Original Paper Eur Neurol 2015;73:164–170 DOI: 10.1159/000370240
Received: September 30, 2014 Accepted: November 30, 2014 Published online: January 13, 2015
Timing of Neurological Improvement after Acute Ischemic Stroke and Functional Outcome Young-Mok Song Geun Ho Lee Jae Il Kim Department of Neurology, Dankook University Hospital, Cheonan, South Korea
Abstract Background: The time of neurological improvement (TNI) after acute ischemic stroke may have a predictive value. Methods: We evaluated 410 consecutive patients who were admitted within 12 hours of stroke onset. The National Institutes of Health Stroke Scale (NIHSS) was measured on admission and at 1, 3, 7, and 14 days. Neurological improvement was defined as an improvement in the NIHSS score by ≥2 points (NI2) or ≥4 points (NI4) or an NIHSS score of 0. Patients with a Modified Rankin scale (mRS) score of ≤2 were considered to have a good outcome. Results: Patients with earlier TNIs had a lower 3-month mRS score and a higher probability for a good outcome. In the binary and ordinal regression analyses, age, NIHSS score, atrial fibrillation and TNI were independently associated with a good outcome. Receiver operating characteristic curve analyses demonstrated that TNI2 had higher sensitivity and lower specificity than TNI4. The best threshold for predicting outcome was day 3 for TNI2 and day 14 for TNI4. Conclusions: These results suggest that TNI is independently associated with functional outcome at 90 days. TNI2 may be more useful than TNI4 for early prediction of stroke outcome. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0014–3022/15/0734–0164$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
The clinical course and prognosis of stroke patients are highly variable. Therefore, the prediction of outcome after acute stroke has been an important research issue. The stroke outcome is influenced by multiple factors. Some factors, such as age and the initial National Institutes of Health Stroke Scale (NIHSS) score [1], have been recognized as prognostic factors [2–7]. However, the current predictors are not sufficient for precise prediction of prognosis, and identification of more predictive factors is necessary. The clinical course during the acute phase of stroke may have a predictive value. Indeed, it has been reported that patients who improved within the first 48 hours of stroke onset had a better prognosis [8, 9], suggesting that early neurological improvement is predictive of a good prognosis. However, a detailed relationship between the time of neurological improvement (TNI) and functional outcome has not been elucidated. The purpose of this study was to investigate the relationship between the TNI after acute ischemic stroke and functional outcome at 3 months. Methods We prospectively studied consecutive patients with acute ischemic stroke who were admitted to the Dankook University hospital between January 2010 and December 2013. A total of 579 pa-
Young-Mok Song, MD Department of Neurology, Dankook University Hospital 119, Dandae-ro, Dongnam-gu Cheonan, Chungnam, 330–714 (South Korea) E-Mail ymsong @ medimail.co.kr
Downloaded by: Göteborgs Universitet 130.241.16.16 - 11/15/2017 8:33:38 PM
Key Words Stroke · Neurological improvement · Outcome
covariates related to dichotomized mRS in the binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the usefulness of the TNI2 and TNI4 for predicting a good outcome. We assessed the discrimination by calculating the area under the ROC curve of sensitivity versus 1 minus the specificity. The sensitivity, specificity, and positive and negative predictive values of the TNI2 and TNI4 were calculated to validate the TNIs in predicting a good outcome at 3 months. Statistical significance was established at p < 0.05. Statistical analyses were performed using SPSS (version 18.0, Chicago, Ill., USA) and Medcalc (version 13.3).
