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Table of Contents
Year : 2021  |  Volume : 9  |  Issue : 3  |  Page : 137-138

Biomarkers in assessing the severity of stroke

Department of Neurology, NIMHANS, Bengaluru, Karnataka, India

Date of Submission31-May-2021
Date of Acceptance01-Jun-2021
Date of Web Publication16-Jul-2021

Correspondence Address:
Dr. Girish Baburao Kulkarni
Department of Neurology, Room No. B9, First Floor, Neuroscience Faculty Block, Hosur Road, NIMHANS, Bengaluru - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_57_21

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How to cite this article:
Kulkarni GB. Biomarkers in assessing the severity of stroke. APIK J Int Med 2021;9:137-8

How to cite this URL:
Kulkarni GB. Biomarkers in assessing the severity of stroke. APIK J Int Med [serial online] 2021 [cited 2022 Aug 17];9:137-8. Available from: https://www.ajim.in/text.asp?2021/9/3/137/321660

Stroke is one of the leading causes of mortality and morbidity around the world. It is classified into ischemic (about 70%–80%) and hemorrhagic (20%–30%) types. Ischemic stroke may be due to large artery atherosclerosis, cardioembolic, lacunar, due to specific causes, and cryptogenic.[1] Currently, clinicians are dependent on clinical and radiological features for diagnosis, assessing the severity and prognostication, but there is a need for simple, easily available marker for stroke like in other diseases (myocardial infarction [troponin], infection [procalcitonin], and thrombosis [D-dimer]). A biomarker is defined by the US NIH working group as “a marker or a characteristic that can be objectively measured and evaluated as an indicator of disease, health or response to treatment.”[2] It can be clinical, imaging, or blood measurements, but usually, it is meant to be a substance found in blood, body fluids, or cells.[3] The brain tissue consists of neurons, astrocytes, oligodendrocytes, microglia, and blood vessels with blood-brain barrier (BBB). Each of them may have a specific biomarker, which may be released locally into bloodstream and into cerebrospinal fluid depending on the mechanism of injury, the amount of damage, rapidity, and other associated factors.[4] The biomarkers estimation may help in screening high-risk (asymptomatic) patients, rapid stroke diagnosis, detection of possible stroke mechanisms and severity, predicting the drug response, predicting the outcome, and used as surrogate endpoints in clinical trials. Types of biomarkers in stroke include traditional proteins, novel genetic, microvesicle, and metabolites.[5]

The stroke severity is measured clinically by the National Institutes of Health Stroke Scale (NIHSS), with score ranging from 0 to 42 points. The higher the number, the greater the severity. The limitations of NIHSS are not all stroke-related impairments are captured, difficult to assess in patients in coma or intubated or aphasic, heavily weighted to left side stroke, and also depends on the evaluator. Hence, there is a need for an objective, measurable parameter for assessing the severity of stroke which can repeatable also. The well-defined biomarkers studied in stroke severity are serum calcium-binding protein (S100B), neuron-specific enolase (NSE), matrix metalloproteinase (MMP)-9, inflammatory biomarkers, C-reactive protein (CRP), and recently human carcinoembryonic antigen (CEA). S100-β is a calcium-binding peptide secreted by astrocytes. In ischemic stroke, the S100B-β reaches a maximum concentration between days 2 and 4, and the peak concentration correlates with higher NIHSS scores, infarct size, and the clinical course.[6],[7] NSE is one of the enzymes in the glycolysis pathway. It is detectable between 4 and 8 h after the onset of stroke. The peak concentration after ischemic stroke correlates with baseline NIHSS score.[7] Among the pro-inflamamtory and anti-inflammatory cytokines, serum levels of patients with ischemic stroke have shown elevation in interleukins (ILs): IL-1, IL-6, IL-8, IL-10, and IL-13. Elevated levels of pro-inflamamtory cytokines and low levels of anti-inflammatory markers are associated with severity, infarct volume, clinical worsening, and long-term outcome. The inflammatory biomarkers have been used as surrogate markers of efficacy for neuroprotective medications.[8] CRP is an acute-phase protein associated with inflammation, produced by the liver. As atherosclerosis is associated with inflammation, elevations in CRP levels have been correlated to increased risk for stroke due to it. After a stroke, CRP levels increase rapidly and its level at admission has been shown to predict mortality in tissue plasminogen activator (tPA)-treated patients, infarct volume, stroke severity, and long-term outcome.[9] MMP levels are elevated after both ischemic stroke and hemorrhagic stroke, and serial measurements of MMP-2 and MMP-9 levels demonstrate a correlation with NIHSS scores and initial and final diffusion-weighted imaging infarct volumes. The peak concentration is associated with late hemorrhagic transformation and postrecombinant tPA hemorrhage in hemorrhagic stroke, higher MMP-9 is associated with perihematomal edema.[8] Human CEA is one of the widely used tumor markers and also elevated in atherosclerotic disease involving coronary and large blood vessels in the body. In the current volume of the journal, Krishnamurthy et al.[10] have come out with an interesting study on blood levels of CEA in predicting the severity of stroke. The authors have shown that the CEA levels are significantly elevated in stroke patients compared to nonstroke controls, increasing levels are associated with more severe disease and poorer outcome. This calls for further studies on this biomarker with respect to type of ischemic stroke, radiological correlation, and outcome (assessed by modified Rankin scale at 3 months) and role of serial level measurements.

