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

Abstract

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.

Acute in‐hospital blood pressure variability predicts early neurological deterioration in acute minor stroke or transient ischemic attack with steno‐occlusive arterial disease

“…To prove the association of BPV and END, we adopted a definition of END as a ≥1‐point increase in NIHSS score during the first 72 hours after admission. And, the rate of END was 32.5% in this study, which was consistent with the rates in previous studies . And also, our findings were similar to that in the Chungs' study .…”

“…And, the rate of END was 32.5% in this study, which was consistent with the rates in previous studies. [4][5][6][7][8][9][10] And also, our findings were similar to that in the Chungs' study. 16 Both studies suggested that the acute in-hospital BPV was strongly associated with the risk of having a END.…”

“…Therefore, it is of great importance to identify factors associated with END in patients with acute minor stroke or TIA due to steno‐occlusive arterial disease. Based on the previous studies, several clinical and biological factors, such as older age, the initial neurological severity, diabetes mellitus, and blood pressure, might influent the development of END in patients with general ischemic stroke . To our best known, few studies focus on patients with acute minor stroke or TIA due to steno‐occlusive arterial disease.…”

“…Based on the previous studies, several clinical and biological factors, such as older age, the initial neurological severity, diabetes mellitus, and blood pressure, might influent the development of END in patients with general ischemic stroke. [8][9][10][11] To our best known, few studies focus on patients with acute minor stroke or TIA due to steno-occlusive arterial disease.…”

The association between high-sensitivity C-reactive protein at admission and progressive motor deficits in patients with penetrating artery infarctions

“…The influence of hs-CRP on ischemic stroke has been well established, and hs-CRP has been reported as a predictor of disease severity, prognosis and mortality in patients with ischemic stroke [19, 29]. Furthermore, high plasma hs-CRP levels are associated with clinical complications following acute ischemic stroke [18, 30] PMD, which may result in severe morbidity, commonly occurs in patients with PAI during the acute stage. This is the first study to explore the relationship between hs-CRP and PMD in patients with penetrating artery ischemic stroke.…”