Blood Biomarkers for the Early Diagnosis of Stroke

Bustamante, Alejandro; López‐Cancio, Elena; Pich, Sara; Peñalba, Anna; Giralt, Dolors; García‐Berrocoso, Teresa; Ferrer-Costa, Carles; Gasull, Teresa; Hernández‐Pérez, María; Millán, Mònica; Rubiera, Marta; Cardona, Pedro; Cano, Luis; Quesada, Helena; Terceño, Mikel; Silva, Yolanda; Castellanos, Mar; Garcés, Moisès; Reverté, Sílvia; Ustrell, Xavier; Marés, Rafael; Baiges, Joan Josep; Serena, Joaquı́n; Rubio, Francisco; Salas, Eduardo; Dávalos, Antoni; Montaner, Joan

doi:10.1161/strokeaha.117.017076

Cited by 115 publications

(65 citation statements)

References 23 publications

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“…[ [25][26][27][28] NSE and S100B are considered as biomarkers of glial cell damage or neuronal damage in patients with stroke or injury of the CNS. [29][30][31][32][33][34][35][36][37] Increased blood concentrations of NSE and/or S100B occur after hypoxia, hemorrhage, and injury to the CNS and always indicate that the BBB has been damaged. [38,39] We obtained a positive correlation between the presence of NSE and a worse neurological status on the first day, and between S100B and a poor status on the first and 30th day of stroke, which is consistent with the observations reported by other authors.…”

Section: Discussionmentioning

confidence: 99%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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Acute cerebral ischemia triggers local and systemic immune response. The aims of this project was to assess the blood serum concentration of the markers of inflammation and markers of the blood brain barrier damage on the first day of ischemic stroke, and the mutual correlations between these marker levels. Methods Our prospective study included 138 patients with first-in-life stroke, who were analyzed according to: plasma concentration of the following markers on the first day of stroke: Il-2 and IL-6, S100B, TNF alfa, GRN, NSE, uPA, VEGF, BDNF, CRP, leucocyte and thrombocyte counts; their neurological status on the first day of stroke (NIHSS) and their functional status at 30 days following stroke (mRS). Result The study included 138 patients with mean age: 73.11 ± 11.48 [36-103]. Patients with a higher score on the NIHSS than those obtaining lower scores showed significantly higher concentrations of TNF-alpha, WBC, CRP, NSE, IL-6 and S100B. Patients with a higher score on the mRS than those obtaining lower scores showed significantly higher concentrations of WBC, CRP, GRN, IL-6, S100B. Factors with an independent influence on the neurological status on the first day of stroke were: sex, WBC, PLT, CRP, S100B and IL-6 levels. Atrial fibrillation, leukocyte count, CRP, NSA, uPA, interleukin 6 and S100B showed an independent impact on the functional status on the 30th day of stroke. Patients with symptomatic atherosclerosis of carotid/cerebral and/or coronary arteries, as compared to others, were older (p= 0.003) and had higher levels of CRP, Il-6, and S100B. In each case, the differences were statistically significant. Conclusions The concentration of Il-6 and S100B on the first day of stroke are significant for both the neurological status and the functional status in the acute period of the disease. Increased CRP and leukocyte count are associated with a worse prognosis regarding the course of acute stroke. The expression of pro-inflammatory agents and markers of blood-brain barrier damage in the acute phase of stroke is more prominent in patients with symptomatic atherosclerosis than in patients with no clinical features of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

Lasek–Bal

Jędrzejowska–Szypułka

Student

et al. 2018

Preprint

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“…Simultaneous measurement of multiple biomarkers in a single panel has been proposed, combined with recent developments in genomics and proteomics, approaches which have not yet been taken in END. However, as reported by the StrokeChip study following evaluation of an assay panel for stroke diagnosis, many biomarkers are not independent of one another and may not be significantly better than clinical judgement and radiological data [63]. Amongst investigations, which are already routinely available clinically, the results of the meta-analysis suggest that it would be reasonable to increase monitoring intensity for those acute stroke patients where venipuncture reveals a low haemoglobin or elevated glucose, glycosylated haemoglobin, urea, osmolality, CRP, ESR or leucocytes.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

