Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke

Abstract

Background and Purpose-One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. Methods-A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, D-dimer, and protein S100␤. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. Results-A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, D-dimer, and S-100␤ into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test PϽ0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. Conclusions-These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.

Blood Biomarkers of Ischemic Stroke

“…In a study of 31 patients, apolipoprotein CI and apolipoprotein CIII were shown to distinguish hemorrhagic from ischemic stroke with 94% sensitivity and 87% specificity [23]. In a larger study of 1146 patients, a 4 panel marker (S100B, MMP9, D-dimer and brain natriuretic factor) was able to distinguish ischemic stroke from stroke mimics including hemorrhagic stroke with 85% sensitivity; however, specificity was only 34% [24]. Thus, though ischemic stroke can be identified reasonably well, many non-ischemic stroke patients are also incorrectly predicted to be ischemic stroke.…”

To Optimize the Therapeutic Dose and Time Window of Picroside II in Cerebral Ischemic Injury in Rats by Orthogonal Test

“…Tracing S100B may advance the extension of neuron axons and enhance the survival rate of neurons, while a great deal of it may generate toxic and side-effect [1]. A large number of activated S100B protein which is produced by glial cells is released into the extracellular after brain tissue injury [17], and then leaks into CSF and blood through damaged blood brain barrier, and S100B level in serum is positively correlated with the severity of the injury of cerebral ischemia [18]. Brouns and his group have also found that the concentration of S100B, which is in the cerebral spinal fluid (CSF) of the patients with acute ischemic stroke, is highly correlated to the severity of the injury and the prognosis of cerebral ischemia [19].…”

Advances in biomarker for stroke patients: from marker to regulator

“…For instance, a diagnostic panel incorporating the levels of matrix metalloproteinase 9 (MMP9), Btype natriuretic peptide, Ddimer, and S100β into a composite score enhanced sensitivity of early noncontrast computed tomography (CT) alone for acute stroke, although the diagnostic accuracy was clearly imperfect [15]. Further more, the approach was feasible as a pointofcare test in the emergency setting [15]. As the number of presumed bio markers for stroke expands at an exponential rate, it would be expected to develop improved biomarker combinations for more accurate diagnosis of stroke.…”

“…Many epidemiological studies suggested that stroke has ge ADMA for silent brain infarcts on MRI [9] Genomewide association studies of stroke [14] Rapid stroke diagnosis Protein biomarkers associated with glial and neuronal cells (S100β, GFAP, NSE, MBP), inflammation (CRP, MMP9, VCAM, TNFα, IL6, VEGF), thrombosis (vWF, Ddimer), and others (BNP, homocysteine) [15,2628] Detection of stroke mechanisms and moleculartargeted treatment Mechanisms of neuronal death, e.g. glutamate, GABA [16,17] Etiologic diagnosis of ischemic stroke, e.g., atherosclerotic (inflammatory markers) vs. [53].…”