Association of serum A20 levels with stroke-associated pneumonia, early neurological deterioration, and poor neurological prognosis following acute supratentorial intracerebral hemorrhage: a prospective cohort study

Abstract

Background: A20 is an endogenous protective protein. We quantified serum A20 levels following acute intracerebral hemorrhage (ICH) and assessed their association with the severity of illness and clinical outcomes of patients.

Methods: In total, 243 patients with acute supratentorial ICH and 76 controls were included in this prospective cohort study. Serum A20 levels were measured at admission in all patients, at study entry in all controls, and on post-ICH days 1, 3, 5, 7, 10, and 14 in 76 patients. The National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume were used to estimate the severity. Stroke-associated pneumonia (SAP), early neurological deterioration (END), and post-ICH 6-month poor prognosis (modified Rankin Scale scores: 3-6) were considered as the three outcome variables of interest.

Results: Patients, as opposed to controls, exhibited significantly heightened serum A20 levels from admission until 14 days following ICH, with a peak value at day 3. Serum A20 levels at all-time points after ICH, which were significantly correlated with NIHSS scores and hematoma volume, were significantly higher in patients with END, SAP, or poor prognosis than in those without the corresponding one. Serum A20 levels at admission possessed similar predictive ability of these clinical outcomes to those at other time points. Serum A20 levels at admission, along with initial NIHSS scores and hematoma volume, remained independent predictors of clinical outcomes among patients. As confirmed by numerous statistical approaches, their conjunctions comprised three prediction models: satisfactory stability, clinical validity, and discrimination efficiency.

Conclusion: Serum A20 levels were significantly increased following ICH and may accurately reflect hemorrhagic severity and effectively predict END, SAP, and poor neurological prognosis, suggesting that serum A20 may be a promising prognostic biomarker for ICH.

Keywords: A20; biomarkers; intracerebral hemorrhage; outcome; severity.

Figure 1

Schematic illustration of the study design and enrollment in the assessment of serum A20 as a prognostic marker for acute intracerebral hemorrhage. This clinical survey comprised two sub-studies, a cross-sectional study and a prospective cohort study, to identify serial changes in serum A20 levels post-acute intracerebral hemorrhage and their prognostic significance.

Figure 2

Time course of serum A20 levels in 76 patients with acute intracerebral hemorrhage. Serum A20 levels were significantly elevated at admission in patients with acute intracerebral hemorrhage, peaked on day 3, and remained significantly higher than those in controls until day 14 after stroke onset (p < 0.001). ICH, intracerebral hemorrhage.

Figure 3

Distinction of serum A20 levels across poor prognosis at 6 months after intracerebral hemorrhage in 76 patients. Individuals with a 6-month poor prognosis had significantly higher serum A20 levels at admission and on days 1, 3, 5, 7, 10, and 14 following acute intracerebral hemorrhage than those with a good prognosis (^*p < 0.05, ^**p < 0.01). ICH, intracerebral hemorrhage.

Figure 4

Disparities in discrimination abilities of serum A20 levels, the combination model, and other variables on the likelihood of poor prognosis at 6 months following acute intracerebral hemorrhage among all 243 patients. Serum A20 levels had an area under the receiver operating characteristic curve analogous to the National Institutes of Health Stroke Scale scores and hematoma volume (both p > 0.05). Regarding predictive ability, serum A20 levels combined with National Institutes of Health Stroke Scale scores and hematoma volume outperformed each of them (^*p < 0.05, ^**p < 0.01) in this cohort of 243 patients with acute intracerebral hemorrhage. AUC, area under the curve; 95% CI, 95% confidence interval; ns, non-significant; NIHSS, National Institutes of Health Stroke Scale.

Figure 5

Difference in serum A20 levels across 76 patients with stroke-associated pneumonia following intracerebral hemorrhage. Patients who developed stroke-associated pneumonia, than those who did not, had significantly higher serum A20 levels at admission and on days 1, 3, 5, 7, 10, and 14 post-acute intracerebral hemorrhage among 76 patients (^*p < 0.05, ^**p < 0.01). ICH, intracerebral hemorrhage; SAP, stroke-associated pneumonia.

Figure 6

Comparison of discrimination values between serum A20 levels, combination model, and other variables on the likelihood of stroke-associated pneumonia post-acute intracerebral hemorrhage among all 243 patients. Serum A20 levels occupied the area under the receiver operating characteristic curve, similar to the National Institutes of Health Stroke Scale scores and hematoma volume (both p > 0.05). Regarding predictive ability, serum A20 levels combined with the National Institutes of Health Stroke Scale scores and hematoma volume surpassed each individually (^*p < 0.05, ^**p < 0.01) among all 243 patients with acute intracerebral hemorrhage. AUC, area under the curve; 95% CI, 95% confidence interval; ns, non-significant; NIHSS, National Institutes of Health Stroke Scale.

Figure 7

Change in serum A20 levels during early neurological deterioration in 76 patients with acute intracerebral hemorrhage. Patients with early neurological deterioration than those without such an adverse event exhibited significantly higher serum A20 levels at admission and on days 1, 3, 5, 7, 10, and 14 after acute intracerebral hemorrhage (^*p < 0.05, ^**p < 0.01). ICH, intracerebral hemorrhage; END, early neurological deterioration.

Figure 8

Differences in discrimination performances of serum A20 levels, the joint model, and other parameters on the likelihood of early neurological deterioration following acute intracerebral hemorrhage among all 243 patients. When serum A20 levels were compared with National Institutes of Health Stroke Scale scores and hematoma volume, the areas under the receiver operating characteristic curve were not significantly different (both p > 0.05). Regarding predictive capability, serum A20 levels combined with the National Institutes of Health Stroke Scale scores and hematoma volume exceeded each individually (^*p < 0.05, ^**p < 0.01) in all 243 patients with acute intracerebral hemorrhage. AUC, area under the curve; 95% CI, 95% confidence interval; ns, non-significant; NIHSS, National Institutes of Health Stroke Scale.