1 Introduction

A biomarker is defined as “any substance, structure, or process that can be measured in the body or its products that influences or predicts the incidence or outcome of disease” [1, 2]. This includes disease risk and diagnosis of acute and chronic conditions in cardiovascular and cerebrovascular circulation such as heart attack and stroke.

Stroke, also known as cerebrovascular accident (CVA), is now characterized as a “brain attack,” which is both the most descriptive and realistic image of stroke. As with a heart attack, the appropriate response to a brain attack is emergency action, both by the person it strikes and the medical community. Delays in diagnosis and medical intervention beyond 4–6 h of stroke onset may contribute to clinical deterioration and disability.

As the population ages, stroke has the potential to become an even larger medical and economic burden on the healthcare system. The public misperception that nothing can be done about stroke has prevailed for too long. Recent progress in biomarker research, neuromethods, and clinical practice has contributed to advances in stroke diagnoses and treatment optimization. Additionally, in spite of the important role that brain biomarkers could have in emergency diagnosis, there currently exists no “perfect” biomarker(s) for stroke. A single blood sample collected by first responders and processed rapidly for biomarker(s) testing might help to stratify patients into main stroke groups even prior to admission to hospital.

A “perfect” molecular biomarker could assist in risk assessment, predict and distinguish the stroke from mimicking conditions, and measure disease progression. Specifically, the “perfect” molecular biomarker testing combined with other markers (functional and structural) should meet certain requirements: (1) reflect an early pathology of brain damage; (2) reveal structural impairment(s) in certain brain areas; (3) allow early assessment in biological fluids (within minutes to hours); and (4) correlate with severity of disease progression.

Functional genomics, proteomics, and molecular imaging represent robust and evolving areas of molecular biomarker research that have the potential to revolutionize the screening, diagnosis, prognosis, and prediction of disease recurrence as well as therapeutic monitoring of stroke and transient ischemic attack (TIA).

Functional markers. The primary tool available for assessing TIA or stroke is patient history and physical examination of neurological symptoms. Physicians can track changes in cerebrovascular disease by localizing the disease to specific vessels using various stroke scales. The NIH Stroke Scale defines the most employed scale in the USA that rates severity of symptoms with stroke diagnosis. The rationale for emergent patient care is to improve diagnostic certainty, obtain objective results within minutes, evaluate risks for future events, monitor the patient for recurrence or worsening symptoms, and institute personal timely needed interventions while including operative critical care.

The second biomarker approach is defining structural alterations by neuroimaging. Current clinical neuroradiological methods allow the visualization of cerebral lesions and play an important role in decision making in both diagnosis and thrombolytic treatment. Two primary diagnostic modalities are used to distinguish ischemic from hemorrhagic stroke: computed tomography (CT) and, to a lesser extent, magnetic resonance imaging (MRI). More than 90% of hospitals have access to CT scanners, enabling them to evaluate a hemorrhagic stroke within 15 min. The overall accuracy of recognition of hemorrhagic vs. ischemic stroke is 67–85%. A large proportion of hospitals have MRI capability as well. However, MRI scans require a longer time window for image-reading and cannot distinguish ischemic from hemorrhagic stroke within the first 6 h of onset. Comparison of MRI and CT showed sensitivity of 83% vs. 26%, respectively, to detect acute ischemia as well as acute and chronic hemorrhage. There still remains an option to improve diagnostic certainty of early stroke onset by combining advanced neuroimaging with key biomarkers measured in biological fluids.

The third approach is substance or biological markers and is still being researched. Efforts are being directed to finding molecular markers in diseased biological tissues and fluids, particularly the blood.