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문제 정의
- This study was a hospital-based, retrospective observational study. There were 7,462 candidates who were admitted to the neurology department because of acute brain infarction or TIA within 7 days of symptom onset, between January 2001 and December 2014, and were prospectively registered in the Yonsei Stroke Registry.
- Although previous study reported that TCD had a high level of interobserver agreement in skilled personnel [22], technical difference may exist. Thus, the same skilled and well trained technicians are needed to improve the reliability in further studies. Finally, the MCA asymmetry index presented in this study is not an intrinsic value.
- 본 연구는 일과성허혈발작 및 급성뇌경색환자에서 양쪽 중간대뇌동맥의 혈류속도 차이가 예후를 예측할 수 있는 지표가될 수 있고, 이러한 예후예측력이 뇌졸중 아형 간에 차이가 있는 지를 관찰하는 것이다. 모든 대상자는 일과성허혈발작 및 급성뇌경색환자들이며, 기본적인 평가와 경두개도플러검사(TCD)가 실시되었다.
제안 방법
- According to the mRS score at 3 months after stroke onset, the patients were subdivided into 2 groups: good functional outcome (mRS score ＜3) and poor functional outcome (mRS score ≥3) [12].
- (B) Change in the AUC after the addition of the cutoff value of the MCA asymmetry index to the multivariable model for predicting poor functional outcome. Adjustments were made for following variables: sex, age, National Institute of Health Stroke Scale score at admission, use of thrombolysis treatment, stroke subtype, hemoglobin level, high-sensitivity C-reactive protein level, triglyceride level, albumin level, premorbid medication (antihypertensive) use, pulsatility index of the right MCA, pulsatility index of the left MCA, and brachial-ankle pulse wave velocity. AUC, area under the curve; CI, confidence interval; MCA, middle cerebral artery.
- test for categorical variables and the Mann-Whitney U-test for non-normal continuous variables. After yielding the cutoff value of the MCA asymmetry index, the X2 test was used to analyze the association between stroke subtype and MCA asymmetry index cutoff value. Before investigating the predictive effect of the MCA asymmetry index for poor functional outcome, the patients were subdivided into tertile groups (T1-T3) according to the level of MCA asymmetry index.
- After yielding the cutoff value of the MCA asymmetry index, the X2 test was used to analyze the association between stroke subtype and MCA asymmetry index cutoff value. Before investigating the predictive effect of the MCA asymmetry index for poor functional outcome, the patients were subdivided into tertile groups (T1-T3) according to the level of MCA asymmetry index. Then, we performed multivariable logistic regression with adjustments for sex, age, and variables that exhibited a P-value of ＜0.
- Standard systemic investigations were performed in every patient, which included 12-lead electrocardiography (ECG), chest radiography, and blood tests. Carotid duplex sonography, transthoracic echocardiography, transesophageal echocardiography, and 24-h Holter ECG monitoring were performed in selected patients. TCD was a part of the standard evaluation to obtain the MCA asymmetry index, except in patients with poor temporal window in either temple.
- We used the TOAST (Trial of Org 10172 in the Acute Stroke Treatment) classification to subdivide the patients into 4 groups: those with small vessel occlusion (LAC), large-artery atherosclerosis (LAA), cardioembolism (CE), and stroke of undetermined cause (SUD) [12]. Cerebral angiographic findings were obtained from digital subtraction angiography, MRA, or CTA, which were performed at admission, to classify the stroke subtype. All cerebral angiographic findings and the stroke subtypes were evaluated and determined during the weekly stroke conference, after a consensus was reached by stroke specialists.
- Although their study might be similar in design to our study, the Barthel index does not completely correspond with the mRS used in our study. In addition, we presented the MCA asymmetry index of ＜16.53 as an independent predictor of poor outcome, and then demonstrated that adding the independent predictor into the prediction model improved the discrimination of poor long-term outcome in patients with acute ischemic stroke.
