Elevated Serum S100B Levels Indicate a Higher Risk of Hemorrhagic Transformation After Thrombolytic Therapy in Acute Stroke

Abstract

Background and Purpose-Intracerebral hemorrhage constitutes an often fatal sequela of thrombolytic therapy in patients with ischemic stroke. Early blood-brain barrier disruption may play an important role, and the astroglial protein S100B is known to indicate blood-brain barrier dysfunction. We investigated whether elevated pretreatment serum S100B levels predict hemorrhagic transformation (HT) in thrombolyzed patients with stroke. Methods-We retrospectively included 275 patients with ischemic stroke (mean age of 69Ϯ13 years; 46% female) who had received thrombolytic therapy within 6 hours of symptom onset. S100B levels were determined from pretreatment blood samples. Follow-up brain scans were obtained 24 hours after admission, and HT was classified as either hemorrhagic infarction (1, 2) or parenchymal hemorrhage (1, 2). Results-HT occurred in 80 patients (29%; 45 hemorrhagic infarction, 35 parenchymal hemorrhage). Median S100B values were significantly higher in patients with HT (0.14 versus 0.11 g/L; Pϭ0.017). An S100B value in the highest quintile corresponded to an OR for any HT of 2.87 (95% CI: 1.55 to 5.32; Pϭ0.001) in univariate analysis and of 2.80 (1.40 to 5.62; Pϭ0.004) after adjustment for age, sex, symptom severity, timespan from symptom onset to hospital admission, vascular risk factors, and storage time of serum probes. A pretreatment S100B value above 0.23 g/L had only a moderate sensitivity (0.46) and specificity (0.82) for predicting severe parenchymal bleeding (parenchymal hemorrhage 2). Conclusions-Elevated S100B serum levels before thrombolytic therapy constitute an independent risk factor for HT in patients with acute stroke. Unfortunately, the diagnostic accuracy of S100B is too low for it to function in this context as a reliable biomarker in clinical practice.

Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

“…This process evolves over several days and even weeks post-stroke. In keeping with this concept, Foerch and coworkers reported that serum 100B levels assessed within the early stages of stroke onset did not reflect infarct size [20]. This finding is also supported by several reports that S100B levels only correlate with final infarct volume if determined [24 h after symptom onset [6,7,21].…”

Copeptin adds prognostic information after ischemic stroke

“…While several markers, such as NT-BNP, 5,20,21 CRP, [21][22][23][24] D-Dimers, 20,25,26 Interleukin-6, 21,24,27 von Willebrand factor, 28, 29 S-100β, 30 and neuron specific enolase (NSE), 31 have been associated with functional outcome or mortality, only a few biomarkers added to prognosis based on clinical assessment. None of these markers, however, were fully evaluated including assessment of accuracy (i.e.…”

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

“…Patients at increased risk for HT might have their tPA therapy modified or be administered a drug to prevent HT. Blood biomarkers that have been associated with HT in ischemic stroke include MMP-9, 60,61,122 cellular fibronectin, 62 fibrinogen, 180 S100B, 181 ferritin, 182 activated protein C, 183 thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 184 (Table 1). Other molecules that predict HT include: Vascular Adhesion Protein-1, 185 a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils; serum levels of TJPs (CLDN5, OCLN, and CLDN5/ZO1 ratio); 75 and PDGF-CC isoforms, 37 which is activated by tPA and acts on astrocyte PDGFRa (Figure 2).…”