Three-biomarker panel differentiates ischemic stroke from intracerebral hemorrhage
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A biomarker panel with retinol binding protein 4, N-terminal pro B-type natriuretic peptide and glial fibrillary acid protein discerned ischemic stroke from intracerebral hemorrhage with modest accuracy, researchers reported in Neurology.
According to Alejandro Bustamante, MD, PhD, of the Neurovascular Research Laboratory at the Vall d’Hebron Institute of Research and the department of neurology at the Autonomous University of Barcelona in Spain, and colleagues, use of this biomarker panel may enable certain patients to receive pre-hospital treatment if future research efforts confirm the current results.
“A few years ago, we identified the biomarker retinol binding protein-4 (RBP-4) as a marker of [ischemic stroke] and, when combined with [glial fibrillary acid protein (GFAP)], it provided high specificity, but low sensitivity, for the differentiation of the subtypes,” Bustamante and colleagues wrote. “In addition, in the Stroke-Chip study, N-terminal pro B-type natriuretic peptide (NT-proBNP) and endostatin were able to provide an 80% accuracy in the differentiation of [ischemic stroke] and [intracerebral hemorrhage] when combined with clinical variables.”
The researchers sought to create and test a panel of blood biomarkers with sufficient accuracy to guide pre-hospital thrombolysis in certain patients with ischemic stroke. They also set up point-of-care devices for the biomarkers using lateral-flow immunoassays to enable “a fast and reliable measure” that could be assessed outside of hospitals.
They included those with suspected stroke who entered the hospital no more than 4.5 hours after onset of the medical event and obtained blood samples upon admission. Immunoassays provided measurements of GFAP, RBP-4, NT-proBNP and endostatin. For ischemic stroke, Bustamante and colleagues utilized cut-off points with 100% specificity. Among subsets of participants, they measured GFAP, as well as RBP-4 and NT-proBNP, via a high-sensitivity assay and rapid point-of-care tests, respectively. They also assessed biomarker panels among a separate cohort that included 62 stroke mimics.
The final analysis comprised 189 patients, including 154 who had an ischemic stroke and 35 who had an intracerebral hemorrhage.
Findings demonstrated increased levels of RBP-4, NT-proBNP and endostatin and decreased levels of GFAP among patients with ischemic stroke compared with patients with intracerebral hemorrhage. RBP-4 plus NT-proBNP pinpointed 29.7% of patients with ischemic stroke with 100% specificity, making this the “best biomarker combination” for identifying ischemic stroke, according to the researchers. Among those whose GFAP data were available via the high-sensitivity assay, RBP-4, NT-proBNP and GFAP identified 51.5% of patients with ischemic stroke with 100% specificity. Specificities decreased to 98.4% and 96.8%, respectively, upon inclusion of stroke mimics. RBP-4 and NT-proBNP point-of-care tests demonstrated similar outcomes to those of standard Enzyme-Linked Immunosorbent Assays.
“... Our study provides for the first time a biomarker panel that might be useful to safely identify selected [ischemic stroke] patients who might receive [tissue plasminogen activator] even in the absence of neuroimaging,” Bustamante and colleagues wrote. “This biomarker panel might open a new field in acute [ischemic stroke] care if confirmed in future, ongoing studies with validated [point-of-care] devices and pre-hospital samples.”
In a related editorial, Glen C. Jickling, MD, of the division of neurology in the department of medicine at the University of Alberta in Canada, and Katja E. Wartenberg, MD, of the department of neurology at the University of Leipzig in Germany, emphasized the role the panel developed by Bustamante and colleagues may have in the future care of individuals with acute stroke.
“Many challenges exist in the development of an acute biomarker for stroke,” they wrote. “However, with the goal of improving patient outcomes after stroke by rapidly confirming the diagnosis and reducing the time to treatment, there is great interest in proceeding with further development of a biomarker panel and the corresponding technology. As a complementary tool to brain imaging and clinical evaluation, a panel such as the [three]-biomarker panel described by Bustamante [and colleagues] may play a role in the prehospital diagnosis and management of patients with acute stroke.”