Martin

Price

2018

Cerebrovasc Dis

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Background: Early neurological deterioration (END) following acute stroke is associated with poorer long-term outcomes. Identification of patients at risk could assist early monitoring and treatment decisions. This review summarised the evidence describing non-radiological biomarkers for END. Summary: Electronic searches from January 1990 to March 2017 identified studies reporting a blood/cerebrospinal fluid (CSF)/urine biomarker measurement within 24 h of acute stroke and at least 2 serial assessments of clinical neurological status (< 24 h and < 7 days). Out of 12,895 citations, 82 studies were included, mostly focusing on ischaemic stroke. Using higher neurological thresholds, the n-weighted END incidence for ischaemic stroke was 11.9% (95% CI 11.4–12.4%) and 18.6% (17.9–19.2%) for lower thresholds. Incidence decreased with advancing study publication year (Pearson r-squared 0.23 and 0.15 for higher and lower threshold studies). After classification into 3 broad categories, meta-analysis showed that biomarkers associated with increased END risk (n; fixed-effects mean difference; 95% CI) were “metabolic” (glucose [n = 9,481; 0.90 mmol/L; 0.74–1.06], glycosylated haemoglobin [n = 3,146; 0.33%; 0.19–0.46], low-density lipoprotein [n = 4,839; 0.13 mmol/L; 0.06–0.21], total cholesterol [n = 4,762; 0.21 mmol/L; 0.11–0.31], triglycerides [n = 4,820; 0.11 mmol/L; 0.06–0.17], urea [n = 1,351; 0.55 mmol/L; 0.14–0.96], decreasing albumin [n = 513; 0.33 g/dL; 0.05–0.61]); “inflammatory and excitotoxic” (plasma glutamate [n = 688; 60.13 µmol/L; 50.04–70.22], CSF glutamate [n = 369; 7.50 µmol/L; 6.76–8.23], homocysteine [n = 824; 2.15 µmol/L; 0.68–3.61], leucocytes [n = 3,766; 0.54 × 10⁹/L; 0.34–0.74], high-sensitivity C-reactive protein [n = 1,707; 3.79 mg/L; 1.23–6.35]); and “coagulation/haematological” (fibrinogen [n = 3,132; 0.32 g/L; 0.25–0.40]; decreasing haemoglobin [n = 3,586; 2.38 g/L; 0.15–4.60]). Key Messages: Declining incidence of END may represent improving care standards; however, it remains a frequent occurrence. Although statistical associations exist between biomarkers and an increased risk of END, the most promising still need prospective evaluation to determine their additional value relative to baseline radiological and clinical characteristics.

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“…However, the applicability of this to the pre-hospital setting is currently unconfirmed. There are many other candidate stroke diagnostic biomarkers [55][56][57][58][59][60][61][62][63][64][65]. Inflammatory and anti-inflammatory cytokines may have utility in diagnosing ischaemia [62][63][64][65], but may not be useful in the hyper-acute phase due to their late temporality after stroke onset [63][64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

A scoping review of pre-hospital technology to assist ambulance personnel with patient diagnosis or stratification during the emergency assessment of suspected stroke

et al. 2020

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Background: Pre-hospital identification of key subgroups within the suspected stroke population could reduce delays to emergency treatment. We aimed to identify and describe technology with existing proof of concept for diagnosis or stratification of patients in the pre-hospital setting. Methods: A systematic electronic search of published literature (from 01/01/2000 to 06/06/2019) was conducted in five bibliographic databases. Two reviewers independently assessed eligibility of studies or study protocols describing diagnostic/stratification tests (portable imaging/biomarkers) or technology facilitating diagnosis/ stratification (telemedicine) used by ambulance personnel during the assessment of suspected stroke. Eligible descriptions required use of tests or technology during the actual assessment of suspected stroke to provide information directly to ambulance personnel in the pre-hospital setting. Due to study, intervention and setting heterogeneity there was no attempt at meta-analysis.

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Blood Biomarkers for the Early Diagnosis of Stroke

Abstract: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.

Cited by 115 publications

References 23 publications

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

The importance of selected markers of inflammation and blood-brain barrier damage for short-term post-stroke prognosis

A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

A scoping review of pre-hospital technology to assist ambulance personnel with patient diagnosis or stratification during the emergency assessment of suspected stroke

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