Cut-off values of factors in relation to predict early neurological improvement after intravenous thrombolysis : a retrospective single center study in Korea

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Methods : A total of 135 patients with acute ischemic stroke treated with tissue plasminogen activator within 4.5 hours of stroke onset were enrolled at a single center. Therapy outcomes were based on early neurological improvement, defined as when the NIHSS score after 24 hours of tPA treatment decreased by ≥ 40% from the baseline value. Binary logistic linear regression analysis was used to identify the factors affecting early neurological improvement. Results : Sixty-nine (51.1%) patients had early neurological improvement. Multivariate analysis of these significant factors revaealed low serum homocysteine (odds ratio, 0.865; 95% confidence interval, 0.787–0.950; P=0.003) and high-sensitivity C-reactive protein (0.345; 0.203–0.586; P<0.001) levels were significantly associated with a high incidence of early neurological impairment. The cut-off values of serum homocysteine and high-sensitivity C-reactive protein were 11.99umol/L and 1.16mg/L, respectively. Conclusions : Serum homocysteine and high-sensitivity C-reactive protein were associated with early neurological improvement in patients with acute ischemic stroke who received therapy and their cut-off values mightbe promising criteriafor predicting early prognosis of acute ischemic stroke treated with intravenous thrombolysis. homocysteine high-sensitivity C-reactive protein large artery atherosclerosis early neurological improvement recombinant tissue plasminogen activator Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Highlights We aimed to redefine early neurological improvement and find out factors affecting early neurological improvement after recombinant tPA therapy for AIS. Early neurological improvement is defined as when the NIHSS score after 24 hours of tPA treatment decreased by ≥ 40% from the baseline value. Significant factors affecting early neurological improvement were serum homocysteine and high-sensitivity CRP levels. Optimal cut-off values of serum homocysteine and high-sensitivity CRP levels for predicting early neurological improvement after intravenous thrombolysis were 99umol/L and 1.16mg/L. Introduction Acute ischemic stroke (AIS) is the second leading cause of death worldwide, with increasing mortality rates. 1 In Korea, in 2020, the prevalence of stroke among adults over 19 years of age was 1.71%, with approximately 105,000 cases occurring every year. Of these, 76% were ischemic stroke cases, and the remaining 24% were cases of stroke resulting from intracerebral or subarachnoid hemorrhage. 2 In patients with AIS due to large vessel occlusion, recanalization of the occluded vessel is the most important factor affecting the prognosis. 3 Intravenous recombinant tissue plasminogen activator (tPA), also known as alteplase, is a glycoprotein that directly activates and induces plasminogen-converted plasmin. This results in fibrin degradation and thrombolysis. 4 tPA is used for primary reperfusion therapy and is the most economical and convenient treatment method. Early neurological improvement (ENI) assessment has been used as a 24-hour measurement to assess changes in neurological function. 5 There have been attempts to use ENI as a treatment outcome of AIS patients and it also indicates a good prognosis. 6 7 However, the definition of ENI and the factors associated with ENI among patients treated with alteplase remain ambiguous. 8 Researchers have not applied consistent definitions of ENI. 9 Therefore, the purpose of the present study was to redefine ENI and find out factors affecting ENI. Furthermore, we aimed to determine ideal cut-off values of the factors. Methods Patient information This retrospective study was conducted in accordance with the tenets of the 1964 Declaration of Helsinki. The study was approved by the institutional review board of Chung-Ang University Hospital, which waived the requirement for informed consent. However, all patients whose data were retrospectively analyzed were informed of the use of their anonymized clinical information and were offered the opportunity to object to its use or publication. Patients were enrolled between October 2008 and September 2023 at a single stroke center (Department of Neurology, Chung-Ang University Hospital, Chung-Ang University School of Medicine). Patients and family members provided informed consent for IVT. The inclusion criteria were (i) diagnosis of AIS confirmed within 4.5 hours of symptom onset, with initiation of tPA treatment, and (ii) age > 18 years. The exclusion criteria were (i) history of further therapies except for IVT, (ii) ongoing intracranial hemorrhage, (iii) a history of a bleeding disorder, and (iv) incomplete clinical data. Additional exclusion criteria during the 3–4.5-hour window period were (i) age > 80 years, (ii) severe stroke (National Institutes of Health Stroke Scale [NIHSS] score > 25), (iii) history of diabetes mellitus (DM) or stroke, and (iv) oral anticoagulant therapy, regardless of the prothrombin time international normalized ratio. 10 The eligibility criteria for tPA therapy were (i) an initial NIHSS score ≥ 4 or disabling stroke and (ii) the absence of any definite exclusion criteria for tPA therapy. Figure 1 presents a flowchart of the study population. Thrombolysis methods Alteplase was used because it is the only thrombolytic agent approved by the United States Food and Drug Administration for AIS. 11 The recommended alteplase was 0.9 mg/kg. Initially, 10% of the total treatment dose was administered as a bolus for 1 min. The remaining 90% was dissolved in normal saline and infused intravenously for 60 minutes. 12 Definition of early neurological improvement Patients were evaluated based on the differences between baseline NIHSS and NIHSS scores after 24 hours of IVT. The results are expressed as the ENI. Researchers have commonly defined ENI as a reduction in the NIHSS score by ≥ 4 or ≥ 30% reduction in NIHSS score. 13 However, some studies suggested that percent change improvement in NIHSS may be a better marker of thrombolytic activity. 14 Therefore, we defined ENI as when the NIHSS score after 24 hours of tPA treatment decreased by ≥ 40% from the baseline value in order to apply more stringent standards compared to existing studies. Statistical analysis Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using SPSS™ statistics v25.0(IBM, Armonk, NY, USA). Quantitative data were presented as mean±standard deviation values, while categorical variables were expressed as absolute values (percentages). The chi-square test was used to compare patients with favorable and unfavorable outcomes as categorical variables. The Student’s t-test was used to compare groups with normally distributed quantitative variables. Binary logistic regression models were used to evaluate the association between serum homocysteine (Hcy) and high-sensitive C-reactive protein (hsCRP) levels and stroke outcomes according to NIHSS scores. Receiver operating characteristic(ROC) curve was constructed to measure the predictive value of serum Hcy and hsCRP for ENI. The cut-off point for each variable was assessed by Youden index. P value < 0.05 was considered statistically significant. Results General patient characteristics This retrospective study included 135 patients with AIS eligible for tPA treatment. Among them, 69 patients (51.1%) had good outcomes (ENI). The mean age of the patients was 68.70±12.95 years. Regarding the risk factors for stroke, 58.5% of the included patients had hypertension (HTN), 31.9% had atrial fibrillation, 22.2% had a habit of smoking, and 17.8% had a history of stroke. Patients without ENI (n = 66) had higher mean serum Hcy, hsCRP, initial systolic blood pressure(SBP), and serum low-density lipoprotein cholesterol (LDL-C), triglyceride(TG), and creatinine levels than those with ENI. The baseline clinical findings and demographic characteristics are summarized in Table 1, Figure 2-1, and Figure 2-2. The