVR), which increases the risk of cerebral ischemic events. And intracranial artery occlusive diseases, especially middle cerebral artery (MCA) stenosis, are major causes of ischemic stroke in Chinese populations. However such studies in intracranial artery stenosis are lacking.Purpose:We sought to investigate the capacity of cerebral autoregulation and CVR in patients with MCA stenosis.Methods:Twenty-one patients with MCA stenosis diagnosed by magnetic resonance angiography and15healthy controls were enrolled. Cerebral autoregulation was assessed by autoregulatory parameters (rate of recovery/phase/gain) derived from transfer function from spontaneous oscillations of cerebral blood flow velocity and blood pressure. CVR was tested by a rebreathing maneuver.Results:Rate of recovery, phase and CVR estimated from moderate MCA stenosis (rate of recovery=17.76±8.21%/s, phase=26.93±15.67°,and CVR=1.53±0.84%/mmHg, respectively) were significantly different (p<0.05) from controls (rate of recovery=39.62±27.99%/s, phase=55.66±22.1°, and CVR=2.18±0.80%/mmHg, respectively). Rate of recovery (r=-0.698, p<0.001), phase (r--0.738, p<0.001)) and CVR (r=-0.690, p<0.001) were all significantly correlated with the degree of stenosis.Conclusion:Cerebral autoregulation and CVR were impaired in patients with≥50%MCA stenosis. The measures of both hemodynamic properties were inversely correlated with the stenotic degree.更多还原