临床—弥散不匹配与急性缺血性卒中患者临床结局及中医证候的关系
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摘要
背景
卒中试验已经证明超过溶栓时间窗的患者并不能从溶栓治疗中获益,大部分患者都无法获得溶栓治疗。但是通过一定方法筛选那些具有缺血半暗带的超窗患者却有可能从溶栓治疗中获益。目前的临床试验广泛采用核磁灌注-弥散不匹配法选择具有半暗带的患者进行溶栓治疗,但由于灌注检查条件要求较高,限制了其在临床中的应用。卒中试验NIHSS评分评估缺血性卒中的严重程度与其弥散加权成像(DWI)所示的梗死容积不匹配即临床-弥散不匹配(Clinical-Diffusion Mismatch,CDM)被认为是最有可能代替核磁灌注-弥散不匹配识别那些可能从再灌注治疗中获益患者的方法。但目前国内外对临床-弥散不匹配的研究多选择超早期的患者进行研究,很少有研究者将视野扩展到更晚时间。发病1周内的患者是否存在半暗带,其与临床结局及中医证候的相关性仍然不清楚。
目的
初步研究急性缺血性卒中发病后1周内患者临床-弥散不匹配规律,并分析其与临床结局及中医证候演变的关系,为不同患者的临床管理策略制定提供依据。
方法
本研究为前瞻性研究,56例卒中发病72h内入院的急性缺血性卒中患者,在发病1周内完成头颅核磁检查,并诊断为大脑中动脉供血区域梗死,采用计算机软件半自动方法计算其DWI梗死容积,并分别在在入院时、入院第7天、入院第15天、第30天分别对患者进行NIHSS评分,mRS评分及中医证候评分。临床-弥散不匹配定义为：DWI容积≤5mL而NIHSS评分≥8分。良好临床结局定义如下：(1)NIHSS评分改善≥8分或观察终点NIHSS评分为0-1分；(2)观察终点mRS评分为0-2分。
结果
1.56例患者中的16例(28.6%)患者存在临床-弥散不匹配。存在CDM和无CDM的患者良好临床结局和死亡病例数统计均无显著差异(P值分别为0.091和1.000)。CDM组和无CDM组患者分别有4例(25%)和14例(35%)患者神经恶化,但无统计学差异(p=0.473)。
2.患者从入院基线至入院第7天,存在CDM组和无CDM组NIHSS评分分别减少2.7分和0.4分,且有统计学差异(p=0.026)；从基线时间至入院第15天,有CDM组NIHSS评分减少2.3分；无CDM组NIHSS评分减少0.7分(p=0.022)；至第30天,两组NIHSS评分减少分别为2.5分和1.7分(p=0.040)。
3. NIHSS评分与DWI梗死容积具有很好的相关性(rs=0.721,p=0.009),但CDM组(rs=0.610,P=0.012)与无CDM组(rs=0.847,P=0.000)患者DWI梗死容积与NIHSS相关性却有所不同：无CDM组NIHSS评分与DWI容积相关性优于CDM组。
4.随着卒中发病时间的延长,临床-弥散不匹配出现比例降低。发病72h内行头颅核磁检查的33例患者中,共有12例(36.3%)患者出现CDM,而在72h后行头颅核磁检查的23例患者中,共有4例(17.4%)患者出现CDM。
5.所有患者卒中发病72h内,以风证和血瘀证候评分最高,中位数均为6.0分。入院第7天,痰证较重(中位数=7分),火热证(中位数=3分)和瘀血(中
位数=6分)证候评分较前无明显变化,而气虚证候加重(中位数=6分)。入院第15天,风证证候评分继续下降(中位数=2分),火热证较前无明显变化[中位数=3.5分),痰证评分较前下降(中位数=6分),血瘀证较前无明显变化,气虚证候较前加重(中位数=7.5分)。入院第30天,风证评分继续较前无变化,而痰证和瘀血证较前减低,气虚证候有所缓解(中位数=6.0分)。
6.两组患者从基线时间至发病第30天瘀血证评分和气虚证评分变化有显著统计学差异：CDM组瘀血证评分变化中位数为-1.0分,而这一数值在无CDM组为-5.5分(p=0.040)；对气虚证候评分30天内变化,两组分别为-0.5分和3.0分(p=0.004)。其余证候得分变化均无显著差异。
7.对所有患者,只有活血化瘀治疗与mRS变化显著相关(rs=-0.331,p=0.013)；对CDM组患者,抗血小板聚集与mRS改变成负相关(rs=-0.504),且有统计学意义(p=0.047),对无CDM组患者,抗血小板聚集与mRS改变无显著相关性(rs=-0.204,p=0.206)；另一方面,活血化瘀治疗与CDM组患者mRS改变无显著相关性(rs=-0.385,p=0.141),而与无CDM组患者mRS改变却显著相关(rs=-0.377,p=0.016)。
结论
急性缺血性卒中患者发病1周内,仍然可能存在可挽救组织；存在CDM的患者与无CDM的患者临床结局无显著差异；但存在CDM的患者NIHSS评分改善更明显,神经学结局优于无CDM组；两组患者中医证候演变有所差异,主要体现在瘀血和气虚证候的演变上；这两类患者对相同治疗药物的临床反应不同；针对这两类患者应该制定不同的临床管理方案。
Background Stroke trials have failed to show a significant benefit of intravenous tissue plasminogen activator(tPA) when administered beyond time window. More importantly, most patients do not have a chance to get thrombolytic therapy. However, there is evidence that even at later treatment times, carefully selected patients may benefit from reperfusion. Currently, Perfusion-weighted MRI (PWI) and diffusion-weighted MRI(DWI)mismatch is used for selecting patients with a penumbra to take thrombolytic