more atherosclerotic burden was the main mechanism of stroke, the more likely it was that ENI would occur. Table 1. Baseline clinical and demographic characteristics of the included patients Patients (n = 135) Patients without ENI (n = 66) Patients with ENI (n = 69) P-value Age, years 68.70 ±12.95 66.18 ±11.43 71.10 ±13.92 0.065 Gender, male 90 (66.7%) 45 (68.2%) 45 (65.2%) 0.201 HTN 79 (58.5%) 34 (51.5%) 45 (65.2%) 0.056 DM 27 (20.0%) 14 (21.2%) 13 (18.8%) 0.052 A.fib 43 (31.9%) 22 (33.3%) 21(30.4%) 0.467 IHD 18 (13.3%) 9 (13.6%) 9 (13.0%) 0.207 History of stroke 24 (17.8%) 13 (19.7%) 11 (15.9%) 1.000 Current smoking 30 (22.2%) 17 (25.8%) 13 (18.8%) 0.680 TOAST - LAA 46 (34.1%) 18 (27.3%) 28 (40.6%) 0.738 - CE 9 (6.7%) 6 (9.1%) 3 (4.3%) - SVO 44 (32.6%) 23 (34.8%) 21 (30.4%) - UD 36 (26.7%) 19 (28.8%) 17 (24.6%) Initial NIHSS score 9.44 ±5.44 9.97 ±5.76 8.93 ±5.11 0.894 Initial SBP (mmHg) 153.37 ±28.29 153.82 ±29.56 152.94 (27.23) 0.094 Initial DBP (mmHg) 87.50 ±15.18 87.35 ±14.92 87.65 ±15.54 0.361 Hcy (umol/L) 13.79 ±7.52 15.53 ±9.05 12.13 ±5.24 0.003 hsCRP (mg/L) 2.05 ±3.02 2.21 ±3.19 1.89 ±2.86 < 0.001 Hb (g/dl) 14.00 ±1.61 13.99 ±1.54 14.00 ±1.69 0.304 Plt (K) 219.73 ±48.36 222.17 ±43.40 217.39 ±52.89 0.710 LDL-C (mg/dL) 115.08 ±39.10 117.61 ±39.69 112.67 ±38.66 0.009 TG (mg/dL) 144.15 ±164.87 144.65 ±169.93 143.67 ±161.13 0.001 Cr (mg/dL) 1.04 ±0.50 1.09 ±0.53 0.98 ±0.47 0.094 HbA1c (%) 6.15 ±1.31 6.21 ±1.37 6.09 ±1.26 0.141 PT (INR) 1.21 ±2.24 1.03 ±0.08 1.38 ±3.13 0.062 Abbreviations : A.fib, atrial fibrillation; CE, cardioembolism; Cr, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; ENI, early neurological improvement; Hb, hemoglobin; HbA1c, hemoglobin A1c; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; HTN, hypertension; IHD, ischemic heart disease; LAA, large artery atherosclerosis; LDL-C, low density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale; Plt, platelet; PT (INR), prothrombin time (international normalized ratio); SBP, systolic blood pressure; SVO, small vessel occlusion; TG, triglyceride; TOAST, Trial of Org 10172 in Acute Stroke Treatment; UD, undetermined Binary logistic regression analysis A binary logistic regression model was used to identify statistically significant factors affecting ENI. In univariate analysis, significant factors were age(OR, 0.996; 95% CI, 0.938–0.994; P = 0.017), underlying HTN(OR, 2.000; 95% CI, 0.998–4.008; P = 0.051), diabetes mellitus(DM)(OR, 0.400; 95% CI, 0.165–0.970; P = 0.043), initial diastolic blood pressure(DBP) (OR, 0.981; 95% CI, 0.958–1.004; P = 0.097), Hcy level (OR, 0.829; 95% CI, 0.754–0.911; P < 0.001), hsCRP(OR, 0.451; 95% CI, 0.306–0.662; P < 0.001), LDL-C(OR, 0.983; 95% CI, 0.974–0.993; P = 0.001), and TG(OR, 0.997; 95% CI, 0.994–1.000; P = 0.070). Multivariate logistic regression analysis was performed on the factors that yielded significant results in the univariate logistic regression analysis. Young age (OR, 0.958; 95% CI, 0.922–0.996; P = 0.029), absence of DM (OR, 0.212; 95% CI, 0.055–0.819; P = 0.024), low serum Hcy level (OR, 0.865; 95% CI, 0.787–0.950; P = 0.003), and hsCRP level (OR, 0.345; 95% CI, 0.203–0.586; P < 0.001) were significantly associated with a high incidence of ENI after tPA therapy. Underlying HTN (OR, 6.139; 95% CI, 2.016–18.698; P = 0.001) was associated with ENI. (Table 2). Furthermore, serum Hcy and hsCRP were also related to absolute change in NIHSS 24hours after IVT. Figure 3 presents scatter diagram and regression line. The lower the initial values of serum Hcy and hsCRP, the greater the change in NIHSS scores 24hours after tPA. Table 2. Factors affecting ENI after IVT using binary logistic regression models Univariate analysis Multivariate analysis P-value Odds ratio 95% CI P-value Odds ratio 95% CI Age, years 0.017 0.966 0.938-0.994 0.029 0.958 0.922-0.996 Gender, male 0.146 1.711 0.830-3.525 HTN 0.050 2.000 0.998-4.008 0.001 6.139 2.016-18.698 DM 0.043 0.400 0.165-0.970 0.024 0.212 0.055-0.819 A.fib 0.455 1.319 0.637-2.731 IHD 0.163 2.105 0.740-5.985 History of stroke 0.904 0.947 0.392-2.290 Current smoking 0.581 0.795 0.353-1.794 Initial NIHSS 0.653 0.986 0.926-1.049 Hcy (umol/L) < 0.001 0.829 0.754-0.911 0.003 0.865 0.787-0.950 hsCRP (mg/L) < 0.001 0.451 0.306-0.662 <0.001 0.345 0.203-0.586 LDL-C (mg/dL) 0.001 0.983 0.974-0.993 0.093 0.988 0.975-1.002 TG (mg/dL) 0.070 0.997 0.994-1.000 Cr (mg/dL) 0.199 0.612 0.289-1.295 PT (INR) 0.592 0.853 0.477-1.525 Abbreviations : A.fib, atrial fibrillation; CE, cardioembolism; CI, confidence intervals; Cr, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; Hb, hemoglobin; HbA1c, hemoglobin A1c; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; HTN, hypertension; IHD, ischemic heart disease; LAA, large artery atherosclerosis; LDL-C, low density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale; Plt, platelet; PT (INR), prothrombin time (international normalized ratio); TG, triglyceride; SBP, systolic blood pressure; SVO, small vessel occlusion; TOAST, Trial of Org 10172 in Acute Stroke Treatment; UD, undetermined ROC curve and cut-off values for predicting ENI As shown Table 3 and Figure 4, ROC curve and optimal cut-off values of serum Hcy and hsCRP for predicting ENI were measured. Areas under ROC curve(AUC) and cut-off points of serum Hcy and hsCRP were 0.743, 11.99 umol/L, 0.747, and 1.16 mg/L, respectively. Sensitivity and and specificity of Hcy were 68.1 and 72.7%. In addition, sensitivity and specificity of hsCRP were 73.9 and 68.2%. Table 3. Optimal cut-off values of Hcy and hsCRP for predicting ENI Areas under ROC curve 95% CI P-value Optimal cut-off value Hcy(umol/L) 0.743 0.660-0.814 <0.001 11.99 hsCRP(mg/L) 0.747 0.665-0.818 <0.001 1.16 Abbreviations : CI, confidence intervals; ENI, early neurological improvement; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; ROC, receiver operating characteristic Discussion We investigated factors affecting treatment outcomes in patients with AIS who received tPA therapy. The results showed that age, serum Hcy and hsCRP levels, HTN, and DM were associated with ENI. Among the mechanisms of AIS, atherosclerosis can induce vascular endothelial dysfunction and instability of lipid plaques. Previous studies reported that serum Hcy and hsCRP levels are associated with atherosclerosis. 15 Hyperhomocysteinemia increases the risk of cerebral stroke, potentially owing to vascular atherosclerotic modifications. 16 Hcy promotes the production of nitrogen oxide, which causes overgrowth of vascular smooth muscles, eventually leading to the dilatation of blood vessels and accumulation of cholesterol. 17 18 hsCRP is the most sensitive indicator of atherosclerosis and increases rapidly during ischemic stroke, initiating lipid accumulation in vascular endothelial cells. 19 20 This activates the production of chemicals that attract monocytes and may increase plasma thrombin levels, which has a significant impact on the formation of blood clots. 21 Epidemiological research has been conducted on the roles of Hcy and hsCRP. Several studies suggested that serum Hcy levels are related to functional disability in the acute phase of stroke. 22 23 24 Elevated serum hsCRP level has also been suggested to be a risk factor for poor outcomes in patients with AIS. Some studies reported that the median serum hsCRP level was higher in the unfavorable functional outcome group than in the favorable functional outcome group. 25 2627 However, the impact of Hcy and hsCRP on ENI has not closely studied until now and the definition of ENI remains ambiguous. In this study, we redefined the definition of ENI and presented cut-off points for Hcy and hsCRP that help predict ENI. This can be seen as a difference from other studies. Factors other than serum Hcy and hsCRP levels that affected ENI after tPA included age, HTN, and DM. Increased age and underlying DM are well-known risk factors for AIS. 28 Hypertension is a major risk factor for stroke; however, in patients with AIS, high blood pressure should be maintained to allow recanalization of the ischemic vessels. A previous study reported that fluctuations in blood pressure during the first 24 hours of AIS significantly contributed to penumbral tissue loss and were significantly associated with infarct progression in the ischemic penumbra. 