Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research

Fast and accurate diagnosis of stroke is crucial for the immediate application of the right therapy to patients. However, rapid diagnosis is still a challenge since an ischemic stroke cannot be identified based only on clinical assessment. CT or MRI imaging is required to rule out hemorrhagic stroke since thrombolytic therapy can lead to increased intracranial bleeding and further aggravation of hemorrhagic stroke. In addition, clinical situations that imitate the signs and symptoms of stroke may also impede the rapid diagnosis and treatment of stroke victims. It is therefore of value to discover non-invasive tests that aim to quickly distinguish stroke from stroke mimics and distinguish ischemic from hemorrhagic stroke. Identifying blood biomarkers of stroke is an active area of research since their potential use is not limited to diagnosis and differentiation, but can be applied to prognosis and patient monitoring - monitoring the effectiveness of applied therapy and/or diagnose possible complications. However, their use has been limited so far not only for reasons related to patients and the disease (heterogeneity of stroke etiology, the complexity of the ischemic cascade, the impact of the blood-brain barrier (BBB) on diffusion of blood biomarkers, and difficulties in obtaining consent from stroke patients) but also for reasons that related to laboratory measurement of these biomarkers (pre-analytical and analytical issues as well as interpretation of laboratory measurements). Until today, many biomarkers have been identified, however none so far have shown sufficient sensitivity and specificity in order to be used in the clinical setting. In this review, we will focus on ischemic stroke and we aim to highlight these problems and also investigate if these are due to stroke complexity or due to our limited knowledge of pre-analytical requirements for many of these molecules and the questionable quality of the assays used.