therapy, which is widely used in clinical trials. A limitation of this model is the comparatively high requirement, which have limited its routine clinical use. Mismatch between stroke severity, assessed with the national institutes of health stroke scale(NIHSS), and the volume of the DWI lesion(clinical diffusion mismatch, CDM) has been suggested as a most promising select tool for identifying patients with penumbral tissue, replacing PWI-DWI mismatch.
Purpose The aim of this study is to evaluate the law of CDM within1week of symptom onset and analysis the relationship between CDM and outcomes and TCM Syndromes in Patients with Acute Ischemic Stroke. Consequently, we pursue to provide evidence for clinical management strategies for different patients.
Methods We conducted a prospective study. Fifty-six patients with middle cerebral artery (MCA) were admitted to hospital within72hours and imaged within168hours of symptom onset. DWI volumes were measured with using semi-automated thresholding technique. We performed clinical assessment including NIHSSS, mRS, TCM syndromes in admission time points,7days,15days and30days after symptom onset, respectively. CDM was defined as NIHSS>8and DWI<25mL. favorable clinical outcome was defined as an improvement on the NIHSS at least8points between baseline and30days or NIHSS<1at30days or mRS<2at30days.
Results
1. A total of16of56(28.6%) patients fulfilled the proposed definition of CDM. favorable clinical outcome and death cases were not significantly different between with CDM and without CDM (p=0.091,1.000, respectively). And then, the CDM group and without CDM group have4of16and14of40cases got neurologic deterioration, but not significant (p=0.473).
2. The changes of NIHSS between the two groups were significantly different. From the baseline to day7, the NIHSS of with CDM group declined2.7while this figure in the without CDM group is0.4(p=0.026). At day15, the changes of with CDM and without CDM group were-2.3and-0.7respectively (p=0.022). At the endpoint of our observation (day30), the changes of NIHSS for the two groups were-2.5and-1.7, respectively (p=0.04).
3. There was a highly significant positive correlation between NIHSS and DWI volume(rs=0.721, p=0.009), but the data in without CDM group(rs=0.847, P=0.000) is better correlated with NIHSS than that of with CDM group (rs=0.610, P=0.012).
4. With the extension of onset time, the ratio of CDM declined gradually.12of33(36.3%) patients who were performed with MRI examinations within72hours after onset while the figure in the others who took MRl examinations beyond72hours was4of23(17.4%).