29 Our study produced results that well reflect these aspects. We excluded patients who experienced further therapies except for IVT. If we chose patients who underwent treatments other than tPA, the success rate of the procedure itself could have influenced neurological functions apart from any other risk factor. 30 31 In other words, if the initial NIHSS score is high enough to undergo mechanical thrombectomy or other surgical treatments, the patient’s neurological prognosis worsens, regardless of serum Hcy and hsCRP levels. The study has some limitations. First, this was a single-center, retrospective study with a small sample size. We need to increase the number of participating institutions and patients to obtain more generalizable results. Second, the present study was designed to determine the effects of serum Hcy and hsCRP levels on the prognosis of patients who received IVT. Therefore, we did not include patients who did not undergo thrombolysis. This may have induced selection bias. Finally, serum Hcy levels may depend on factors such as genetics and sex. 32 We did not perform a real-time evaluation of these factors; this was difficult to do so due to the retrospective nature of the study. A more extensive prospective study must be conducted to address these limitations. Conclusion Considering that a large national budget is allocated annually to AIS treatment, studying the prognostic factors of AIS is valuable. Optimal cut-off values of Hcy and hsCRP that we suggested may be clinically used as promising prognostic predictors in AIS patients treated with tPA. Declarations Acknowledgments We are grateful to all those who were involved in the data collection. Author Contributions M-SO contributed to the concept and design of the study, and analysis and interpretation of the data. C-YP contributed to the analysis of the work, drafting of the content and critical revision of the content. K-YP, H-BJ, and S-HC contributed to data acquisition and analysis . All authors have contributed to the manuscript and approved the submitted version. Funding The authors have no funding to report. Availability of data and materials The data supporting the findings of this study are available in the supplementary materials. Further inquiries can be directed to the authors. Ethics approval and consent to participate Studies involving human participants were reviewed and approved by Chung-ang University Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and institutional requirements. Consent for publication Not applicable. Competing interest The authors have no conflict of interest to report. References Johnson, W., O. Onuma, M. Owolabi and S. Sachdev (2016). "Stroke: a global response is needed." Bulletin of the World Health Organization 94(9): 634. Endovascular Treatment of Acute Ischemic Stroke. Taehan Yongsang Uihakhoe Chi.(2020) May;81(3):562-576. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 06 Aug, 2024 Reviews received at journal 19 Jul, 2024 Reviewers agreed at journal 10 Jul, 2024 Reviews received at journal 25 May, 2024 Reviewers agreed at journal 23 May, 2024 Reviewers agreed at journal 23 May, 2024 Reviewers invited by journal 23 May, 2024 Editor invited by journal 23 May, 2024 Submission checks completed at journal 23 May, 2024 Editor assigned by journal 23 May, 2024 First submitted to journal 22 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4463740","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":309256675,"identity":"45d9013a-4d9e-4987-bfe2-1fdcd3b4d700","order_by":0,"name":"Misuk Oh","email":"","orcid":"","institution":"Chung-Ang University hospital","correspondingAuthor":false,"prefix":"","firstName":"Misuk","middleName":"","lastName":"Oh","suffix":""},{"id":309256676,"identity":"bfcbab95-155c-46c3-84dc-cb8c5e931ae9","order_by":1,"name":"Soohyun Cho","email":"","orcid":"","institution":"Chung-Ang University hospital","correspondingAuthor":false,"prefix":"","firstName":"Soohyun","middleName":"","lastName":"Cho","suffix":""},{"id":309256677,"identity":"e8151ecb-1139-4255-9289-c43321a013b5","order_by":2,"name":"Kwangyeol Park","email":"","orcid":"","institution":"Chung-Ang University hospital","correspondingAuthor":false,"prefix":"","firstName":"Kwangyeol","middleName":"","lastName":"Park","suffix":""},{"id":309256678,"identity":"8b50c748-3764-4224-bad3-897c3f004874","order_by":3,"name":"Haebong Jeong","email":"","orcid":"","institution":"Chung-Ang University hospital","correspondingAuthor":false,"prefix":"","firstName":"Haebong","middleName":"","lastName":"Jeong","suffix":""},{"id":309256679,"identity":"a2a45d96-59b6-4dd0-8bd4-8cdc3066ab94","order_by":4,"name":"Chanyoung Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACAyA+AGEyH4CzGRuI08KWQLwWKOBBaMerxVz68MPDBX/sEvulz3z88LPtjj0De+8Dxpl7cGux7EszODyzLTlxZl/uZsnetmeJDTzHDRg3PMPjsDMMBod5G5iNDc7wbmPgbTucwCCRxsD44AA+LewfDvP8qTe2P8PzjPFv22F7IrTwGBzmYTssZ8DDw8YMtIWxAaRlAx4tlj08BYd5247LSZxhM5aWOXc4sY3nGMPBGXi0mPOwb/7M86eah7+H+eHHN2WH7fnZ2xgf9uDRggnYGOCROwpGwSgYBaOAXAAAAJ9RApZb+zUAAAAASUVORK5CYII=","orcid":"","institution":"Chung-Ang University hospital","correspondingAuthor":true,"prefix":"","firstName":"Chanyoung","middleName":"","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2024-05-23 02:44:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4463740/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4463740/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58069276,"identity":"93805ff6-8d95-418c-b2e2-500f9ba9f462","added_by":"auto","created_at":"2024-06-10 18:17:21","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":165048,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study population\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/1101dbbd5b5d6e656e453cc1.jpg"},{"id":58069272,"identity":"51020235-b2cb-4a5a-a013-f2d6765956cf","added_by":"auto","created_at":"2024-06-10 18:17:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":100171,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-1. General TOAST distribution of the study population\u003c/p\u003e","description":"","filename":"Figure21.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/619a7e3d053a2a39cbf9d968.jpg"},{"id":58069274,"identity":"647d76f1-64a2-436c-84f3-923892c98c6c","added_by":"auto","created_at":"2024-06-10 18:17:21","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":101638,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 2-2. TOAST distribution according to ENI\u003c/p\u003e","description":"","filename":"Figure22.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/baf3a66341a39e0175654a9a.jpg"},{"id":58069275,"identity":"3e5022e8-6d7b-47c3-a728-3978ffdc0f82","added_by":"auto","created_at":"2024-06-10 18:17:21","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":147371,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3. Association between serum Hcy, hsCRP, and absolute change in NIHSS 24hours after IVT\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/79d3c988ff1ad62f5e02cd5e.jpg"},{"id":58070123,"identity":"ea8af34c-a49f-42ee-ae3b-6bd9445673b8","added_by":"auto","created_at":"2024-06-10 18:25:21","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":135064,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 4. ROC curves of serum Hcy and hsCRP for predicting ENI\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/a8a84b8bba7df0514819f22e.jpg"},{"id":58070151,"identity":"6463db25-b2f4-4d99-8bfe-70bc4748726b","added_by":"auto","created_at":"2024-06-10 18:25:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1184351,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4463740/v1/27b529b6-290a-4674-8010-f69d4ad4b5b0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cut-off values of factors in relation to predict early neurological improvement after intravenous thrombolysis : a retrospective single center study in Korea","fulltext":[{"header":"Highlights","content":"\u003cul\u003e\n\u003cli\u003eWe aimed to redefine early neurological improvement and find out factors affecting early neurological improvement after recombinant tPA therapy for AIS.