Role of Blood-Based Biomarkers in Ischemic Stroke Prognosis

Abstract

Background and Purpose: Outcome prognostication in ischemic stroke patients remains challenging due to limited predictive properties of existing models. Blood-based biomarkers might provide additional information to established prognostic factors. We intended to identify the most promising prognostic biomarkers in ischemic stroke, their incremental prognostic value, and whether their predictive value differs among etiologies. Methods: We searched MEDLINE (Ovid) and Institute for Scientific Information Web of Knowledge for articles reporting the predictive performance of blood-based biomarkers measured up to 7 days after ischemic stroke and reporting functional outcome or death at least 7 days after stroke. This work updates a previous systematic review (up to January 2007), follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and was registered (International Prospective Register of Systematic Reviews PROSPERO 2018; https://www.crd.york.ac.uk/PROSPERO /; Unique identifier: CRD42018094671). Results: Two hundred ninety-one articles published between January 2007 and August 2018 comprising 257 different biomarkers met inclusion criteria. Median sample size was 232 (interquartile range, 110–455); 260 (89%) articles reported regression analyses with 78% adjusting for stroke severity, 82% for age, 67% for both, and 9% for none of them; 37% investigated discrimination, 5% calibration, and 11% reclassification. Including publications from a previous systematic review (1960–January 2007), natriuretic peptides, copeptin, procalcitonin, mannose-binding lectin, adipocyte fatty acid–binding protein, and cortisol were the biomarkers most consistently associated with poor outcome in higher-quality studies showing an incremental value over established prognostic factors. Other biomarkers were less consistently associated with poor outcome or were reported in lower quality studies. High heterogeneity among studies precluded the performance of a meta-analysis. Conclusions: The number of reports on prognostic blood-based biomarkers in ischemic stroke increased 3.5-fold in the period January 2007 to August 2018. Although sample size increased, methodological flaws are still common. Natriuretic peptides and markers of inflammation, atherogenesis, and stress response are the most promising prognostic biomarkers among identified studies.

Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy

“…Studies have suggested that various circulating proteins are directly related to acute ischemic injury or inflammation of the CNS [5][6][7]. Brain tissues that become necrotic after stroke and the associated inflammation may release neuronal or glialspecific proteins into the cerebrospinal fluid and the blood, but their concentration in the peripheral blood is usually extremely low [8]. With advancements in detection technology, such as ultrasensitive immunoassays, these trace biomarkers can now be measured with confidence, potentially assisting in stroke prognosis prediction.…”

The Role of Biomarkers in Atherothrombotic Stroke—A Systematic Review

“…The final phase of stroke is the chronic stage that sets after approximately six weeks from the initial event. The BBB permeability is restored to almost the same level as before, even if the neuroinflammation response is still present, as cytokines levels are still raised above normal [8][9][10][11] (Figure 2). The purpose of this article is to review the current biomarkers related to atherothrombotic stroke, focusing on their roles as a risk factor, detection marker, and prognostic predictor, and therapeutic targets.…”

Sterile Leukocytosis Predicts Hemorrhagic Transformation in Arterial Ischemic Stroke: A National Inpatient Sample Study

“…These immune cells exacerbate the injury by releasing additional inflammatory factors, such as ROS, MMP-9, and neutrophil elastase, which are prominent effectors of BBB disruption [17]. It also has been shown that most AIS patients course some degree of immune dysregulation; however, when these mechanisms are overstimulated worsen short and long-term clinical outcomes are expected [18][19][20].…”