Predicting functional outcome of ischemic stroke patients in Romania based on plasma CRP, sTNFR-1, D-Dimers, NGAL and NSE measured using a biochip array

Abstract

In cerebral ischemia, evaluation of multiple biomarkers involved in various pathological pathways is a useful tool in assessing the outcome of the patients even from the early stages of the disease. In this study we investigated the utility of a panel of 5 peripheral biomarkers of inflammatory status, neuronal destruction and secondary fibrinolysis in the acute phase of ischemia, and evaluated the impact of these biomarkers on functional outcome after ischemic stroke. The 5 biomarkers (plasma CRP, D-Dimers, sTNFR-1, NGAL and NSE) were measured using a biochip array technology. Eighty nine patients in Romania were divided into 2 subgroups using the modified Rankin Scale evaluated at 3 months after ischemic stroke; the possible impact of analyzed biomarkers on unfavorable functional outcome was tested by binomial logistic regression. The subgroup with unfavorable outcome had higher concentrations of CRP, NGAL, sTNFR-1 and D-dimers, but CRP and NGAL values were not statistically different between the two subgroups. The univariate logistic regression analysis of plasma biomarkers revealed that CRP, D-Dimers, NGAL, sTNFR-1 were significant predictors of unfavorable clinical outcome. In the case of D-Dimers and sTNFR-1 we noticed an increased discrimination ability (versus baseline clinical model) to classify poor functional outcome with a tendency toward statistical signification. During the acute phase of the ischemic stroke, plasma concentrations of CRP, D-Dimers and sTNFR-1 were elevated in unfavorable outcome patients. D-Dimers and sTNFR-1 were independent predictors of poor outcome at 3 months after ischemic stroke. The biochip array technology offers the possibility to simultaneously measure several parameters involved in multiple pathophysiological pathways, in a small sample volume.

Laboratory medicine in the era of precision medicine – dream or reality?

“…One of the recent challenging multiple biomarker screening (255 plasma proteins) was performed from the ARIS-TOTLE trial in order to identify novel prognostic markers for major bleeding in patients with atrial fibrillation on oral anticoagulation (20). In our population we measured a panel of five peripheral biomarkers for neuronal damage, inflammation, and fibrinolysis and we found that D-Dimers and sTNFR-1 have increased discrimination ability to classify poor functional outcome at 3 months after ischemic stroke (21).…”

Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches

“…Indeed, TNF-α’s appearance in the brain following the damage induced by ischemia is quick and has a first peak in the early hours [1–3 h] and a successive one after more than 24–36 h [ 34 , 35 ]. In the literature, some reports indicate that TNF-α represents an accurate indicator that can be useful to define the beginning of the inflammatory reaction and a helpful one for the evaluation of the patient’s outcome [ 36 ]. A rising quantity of TNF-α can be seen in patients affected by a stroke just 6–12 h following the appearance of the symptomatology [ 37 ].…”

<p>The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke</p>

“…88 The authors claim that TNF-α is a sensitive parameter determining the onset of an inflammatory response and a useful indicator for the assessment of prognosis. 65,89 An increase in the concentration of TNF-α is observed in stroke patients as soon as 6-12 hrs after the onset of symptoms. 47 An increase in TNF-α concentration within 24 and 48 hrs after a stroke has also been shown, and the observed slow decrease occurring within 72 and 144 hrs after a stroke correlates with a clinical improvement in patients in the acute phase of ischemic stroke.…”