\u003c/li\u003e\n\u003cli\u003eEarly neurological improvement is defined as when the NIHSS score after 24 hours of tPA treatment decreased by \u0026ge; 40% from the baseline value.\u003c/li\u003e\n\u003cli\u003eSignificant factors affecting early neurological improvement were serum homocysteine and high-sensitivity CRP levels.\u003c/li\u003e\n\u003cli\u003eOptimal cut-off values of serum homocysteine and high-sensitivity CRP levels for predicting early neurological improvement after intravenous thrombolysis were 99umol/L and 1.16mg/L.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eAcute ischemic stroke (AIS) is the second leading cause of death worldwide,\u0026nbsp;with increasing mortality rates.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e In Korea, in 2020, the prevalence\u0026nbsp;of stroke among adults over 19 years of age was 1.71%, with approximately 105,000 cases occurring every year. Of these, 76% were ischemic stroke cases, and the remaining 24% were cases of stroke resulting from intracerebral or subarachnoid hemorrhage.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn patients with AIS due to large vessel occlusion, recanalization of the occluded vessel is the most important factor affecting the prognosis.\u003csup\u003e3\u003c/sup\u003e Intravenous recombinant tissue plasminogen activator (tPA), also known as alteplase, is a glycoprotein that directly activates and induces plasminogen-converted plasmin. This results in fibrin degradation and thrombolysis.\u003csup\u003e4\u003c/sup\u003e tPA is used for primary reperfusion therapy and is the most economical and convenient treatment method.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEarly neurological improvement (ENI) assessment has been used as a 24-hour measurement to assess changes in neurological function.\u003csup\u003e5\u003c/sup\u003e There have been attempts to use ENI as a treatment outcome of AIS patients and it also\u0026nbsp;indicates a good prognosis.\u003csup\u003e6\u003c/sup\u003e \u003csup\u003e7\u003c/sup\u003e However, the definition of ENI and the factors associated with ENI among patients treated with alteplase remain ambiguous.\u003csup\u003e8\u003c/sup\u003e Researchers have not applied consistent definitions of ENI.\u003csup\u003e9\u003c/sup\u003e Therefore, the purpose of the present study was to redefine ENI and find out factors affecting ENI. Furthermore, we aimed to determine ideal cut-off values of the factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003e\u003cstrong\u003ePatient information\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis retrospective study was conducted in accordance with the tenets of the 1964 Declaration of Helsinki. The study was approved by the institutional review board of Chung-Ang University Hospital, which waived the requirement for informed consent. However, all patients whose data were retrospectively analyzed were informed of the use of their anonymized clinical information and were offered the opportunity to object to its use or publication. Patients were enrolled between October 2008 and September 2023 at a single stroke center (Department of Neurology, Chung-Ang University Hospital, Chung-Ang University School of Medicine). Patients and family members provided informed consent for IVT.\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria were (i) diagnosis of AIS confirmed within 4.5 hours of symptom onset, with initiation of tPA treatment, and (ii) age \u0026gt; 18 years. The exclusion criteria were (i) history of\u0026nbsp;further therapies except for IVT, (ii) ongoing intracranial hemorrhage, (iii) a history of a bleeding disorder, and (iv) incomplete clinical data. Additional exclusion criteria during the 3\u0026ndash;4.5-hour window period were (i) age \u0026gt; 80 years, (ii) severe stroke (National Institutes of Health Stroke Scale [NIHSS] score \u0026gt; 25), (iii) history of diabetes mellitus (DM) or stroke, and (iv) oral anticoagulant therapy, regardless of the prothrombin time international normalized ratio.\u003csup\u003e10\u003c/sup\u003e The eligibility criteria for tPA therapy were (i) an initial NIHSS score \u0026ge; 4 or disabling stroke and (ii) the absence of any definite exclusion criteria for tPA therapy. Figure 1 presents a flowchart of the study population.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eThrombolysis methods\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eAlteplase was used because it is the only thrombolytic agent approved by the United States Food and Drug Administration for AIS.\u003csup\u003e11\u003c/sup\u003e The recommended alteplase was 0.9 mg/kg. Initially, 10% of the total treatment dose was administered as a bolus for 1 min. The remaining 90% was dissolved in normal saline and infused intravenously for 60 minutes.\u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eDefinition of early neurological improvement\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003ePatients were evaluated based on the differences between baseline NIHSS and NIHSS \u0026nbsp;scores\u0026nbsp;after 24 hours of IVT. The results are expressed as the ENI.\u0026nbsp;Researchers have\u0026nbsp;commonly\u0026nbsp;defined ENI as a reduction in the NIHSS score by\u0026nbsp;\u0026ge;\u0026nbsp;4\u0026nbsp;or\u0026nbsp;\u0026ge;\u0026nbsp;30% reduction in NIHSS score.\u003csup\u003e13\u003c/sup\u003e However, some studies suggested that percent change improvement in NIHSS may be a better marker of thrombolytic activity.\u003csup\u003e14\u003c/sup\u003e Therefore, we\u0026nbsp;defined\u0026nbsp;ENI\u0026nbsp;as when the NIHSS score after 24 hours of tPA treatment decreased by \u0026ge; 40% from the baseline value\u0026nbsp;in order to apply more stringent standards compared to existing studies.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eOdds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using SPSS\u0026trade; statistics v25.0(IBM, Armonk, NY, USA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQuantitative data were presented as mean\u0026plusmn;standard deviation values, while categorical variables were expressed as absolute values (percentages). The chi-square test was used to compare patients with favorable and unfavorable outcomes as categorical variables. The Student\u0026rsquo;s t-test was used to compare groups with normally distributed quantitative variables.\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBinary logistic regression models\u0026nbsp;were used to evaluate the association between serum homocysteine (Hcy) and high-sensitive C-reactive protein (hsCRP) levels and stroke outcomes according to NIHSS scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic(ROC) curve was constructed to measure the predictive value of serum Hcy and hsCRP for ENI. The cut-off point for each variable was assessed by Youden index. P value \u0026lt; 0.05 was considered statistically significant.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003e\u003cstrong\u003eGeneral patient characteristics\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis retrospective study included 135 patients with AIS eligible for tPA treatment. Among them, 69 patients (51.1%) had good outcomes (ENI). The mean age of the patients was 68.70\u0026plusmn;12.95 years. Regarding the risk factors for stroke, 58.5% of the included patients had hypertension (HTN), 31.9% had atrial fibrillation, 22.2% had a habit of smoking, and 17.8% had a history of stroke. Patients without ENI (n = 66) had higher mean serum Hcy, hsCRP, initial systolic blood pressure(SBP), and serum low-density lipoprotein cholesterol (LDL-C), triglyceride(TG), and creatinine levels than those with ENI. The baseline clinical findings and demographic characteristics are summarized in Table 1, Figure 2-1, and Figure 2-2.\u0026nbsp;The more atherosclerotic burden was the main mechanism of stroke, the more likely it was that ENI would occur.