5. The wind syndrome and blood stasis syndrome got the highest score (median of both=6.0). At day7, phegmdampness syndrome was comparatively severity (median=7.0). Firehot and blood stasis syndrome remained stable(median=:3.0and6.0,respectively). However, Qi deficiency syndrome became more serious(median=6.0).at day15,both wind syndrome and phegmdampness experienced an consistent decline(median=2.0and6.0,respectively). firehot did not show a significant fluctuation(median=3.5). at the same time, qi deficiency showed an increasing trends(median=7.5). After that, the wind syndrome showed little change. The phegmdampbess syndrome and blood stasis syndrome descend, qi deficiency also released at some extent.
6. From baseline to day30, The two groups were significantly different in the scores change of Blood stasis (median-1.0vs-5.5, p=0.040) and Qi deficiency (median=-0.5vs3.0, p=0.004). The change of the rest TCM syndromes were not significantly.
7. There was a highly significant negative correlation between promoting blood circulation for removing blood stasis and mRS (rs=-0.331, p=0.013). precisely, in the patients with CDM, inhibition of platelet aggregation also showed a negative correlation with the transformation of mRS (rs=-0.504, p=0.047). for the other group, Inhibition of platelet aggregation did not show a significantly correlation with the fluctuation of mRS (rs=-0.204, p=0.206); promoting blood circulation for removing blood stasis was not significantly correlated with the change of mRS (rs=-0.385, p=0.141),on the other hand, it was significantly correlated with mRS change(rs=-0.377, p=0.016).
Conclusion Potential salvageable tissue may still exist in patients with acute ischemic stroke within1week, in the daily clinical routines, there are no significantly difference in clinical outcomes between patients with CDM and without CDM. however, the improvement of NIHSS for with CDM group was more obvious than that of without CDM group, and the neurological outcome of CDM group was better than the other group.The evolutions of TCM syndromes in the two groups are vary from each other, which was shown in the change of Blood stasis and Qi deficiency. Also, the clinical responses of them are different. We should develop different clinical management strategies for the two types of patients.
卒中试验已经证明超过溶栓时间窗的患者并不能从溶栓治疗中获益,大部分患者都无法获得溶栓治疗。但是通过一定方法筛选那些具有缺血半暗带的超窗患者却有可能从溶栓治疗中获益。目前的临床试验广泛采用核磁灌注-弥散不匹配法选择具有半暗带的患者进行溶栓治疗,但由于灌注检查条件要求较高,限制了其在临床中的应用。卒中试验NIHSS评分评估缺血性卒中的严重程度与其弥散加权成像(DWI)所示的梗死容积不匹配即临床-弥散不匹配(Clinical-Diffusion Mismatch,CDM)被认为是最有可能代替核磁灌注-弥散不匹配识别那些可能从再灌注治疗中获益患者的方法。但目前国内外对临床-弥散不匹配的研究多选择超早期的患者进行研究,很少有研究者将视野扩展到更晚时间。发病1周内的患者是否存在半暗带,其与临床结局及中医证候的相关性仍然不清楚。