Unlike the other clinical conditions (such as myocardial infarction) where biomarkers are used in clinical practice, there is no single biomarker which is sensitive and specific for the stroke diagnosis or other aspects of the disease. The presence of the BBB may prevent the appearance of stroke biomarkers in circulation. The biomarkers level can change due to the variety of comorbid conditions or brain damage itself. There is a lack of availability of the technology and methods of estimating these biomarkers in clinical laboratories. Currently, no biomarkers have been consistently used clinically in predicting stroke severity, though CRP is sometimes ordered by the stroke clinicians in tertiary care centers for diagnosing atherosclerotic strokes.

In conclusion, stroke with its diverse etiologies and presentations challenges the researcher and clinician for improving the care of these patients and predicting the severity. With the advent of newer technology, and in the era of multilevel omics (protein, genes, and metabolites), probably, we may have single or panel of biomarker in predicating the severity and management of these patients.

  References Top

Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.  Back to cited text no. 1
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89-95.  Back to cited text no. 2
Whiteley W, Tian Y, Jickling GC. Blood biomarkers in stroke: Research and clinical practice. Int J Stroke 2012;7:435-9.  Back to cited text no. 3
Dagonnier M, Donnan GA, Davis SM, Dewey HM, Howells DW. Acute Stroke Biomarkers: Are We There Yet? Front Neurol. 2021 Feb 5;12:619721. doi: 10.3389/fneur.2021.619721. PMID: 33633673; PMCID: PMC7902038.  Back to cited text no. 4
Kim SJ, Moon GJ, Bang OY. Biomarkers for stroke. J Stroke 2013;15:27-37.  Back to cited text no. 5
Foerch C, Otto B, Singer OC, Neumann-Haefelin T, Yan B, Berkefeld J, et al. Serum S100B predicts a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke 2004;35:2160-4.  Back to cited text no. 6
Jauch EC, Lindsell C, Broderick J, Fagan SC, Tilley BC, Levine SR, et al. Association of serial biochemical markers with acute ischemic stroke: The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke 2006;37:2508-13.  Back to cited text no. 7
Maas MB, Furie KL. Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med 2009;3:363-83.  Back to cited text no. 8
Arenillas JF, Alvarez-Sabín J, Molina CA, Chacón P, Rovira A, Quintana M, et al. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke 2003;34:2463-8.  Back to cited text no. 9
Krishnamurthy V, Srinivas S, Sujatha KJ, Narayan A, Reddy M, Patted A. A study of human carcinoembryonic antigen as a biomarker for assessing the severity of stroke. APIK J Internal Med 2021;9:171-5.  Back to cited text no. 10


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