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1. Baseline clinical and demographic characteristics of the included patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003cp\u003e(n = 135)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003ePatients without ENI (n = 66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with ENI (n = 69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e68.70\u0026nbsp;\u0026plusmn;12.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e66.18\u0026nbsp;\u0026plusmn;11.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e71.10\u0026nbsp;\u0026plusmn;13.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eGender, male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e90 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e45 (68.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e45 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eHTN\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e79 (58.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e34 (51.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e45 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eDM\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e27 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e14 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e13 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eA.fib\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e43 (31.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e22 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e21(30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.467\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eIHD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e18 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e9 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e9 (13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of stroke\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e24 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e13 (19.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e11 (15.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent smoking\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e30 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e17 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e13 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eTOAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003e- LAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e46 (34.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e18 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e28 (40.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.93069306930693%\" valign=\"top\"\u003e\n \u003cp\u003e- CE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.198019801980198%\" valign=\"top\"\u003e\n \u003cp\u003e9 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.128712871287128%\" valign=\"top\"\u003e\n \u003cp\u003e6 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.742574257425744%\" valign=\"top\"\u003e\n \u003cp\u003e3 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.93069306930693%\" valign=\"top\"\u003e\n \u003cp\u003e- SVO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.198019801980198%\" valign=\"top\"\u003e\n \u003cp\u003e44 (32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.128712871287128%\" valign=\"top\"\u003e\n \u003cp\u003e23 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.742574257425744%\" valign=\"top\"\u003e\n \u003cp\u003e21 (30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.93069306930693%\" valign=\"top\"\u003e\n \u003cp\u003e- UD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.198019801980198%\" valign=\"top\"\u003e\n \u003cp\u003e36 (26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.128712871287128%\" valign=\"top\"\u003e\n \u003cp\u003e19 (28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.742574257425744%\" valign=\"top\"\u003e\n \u003cp\u003e17 (24.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eInitial NIHSS score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e9.44\u0026nbsp;\u0026plusmn;5.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e9.97\u0026nbsp;\u0026plusmn;5.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e8.93\u0026nbsp;\u0026plusmn;5.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.894\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eInitial SBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e153.37\u0026nbsp;\u0026plusmn;28.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e153.82\u0026nbsp;\u0026plusmn;29.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e152.94 (27.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eInitial DBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e87.50\u0026nbsp;\u0026plusmn;15.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e87.35\u0026nbsp;\u0026plusmn;14.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e87.65\u0026nbsp;\u0026plusmn;15.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eHcy (umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e13.79\u0026nbsp;\u0026plusmn;7.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e15.53\u0026nbsp;\u0026plusmn;9.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e12.13\u0026nbsp;\u0026plusmn;5.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003ehsCRP (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e2.05\u0026nbsp;\u0026plusmn;3.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e2.21\u0026nbsp;\u0026plusmn;3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e1.89\u0026nbsp;\u0026plusmn;2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eHb (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e14.00\u0026nbsp;\u0026plusmn;1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e13.99\u0026nbsp;\u0026plusmn;1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e14.00\u0026nbsp;\u0026plusmn;1.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003ePlt (K)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e219.73\u0026nbsp;\u0026plusmn;48.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e222.17\u0026nbsp;\u0026plusmn;43.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e217.39\u0026nbsp;\u0026plusmn;52.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.710\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eLDL-C (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e115.08\u0026nbsp;\u0026plusmn;39.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e117.61\u0026nbsp;\u0026plusmn;39.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e112.67\u0026nbsp;\u0026plusmn;38.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eTG (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e144.15\u0026nbsp;\u0026plusmn;164.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e144.65\u0026nbsp;\u0026plusmn;169.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e143.67\u0026nbsp;\u0026plusmn;161.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eCr (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e1.04\u0026nbsp;\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e1.09\u0026nbsp;\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u0026nbsp;\u0026plusmn;0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003eHbA1c (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e6.15\u0026nbsp;\u0026plusmn;1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e6.21\u0026nbsp;\u0026plusmn;1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e6.09\u0026nbsp;\u0026plusmn;1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.591362126245848%\" valign=\"top\"\u003e\n \u003cp\u003ePT (INR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.943521594684384%\" valign=\"top\"\u003e\n \u003cp\u003e1.21\u0026nbsp;\u0026plusmn;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.757475083056477%\" valign=\"top\"\u003e\n \u003cp\u003e1.03\u0026nbsp;\u0026plusmn;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.59468438538206%\" valign=\"top\"\u003e\n \u003cp\u003e1.38\u0026nbsp;\u0026plusmn;3.