对比增强TCD方法优化及在PFO封堵治疗右向左分流相关偏头痛中的应用

发布时间：2019-06-22 11:19

【摘要】：第一部分:对比增强TCD诊断右向左分流的方法学优化近年来,研究发现右向左分流(right-to-left shunt,RLS)可能与缺血性卒中、偏头痛、减压病、斜卧呼吸-直立型低氧血症、外周动脉栓塞、阻塞性睡眠呼吸暂停综合征等疾病相关。对比增强经颅多普勒超声(contrast-enhanced transcranial Doppler,c-TCD)以灵敏度高、安全无创、易于重复操作的特点,广泛应用于RLS的诊断。然而,c-TCD方法学方面仍存在较大差异。本部分研究就以下几方面对c-TCD诊断RLS方法学进行优化:1.常规经颞窗监测大脑中动脉(middle cerebral artery,MCA)不适用于颞窗穿透不良的患者,而颈动脉严重狭窄也会影响常规RLS诊断。近期还有研究表明RLS相关缺血性卒中患者的缺血灶及梗死灶多位于后循环椎基底动脉系统。为探讨c-TCD诊断RLS中椎动脉(vertebral artery,VA)监测的可行性,我们同步对比了c-TCD经枕窗监测VA与经颞窗监测MCA诊断RLS的差异。2.Valsalva动作是c-TCD探查RLS过程中的辅助手段,其执行方式及效力评判标准关乎潜在型RLS的检出。目前c-TCD探查RLS研究多沿用传统的Valsalva动作,以MCA流速下降20~25%作为评判其效力的标准。然而,百分比并不适合操作过程中的快速评判。为此,我们比较了传统的Valsalva动作与改良的Valsalva动作对c-TCD探查RLS的影响,并进一步测量了Valsalva动作过程中血流速度的变化差值。1.对比增强TCD诊断右向左分流中椎动脉监测的可行性本研究从临床实际出发,以2015年2月至4月在吉林大学第一医院神经内科就诊的318名需行c-TCD筛查RLS情况的患者为主要研究对象,对满足入排标准的194名患者行c-TCD同步监测VA和MCA,以进一步探讨c-TCD诊断RLS中VA监测的可行性。主要研究结果表明:1c-TCD中VA监测与MCA监测相比,总体、固有型及潜在型RLS检出情况均无统计学差异,灵敏度和特异性均较高;2c-TCD中VA监测比MCA监测探查的RLS等级略低,但差异无统计学意义(P=0.079);3c-TCD静息状态及Valsalva动作下VA监测RLS第一个微气泡出现均比MCA监测略晚(P0.001)。2.对比增强TCD检查过程中改良Valsalva动作的价值探讨及血流评判标准的建立本研究从临床实际出发,以2014年11月至12月在吉林大学第一医院神经内科就诊的317名需行c-TCD筛查RLS情况的患者为主要研究对象,对满足入排标准的298名患者行c-TCD随机完成以下3段监测:1)静息状态;2)传统的Valsalva动作:深吸气后紧闭声门下的屏气动作,持续10秒;3)改良的Valsalva动作:向连通压力计的管子用力吹气,使压力计达到40 mm Hg维持10秒。通过比较RLS阳性检出率、RLS等级及第一个微气泡出现的时间,探讨改良Valsalva动作的价值。进一步回顾性分析,线下回放c-TCD监测记录,对满足入排标准的共114例患者,选取并记录压力计控制的Valsalva动作下血流趋势曲线上流速最高和最低点对应的收缩期流速与平均流速,计算差值变化,以期建立Valsalva动作效力的血流评判标准。主要研究结果表明:1静息状态、传统的Valsalva动作和改良的Valsalva动作下,c-TCD探查RLS检出率分别为21.8%、36.9%和47.3%,改良的Valsalva动作下RLS检出率高于传统的Valsalva动作(P=0.010);2改良的Valsalva动作下c-TCD探查RLS等级较高(P0.001);3改良的Valsalva动作下第一个微气泡出现略晚于传统的Valsalva动作(P0.05)。4收缩期流速变化为30±9.7cm/s(95%置信区间为28.2~31.5);5平均流速变化为24±5.3 cm/s(95%置信区间为22.6~24.5)。结论:1c-TCD监测左侧VA与MCA相比,在静息状态和Valsalva动作下对RLS诊断的灵敏度、特异性均较高,可以作为一种替代方法,应用于颞窗穿透不良或颈内动脉严重狭窄患者的RLS探查。2通过对比两种不同Valsalva动作对RLS探查的影响,研究发现改良的Valsalva动作比传统的Valsalva动作RLS阳性检出率及检出等级更高。改良的Valsalva动作可以作为一种替代方法,尤其是对难以配合传统Valsalva动作但高度怀疑存在RLS的患者。3正常左侧MCA监测下收缩期流速降低30 cm/s或平均流速降低25 cm/s可作为c-TCD操作过程中快速评判Valsalva动作效力的血流参考指标。第二部分:PFO封堵治疗RLS相关偏头痛安全性与疗效评估近年来,大量报道指出偏头痛,尤其是先兆偏头痛与卵圆孔未闭(patent foramen ovale,PFO)相关。假说机制为神经递质或微栓子避过肺部的滤过灭活经PFO随右向左分流(right-to-left shunt,RLS)进入颅内循环引发偏头痛发作或降低其阈值。有研究表明PFO封堵手术可减轻偏头痛,但其适用人群及封堵器选择存在争议。目前,我国在此领域仍缺乏大样本前瞻性研究。本研究旨在评估PFO封堵手术对偏头痛的安全性和长期疗效,同时验证c-TCD在诊断RLS相关的偏头痛及PFO封堵治疗术后随访残余分流方面的重要作用。本部分研究从临床实际出发,前瞻性连续纳入2013年至2015年在吉林大学第一医院神经内科就诊的偏头痛患者,基线HIT-6评分后行c-TCD探查RLS,中至大量RLS患者进一步行心脏超声明确PFO后,根据患者意愿分为手术组和对照组,并随访1年内HIT-6评分。满足入排标准的患者共258例,130例要求或同意手术的患者入手术组,其余128例拒绝手术的患者入对照组。术后患者需口服阿司匹林6个月并于1个月、3个月、6个月和1年随访复查c-TCD。主要研究结果表明:1共241例患者完成了随访,手术组125例,对照组116例。125例均成功置入封堵器,仅1例出现心包填塞,无严重不良反应;21年随访期间复查c-TCD的残余分流患者85.71%转为阴性或小量分流;3封堵器内皮化不完全所致的残余分流和安慰效应在1年时基本消除;4术后1年患者头痛HIT-6随访最终评级92例(73.6%)降低、31例(24.8%)未变动、2例(1.6%)升高;5剔出基线HIT-6评分影响,手术组与对照组随访最终HIT-6评分比较表明手术组患者长期头痛缓解更明显(48.77 vs.57.85,P0.001);6手术组患者HIT-6基线评分与1年后的差值减少程度明显大于对照组(16.35 vs.5.59,P0.001);7除男性及潜在型RLS组外,其他亚组分析进一步验证了手术组疗效优于对照组。结论:本研究表明PFO封堵手术是一项安全有效治疗RLS相关偏头痛的手段,同时c-TCD在诊断RLS相关的偏头痛及PFO封堵治疗后随访残余分流方面具有重要的指导及预测价值。
[Abstract]:The first part: In recent years, the right-to-left shunt (RLS) of the right-to-left shunt (RLS) may be associated with ischemic stroke, migraine, decompression sickness, oblique-lying breathing-orthostatic hypoxemia, peripheral arterial embolism, Obstructive sleep apnea syndrome. Contrast-enhanced transcranial Doppler (c-TCD) is widely used in the diagnosis of RLS. However, there are still significant differences in the c-TCD methodology. This part studies the optimization of the method for the diagnosis of RLS with c-TCD in the following aspects:1. The middle cerebral artery (MCA) in the middle cerebral artery (MCA) is not suitable for the patients with bad through-window penetration, and the carotid artery stenosis will also affect the conventional RLS diagnosis. Recent studies have shown that the ischemic range and the infarct focus