Correlation Of Neurofilament Light With Early Neurological Deterioration And Prognosis After Cerebral Infarction

Objective: To investigate the incidence of early neurological deterioration(END)in acute cerebral infarction(CI),the correlation of serum Neuroflament light(Nf L)with END and its predictive value for END,and the effects of END and Nf L on functional prognosis at 3 months after CI.Methods: This is a prospective,observational cohort study.A total of 321 patients with acute CI within 72 hours of onset were included in a tertiary hospital from March 2019 to July 2021.The characteristics data and risk factors of these patients were recorded.All enrolled patients were evaluated using the National Institutes of Health Stroke Scale(NIHSS)at admission and every day within a week.At the same time,38 healthy controls were selected to assess Nf L baseline level.Fasting venous blood 4 m L was drawn from all subjects in the morning of the next day.Serum Nf L levels were measured by ELISA.The primary endpoint was END.END was defined as in NIHSS increased by 2 or more points within 7 days after admission,with at least 1 point increase in motor function scores,while excluding hemorrhagic transformation of infarct,a new infarct in another vascular territory,cerebral edema and systemic diseases.The secondary endpoint was functional prognosis at 3 months after admission.Functional prognosis was evaluated by modified Rankin Scale(m RS)score.The m RS score ≤ 2 was defined as good functional prognosis,while the m RS score > 2 was defined as poor functional prognosis.SPSS 21.0 software was used for statistical analysis.Cox proportional hazard model was used to analyze the risk factors of END.Receiver operator characteristic curve(ROC curve)was used to evaluate the predictive value of Nf L for END.Multivariate Logistic regression analysis was used to analyze the effect of Nf L and END on the functional prognosis at 3 months after admission.Results: 1.The mean Nf L level was 65.38 ? 19.78 pg/m L in patients with acute CI,which was significantly higher than 47.27 ? 13.78 pg/m L in healthy controls(t’ = 7.268,P < 0.001).2.Of the 321 patients,74 patients developed END within one week after admission,and the incidence of END was 23.05 %.3.Compared with patients without END,the Nf L level(79.69 ? 17.11 pg/m L in END group vs.61.10 ? 18.50 pg/m L in non-END group)and NIHSS score at admission(5.55 ? 2.41 in END group vs.3.64 ? 2.15 in non-END group)were significantly higher in patients with END(P < 0.001).4.Patients were divided into four groups according to the Nf L level from low to high using the quartile method,namely,the first quartile(Q1),the second quartile(Q2),the third quartile(Q3)and the fourth quartile(Q4).The incidence of END in Q1-Q4 group was 2.50%(2/80),16.05%(13/81),25.00%(20/80)and 48.75%(39/80),respectively.The incidence of END in Q3 and Q4 groups was significantly higher than that in Q1 and Q2 groups(P < 0.001).According to this,patients were divided into lower Nf L group(Q1 and Q2)and higher Nf L group(Q3 and Q4).Compared with the lower Nf L group,we found that onset to admission time was longer(18.70 ? 21.9 hours vs.13.38 ? 15.12 hours),proportion of minor stroke was smaller(71.25% vs.82.61%),NIHSS score was higher(4.34 ? 2.44 points vs.3.83 ? 2.24 points)in the higher Nf L group using the single factor analysis.5.Cox proportional hazard model analysis showed that Nf L level(HR = 1.036,95%CI = 1.024-1.049,P < 0.001),NIHSS score at admission(HR = 1.328,95%CI = 1.196-1.474,P < 0.001)were independently associated with END.6.The area under the ROC curve(AUC)of Nf L in predicting END was 0.769(95% CI : 0.711-0.827,P < 0.001),and the optimal cut-off point was 69.805 pg/m L.The sensitivity and specificity of Nf L in predicting END were 70.3% and 70.9%,respectively.7.Among the 321 patients,316 completed 3 months follow-up,5 cases were lost,the loss rate was1.56%(5/321).Among 316 patients who completed follow-up,257(81.33%)had good functional prognosis,and 59(18.67%)had poor functional prognosis.Single factor analysis showed that the incidence of poor functional prognosis was significantly higher in patients with END than in patients without END(38.36% vs.12.76%).Compared with patients of the good functional prognosis,the age was older,NIHSS score at admission was higher,proportion of Cardioembolism was higher,proportion of patients with Small-artery disease was lower,proportion of single antiplatelet therapy was higher,and proportion of dual antiplatelet therapy was lower in the patients of poor functional prognosis(P < 0.05).Multivariate Logistic regression analysis found that age(OR = 1.046,95% CI : 1.012-1.081,P = 0.008),END(OR = 3.445,95% CI :1.501-7.906,P = 0.004),admission NIHSS score(OR = 1.447,95% CI :1.236-1.695,P < 0.001),dual antiplatelet therapy(OR = 0.090,95% CI :0.015-0.540,P = 0.008)were independently associated with poor functional prognosis in patients at 3 months afer admission.Among them,age,END and NIHSS were the risk factors for poor functional prognosis,and dual antiplatelet therapy was the protective factor for poor functional prognosis.However,no independent correlation was found between Nf L level and poor functional prognosis at 3 months(OR = 0.993,95% CI : 0.974–1.013,P = 0.516).Conclusion: 1.The incidence of END in patients with acute CI was as high as 23.05%.2.Nf L level and admission NIHSS score were independently associated with END.3.The area under the ROC curve of Nf L in predicting END was 0.769,and the optimal cut-off point was 69.805 pg/m L.The sensitivity and specificity of END were 70.3% and 70.9%,respectively.It indicates that Nf L may have good predictive value for END after CI.4.Older age,higher NIHSS score and END were the risk factors for poor functional prognosis at 3 months,while dual antiplatelet therapy was the protective factor.