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.11295681063123%\" valign=\"top\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: A.fib, atrial fibrillation; CE, cardioembolism; Cr, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; ENI, early neurological improvement; Hb, hemoglobin; HbA1c, hemoglobin A1c; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; HTN, hypertension; IHD, ischemic heart disease; LAA, large artery atherosclerosis; LDL-C, low density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale; \u0026nbsp;Plt, platelet; PT (INR), prothrombin time (international normalized ratio); SBP, systolic blood pressure; SVO, small vessel occlusion; TG, triglyceride; TOAST, Trial of Org 10172 in Acute Stroke Treatment; UD, undetermined\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eBinary\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;logistic regression analysis\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eA binary logistic regression model was used to identify statistically significant factors affecting ENI.\u0026nbsp;In univariate analysis, significant\u0026nbsp;factors\u0026nbsp;were age(OR, 0.996; 95% CI, 0.938\u0026ndash;0.994; P = 0.017),\u0026nbsp;underlying HTN(OR, 2.000; 95% CI, 0.998\u0026ndash;4.008; P = 0.051),\u0026nbsp;diabetes mellitus(DM)(OR, 0.400; 95% CI, 0.165\u0026ndash;0.970; P = 0.043), initial diastolic blood pressure(DBP)\u0026nbsp;(OR, 0.981; 95% CI, 0.958\u0026ndash;1.004; P = 0.097), Hcy\u0026nbsp;level (OR, 0.829; 95% CI, 0.754\u0026ndash;0.911; P \u0026lt; 0.001), hsCRP(OR, 0.451; 95% CI, 0.306\u0026ndash;0.662; P \u0026lt; 0.001), LDL-C(OR, 0.983; 95% CI, 0.974\u0026ndash;0.993; P = 0.001), and TG(OR, 0.997; 95% CI, 0.994\u0026ndash;1.000; P = 0.070).\u0026nbsp; \u0026nbsp;Multivariate logistic regression analysis was performed on the factors that yielded significant results in the univariate logistic regression analysis. Young age (OR, 0.958; 95% CI, 0.922\u0026ndash;0.996; P = 0.029), absence of DM (OR, 0.212; 95% CI, 0.055\u0026ndash;0.819; P = 0.024), low serum Hcy level (OR, 0.865; 95% CI, 0.787\u0026ndash;0.950; P = 0.003), and hsCRP level (OR, 0.345; 95% CI, 0.203\u0026ndash;0.586; P \u0026lt; 0.001) were significantly associated with a high incidence of ENI after tPA therapy. Underlying HTN (OR,\u0026nbsp;6.139; 95% CI,\u0026nbsp;2.016\u0026ndash;18.698; P = 0.001) was associated with ENI.\u0026nbsp;(Table 2). Furthermore, serum Hcy and hsCRP were also related to\u0026nbsp;absolute change in NIHSS 24hours after IVT. Figure 3 presents scatter diagram and regression line. The lower the initial values of serum Hcy and hsCRP, the greater the change in NIHSS scores 24hours after tPA.\u003c/p\u003e\n\u003cp\u003eTable 2. \u0026nbsp;Factors affecting ENI after IVT using\u0026nbsp;binary logistic regression models\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.332784184514002%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.833607907743%\" colspan=\"3\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.833607907743%\" colspan=\"3\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.938-0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.922-0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eGender, male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.711\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.830-3.525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.998-4.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e6.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e2.016-18.698\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.165-0.970\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.055-0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eA.fib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.637-2.731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eIHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.740-5.985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eHistory of stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.392-2.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eCurrent smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.353-1.794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eInitial NIHSS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.653\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.926-1.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eHcy (umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.829\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.754-0.911\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.865\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.787-0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003ehsCRP (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.306-0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.203-0.586\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eLDL-C (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.983\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.974-0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.975-1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eTG (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.994-1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003eCr (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.289-1.295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003ePT (INR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.477-1.525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: A.fib, atrial fibrillation; CE, cardioembolism; CI, confidence intervals; Cr, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; Hb, hemoglobin; HbA1c, hemoglobin A1c; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; HTN, hypertension; IHD, ischemic heart disease; LAA, large artery atherosclerosis; LDL-C, low density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale; Plt, platelet; PT (INR), prothrombin time (international normalized ratio); TG, triglyceride; SBP, systolic blood pressure; SVO, small vessel occlusion; TOAST, Trial of Org 10172 in Acute Stroke Treatment; UD, undetermined\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eROC curve and cut-off values for predicting ENI\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eAs shown Table 3 and Figure 4, ROC curve and optimal cut-off values of serum Hcy and hsCRP for predicting ENI were measured. Areas under ROC curve(AUC) and cut-off points of serum Hcy and hsCRP were 0.743, 11.99\u0026nbsp;umol/L, 0.747, and 1.16\u0026nbsp;mg/L, respectively. Sensitivity and and specificity of Hcy were 68.1 and 72.7%. In addition, sensitivity and specificity of hsCRP were 73.9 and 68.2%.\u003c/p\u003e\n\u003cp\u003eTable 3. Optimal cut-off values of Hcy and hsCRP for predicting ENI\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eAreas under ROC curve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eOptimal cut-off value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eHcy(umol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.660-0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e11.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003ehsCRP(mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.665-0.818\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: CI, confidence intervals; ENI, early neurological improvement; Hcy, homocysteine; hsCRP, high-sensitivity C-reactive protein; ROC, receiver operating characteristic\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe investigated factors affecting treatment outcomes in patients with AIS who received tPA therapy. The results showed that age, serum Hcy and hsCRP levels, HTN, and DM were associated with ENI.\u003c/p\u003e\n\u003cp\u003eAmong the mechanisms of AIS, atherosclerosis can induce vascular endothelial dysfunction and instability of lipid plaques. Previous studies reported that serum Hcy and hsCRP levels are associated with atherosclerosis.\u003csup\u003e15\u003c/sup\u003e Hyperhomocysteinemia increases the risk of cerebral stroke, potentially owing to vascular atherosclerotic modifications.\u003csup\u003e16\u003c/sup\u003e Hcy promotes the production of nitrogen oxide, which causes overgrowth of vascular smooth muscles, eventually leading to the dilatation of blood vessels and accumulation of cholesterol.