of patients with RLS-associated ischemic stroke are located in the posterior circulation vertebrobasilar system. In ord to investigate that feasibility of c-TCD in the diagnosis of the vertebral artery (VA) in the RLS, we compare the difference between the monitor VA of c-TCD and the diagnostic RLS of the MCA through the window.2. Valsalva's action is the aid of c-TCD in the exploration of RLS. At present, the traditional Valsalva maneuver is used to explore the RLS in the C-TCD exploration, and the MCA flow rate is reduced by 20-25% as the criterion for judging its effectiveness. However, the percentage is not suitable for rapid evaluation during operation. To this end, we compared the traditional Valsalva's action with the modified Valsalva's action on the detection of RLS by c-TCD, and further measured the difference of blood flow velocity during Valsalva's motion. In contrast, the feasibility of contrast-enhanced TCD in the diagnosis of the right-to-left shunt in the right-to-left shunt is the main study of the 318 patients who need c-TCD to screen the RLS in the first hospital of Jilin University from February to April,2015. The VA and MCA were monitored by c-TCD in 194 patients who met the entry criteria to further investigate the feasibility of VA monitoring in the diagnosis of RLS with c-TCD. The results showed that VA monitoring in 1c-TCD did not have statistical difference, sensitivity and specificity were higher than that of MCA, and VA monitoring in 2c-TCD was lower than that of MCA, but the difference was not significant (P = 0.079). In the 3-TCD resting state and Valsalva's operation, the first micro-bubble in the VA-monitored RLS was slightly lower than that of the MCA (P 0.001). In order to improve the value of Valsalva's motion and the establishment of the criteria for the evaluation of blood flow in the course of enhancing the TCD examination, the clinical practice of the study is to study 317 patients with RLS in the neurology of the first hospital in Jilin University from November to December of 2014 as the main research object. the following three monitoring:1) resting state for 298 patients meeting the entry criteria:1) resting state;2) conventional valsalva motion: a breath-holding action under the closed acoustic door after deep inhalation for 10 seconds; and 3) an improved valsalva motion: a forced air blow to the tube in communication with the pressure gauge, Maintain the pressure gauge up to 40 mm Hg for 10 seconds. The value of modified Valsalva's action was discussed by comparing the positive rate of RLS, the level of RLS and the time of the first micro-bubble. Further retrospective analysis, offline playback of c-TCD monitoring records, a total of 114 patients who met the entry criteria, the systolic flow rate and the mean flow rate corresponding to the highest and lowest points on the blood flow trend curve under the control of the pressure gauge were selected and recorded, and the difference was calculated. So as to establish a blood flow evaluation standard for Valsalva's action effectiveness. The results showed that the detection rate of RLS was 21.8%, 36.9% and 47.3%, respectively, and that of the modified Valsalva was higher than that of the traditional Valsalva (P = 0.010). The first micro-bubble in the modified Valsalva maneuver was higher than that of the traditional Valsalva (P.001). The first micro-bubble in the modified Valsalva maneuver was slightly later than that of the traditional Valsalva (P0.05). The change of systolic velocity was 30-9.7 cm/ s (95% confidence interval was 28.2-31.5), and the mean flow rate was 24-5.3 cm/ s (95% confidence interval is 22.6-24.5). Conclusion: The sensitivity and specificity of 1c-TCD in the diagnosis of RLS under the action of resting and Valsalva can be used as an alternative. By comparing the effects of two different