Results
Statistical Analysis A comparison of the baseline characteristics and outcome profiles among patients with different time of neurological improvement was performed by the ANOVA test for continuous variables and by the χ2 test for dichotomized variables. Binary logistic and ordinal regression analyses were used to assess the effects of TNIs on clinical outcome adjusted for variables showing a p < 0.2 in univariate analysis. In binary logistic models, mRS was dichotomized (mRS ≤2 vs. mRS >2) and a backward stepwise strategy was used to select the variables remaining in the final model. We constructed ordinal regression models to verify that the results were consistent across the levels of the mRS adjusted for factors and
There were 243 men and 167 women, and the mean age was 65.6 ± 11.9 years (range, 26–93 years). The TNI2 was day 1 in 95 (23%) patients, day 3 in 131 (32%) patients, day 7 in 92 (22%) patients, day 14 in 36 (9%) patients, and no improvement within 14 days was observed in 56 (14%) patients. The TNI4 was day 1 in 28 (7%) patients, day 3 in 54 (13%) patients, day 7 in 83 (20%) patients, day 14 in 84 (21%) patients, and no improvement in 161 (39%) patients. The clinical characteristics of patients who showed different TNI2 and TNI4 are listed in tables 1 and 2. The mean time from symptom onset to study entry was 4.6 ± 3.3 h. The mean initial NIHSS score was 6.9 ± 5.1 (range, 1–29; median, 5; interquartile range, 4–9). There was no difference in terms of age, sex, vascular risk factors, and stroke subtype between patients with different TNI2 or TNI4. The initial neurological deficits measured by the NIHSS were the most severe in patients who showed no improvement within 14 days of stroke onset (10.7 ± 7.8 for TNI2, p < 0.01 and 7.6 ± 5.9 for TNI4, p < 0.01). Patients who showed earlier improvement had a higher probability for a good outcome. Most (86% for TNI2 and 92% for TNI4) of the patients who improved within one day had a good outcome and the rate of good outcome decreased as the neurological improvement occurred later. Of the patients who did not show improvement within 14 days, 30% (TNI2) and 52% (TNI4) of them achieved a good outcome. Univariate logistic regression analysis revealed that the outcome was associated with age, NIHSS score, atrial fibrillation, stroke subtype, TNI2, and TNI4 (table 3). Among these variables, age, NIHSS score, atrial fibrillation, and TNI2 or TNI4 were selected in the final model (table 4). TNI2 (OR, 2.23; 95% CI, 1.73–2.87; p < 0.01) and TNI4 (OR, 2.30; 95% CI, 1.71–3.10; p < 0.01) were independently associated with an outcome at 90 days in the adjusted binary regression model. Ordinal regression
Timing of Improvement and Stroke Outcome
Eur Neurol 2015;73:164–170 DOI: 10.1159/000370240
165
Downloaded by: Göteborgs Universitet 130.241.16.16 - 11/15/2017 8:33:38 PM
tients eligible for the study had focal neurologic deficits with relevant lesions on diffusion-weighted imaging and were examined within 12 h of symptom onset. Among them, we excluded the patients who had preexisting neurological deficits (65 patients), those who received thrombolytic therapy (57 patients), and those who did not undergo complete workups (22 patients) or were lost to follow-up (25 patients). Thus, 410 patients with acute ischemic stroke were finally selected for the analyses. Demographic data and stroke risk factors were recorded in the registry. Data on risk factors were collected and defined as follows: hypertension was defined as repeated detection of blood pressure >140/90 mm Hg before stroke or use of antihypertensive medication; diabetes mellitus was defined as repeated detection of fasting blood glucose level >140 mg/dl before stroke or use of antidiabetic medication; hypercholesterolemia was defined as repeated detection of total cholesterol >220 mg/dl or use of lipidlowering medication; smoking was defined as current smoking at the time of stroke; and potential sources of cardioembolism were defined as atrial fibrillation, myocardial infarction within 6 weeks, congestive heart failure, mitral stenosis, and prosthetic valve. All of the patients underwent laboratory workups that included brain MRI, MR angiography, transthoracic echocardiography, 12lead ECG, and standard blood tests. Conventional angiography, transcranial Doppler, transesophageal echocardiography, and Holter monitoring were performed in selected patients as required. An etiologic subtype of ischemic stroke was classified into large artery disease, cardioembolism, small vessel disease, and undetermined cause according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria [10]. The severity of the neurological deficits was assessed using the NIHSS. The NIHSS score was serially measured on admission and at 1, 3, 7, and 14 days after stroke onset. Neurological improvement (NI4) was defined as a decrease in the NIHSS score by ≥4 points from the baseline NIHSS score or a NIHSS score of 0. We also considered minor neurological improvement (NI2) as a NIHSS score change by ≥2 points or a NIHSS score of 0. The time of neurological improvement (TNI4) or the time of minor neurological improvement (TNI2) was classified into day 1, 3, 7, 14, and no improvement. Modified Rankin Scale (mRS) was used to assess the functional outcome at 3 months [11]. For the purpose of the analysis, patients who had an mRS score of 0–2 were considered to have a good outcome. If patients were discharged from the hospital during the study period, they were evaluated at the outpatient clinic on the scheduled day. If patients could not visit the hospital at 3 months because of severe disability or other causes, the mRS score was measured by a telephone interview.
