Abstract 2874: Functional Polymorphisms in Toll-like Receptor 4 Predict Worse Outcome in Acute Ischemic Stroke Patients

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jonathan R Weinstein ◽  
Juliane Schulze ◽  
Richard V Lee ◽  
Dannielle Zierath ◽  
Patricia Tanzi ◽  
...  

Background: Toll-like receptor-4 (TLR4) plays a central role in the pathophysiology of acute ischemic stroke (AIS). Specific single nucleotide polymorphisms (SNPs) in TLR4 including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile] alter immune cell responsiveness to lipopolysaccharide (LPS) and are associated with increased rates of infection. The effect of these TLR4 SNPs on outcome following AIS is unknown. Methods: Patients were prospectively enrolled after onset of AIS. Clinical and demographic data were collected and neurological outcomes assessed at 3 months. Blood was drawn at multiple time points to quantify leukocyte subsets and assess plasma levels of C-reactive protein and a panel of cytokines. Genotyping for the TLR4 SNPs was also performed on blood samples. Uni- and multivariate analyses were performed to assess associations between TLR4 SNP haplotype and (i) each laboratory parameter noted above, (ii) infection risk and (iii) stroke outcome. Results: Of the 42 patients included; 6 (14%) were heterozygous for either one or both TLR4 SNPs. Baseline characteristics were similar in patients with or without a TLR4 SNP. In analyses adjusted for both initial stroke severity and age, the presence of a TLR4 SNP was associated with increases in blood leukocytes, plasma C-reactive protein and the cytokine interleukin-1 receptor antagonist (IL-1ra). The presence of either TLR4 SNP was also associated with a trend toward increased rates of infection (adjusted odds ratio and 95% confidence interval of 8.20 and 0.826-81.5, respectively) and a decreased likelihood of favorable outcome as defined by a modified Rankin Scale score of two or less at three months from stroke onset (0.014, 0.00-0.759). Conclusions: In AIS patients, functionally significant genetic variations in TLR4 influence both rates of stroke-associated infection and neurological outcome. These data suggest a direct connection between TLR4 function and stroke pathophysiology.

Neuroreport ◽  
2014 ◽  
pp. 1 ◽  
Author(s):  
Jonathan R. Weinstein ◽  
Juliane Schulze ◽  
Richard V. Lee ◽  
Hunter Phillips ◽  
Dannielle Zierath ◽  
...  

2012 ◽  
Vol 9 (4) ◽  
pp. 252-255 ◽  
Author(s):  
K R Dewan ◽  
P V S Rana

Background There is growing evidence that inflammation plays an important role in atherogenesis. Several studies have shown that C-reactive protein (CRP), an inflammatory marker, is associated with stroke severity and outcome. But limited studies are there which show the relationship of CRP with early mortality i.e within seven days. Objective To study the association of CRP within 24 hours after acute ischemic stroke onset with severity during admission, types of ischemic stroke and outcome. Methods This cross sectional study was done including 100 consecutive cases of acute ischemic stroke admitted to Neurology center of College of Medical Sciences, Bharatpur (Chitwan), Nepal. The cases were classified as per TOAST classification and severity at admission assessed using National Institutes of Health Stroke Scale. C-reative protein (CRP) level was estimated by latex particle agglutination test. Result Thirteen percent patients expired by 7th day. In the expired group, CRP was positive in 15.3 percent, 15.3 percent and 61.5 percent in patients with lacunar, cardioembolic and large artery atherosclerotic infarction respectively (p 0.19). CRP was positive in all 7 patients (53.8%) who had expired with severe NIHS scale (p 0.004). ConclusionHigh CRP level is associated with stroke severity at admission and is an independent predictor of early seven day mortality after ischemic strokeDOI: http://dx.doi.org/10.3126/kumj.v9i4.6339 Kathmandu Univ Med J 2011;9(4):252-5 


2020 ◽  
Vol 17 ◽  
Author(s):  
Shiling Chen ◽  
Chao Pan ◽  
Ping Zhang ◽  
Yingxin Tang ◽  
Zhouping Tang

Abstract:: Acute Ischemic Stroke (AIS) is currently the most frequently reported neurological complication of Coronavirus disease 2019 (COVID-19). This article will elaborate on the clinical features of inpatients with COVID-19 and AIS and the pathophysiological mechanism of AIS under the background of COVID-19. Through a detailed search of relevant studies, we found that the incidence of AIS among COVID-19 patients varied from 0.9% to 4.6%, and AIS has been observed in many people without underlying diseases and cardiovascular risk factors as well as young people. The National Institute of Health Stroke Scale (NIHSS) score of COVID-19 patients with AIS was higher than historical AIS patients, and the proportion of large vessel occlusion (LVO) was about 64.2%. COVID-19 patients with AIS have commonly high levels of D-D dimer, fibrinogen, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), suggesting systemic hyperinflammatory and hypercoagulable state. The pooled mortality of COVID-19 patients with AIS was 38% and the mortality of LVO patients is higher (45.9%). Compared with COVID-19-negative AIS patients in the same period in 2020 and 2019, COVID- 19 patients with AIS had a worse prognosis.


2021 ◽  
Vol 10 (8) ◽  
pp. 1610
Author(s):  
Marcin Wnuk ◽  
Justyna Derbisz ◽  
Leszek Drabik ◽  
Agnieszka Slowik

Background: Previous studies on inflammatory biomarkers in acute ischemic stroke (AIS) produced divergent results. We evaluated whether C-reactive protein (CRP) and white blood cell count (WBC) measured fasting 12–24 h after intravenous thrombolysis (IVT) were associated with outcome in AIS patients without concomitant infection. Methods: The study included 352 AIS patients treated with IVT. Excluded were patients with community-acquired or nosocomial infection. Outcome was measured on discharge and 90 days after stroke onset with the modified Rankin scale (mRS) and defined as poor outcome (mRS 3–6) or death (mRS = 6). Results: Final analysis included 158 patients (median age 72 years (interquartile range 63-82), 53.2% (n = 84) women). Poor outcome on discharge and at day 90 was 3.8-fold and 5.8-fold higher for patients with CRP ≥ 8.65 mg/L (fifth quintile of CRP), respectively, compared with first quintile (<1.71 mg/L). These results remained significant after adjustment for potential confounders (odds ratio (OR) on discharge = 10.68, 95% CI: 2.54–44.83, OR at day 90 after stroke = 7.21, 95% CI: 1.44–36.00). In-hospital death was 6.3-fold higher for patients with fifth quintile of CRP as compared with first quintile and remained independent from other variables (OR = 4.79, 95% CI: 1.29–17.88). Independent predictors of 90-day mortality were WBC < 6.4 × 109 /L (OR = 5.00, 95% CI: 1.49–16.78), baseline National Institute of Health Stroke Scale (NIHSS) score (OR = 1.13 per point, 95% CI: 1.01–1.25) and bleeding brain complications (OR = 5.53, 95% CI: 1.59–19.25) but not CRP ≥ 8.65 mg/L. Conclusions: Non-infective CRP levels are an independent risk factor for poor short- and long-term outcomes and in-hospital mortality in AIS patients treated with IVT. Decreased WBC but not CRP is a predictor for 90-day mortality.


2021 ◽  
Vol 28 (5) ◽  
pp. 879
Author(s):  
Nalan Kozaci ◽  
Cafer Caliskan ◽  
Mustafa Avci ◽  
Gulsum Caliskan ◽  
Ilhan Uysal

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