Association of serum macrophage migration inhibitory factor with large hemisphere infarction and malignant cerebral edema after acute ischemic stroke

Abstract

Abstract Background：Macrophage migration inhibitory factor (MIF) is a crucial cytokine involved in inflammation after ischemic stroke, but little is known about its role in large hemisphere infarction (LHI) and malignant cerebral edema (MCE). We aimed to explore whether MIF and its related biomarkers (toll-like receptors [TLRs] and matrix metalloproteinase-9 [MMP-9]) were associated with LHI and MCE in patients with acute ischemic stroke (AIS). Methods: We prospectively enrolled patients with AIS within 24 h from symptom onset. LHI was defined as cerebral infarction involving more than 1/3 of middle cerebral artery territory within 6 hours from onset or over 1/2 within 48 hours from onset. MCE was defined as a decreased level of consciousness, anisocoria and (or) midline shift over 5mm, basal cistern effacement, or an indication for decompressive craniectomy during hospitalization. Follow-up CTs within 7 days were needed for screening the presence of MCE. Logistic regression was performed to analyze the association of the above inflammatory biomarkers with LHI and MCE. Results: Our present study included 263 patients (median age: 72 years; male: 50.6%), and 49.4% (130/263) developed LHI (median time from onset to LHI: 3h). Compared with patients without LHI, patients with LHI had a higher median serum level of MIF (median time from onset to blood collection: 3h; 9.51 vs. 7.26 ng/ml, p=0.036) and MMP-9 (36.77 vs. 29.88 ng/ml, p<0.001). MIF over 7.94 ng/ml (adjusted odds ratio [adOR] 1.836, 95% CI 0.988-3.415, p=0.055) and MMP-9 over 34.91ng/ml (adOR 3.283, 95% CI 1.722-6.258, p<0.001) were associated with an increased risk of LHI, separately. Fifty-five patients developed MCE, and the median time from onset to MCE was 32.06 h. Compared with patients without MCE, patients with MCE had a higher level of MIF (9.41 vs. 8.30 ng/ml, p=0.516) and MMP-9 (36.18 vs. 32.35 ng/ml, p=0.006), although the difference was not statistically significant for the former. After adjusted for confounders, neither MIF nor MMP-9 level was significantly associated with the risk of MCE. We did not find any independent association of TLR2/4 with either LHI or MCE. Conclusions: This study indicated that higher levels of MIF and MMP-9 were related to LHI. There were trends of association between a higher level of serum MIF/MMP-9 and an increased risk of MCE after AIS, which was warranted further validation in future larger studies.