Table 1. Clinical characteristics of patients with different time of minor neurological improvement (TNI2)
Patients, n Age, years (mean ± SD) Males, n (%) Time from onset to entry, h (mean ± SD) Initial NIHSS score (mean ± SD) Median (interquartile range) Risk factors, n (%) Hypertension Diabetes mellitus Hyperlipidemia Smoking Atrial fibrillation Previous stroke Stroke subtypes, n (%) Large artery disease Cardioembolism Small vessel disease Undetermined mRS at 3 months (mean ± SD) Good outcome*, n (%)
Day 1
Day 3
Day 7
Day 14
No NI
95 66.1±12.4 61 (64) 3.9±3.2 6.5±4.2 5 (3–9)
131 64.5±11.4 75 (57) 5.3±3.6 6.3±4.2 5 (3.25–8)
92 36 56 64.6±11.5 63.8±12.8 69.9±12.0 0.39 58 (63) 21 (58) 28 (50) 0.44 6.0±3.8 3.9±2.2 3.5±2.2
Received: September 30, 2014 Accepted: November 30, 2014 Published online: January 13, 2015
Timing of Neurological Improvement after Acute Ischemic Stroke and Functional Outcome Young-Mok Song Geun Ho Lee Jae Il Kim Department of Neurology, Dankook University Hospital, Cheonan, South Korea
Abstract Background: The time of neurological improvement (TNI) after acute ischemic stroke may have a predictive value. Methods: We evaluated 410 consecutive patients who were admitted within 12 hours of stroke onset. The National Institutes of Health Stroke Scale (NIHSS) was measured on admission and at 1, 3, 7, and 14 days. Neurological improvement was defined as an improvement in the NIHSS score by ≥2 points (NI2) or ≥4 points (NI4) or an NIHSS score of 0. Patients with a Modified Rankin scale (mRS) score of ≤2 were considered to have a good outcome. Results: Patients with earlier TNIs had a lower 3-month mRS score and a higher probability for a good outcome. In the binary and ordinal regression analyses, age, NIHSS score, atrial fibrillation and TNI were independently associated with a good outcome. Receiver operating characteristic curve analyses demonstrated that TNI2 had higher sensitivity and lower specificity than TNI4. The best threshold for predicting outcome was day 3 for TNI2 and day 14 for TNI4. Conclusions: These results suggest that TNI is independently associated with functional outcome at 90 days. TNI2 may be more useful than TNI4 for early prediction of stroke outcome. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0014–3022/15/0734–0164$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
The clinical course and prognosis of stroke patients are highly variable. Therefore, the prediction of outcome after acute stroke has been an important research issue. The stroke outcome is influenced by multiple factors. Some factors, such as age and the initial National Institutes of Health Stroke Scale (NIHSS) score [1], have been recognized as prognostic factors [2–7]. However, the current predictors are not sufficient for precise prediction of prognosis, and identification of more predictive factors is necessary. The clinical course during the acute phase of stroke may have a predictive value. Indeed, it has been reported that patients who improved within the first 48 hours of stroke onset had a better prognosis [8, 9], suggesting that early neurological improvement is predictive of a good prognosis. However, a detailed relationship between the time of neurological improvement (TNI) and functional outcome has not been elucidated. The purpose of this study was to investigate the relationship between the TNI after acute ischemic stroke and functional outcome at 3 months. Methods We prospectively studied consecutive patients with acute ischemic stroke who were admitted to the Dankook University hospital between January 2010 and December 2013. A total of 579 pa-