目的
初步研究急性缺血性卒中发病后1周内患者临床-弥散不匹配规律,并分析其与临床结局及中医证候演变的关系,为不同患者的临床管理策略制定提供依据。
方法
本研究为前瞻性研究,56例卒中发病72h内入院的急性缺血性卒中患者,在发病1周内完成头颅核磁检查,并诊断为大脑中动脉供血区域梗死,采用计算机软件半自动方法计算其DWI梗死容积,并分别在在入院时、入院第7天、入院第15天、第30天分别对患者进行NIHSS评分,mRS评分及中医证候评分。临床-弥散不匹配定义为：DWI容积≤5mL而NIHSS评分≥8分。良好临床结局定义如下：(1)NIHSS评分改善≥8分或观察终点NIHSS评分为0-1分；(2)观察终点mRS评分为0-2分。
结果
1.56例患者中的16例(28.6%)患者存在临床-弥散不匹配。存在CDM和无CDM的患者良好临床结局和死亡病例数统计均无显著差异(P值分别为0.091和1.000)。CDM组和无CDM组患者分别有4例(25%)和14例(35%)患者神经恶化,但无统计学差异(p=0.473)。
2.患者从入院基线至入院第7天,存在CDM组和无CDM组NIHSS评分分别减少2.7分和0.4分,且有统计学差异(p=0.026)；从基线时间至入院第15天,有CDM组NIHSS评分减少2.3分；无CDM组NIHSS评分减少0.7分(p=0.022)；至第30天,两组NIHSS评分减少分别为2.5分和1.7分(p=0.040)。
3. NIHSS评分与DWI梗死容积具有很好的相关性(rs=0.721,p=0.009),但CDM组(rs=0.610,P=0.012)与无CDM组(rs=0.847,P=0.000)患者DWI梗死容积与NIHSS相关性却有所不同：无CDM组NIHSS评分与DWI容积相关性优于CDM组。
4.随着卒中发病时间的延长,临床-弥散不匹配出现比例降低。发病72h内行头颅核磁检查的33例患者中,共有12例(36.3%)患者出现CDM,而在72h后行头颅核磁检查的23例患者中,共有4例(17.4%)患者出现CDM。
5.所有患者卒中发病72h内,以风证和血瘀证候评分最高,中位数均为6.0分。入院第7天,痰证较重(中位数=7分),火热证(中位数=3分)和瘀血(中
位数=6分)证候评分较前无明显变化,而气虚证候加重(中位数=6分)。入院第15天,风证证候评分继续下降(中位数=2分),火热证较前无明显变化[中位数=3.5分),痰证评分较前下降(中位数=6分),血瘀证较前无明显变化,气虚证候较前加重(中位数=7.5分)。入院第30天,风证评分继续较前无变化,而痰证和瘀血证较前减低,气虚证候有所缓解(中位数=6.0分)。
6.两组患者从基线时间至发病第30天瘀血证评分和气虚证评分变化有显著统计学差异：CDM组瘀血证评分变化中位数为-1.0分,而这一数值在无CDM组为-5.5分(p=0.040)；对气虚证候评分30天内变化,两组分别为-0.5分和3.0分(p=0.004)。其余证候得分变化均无显著差异。
7.对所有患者,只有活血化瘀治疗与mRS变化显著相关(rs=-0.331,p=0.013)；对CDM组患者,抗血小板聚集与mRS改变成负相关(rs=-0.504),且有统计学意义(p=0.047),对无CDM组患者,抗血小板聚集与mRS改变无显著相关性(rs=-0.204,p=0.206)；另一方面,活血化瘀治疗与CDM组患者mRS改变无显著相关性(rs=-0.385,p=0.141),而与无CDM组患者mRS改变却显著相关(rs=-0.377,p=0.016)。
结论
急性缺血性卒中患者发病1周内,仍然可能存在可挽救组织；存在CDM的患者与无CDM的患者临床结局无显著差异；但存在CDM的患者NIHSS评分改善更明显,神经学结局优于无CDM组；两组患者中医证候演变有所差异,主要体现在瘀血和气虚证候的演变上；这两类患者对相同治疗药物的临床反应不同；针对这两类患者应该制定不同的临床管理方案。
Background Stroke trials have failed to show a significant benefit of intravenous tissue plasminogen activator(tPA) when administered beyond time window. More importantly, most patients do not have a chance to get thrombolytic therapy. However, there is evidence that even at later treatment times, carefully selected patients may benefit from reperfusion. Currently, Perfusion-weighted MRI (PWI) and diffusion-weighted MRI(DWI)mismatch is used for selecting patients with a penumbra to take thrombolytic therapy, which is widely used in clinical trials. A limitation of this model is the comparatively high requirement, which have limited its routine clinical use. Mismatch between stroke severity, assessed with the national institutes of health stroke scale(NIHSS), and the volume of the DWI lesion(clinical diffusion mismatch, CDM) has been suggested as a most promising select tool for identifying patients with penumbral tissue, replacing PWI-DWI mismatch.
