Prognostic potential of serum mesencephalic astrocyte-derived neurotrophic factor in acute intracerebral hemorrhage: a prospective observational study.

OBJECTIVE: Mesencephalic astrocyte-derived neurotrophic factor (MANF) expressions are dramatically up-regulated in injured brain tissues, thereby conferring neurological protective effects. We intended to determine significance of serum MANF as a prognostic biomarker of intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study done from February 2018 to July 2021, 124 patients with new-onset primary supratentorial ICH were consecutively enrolled. Also, a group of 124 healthy individuals constituted controls. Their serum MANF levels were detected using the Enzyme-Linked Immunosorbent Assay. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were designated as the two severity indicators. Early neurologic deterioration (END) was referred to as an increase of 4 or greater points in NIHSS scores or death at post-stroke 24 h. Post-stroke 90-day modified Rankin scale (mRS) scores of 3-6 was considered as a poor prognosis. Serum MANF levels were analyzed using multivariate analysis with respect to its association with stroke severity and prognosis. RESULTS: Patients, in comparison to controls, displayed markedly elevated serum MANF levels (median, 24.7 versus 2.7 ng/ml; P < 0.001), and serum MANF levels were independently correlated with NIHSS scores (beta, 3.912; 95% confidence interval (CI), 1.623-6.200; VIF = 2.394; t = 3.385; P = 0.002), hematoma volumes (beta, 1.688; 95% CI, 0.764-2.612; VIF = 2.661; t = 3.617; P = 0.001) and mRS scores (beta, 0.018; 95% CI, 0.013-0.023; VIF = 1.984; t = 2.047; P = 0.043). Serum MANF levels significantly predicted END and poor 90-day prognosis with areas under receiver operating characteristic curve at 0.752 and 0.787 respectively. END and prognostic predictive abilities were similar between serum MANF levels and NIHSS scores plus hematoma volumes (all P > 0.05). Combination of serum MANF levels with NIHSS scores and hematoma volumes had significantly higher prognostic capability than each of them (both P < 0.05). Serum MANF levels above 52.5 ng/ml and 62.0 ng/ml distinguished development of END and poor prognosis respectively with median-high sensitivity and specificity values. Using multivariate analysis, serum MANF levels > 52.5 ng/ml predicted END with odds ratio (OR) value of 2.713 (95% CI, 1.004-7.330; P = 0.042) and > 62.0 ng/ml predicted a poor prognosis with OR value of 3.848 (95% CI, 1.193-12.417; P = 0.024). Using restricted cubic spline, there was a linear correlation between serum MANF levels and poor prognosis or END risk (both P > 0.05). Nomograms were well established to predict END and a poor 90-day prognosis. Under calibration curve, such combination models were comparatively stable (using Hosmer & Lemeshow test, both P > 0.05). CONCLUSION: Increased serum MANF levels after ICH, in independent correlation with disease severity, independently distinguished risks of END and 90-day poor prognosis. Therefore, serum MANF may be a potential prognostic biomarker of ICH.

Elevated serum nuclear factor erythroid 2-related factor 2 levels contribute to a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective cohort study.

Objective: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional factor for antioxidant response element-regulated genes. The purpose of this study was to assess the prognostic role of serum Nrf2 in intracerebral hemorrhage (ICH). Materials and methods: In this prospective observational study, serum Nrf2 levels of 115 acute supratentorial ICH patients and 115 controls were gaged. Early neurologic deterioration (END) was defined as an increase of four or greater points in National Institutes of Health Stroke Scale (NIHSS) score or death at post-stroke 24 h. A poor outcome was referred to as the post-stroke 90-day modified Rankin scale (mRS) score of 3-6. END and a poor outcome were considered as the two prognostic parameters. Results: As compared to controls, serum Nrf2 levels of patients were substantially elevated (P < 0.001), with its levels increasing during the 6-h period immediately, peaking in 12-18 h, plateauing at 18-24 h, and decreasing gradually thereafter (P < 0.05). Serum Nrf2 levels of patients were independently correlated with NIHSS score (t = 3.033; P = 0.003) and hematoma volume (t = 3.210; P = 0.002), independently predicted END (odds ratio 1.125; 95% confidence interval 1.027-1.232; P = 0.011) and poor outcome (odds ratio 1.217; 95% confidence interval 1.067-1.387; P = 0.013), as well as efficiently distinguished END (area under curve 0.771; 95% confidence interval 0.666-0.877; P < 0.001) and poor outcome (area under curve 0.803; 95% confidence interval 0.725-0.882; P < 0.001). Its predictive ability was equivalent to those of NIHSS score and hematoma volume (both P > 0.05), and it also significantly improved their predictive abilities under receiver operating characteristic (ROC) curve (all P < 0.05). Conclusion: Elevated serum Nrf2 levels are closely correlated with severity, END, and 90-day poor outcome following ICH. Hence, Nrf2 may play an important role in acute brain injury after ICH, and serum Nrf2 may have the potential to serve as a prognostic biomarker of ICH.