Young-Mok Song, MD Department of Neurology, Dankook University Hospital 119, Dandae-ro, Dongnam-gu Cheonan, Chungnam, 330–714 (South Korea) E-Mail ymsong @ medimail.co.kr
Downloaded by: Göteborgs Universitet 130.241.16.16 - 11/15/2017 8:33:38 PM
Key Words Stroke · Neurological improvement · Outcome
covariates related to dichotomized mRS in the binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the usefulness of the TNI2 and TNI4 for predicting a good outcome. We assessed the discrimination by calculating the area under the ROC curve of sensitivity versus 1 minus the specificity. The sensitivity, specificity, and positive and negative predictive values of the TNI2 and TNI4 were calculated to validate the TNIs in predicting a good outcome at 3 months. Statistical significance was established at p < 0.05. Statistical analyses were performed using SPSS (version 18.0, Chicago, Ill., USA) and Medcalc (version 13.3).
Results
Statistical Analysis A comparison of the baseline characteristics and outcome profiles among patients with different time of neurological improvement was performed by the ANOVA test for continuous variables and by the χ2 test for dichotomized variables. Binary logistic and ordinal regression analyses were used to assess the effects of TNIs on clinical outcome adjusted for variables showing a p < 0.2 in univariate analysis. In binary logistic models, mRS was dichotomized (mRS ≤2 vs. mRS >2) and a backward stepwise strategy was used to select the variables remaining in the final model. We constructed ordinal regression models to verify that the results were consistent across the levels of the mRS adjusted for factors and
There were 243 men and 167 women, and the mean age was 65.6 ± 11.9 years (range, 26–93 years). The TNI2 was day 1 in 95 (23%) patients, day 3 in 131 (32%) patients, day 7 in 92 (22%) patients, day 14 in 36 (9%) patients, and no improvement within 14 days was observed in 56 (14%) patients. The TNI4 was day 1 in 28 (7%) patients, day 3 in 54 (13%) patients, day 7 in 83 (20%) patients, day 14 in 84 (21%) patients, and no improvement in 161 (39%) patients. The clinical characteristics of patients who showed different TNI2 and TNI4 are listed in tables 1 and 2. The mean time from symptom onset to study entry was 4.6 ± 3.3 h. The mean initial NIHSS score was 6.9 ± 5.1 (range, 1–29; median, 5; interquartile range, 4–9). There was no difference in terms of age, sex, vascular risk factors, and stroke subtype between patients with different TNI2 or TNI4. The initial neurological deficits measured by the NIHSS were the most severe in patients who showed no improvement within 14 days of stroke onset (10.7 ± 7.8 for TNI2, p < 0.01 and 7.6 ± 5.9 for TNI4, p < 0.01). Patients who showed earlier improvement had a higher probability for a good outcome. Most (86% for TNI2 and 92% for TNI4) of the patients who improved within one day had a good outcome and the rate of good outcome decreased as the neurological improvement occurred later. Of the patients who did not show improvement within 14 days, 30% (TNI2) and 52% (TNI4) of them achieved a good outcome. Univariate logistic regression analysis revealed that the outcome was associated with age, NIHSS score, atrial fibrillation, stroke subtype, TNI2, and TNI4 (table 3). Among these variables, age, NIHSS score, atrial fibrillation, and TNI2 or TNI4 were selected in the final model (table 4). TNI2 (OR, 2.23; 95% CI, 1.73–2.87; p < 0.01) and TNI4 (OR, 2.30; 95% CI, 1.71–3.10; p < 0.01) were independently associated with an outcome at 90 days in the adjusted binary regression model. Ordinal regression
Timing of Improvement and Stroke Outcome
Eur Neurol 2015;73:164–170 DOI: 10.1159/000370240
