Abstract
BackgroundWe aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke.MethodsWe prospectively enrolled patients with acute ischemic stroke admitted < 24 h from onset of symptoms. Brain CT was performed on admission and blood samples were collected. Repeated brain CT/MRI was performed < 7 days of admission to identify the presence of MBE, defined as neurological deterioration with imaging signs of midline shift or compressed basal cisterns. Logistic regression analysis was performed to assess the association between inflammatory biomarkers and MBE, adjusted for age and National Institutes of Health Stroke Scale (NIHSS).Results200 patients (69.3 ± 14.3 years; male 55 %) were included for analysis, of whom 26 patients developed MBE (median time from stroke onset to MBE 32.5 h). Compared with patients without MBE, those with MBE had higher level of serum concentration of NLRP3 (median time from onset to blood collection 3 h, 1.85 ng/ml vs. 1.11 ng/ml, P = 0.026). NLRP3 level was positively correlated with NIHSS on admission (Spearman ρ = 0.18, P = 0.01) and the association between NLRP3 and MBE was attenuated (OR 1.47, 95 % CI 0.88–2.46, P = 0.138) after adjusting for age and NIHSS. There was no significant difference in other biomarkers between MBE and non-MBE groups.ConclusionsThere was a trend of association between a higher level of serum concentration of NLRP3 and an increased risk of MBE after ischemic stroke, possibly confounded by the severity of stroke, which is worth further validation in large cohort studies.
Highlights
Stroke is a leading cause of death and disability in the world [1]
Categorical variables were compared between groups with the Chi-squared test or Fisher’s exact test when appropriate, and continuous variables with the Results 1159 patients with acute ischemic stroke were admitted between January 2019 and September 2019, of whom 592 were admitted within 24 h after the onset of stroke. 200 patients (69.3 ± 14.3 years; male 55 %) satisfied the inclusion criteria and consented to participate were included for analysis, where 26 (13 %) patients developed malignant brain edema (MBE), 41 (20.5 %) patients presented parenchymal hematoma, and 21 (10.5 %) patients died in-hospital or within 7 days after discharge
A higher level of NLRP3 was associated with a higher risk of MBE
Summary
Brain edema is the leading cause of death during acute phase of stroke, [2] which can develop rapidly during the first few days after the onset of stroke, causing occupying effect, herniation and even death, known as malignant brain edema (MBE) [3]. A phase 2 A clinical trial reported that intravenous glyburide reduced midline shift and edema-related death in patients with large hemispheric infarction, but it did not reduce the risk of MBE nor improve 3-month functional outcomes [7], where its phase 3 trial (NCT02864953) is ongoing. We aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke
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