Objective To evaluate the associations of 16 variants in clopidogrel-relevant genes with early neurological deterioration (END) in acute ischemic stroke (AIS) patients receiving clopidogrel treatment. Methods AIS patients admitted to the Department of Neurology of three hospitals between June 2014 and January 2015 were included. The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR) methods. The primary outcome was END within the 10 days of admission. Results A total of 375 patients with AIS were included. Among the 375 patients, 95 (25.33%) patients developed END within the first 10 days of admission. Among the 16 variants, only CYP2C19*2 rs4244285 AG+AA was associated with END using single-locus analytical approach (P<0.001). GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 on risk for END (P=0.019). Cox regression analysis showed that the high-risk interactive genotype was independent predictor for END [hazard ratio=2.184, 95% confidence interval (1.472, 3.238), P=0.004]. Conclusions END is very common in patients with AIS. Interactions among CYP2C19*2 rs4244285, P2Y12 rs16863323, and GPⅢa rs2317676 may confer a higher risk for END. It may be very important to modify clopidogrel therapy for the patients carrying the high-risk interactive genotype.
Objective To explore the relationship between neurofilament light chain (NfL) level and early neurological deterioration (END) after acute cerebral infarction (ACI). Methods The means of multi-center observational study were adopted to include patients with ACI within 72 hours of onset in 4 hospitals in Deyang between March 31, 2019 and July 31, 2021, to explore the risk factors of END. Results A total of 339 patients with ACI were included in this study, including 131 women and 208 men, aged (68.1±11.6) years. END occurred in 80 patients within 7 days after admission, and the incidence of END was 23.6%. The National Institute of Health Stroke Scale score and NfL level of patients without END were lower than those with END (P<0.05). Cox proportional risk model showed that NfL level [hazard ratio (HR)=1.037, 95% confidence interval (CI) (1.025, 1.050), P<0.001], admission National Institute of Health Stroke Scale score [HR=1.202, 95% CI (1.127, 1.282), P<0.001], initial blood glucose [HR=1.068, 95% CI (1.006, 1.133), P=0.030] were related to the occurrence of END. Conclusion The level of NfL, the severity of stroke, and the bloodglucose at admission are related to the occurrence of END in patients with ACI. Measures can be taken to control the above problems as soon as possible to prevent the occurrence of END.
Objective To analyze the value of serum levels of miR-141-3p, miR-130a, miR-29a-3p, and miR-210 in predicting early neurological deterioration (END) in non-traumatic intracerebral hemorrhage. Methods The patients with non-traumatic cerebral hemorrhage who met the selection criteria and were admitted to Chengde Central Hospital between February 2021 and October 2022 were prospectively selected by convenience sampling method. The serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels upon admission and the occurrence of neurological deterioration within 24 h were collected, and the patients were divided into a deterioration group and a non-deterioration group according to whether neurological deterioration occurred. The correlation of serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels with the END of non-traumatic intracerebral hemorrhage and their predictive value to the END of non-traumatic intracerebral hemorrhage were analyzed. Results A total of 235 patient were enrolled. Of the 235 patients, 45 (19.1%) showed neurological deterioration and 190 (80.9%) showed no neurological deterioration. The levels of miR-141-3p and miR-29a-3p in the deteriorating group were significantly lower than those in the non-deteriorating group [(1.11±0.32) vs. (1.76±0.51) ng/mL, P<0.001; (1.19±0.31) vs. (1.71±0.51) ng/mL, P<0.001], and the levels of miR-130a and miR-210 were significantly higher than those in the non-deteriorating group [(5.13±1.11) vs. (3.82±1.03) ng/mL, P<0.001; (3.96±0.76) vs. (2.78±0.50) ng/mL, P<0.001]. Multivariate logistic regression analysis showed that serum miR-141-3p and miR-29a-3p levels were protective factors for the occurrence of END in non-traumatic intracerebral hemorrhage patients [odds ratio (OR)=0.513, 95% confidence interval (CI) (0.330, 0.798), P=0.003; OR=0.582, 95%CI (0.380, 0.893), P=0.013], and serum miR-130a and miR-210 levels were independent risk factors for that [OR=2.046, 95%CI (1.222, 3.426), P=0.007; OR=2.377, 95%CI (1.219, 4.638), P=0.011]. The area under the receiver operating characteristic curve was 0.857 [95%CI (0.760, 0.954)] in predicting the END of non-traumatic intracerebral hemorrhage by the combined probability of the serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels obtained by logistic regression, and the sensitivity was 86.7%, the specificity was 94.7%, the positive predictive value was 79.6%, and the negative predictive value was 96.8% according to the cut-off value of the prediction probability of the combined test. Conclusion The combined detection of serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 has a high predictive value in the occurrence of END in non-traumatic intracerebral hemorrhage patients.
