Biomarker panels in ischemic stroke.

B iomarkers have been sought to improve the diagnosis of stroke and determine the cause of stroke. In acute settings distinguishing ischemic stroke from other neurological diseases can be challenging, particularly when symptoms are mild. Determining the cause of stroke can also be challenging and frequently remains unclear or even unknown based on current diagnostic investigations and classification features. Correct diagnosis of ischemic stroke and its causes is essential to optimally treat and prevent stroke. Just as neuroimaging, cardiac evaluation and arterial imaging are used in the diagnosis of stroke and determining its causes, molecular features in the form of proteins, RNA, metabolites, lipids, and other biomarkers may also have utility. Biomarkers are currently used in stroke. In the American Heart Association/American Stroke Association stroke prevention guidelines, class Ia and IIb recommendations are made on the use of low-density lipoprotein-cholesterol and hemoglobin A1c (HgA1c). 1 Likewise, in the American College of Cardiology/ American Heart Association cardiovascular disease risk assessment guidelines, class IIa and IIb recommendations are made for HgA1c, C-reactive protein, lipoprotein-associated phospho-lipase A2, and urinary albumin excretion. 2,3 Other biomarkers have been well studied in stroke including natriuretic peptides, glial fibrillary acidic protein, S100b, neuron-specific enolase, myelin basic protein, interleukin-6, matrix metalloproteinase (MMP)-9, D-dimer, and fibrinogen. Despite considerable effort, a troponin-like biomarker to aid in the diagnosis of stroke has remained elusive. The reasons for this may relate in part to the fact that stroke is a heterogeneous disease with variability in infarct size, location, and cause. The blood–brain barrier has also been suggested to impede release of markers specific to brain injury (eg, neuron-specific enolase, glial fibrillary acidic protein, S100b). In addition, many biomarkers associated with ischemic stroke are not disease specific and have been associated with other acute brain injuries including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury. Given the heterogeneity in ischemic stroke, a single bio-marker may not be able to sufficiently reflect the underlying complexity. This has kindled interest in the use of biomarker panels. A biomarker panel is a group of markers that reflect different pathophysiological processes of a disease. In stroke such markers might provide information about atherosclerosis, thrombus formation, inflammation, oxidative stress, endothelial injury, blood–brain barrier disruption, and cerebral ischemia. A common approach to improve classification is the use of multiple markers. For example, in the classification of fruit an orange can best be distinguished from other produce when multiple features …