\u003csup\u003e17\u003c/sup\u003e \u003csup\u003e18\u003c/sup\u003e hsCRP is the most sensitive indicator of atherosclerosis and increases rapidly during ischemic stroke, initiating lipid accumulation in vascular endothelial cells.\u003csup\u003e19\u003c/sup\u003e \u003csup\u003e20\u003c/sup\u003e This activates the production of chemicals that attract monocytes and may increase plasma thrombin levels, which has a significant impact on the formation of blood clots.\u003csup\u003e21\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEpidemiological research has been conducted on the roles of Hcy and hsCRP.\u0026nbsp;Several\u0026nbsp;studies\u0026nbsp;suggested that serum Hcy levels are related to functional disability in the acute phase of stroke.\u003csup\u003e\u0026nbsp;22\u003c/sup\u003e\u003csup\u003e\u0026nbsp;23 24\u003c/sup\u003e Elevated serum hsCRP level has also been suggested to be a risk factor for poor outcomes in patients with AIS.\u0026nbsp;Some studies\u0026nbsp;reported that the median serum hsCRP level was higher in the unfavorable functional outcome group than in the favorable functional outcome group.\u003csup\u003e25\u003c/sup\u003e \u003csup\u003e2627\u003c/sup\u003e However, the impact of Hcy and hsCRP on ENI has not closely studied until now and the definition of ENI remains ambiguous. In this study, we redefined the definition of ENI and presented cut-off points for Hcy and hsCRP that help predict ENI. This can be seen as a difference from other studies.\u003c/p\u003e\n\u003cp\u003eFactors other than serum Hcy and hsCRP levels that affected ENI after tPA included age, HTN, and DM. Increased age and underlying DM are well-known risk factors for AIS.\u003csup\u003e28\u003c/sup\u003e Hypertension is a major risk factor for stroke; however, in patients with AIS, high blood pressure should be maintained to allow recanalization of the ischemic vessels. A previous study reported that fluctuations in blood pressure during the first 24 hours of AIS significantly contributed to penumbral tissue loss and were significantly associated with infarct progression in the ischemic penumbra.\u003csup\u003e29\u003c/sup\u003e Our study produced results that well reflect these aspects.\u003c/p\u003e\n\u003cp\u003eWe excluded patients who experienced further therapies except for IVT.\u0026nbsp;If we chose patients who underwent treatments other than\u0026nbsp;tPA, the success rate of the procedure itself could have influenced neurological functions apart from any other risk factor.\u003csup\u003e30\u003c/sup\u003e \u003csup\u003e31\u003c/sup\u003e In other words, if the initial NIHSS score is high enough to undergo\u0026nbsp;mechanical thrombectomy\u0026nbsp;or other surgical treatments, the patient\u0026rsquo;s neurological prognosis worsens, regardless of serum Hcy and hsCRP levels.\u003c/p\u003e\n\u003cp\u003eThe study has some limitations. First, this was a single-center, retrospective study with a small sample size. We need to increase the number of participating institutions and patients to obtain more generalizable results. Second, the present study was designed to determine the effects of serum Hcy and hsCRP levels on the prognosis of patients who received IVT. Therefore, we did not include patients who did not undergo thrombolysis. This may have induced selection bias. Finally, serum Hcy levels may depend on factors such as genetics and sex.\u003csup\u003e32\u003c/sup\u003eWe did not perform a real-time evaluation of these factors; this was difficult to do so due to the retrospective nature of the study. A more extensive prospective study must be conducted to address these limitations.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eConsidering that a large national budget is allocated annually to AIS treatment, studying the prognostic factors of AIS is valuable. Optimal cut-off values of Hcy and hsCRP that we suggested may be clinically used as promising prognostic predictors in AIS patients treated with tPA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eWe are grateful to all those who were involved in the data collection.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eM-SO contributed to the concept and design of the study, and analysis and interpretation of the data. C-YP contributed to the analysis of the work, drafting of the content and critical revision of the content. K-YP, H-BJ, and S-HC contributed to data acquisition and analysis . All authors have contributed to the manuscript and approved the submitted version.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors have no funding to report.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAvailability\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eof data and materials\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe data supporting the findings of this study are available in the supplementary materials. Further inquiries can be directed to the authors.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eStudies involving human participants were reviewed and approved by Chung-ang University Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and institutional requirements.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors\u0026nbsp;have no conflict of interest to report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJohnson, W., O. Onuma, M. Owolabi and S. Sachdev (2016). \"Stroke: a global response is needed.\" Bulletin of the World Health Organization 94(9): 634.\u003c/li\u003e\n\u003cli\u003eEndovascular Treatment of Acute Ischemic Stroke. Taehan Yongsang Uihakhoe Chi.(2020) May;81(3):562-576. Korean. doi: 10.3348/jksr.2020.81.3.562. Epub 2020 May 29. PMID: 36238610; PMCID: PMC9431927.\u003c/li\u003e\n\u003cli\u003eTerreros, N. A., A. A. Bruggeman, I. S. Swijnenburg, L. C. van Meenen, A. E. Groot, J. M. Coutinho, Y. B. Roos, B. J. Emmer, L. F. Beenen and E. van Bavel (2022). \"Early recanalization in large-vessel occlusion stroke patients transferred for endovascular treatment.\" Journal of NeuroInterventional Surgery 14(5): 480-484.\u003c/li\u003e\n\u003cli\u003eZhang, S., D. Wang and L. Li (2023). \"Recombinant tissue-type plasminogen activator (rt-PA) effectively restores neurological function and improves prognosis in acute ischemic stroke.\" American Journal of Translational Research 15(5): 3460.\u003c/li\u003e\n\u003cli\u003eSaver, J. L. and H. Altman (2012). \"Relationship between neurologic deficit severity and final functional outcome shifts and strengthens during first hours after onset.\" Stroke 43(6): 1537-1541.\u003c/li\u003e\n\u003cli\u003eXiufu, Z., L. Ruipeng, Z. Jun, L. Yonglong, W. Yulin, Z. Jian, C. Xianglin, S. Lan and Z. Zuowen (2022). \"Analysis of influencing factors of early neurological improvement after intravenous rt-PA thrombolysis in acute anterior circulation ischemic stroke.\" Frontiers in Neurology 13: 1037663.\u003c/li\u003e\n\u003cli\u003eWeyland, C. S., et al. (2021). \"Predictors for failure of early neurological improvement after successful thrombectomy in the anterior circulation.\" Stroke 52(4): 1291-1298.\u003c/li\u003e\n\u003cli\u003eAgarwal, S., et al. (2020). \"Redefining early neurological improvement after reperfusion therapy in stroke.\" Journal of Stroke and Cerebrovascular Diseases 29(2): 104526.\u003c/li\u003e\n\u003cli\u003eKobeissi, H., et al. (2023). \"Early neurological improvement as a predictor of outcomes after endovascular thrombectomy for stroke: a systematic review and meta-analysis.\" Journal of neurointerventional surgery 15(6): 547-551.\u003c/li\u003e\n\u003cli\u003e Kleindorfer, D. O., A. Towfighi, S. Chaturvedi, K. M. Cockroft, J. Gutierrez, D. Lombardi-Hill, H. Kamel, W. N. Kernan, S. J. Kittner and E. C. Leira (2021). \"2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association.\" Stroke 52(7): e364-e467.\u003c/li\u003e\n\u003cli\u003e Alhadid, K., L. Oliveira and M. R. Etherton (2023). \"Intravenous Thrombolytics in the Treatment of Acute Ischemic Stroke.\" Current Treatment Options in Cardiovascular Medicine 25(1): 15-28.\u003c/li\u003e\n\u003cli\u003e Hughes, R. E., P. Tadi and P. C. Bollu (2018). \"TPA therapy.