Objective To explore the correlation between DL-3-n-butylphthalide (NBP) and early neurological deterioration (END) after cerebral infarction in real-world study. Methods A multicenter registry observational study was conducted, enrolling patients with acute cerebral infarction within 72 h of onset from five hospitals in Deyang from March 31st, 2019, to July 31st, 2021. The patients were divided into two groups based on the treatment regimen, whether they received NBP in addition to standard therapy or not. The primary endpoint was END after cerebral infarction, and the secondary endpoint was unfavorable outcome (defined as modified Rankin Scale score of 3 to 6) 90 d after onset. Results A total of 314 patients with cerebral infarction were included in the study, among whom, 126 received standard therapy without NBP treatment (standard treatment group) and 188 received NBP in addition to standard therapy (NBP treatment group). A total of 69 cases occurred END within 10 d after admission. In the NBP treatment group, 32 cases (17.0%) had END within 10 d after admission, while in the standard treatment group, 37 cases (29.4%) occurred END, and the difference between the two groups was statistically significant (P=0.010). Logistic regression analyses showed that the influencing factors related to END included the serum neurofilament light chain level on admission [odds ratio (OR)=1.020, 95% confidence interval (CI) (1.004, 1.035), P=0.013], NBP treatment [OR=0.449, 95%CI (0.253, 0.797), P=0.006], and dual antiplatelet therapy [OR=0.373, 95%CI (0.196, 0.710), P=0.003], and the influencing factors for poor neurological functional prognosis in patients with cerebral infarction included age [OR=1.063, 95%CI (1.024, 1.103), P=0.002], National Institute of Health Stroke Scale score on admission [OR=1.532, 95%CI (1.313, 1.787), P<0.001], NBP treatment [OR=0.375, 95%CI (0.177, 0.794), P=0.010], and END [OR=7.450, 95%CI (3.294, 16.852), P<0.001]. Conclusion The results of our study provide the initial evidence that NBP treatment reduces the occurrence of END, and improves the neurological functional prognosis 90 d after onset in the real world.
Objective To investigate the relationship between systemic inflammation response index (SIRI) and early neurological deterioration (END) and 3-month prognosis in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke treated at West China Hospital of Sichuan University and Deyang People’s Hospital between April 2020 and October 2020 were collected. Clinical data were collected using a unified case form and outcomes were followed up for 3 months. According to the poor prognosis, the patients were divided into END group and non-END group. The multivariate logistic regression analysis was used to explore the relationship of SIRI, END and 3-month prognosis. We drew receiver operating characteristic curve to evaluate the value of related factors in predicting the occurrence of END and poor prognosis after 3 months. Results A total of 242 patients were included, of which 47 (19.42%) were in the END group. There were statistically significant differences between the two groups in National Institutes of Health stroke Scale (NIHSS) score on admission, hypertension, creatinine, urea nitrogen, neutrophils count, lymphocyte count, neutrophil count/lymphocyte count ratio (NLR), lymphocyte count/monocyte count ratio, platelet count/lymphocyte count ratio, complications (besides cerebral edema) and SIRI (P<0.05). Logistic regression analysis showed that NIHSS score on admission, hypertension, SIRI and NLR were independent risk factors for END (P<0.05). SIRI had better predictive value for the occurrence of END than NLR (P<0.05). Compared with the non-END group, the patients in the END group had worse prognosis at 3-month [44.7%(21/47) vs. 17.4% (34/195), P<0.05]. NIHSS score on admission had predictive value for clinical prognosis of acute ischemic stroke patients at 3-month. Conclusion SIRI is an independent risk factor for END in patients with acute ischemic stroke, and there is no independent correlation with the 3-month prognosis.