The Prediction of Malignant Cerebral Infarction by Molecular Brain Barrier Disruption Markers

Abstract

Background and Purpose-Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. The aim of the study was to determine whether molecular markers of endothelial damage may help to predict secondary brain edema and, secondly, to identify patients who could benefit from aggressive therapies such as decompressive hemicraniectomy or hypothermia. Methods-We studied 40 consecutive patients with malignant middle cerebral artery (MCA) infarction and 35 controls with massive MCA infarctions Ͻ70 years of age and matched by stroke severity on admission. Cranial computed tomography (CT) was performed at entry and repeated between days 4 and 7, or earlier if there was neurological worsening. Malignant MCA (m-MCA) infarction was diagnosed when follow-up CT detected a more than two-thirds space-occupying MCA infarction with midline shift, compression of the basal cisterns, and neurological deterioration. Plasma concentrations of glutamate, glycine, ␥-aminobutyric acid, interleukin-6 (IL-6), IL-10, tumor necrosis factor-␣, matrix metalloproteinase-9 (MMP-9), and cellular-fibronectin (c-Fn) were determined in blood samples obtained at admission. Results-Mean time from stroke onset to blood sampling was 6.3Ϯ4.8 in m-MCA and 7.7Ϯ6.0 hours in the control group (Pϭ0.63). Baseline characteristics were comparable in both groups. c-Fn and MMP-9 levels were significantly higher in patients with m-MCA than in controls (all PϽ0.001). c-Fn Ͼ16.6 g/mL had the highest sensitivity (90%), specificity (100%), and negative and positive predictive values (89% and 100%, respectively) for the prediction of m-MCA infarction. Conclusions-A plasma c-Fn concentration Ͼ16.6 g/mL at admission is associated with the development of m-MCA infarction with high sensitivity and specificity, suggesting that c-Fn might be useful in therapeutic decision making.

Blood-Brain Barrier Permeability Assessed by Perfusion CT Predicts Symptomatic Hemorrhagic Transformation and Malignant Edema in Acute Ischemic Stroke

“…tPA upregulation of MMP-9 likely also plays a similar role in the pathogenesis of ME, given that elevated MMP-9 levels have been demonstrated in patients with stroke who develop ME. 39 Most interesting, our data on collaterals, which were derived from admission CTA imaging, added additional information and provided a way to potentially distinguish patients with SHT and ME. Although we were not able to conduct a NCCT revealed no evidence of intracranial hemorrhage, and she was treated with IV tPA at this time.…”

Blood Biomarkers of Ischemic Stroke

“…A plasma level of S-100B >0.35 g/L predicted malignant infarction at 12 hours with a 75% sensitivity and 80% specificity, and at 24 hours with a 94% sensitivity and 83% specificity. A second study found cellular-fibronectin (c-Fn) and MMP-9 levels to predict malignant cerebral infarction [66]. Admission MMP-9 level >140 ng/mL predicted malignant MCA infraction with 64% sensitivity and 88% specificity.…”

“…Early neurological deterioration (END), defined as worsening of neurological status from admission to 48-72 hours after admission, is associated with a number of biomarkers including glutamate, GABA, ferritin, TNF-alpha, ICAM-1, MMP, S100B, MMP and nitric oxide [65,66]. Identifying patients at risk of END may be useful for initiating therapies to prevent such worsening.…”

Adapting Bobbert-Vlieger model to spectroscopic ellipsometry of gold nanoparticles with bio-organic shells

“…Apart from being commonly used as a model protein, biologically cFn plays an important role in cell adhesion, growth, migration and signaling processes. In biosensing and medical diagnostics context it is considered to be a promising biomarker [29][30][31]. Each AuNP functionalization step, including the capture of cFn targets, was characterized by spectroscopic ellipsometry to provide data for comparison with the model predictions.…”