- Stroke-related functional outcome was assessed using the mRS score through a direct interview performed by a physician or through a telephone interview conducted by a well-trained research nurse after 3 months from stroke onset. The mRS consists of 6 different grades of disability, from a score of 0 for “no symptoms at all”; to 5 for “severe disability or bedridden, incontinent, and requiring constant nursing care and attention”; and to 6 for death.
- The recorded MFV and PI values were measured for at least 2 depths to include hemodynamic information on the proximal MCA (M1, 58-68 mm) and the distal MCA (M2, 44-56 mm). The 2 highest MFVs and PIs, measured in both proximal and distal portions, were finally averaged to derive the ultimate MFV and PI for statistical analysis, respectively. We also created an asymmetry index (MCA asymmetry index) by using the bilateral ultimate MFVs to investigate whether the difference of both ultimate MFVs has prognostic value for predicting functional outcome after acute cerebral infarction, and whether the prognostic value differs among stroke subtypes.
- TCD was a part of the standard evaluation to obtain the MCA asymmetry index, except in patients with poor temporal window in either temple. The demographics, vascular risk factors, and neurologic examination including the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at 3 months after stroke onset were collected at baseline. We excluded patients with a history of old stroke, malignancy, and stroke of other causes, and/or those without data on the NIHSS score at admission, mRS score at 3 months after stroke onset, and complete laboratory study or cerebral angiography.
- The patients underwent TCD examination (TC8080, Nicolet, Stockport, UK) within 7 days of admission. All TCD recordings were carried out by 2 medical technicians.
- The area under the curve (AUC) was calculated, and the optimal cutoff value of MCA asymmetry index was determined at the level with the highest Youden index (sensitivity + specificity-1). To measure the improvement in predictive ability by adding the MCA asymmetry index, we computed the change of AUC between the multivariable models with and without the MCA asymmetry index cutoff value. All statistical analyses were performed using the Windows SPSS package version 20.
- 본 연구는 일과성허혈발작 및 급성뇌경색환자에서 양쪽 중간대뇌동맥의 혈류속도 차이가 예후를 예측할 수 있는 지표가될 수 있고, 이러한 예후예측력이 뇌졸중 아형 간에 차이가 있는 지를 관찰하는 것이다. 모든 대상자는 일과성허혈발작 및 급성뇌경색환자들이며, 기본적인 평가와 경두개도플러검사(TCD)가 실시되었다. 중간대뇌동맥 비대칭 지수(MCA asymmetry index)는 다음의 공식에 의해 구해졌다; MCA asymmetry index=(|RMCA MFV-LMCA MFV|/mean MCA MFV) x 100.
대상 데이터
- During the study period, 7,462 patients with acute ischemic stroke were registered in the Yonsei Stroke Registry. After eliminating 3,023 patients according to the exclusion criteria, 4,439 candidates remained for this study. Of these, 988 subjects who had completed the measurements of MFVs of both MCAs were finally included (Figure 1).
- The patients underwent TCD examination (TC8080, Nicolet, Stockport, UK) within 7 days of admission. All TCD recordings were carried out by 2 medical technicians. In all patients, peak systolic flow velocity (PSV) and end-diastolic flow velocity (EDV) were measured with a handheld 2-MHz probe in both MCAs.
- All cerebral angiographic findings and the stroke subtypes were evaluated and determined during the weekly stroke conference, after a consensus was reached by stroke specialists. The patients were then prospectively registered in the Yonsei Stroke Registry.
- This study was a hospital-based, retrospective observational study. There were 7,462 candidates who were admitted to the neurology department because of acute brain infarction or TIA within 7 days of symptom onset, between January 2001 and December 2014, and were prospectively registered in the Yonsei Stroke Registry. Of them, we excluded 3,023 patients according to the exclusion criteria.
- 나쁜 예후(poor functional outcome)는 mRS score ≥3 at 3 months after stroke onset로 정의하였다. 총 988명의 급성뇌경색환자가 분석에 포함되었고, 그 중 157명(15.9%)이 나쁜 예후를 가지고 있었다. 뇌경색 하위유형 및 여러 혼란변수를 보정 후 실시한 다변량분석에서 중간대뇌동맥 비대칭 지수만 유일하게 독립적으로 나쁜 예후와 연관성을 보였다.