Usability of serum annexin A7 as a biochemical marker of poor outcome and early neurological deterioration after acute primary intracerebral hemorrhage: A prospective cohort study.

Objective: Annexin A7 (ANXA7), a calcium-dependent phospholipid-binding protein, may act to aggravate brain injury. This study aimed to assess the clinical utility of serum ANXA7 as a predictor of severity, early neurological deterioration (END), and prognosis after intracerebral hemorrhage (ICH). Methods: A total of 126 ICH patients and 126 healthy controls were enrolled. Symptomatic severity was evaluated utilizing the National Institutes of Health Stroke Scale (NIHSS) score. The lesion volume of ICH was measured according to the ABC/2 method. END was referred to as an increase of 4 or greater points in the NIHSS score or death at post-stroke 24 h. The unfavorable functional outcome was a combination of death and major disability at post-stroke 90 days. Results: Serum ANXA7 levels were significantly higher in patients than in controls (median, 46.5 vs. 9.7 ng/ml; P < 0.001). Serum ANXA7 levels were independently correlated with NIHSS score [beta: 0.821; 95% confidence interval (CI): 0.106-1.514; variance inflation factor: 5.180; t = 2.573; P = 0.014] and hematoma volume (beta: 0.794; 95% CI: 0.418-1.173; variance inflation factor: 5.281; t = 2.781; P = 0.007). Serum ANXA7 levels were significantly elevated with increase in modified Rankin scale scores (P < 0.001). Also, serum ANXA7, which was identified as a categorical variable, independently predicted END and an unfavorable outcome with odds ratio values of 3.958 (95% CI: 1.290-12.143; P = 0.016) and 2.755 (95% CI: 1.051-7.220; P = 0.039), respectively. Moreover, serum ANXA7 levels efficiently differentiated END (area under the curve: 0.781; 95% CI: 0.698-0.849) and an unfavorable outcome (area under the curve: 0.776; 95% CI: 0.693-0.846). Conclusion: Serum ANXA7 may represent a useful blood-derived biomarker for assessing the severity, END, and prognosis of ICH.

Predictive value of serum visinin-like protein-1 for early neurologic deterioration and three-month clinical outcome in acute primary basal ganglia hemorrhage: A prospective and observational study.

BACKGROUND: Visinin-like protein 1 (VILIP-1) appears as a biomarker of neuronal injury. We investigated the correlation of serum VILIP-1 concentrations with severity, early neurologic deterioration (END) and functional outcome of intracerebral hemorrhage (ICH). METHODS: In this prospective and observational study, serum VILIP-1 concentrations were quantified in 106 patients with basal ganglia hemorrhage. Univariate and multivariable logistic regression analyses were used to analyze the relationship between serum VILIP-1 concentrations and END plus worse prognosis (modified Rankin Scale score of 3 or greater) at post-injury 3 months. RESULTS: Serum VILIP-1 concentrations of patients were closely correlated with hematoma volume and National Institutes of Health Stroke Scale score. Serum VILIP-1 concentrations were substantially elevated in patients with END or worse 3-month prognosis, as compared to other remainders. Also, serum VILIP-1 concentrations were independently associated with END and worse 3-month prognosis. Under ROC curve analysis, serum VILIP-1 concentrations exhibited marked accuracy for distinguishing patients with the development of END or worse 3-month prognosis. Its predictive ability was in the range of hematoma volume and National Institutes of Health Stroke Scale score. CONCLUSIONS: Serum VILIP-1 may be a good biomarker for assessing hemorrhagic severity and clinical outcomes after ICH.

Blood levels of adrenomedullin on admission predict outcomes after acute intracerebral hemorrhage.

Increased plasma adrenomedullin level has been associated with critical illness. This study aimed to investigate the correlations of plasma adrenomedullin concentration with 3-month clinical outcomes and early neurological deterioration of patients with acute intracerebral hemorrhage. One hundred fourteen patients and 112 healthy controls were recruited. Relationships of plasma adrenomedullin concentrations with early neurological deterioration, 3-month mortality and unfavorable outcome (modified Rankin Scale score >2) were evaluated. Plasma adrenomedullin concentrations were increased in patients than in healthy individuals and were highly associated with National Institutes of Health Stroke Scale scores. A multivariate analysis selected plasma adrenomedullin concentration as an independent predictor for 3-month clinical outcomes and early neurological deterioration. A receiver operating characteristic curve analysis showed plasma adrenomedullin concentration predicted 3-month clinical outcomes and early neurological deterioration with high area under curves. The predictive value of adrenomedullin was similar to that of National Institutes of Health Stroke Scale score. In a combined logistic-regression model, adrenomedullin did not improve the predictive value of National Institutes of Health Stroke Scale score. Thus, elevated plasma adrenomedullin concentration is highly associated with 3-month clinical outcomes and early neurological deterioration of patients with acute intracerebral hemorrhage.