Purpose The aim of this study is to evaluate the law of CDM within1week of symptom onset and analysis the relationship between CDM and outcomes and TCM Syndromes in Patients with Acute Ischemic Stroke. Consequently, we pursue to provide evidence for clinical management strategies for different patients.
Methods We conducted a prospective study. Fifty-six patients with middle cerebral artery (MCA) were admitted to hospital within72hours and imaged within168hours of symptom onset. DWI volumes were measured with using semi-automated thresholding technique. We performed clinical assessment including NIHSSS, mRS, TCM syndromes in admission time points,7days,15days and30days after symptom onset, respectively. CDM was defined as NIHSS>8and DWI<25mL. favorable clinical outcome was defined as an improvement on the NIHSS at least8points between baseline and30days or NIHSS<1at30days or mRS<2at30days.
Results
1. A total of16of56(28.6%) patients fulfilled the proposed definition of CDM. favorable clinical outcome and death cases were not significantly different between with CDM and without CDM (p=0.091,1.000, respectively). And then, the CDM group and without CDM group have4of16and14of40cases got neurologic deterioration, but not significant (p=0.473).
2. The changes of NIHSS between the two groups were significantly different. From the baseline to day7, the NIHSS of with CDM group declined2.7while this figure in the without CDM group is0.4(p=0.026). At day15, the changes of with CDM and without CDM group were-2.3and-0.7respectively (p=0.022). At the endpoint of our observation (day30), the changes of NIHSS for the two groups were-2.5and-1.7, respectively (p=0.04).
3. There was a highly significant positive correlation between NIHSS and DWI volume(rs=0.721, p=0.009), but the data in without CDM group(rs=0.847, P=0.000) is better correlated with NIHSS than that of with CDM group (rs=0.610, P=0.012).
4. With the extension of onset time, the ratio of CDM declined gradually.12of33(36.3%) patients who were performed with MRI examinations within72hours after onset while the figure in the others who took MRl examinations beyond72hours was4of23(17.4%).
5. The wind syndrome and blood stasis syndrome got the highest score (median of both=6.0). At day7, phegmdampness syndrome was comparatively severity (median=7.0). Firehot and blood stasis syndrome remained stable(median=:3.0and6.0,respectively). However, Qi deficiency syndrome became more serious(median=6.0).at day15,both wind syndrome and phegmdampness experienced an consistent decline(median=2.0and6.0,respectively). firehot did not show a significant fluctuation(median=3.5). at the same time, qi deficiency showed an increasing trends(median=7.5). After that, the wind syndrome showed little change. The phegmdampbess syndrome and blood stasis syndrome descend, qi deficiency also released at some extent.
6. From baseline to day30, The two groups were significantly different in the scores change of Blood stasis (median-1.0vs-5.5, p=0.040) and Qi deficiency (median=-0.5vs3.0, p=0.004). The change of the rest TCM syndromes were not significantly.
7. There was a highly significant negative correlation between promoting blood circulation for removing blood stasis and mRS (rs=-0.331, p=0.013). precisely, in the patients with CDM, inhibition of platelet aggregation also showed a negative correlation with the transformation of mRS (rs=-0.504, p=0.047). for the other group, Inhibition of platelet aggregation did not show a significantly correlation with the fluctuation of mRS (rs=-0.204, p=0.206); promoting blood circulation for removing blood stasis was not significantly correlated with the change of mRS (rs=-0.385, p=0.141),on the other hand, it was significantly correlated with mRS change(rs=-0.377, p=0.016).
Conclusion Potential salvageable tissue may still exist in patients with acute ischemic stroke within1week, in the daily clinical routines, there are no significantly difference in clinical outcomes between patients with CDM and without CDM. however, the improvement of NIHSS for with CDM group was more obvious than that of without CDM group, and the neurological outcome of CDM group was better than the other group.The evolutions of TCM syndromes in the two groups are vary from each other, which was shown in the change of Blood stasis and Qi deficiency. Also, the clinical responses of them are different. We should develop different clinical management strategies for the two types of patients.
引文
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