데이터처리
- Statistical significance of intergroup differences was assessed using the X2test for categorical variables and the Mann-Whitney U-test for non-normal continuous variables. After yielding the cutoff value of the MCA asymmetry index, the X2 test was used to analyze the association between stroke subtype and MCA asymmetry index cutoff value.
이론/모형
- 05 in the univariable analyses. For evaluating the discriminatory ability of the MCA asymmetry index in predicting functional outcomes, receiver operating characteristic curve analysis was used. The area under the curve (AUC) was calculated, and the optimal cutoff value of MCA asymmetry index was determined at the level with the highest Youden index (sensitivity + specificity-1).
- 중간대뇌동맥 비대칭 지수(MCA asymmetry index)는 다음의 공식에 의해 구해졌다; MCA asymmetry index=(|RMCA MFV-LMCA MFV|/mean MCA MFV) x 100. 뇌경색 분류는 TOAST classification에 따라 진행되었다. 나쁜 예후(poor functional outcome)는 mRS score ≥3 at 3 months after stroke onset로 정의하였다.
성능/효과
- Black arrow indicates the optimal cutoff point of the MCA asymmetry index, which maximizes the Youden index. (B) Change in the AUC after the addition of the cutoff value of the MCA asymmetry index to the multivariable model for predicting poor functional outcome. Adjustments were made for following variables: sex, age, National Institute of Health Stroke Scale score at admission, use of thrombolysis treatment, stroke subtype, hemoglobin level, high-sensitivity C-reactive protein level, triglyceride level, albumin level, premorbid medication (antihypertensive) use, pulsatility index of the right MCA, pulsatility index of the left MCA, and brachial-ankle pulse wave velocity.
- In this study, we found that a higher MCA asymmetry index was related to LAA and significantly associated with poor functional outcome. TCD parameters have been used to diagnose and predict intracranial vascular disease.
- Although To help simplify the stratification of high-risk patients, we yielded a cutoff value from the MCA asymmetry index as a continuous variable by using receiver operating characteristic curve analysis. Of the hemodynamic parameters, only the cutoff value had an independent association with poor functional outcome, and adding the MCA asymmetry index to the prediction model significantly improved the discrimination ability for poor functional outcome. This means that the MCA asymmetry index measured during the acute phase of stroke can independently predict the 3-month functional prognosis; thus, this novel index should be considered a crucial marker for identifying patients with severe stroke-related disabilities.
- 뇌경색 하위유형 및 여러 혼란변수를 보정 후 실시한 다변량분석에서 중간대뇌동맥 비대칭 지수만 유일하게 독립적으로 나쁜 예후와 연관성을 보였다. ROC curve 분석에서 중간대뇌동맥 비대칭 지수를 예측모형에 투입하였을 때 투입 전에 비해 나쁜 예후를 예측하는 능력이 상승하는 것을 관찰하였다(from 88.6% [95% CI, 85.2-91.9] to 89.2% [95% CI, 85.9-92.5]). 급성뇌경색환자에서 중대뇌동맥 비대칭 지수는 나쁜 예후를 독립적으로 예측하였다.
- 9%)이 나쁜 예후를 가지고 있었다. 뇌경색 하위유형 및 여러 혼란변수를 보정 후 실시한 다변량분석에서 중간대뇌동맥 비대칭 지수만 유일하게 독립적으로 나쁜 예후와 연관성을 보였다. ROC curve 분석에서 중간대뇌동맥 비대칭 지수를 예측모형에 투입하였을 때 투입 전에 비해 나쁜 예후를 예측하는 능력이 상승하는 것을 관찰하였다(from 88.
후속연구
- 급성뇌경색환자에서 중대뇌동맥 비대칭 지수는 나쁜 예후를 독립적으로 예측하였다. 따라서 경두개도플러검사는 급성뇌경색환자에서 나쁜 예후를 예측하는데 유용하게 사용될 수 있을 것이다.
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