Valsalva actions on the detection of RLS, the results show that the improved Valsalva's action is higher than that of the traditional Valsalva. the modified valsalva action can be used as an alternative, In particular, patients with difficulty in matching the traditional Valsalva maneuver but highly suspected of RLS. The systolic flow rate at normal left MCA monitoring was reduced by 30 cm/ s or the mean flow rate was reduced by 25 cm/ s as the blood flow reference index for the rapid evaluation of the efficacy of the Valsalva operation during the c-TCD operation. The second part: The safety and curative effect of PFO occlusion in the treatment of RLS-associated migraine has been reported in recent years, and it is reported that the migraine, especially the migraine with aura, is associated with the patent foramen ovale (PFO). The hypothesis mechanism is that neurotransmitters or microemboli escape through the PFO with the right-to-left shunt (RLS) into the intracranial cycle to trigger a migraine attack or to reduce its threshold. Studies have shown that PFO occlusion can reduce migraine, but there is a dispute between the appropriate population and the device choice. At present, there is still a lack of large-sample prospective studies in this field in our country. The purpose of this study was to evaluate the safety and long-term efficacy of PFO occlusion in the treatment of migraine and to verify the important role of c-TCD in the diagnosis of RLS-associated migraine and the follow-up residual shunt in the treatment of PFO. This part of the study, from the clinical practice, was forward-looking and continuously included in the first hospital of the first hospital of Jilin University from 2013 to 2015, and after the baseline HIT-6 score, c-TCD was used to explore the RLS, and the middle to large number of RLS patients further underwent cardiac ultrasound to clear the PFO. The patient's will was divided into the surgical group and the control group, and the HIT-6 score was followed for 1 year. Of the 258 patients who met the criteria of entry,130 patients who required or agreed to the procedure were enrolled in the operation group, and the remaining 128 patients who refused to be operated were enrolled in the control group. The postoperative patient was given an aspirin for 6 months and the c-TCD was reviewed at 1 month,3 months,6 months, and 1 year follow-up. The results showed that:1 total of 241 patients had completed the follow-up,125 cases in the operation group and 116 in the control group. 3. The residual shunt and the comfort effect caused by the endothelialization of the occluder were substantially eliminated at 1 year; the final rating of the HIT-6 follow-up in 1 year after the operation was decreased in 92 (73.6%),31 (24.8%) did not change,2 (1.6%) increased, and 5 the baseline HIT-6 score was removed. The result of the follow-up HIT-6 score of the operation group and the control group showed that the long-term headache response of the patients in the operation group was more obvious (48.77 vs. 57.85, P0.001), and the difference between the HIT-6 baseline score and the 1-year post-treatment group in the 6-operation group was significantly higher than that of the control group (16.35 vs. 5.59, P0.001), and that in addition to the male and potential RLS groups, The other subgroup analyses further demonstrated that the efficacy of the surgical group was superior to that of the control group. Conclusion: The study shows that PFO occlusion is a safe and effective means for the treatment of RLS-associated migraine, while c-TCD has important guidance and predictive value in the diagnosis of RLS-associated migraine and the follow-up of residual shunt after PFO occlusion treatment.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R747.2

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