Abstract
BackgroundTimely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT.MethodsWe enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3–6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage).ResultsOf the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03–4.08), T2 (OR, 2.08; 95% CI, 1.05–4.01), and T3 (OR, 3.94; 95% CI, 1.44–10.79) were independent predictors of death or disability at 90 days.ConclusionAmong patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.
Highlights
Acute ischemic stroke (AIS) with large vessel occlusion (LVO) has a considerably poorer prognosis than do other types of stroke [1]
When an intracranial artery becomes occluded, the brain tissues in the relevant region become ischemic within minutes and become irreversibly infarcted if the blood flow is lower than the threshold that brain tissues can tolerate
Followup imaging revealed that 20 patients (33.3%) had hemorrhagic transformation (14 and 6 with hemorrhagic infarction (HI) and parenchymal hemorrhage (PH), respectively)
Summary
Acute ischemic stroke (AIS) with large vessel occlusion (LVO) has a considerably poorer prognosis than do other types of stroke [1]. Successful recanalization may not always translate into favorable outcomes because ischemiareperfusion injury may result in progressive infarct growth or hemorrhagic transformation with detrimental effects; patients for whom recanalization is unsuccessful may experience persistent ischemia [3] In such cases, the complex ischemic cascades, which involves interactions between infiltrated immune cells, circulating cytokines, activated platelets, the endothelium, and even central nervous system (CNS) cells, is a major contributor to post-stroke inflammatory responses that directly influence on the brain cell death [4]. The complex ischemic cascades, which involves interactions between infiltrated immune cells, circulating cytokines, activated platelets, the endothelium, and even central nervous system (CNS) cells, is a major contributor to post-stroke inflammatory responses that directly influence on the brain cell death [4] Fluid biomarkers for such process involving ischemiareperfusion and neuroinflammation may facilitate the prediction of stroke outcome.
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