Acute Stroke Biomarkers: Are We There Yet?

Abstract

Background: Distinguishing between stroke subtypes and knowing the time of stroke onset are critical in clinical practice. Thrombolysis and thrombectomy are very effective treatments in selected patients with acute ischemic stroke. Neuroimaging helps decide who should be treated and how they should be treated but is expensive, not always available and can have contraindications. These limitations contribute to the under use of these reperfusion therapies.Aim: An alternative approach in acute stroke diagnosis is to identify blood biomarkers which reflect the body's response to the damage caused by the different types of stroke. Specific blood biomarkers capable of differentiating ischemic from hemorrhagic stroke and mimics, identifying large vessel occlusion and capable of predicting stroke onset time would expedite diagnosis and increase eligibility for reperfusion therapies.Summary of Review: To date, measurements of candidate biomarkers have usually occurred beyond the time window for thrombolysis. Nevertheless, some candidate markers of brain tissue damage, particularly the highly abundant glial structural proteins like GFAP and S100β and the matrix protein MMP-9 offer promising results. Grouping of biomarkers in panels can offer additional specificity and sensitivity for ischemic stroke diagnosis. Unbiased “omics” approaches have great potential for biomarker identification because of greater gene, protein, and metabolite coverage but seem unlikely to be the detection methodology of choice because of their inherent cost.Conclusion: To date, despite the evolution of the techniques used in their evaluation, no individual candidate or multimarker panel has proven to have adequate performance for use in an acute clinical setting where decisions about an individual patient are being made. Timing of biomarker measurement, particularly early when decision making is most important, requires urgent and systematic study.

Update on Biomarkers Associated to Cardioembolic Stroke: A Narrative Review

“…In many areas of medicine, biomarkers are currently used to help to diagnose, establish prognoses, and to prescribe therapeutics to specific groups of patients that benefit the most from differentiated treatments due to having particular phenotypes [ 1 ]. Moreover, in neurology, several studies that evaluated biomarkers have been conducted in recent years, namely in the area of stroke [ 2 ]. When compared to other medical areas, the application of biomarkers to the field of cerebrovascular pathology has some obstacles: (a) the presence of the blood–brain barrier that poses difficulties and delays the release of proteins of neuronal or glial origin into the bloodstream after stroke; and (b) many of the potential serum biomarkers of cerebral ischemia and inflammation have low specificity and may also be increased in situations that can be confounded with stroke as they may present in a similar way such as acute myocardial infarction or central nervous system inflammation [ 3 ]…”

Development and Validation of a LASSO Prediction Model for Better Identification of Ischemic Stroke: A Case-Control Study in China

“…The comprehensive diagnostic efficacy of blood biomarkers has been seriously underestimated or even ignored in stroke. However, with the recent research development, their application value has been revisited ( El-Serag et al, 2014 ; Valappil et al, 2017 ; Lee et al, 2018 ; Dagonnier et al, 2021 ). Unlike univariate analysis in neuroimaging, some preliminary studies related to stroke classification have focused on models that combine blood biomarkers, showing great potential ( Misra et al, 2017 ; Makris et al, 2018 ).…”

Timely and Blood-Based Multiplex Molecular Profiling of Acute Stroke

“…Plasma molecular biomarkers, including proteins, metabolites, lipids, and nucleic acids, can be used alone or in combination (panels, scores, or indices), are the potential ideal candidates [ 30 ] to detect acute stroke, differentiate IS from HS and stroke mimics, extrapolate the infarct volume, identify the stroke cause, and predict the short/long-term outcome [ 31 ]. This would allow a substantial time gain in prehospital settings and, eventually, avoid futile transfers to comprehensive stroke centers (CSCs) [ 32 , 33 ]. Over the past years, several studies identified more than 150 putative molecular biomarkers in patients’ serum for early diagnosis and prognosis [ 16 , 33 , 34 , 35 , 36 ].…”

“…This would allow a substantial time gain in prehospital settings and, eventually, avoid futile transfers to comprehensive stroke centers (CSCs) [ 32 , 33 ]. Over the past years, several studies identified more than 150 putative molecular biomarkers in patients’ serum for early diagnosis and prognosis [ 16 , 33 , 34 , 35 , 36 ]. Despite several of these having shown great potential, there is currently no blood biomarker for clinical stroke diagnosis.…”