165
Downloaded by: Göteborgs Universitet 130.241.16.16 - 11/15/2017 8:33:38 PM
tients eligible for the study had focal neurologic deficits with relevant lesions on diffusion-weighted imaging and were examined within 12 h of symptom onset. Among them, we excluded the patients who had preexisting neurological deficits (65 patients), those who received thrombolytic therapy (57 patients), and those who did not undergo complete workups (22 patients) or were lost to follow-up (25 patients). Thus, 410 patients with acute ischemic stroke were finally selected for the analyses. Demographic data and stroke risk factors were recorded in the registry. Data on risk factors were collected and defined as follows: hypertension was defined as repeated detection of blood pressure >140/90 mm Hg before stroke or use of antihypertensive medication; diabetes mellitus was defined as repeated detection of fasting blood glucose level >140 mg/dl before stroke or use of antidiabetic medication; hypercholesterolemia was defined as repeated detection of total cholesterol >220 mg/dl or use of lipidlowering medication; smoking was defined as current smoking at the time of stroke; and potential sources of cardioembolism were defined as atrial fibrillation, myocardial infarction within 6 weeks, congestive heart failure, mitral stenosis, and prosthetic valve. All of the patients underwent laboratory workups that included brain MRI, MR angiography, transthoracic echocardiography, 12lead ECG, and standard blood tests. Conventional angiography, transcranial Doppler, transesophageal echocardiography, and Holter monitoring were performed in selected patients as required. An etiologic subtype of ischemic stroke was classified into large artery disease, cardioembolism, small vessel disease, and undetermined cause according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria [10]. The severity of the neurological deficits was assessed using the NIHSS. The NIHSS score was serially measured on admission and at 1, 3, 7, and 14 days after stroke onset. Neurological improvement (NI4) was defined as a decrease in the NIHSS score by ≥4 points from the baseline NIHSS score or a NIHSS score of 0. We also considered minor neurological improvement (NI2) as a NIHSS score change by ≥2 points or a NIHSS score of 0. The time of neurological improvement (TNI4) or the time of minor neurological improvement (TNI2) was classified into day 1, 3, 7, 14, and no improvement. Modified Rankin Scale (mRS) was used to assess the functional outcome at 3 months [11]. For the purpose of the analysis, patients who had an mRS score of 0–2 were considered to have a good outcome. If patients were discharged from the hospital during the study period, they were evaluated at the outpatient clinic on the scheduled day. If patients could not visit the hospital at 3 months because of severe disability or other causes, the mRS score was measured by a telephone interview.
Table 1. Clinical characteristics of patients with different time of minor neurological improvement (TNI2)
Patients, n Age, years (mean ± SD) Males, n (%) Time from onset to entry, h (mean ± SD) Initial NIHSS score (mean ± SD) Median (interquartile range) Risk factors, n (%) Hypertension Diabetes mellitus Hyperlipidemia Smoking Atrial fibrillation Previous stroke Stroke subtypes, n (%) Large artery disease Cardioembolism Small vessel disease Undetermined mRS at 3 months (mean ± SD) Good outcome*, n (%)
Day 1
Day 3
Day 7
Day 14
No NI
95 66.1±12.4 61 (64) 3.9±3.2 6.5±4.2 5 (3–9)
131 64.5±11.4 75 (57) 5.3±3.6 6.3±4.2 5 (3.25–8)
92 36 56 64.6±11.5 63.8±12.8 69.9±12.0 0.39 58 (63) 21 (58) 28 (50) 0.44 6.0±3.8 3.9±2.2 3.5±2.2