\"\u003c/li\u003e\n\u003cli\u003e Kobeissi H, Ghozy S, Bilgin C, Kadirvel R, Kallmes DF. Early neurological improvement as a predictor of outcomes after endovascular thrombectomy for stroke: a systematic review and meta-analysis. J Neurointerv Surg. 2023 Jun;15(6):547-551.\u003c/li\u003e\n\u003cli\u003e Agarwal, S., et al. (2020). \"Redefined measure of early neurological improvement shows treatment benefit of alteplase over placebo.\" Stroke 51(4): 1226-1230.\u003c/li\u003e\n\u003cli\u003e Chen, Q., et al. (2022). \"Study on the Association of Homocysteine and C-Reactive Protein with Neurofunctional Changes in Patients with Acute Ischemic Stroke After Endovascular Stent Treatment.\" Neuropsychiatric Disease and Treatment 18: 881.\u003c/li\u003e\n\u003cli\u003e Poddar, R. (2021). \"Hyperhomocysteinemia is an emerging comorbidity in ischemic stroke.\" Experimental neurology 336: 113541.\u003c/li\u003e\n\u003cli\u003e Guieu, R., J. Ruf and G. Mottola (2022). Hyperhomocysteinemia and cardiovascular diseases. Annales de biologie clinique.\u003c/li\u003e\n\u003cli\u003e Balint, B., et al. (2020). \"Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall.\" Biochimie 173: 100-106.\u003c/li\u003e\n\u003cli\u003e Casas, J. P., L. E. Bautista, L. Smeeth, P. Sharma and A. D. Hingorani (2005). \"Homocysteine and stroke: evidence on a causal link from mendelian randomisation.\" The Lancet 365(9455): 224-232.\u003c/li\u003e\n\u003cli\u003e Tuttolomondo, A., et al. (2020). \"Endothelial dysfunction and inflammation in ischemic stroke pathogenesis.\" Current Pharmaceutical Design 26(34): 4209-4219.\u003c/li\u003e\n\u003cli\u003e Yilmaz, M. I., et al. (2020). \"The effect of corrected inflammation, oxidative stress and endothelial dysfunction on fmd levels in patients with selected chronic diseases: a quasi-experimental study.\" Scientific reports 10(1): 9018.\u003c/li\u003e\n\u003cli\u003e Li, L., X. Ma, L. Zeng, S. Pandey, R. Wan, R. Shen and Q. Zhang (2020). \"Impact of homocysteine levels on clinical outcome in patients with acute ischemic stroke receiving intravenous thrombolysis therapy.\" PeerJ 8: e9474.\u003c/li\u003e\n\u003cli\u003e Zhang, D., et al. (2023). \"Serum homocysteine level is an independent risk factor for 1-year stroke recurrence in patients with acute ischemic stroke and H-type hypertension: results from the Xi'an stroke registry study of China.\" Frontiers in Neurology 14: 1161318.\u003c/li\u003e\n\u003cli\u003e Rabelo, N. N., et al. (2022). \"Homocysteine is associated with higher risks of ischemic stroke: A systematic review and meta-analysis.\" PloS one 17(10): e0276087.\u003c/li\u003e\n\u003cli\u003e Sabir Rashid, A., Y. Huang-Link, M. Johnsson, S. Wetterh\u0026auml;ll and H. Gauffin (2022). \"Predictors of early neurological deterioration and functional outcome in acute ischemic stroke: the importance of large artery disease, hyperglycemia and inflammatory blood biomarkers.\" Neuropsychiatric disease and treatment: 1993-2002.\u003c/li\u003e\n\u003cli\u003e Hou, D., et al. (2017). \"The role of high-sensitivity C-reactive protein levels in functional outcomes in patients with large-artery atherosclerosis and small-artery occlusion.\" Neurological research 39(11): 981-987.\u003c/li\u003e\n\u003cli\u003e Lee, S., et al. (2020). \"Association between long-term functional outcome and change in hs-CRP level in patients with acute ischemic stroke.\" The Neurologist 25(5): 122-125.\u003c/li\u003e\n\u003cli\u003e Howard, G., M. Banach, B. Kissela, M. Cushman, P. Muntner, S. E. Judd and V. J. Howard (2023). \"Age-Related Differences in the Role of Risk Factors for Ischemic Stroke.\" Neurology 100(14): e1444-e1453.\u003c/li\u003e\n\u003cli\u003e Jeong, H.-G., B. J. Kim, H. Kim, C. Jung, M.-K. Han, D. S. Liebeskind and H.-J. Bae (2019). \"Blood pressure drop and penumbral tissue loss in nonrecanalized emergent large vessel occlusion.\" Stroke 50(10): 2677-2684.\u003c/li\u003e\n\u003cli\u003e Jo, H., I.-H. Lee, S.-K. Ha, D.-J. Lim and J.-I. Choi (2023). \"Factors predicting good prognosis of failed intra-arterial thrombectomy cases: A retrospective study.\" Medicine 102(21).\u003c/li\u003e\n\u003cli\u003e Krishnan, R., et al. (2021). \"Complications of mechanical thrombectomy in acute ischemic stroke.\" Neurology 97(20_Supplement_2): S115-S125.\u003c/li\u003e\n\u003cli\u003e Huang, S., J. Cai and Y. Tian (2021). \"The prognostic value of homocysteine in acute ischemic stroke patients: a systematic review and meta-analysis.\" Frontiers in Systems Neuroscience 14: 600582.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"homocysteine, high-sensitivity C-reactive protein, large artery atherosclerosis, early neurological improvement, recombinant tissue plasminogen activator","lastPublishedDoi":"10.21203/rs.3.rs-4463740/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4463740/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: We aimed to determine cut-off values of factorsaffecting early neurological improvementin patients after recombinant tissue plasminogen activator therapy for acute ischemic stroke.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A total of 135 patients with acute ischemic stroke treated with tissue plasminogen activator within 4.5 hours of stroke onset were enrolled at a single center. Therapy outcomes were based on early neurological improvement, defined as when the NIHSS score after 24 hours of tPA treatment decreased by ≥ 40% from the baseline value. Binary logistic linear regression analysis was used to identify the factors affecting early neurological improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Sixty-nine (51.1%) patients had early neurological improvement. Multivariate analysis of these significant factors revaealed low serum homocysteine (odds ratio, 0.865; 95% confidence interval, 0.787–0.950; P=0.003) and high-sensitivity C-reactive protein (0.345; 0.203–0.586; P\u0026lt;0.001) levels were significantly associated with a high incidence of early neurological impairment. The cut-off values of serum homocysteine and high-sensitivity C-reactive protein were 11.99umol/L and 1.16mg/L, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Serum homocysteine and high-sensitivity C-reactive protein were associated with early neurological improvement in patients with acute ischemic stroke who received therapy and their cut-off values mightbe promising criteriafor predicting early prognosis of acute ischemic stroke treated with intravenous thrombolysis.\u003c/p\u003e","manuscriptTitle":"Cut-off values of factors in relation to predict early neurological improvement after intravenous thrombolysis : a retrospective single center study in Korea","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-10 18:17:16","doi":"10.21203/rs.3.rs-4463740/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-06T18:23:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-19T09:08:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135934669441898526384730602004102096579","date":"2024-07-10T14:16:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-25T17:33:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"284932059277447910493819560915149949589","date":"2024-05-23T22:21:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8729675617277355878415591015881069501","date":"2024-05-23T21:54:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-23T21:46:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-23T19:36:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-23T11:59:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-23T11:59:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-05-23T02:42:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2979cc27-a175-48ba-9ea0-774dadb77e05","owner":[],"postedDate":"June 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T10:09:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-10 18:17:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4463740","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4463740","identity":"rs-4463740","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}