Prediction of Functional Outcome in Patients with Acute Stroke by Measuring tRNA Derivatives

2020 ◽  
Vol 49 (6) ◽  
pp. 639-646 ◽  
Author(s):  
Tomohisa Ishida ◽  
Takashi Inoue ◽  
Kuniyasu Niizuma ◽  
Natsumi Konno ◽  
Chitose Suzuki ◽  
...  

<b><i>Background and Purpose:</i></b> Transfer RNA (tRNA) is a noncoding RNA that delivers amino acids to ribosomes for protein synthesis. tRNA is also involved in cell stress response programs. Oxidative stress induces direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine (m1A), we can detect tRNA derivatives such as conformationally changed tRNA, tRNA-derived fragments, and mononucleotide-free m1A. Based on these findings, tRNA derivatives may have potential as an early tissue damage marker. The purpose of this study was to investigate the plasma tRNA derivatives in stroke patients to clarify whether tRNA derivatives in the acute phase can detect early brain damage and then predict the functional outcome. <b><i>Methods:</i></b> Patients (75 patients with ischemic and 66 with hemorrhagic stroke) and 22 healthy volunteers were prospectively enrolled for this study between November 2016 and February 2019. Plasma samples were collected within 24 h and at 1 day, 7 days, and 30 days from the onset. Plasma tRNA derivative concentrations were measured by ELISA kit using the anti-m1A antibody. <b><i>Results:</i></b> The plasma tRNA derivative level on admission was significantly increased in both ischemic (mean ± standard error, 232.2 ± 33.1 ng/mL) and hemorrhagic stroke patients (212 ± 23.4 ng/mL) compared to the healthy volunteers (86.0 ± 7.9 ng/mL) (<i>p</i> = 0.00042 and <i>p</i> = 0.00018, respectively). The infarction size (<i>r</i> = 0.445, <i>p</i> = 0.00018) and hematoma volumes (<i>r</i> = 0.33, <i>p</i> = 0.0072) were also significantly correlated with tRNA derivatives. The concentrations of tRNA derivatives were associated with poor functional outcome (Modified Rankin Scale score 3–6 at 30 days from the onset) in patients with ischemic stroke at 7 days after onset (<i>p</i> = 0.020). <b><i>Conclusions:</i></b> Stress-induced tRNA derivatives can detect brain tissue damage, predicting functional outcome in patients with ischemic stroke.

2015 ◽  
Vol 8 (7) ◽  
pp. 671-676 ◽  
Author(s):  
Justus F Kleine ◽  
Tobias Boeckh-Behrens ◽  
Sascha Prothmann ◽  
Claus Zimmer ◽  
Thomas Liebig

BackgroundStroke in aged patients has a relatively poor prognosis, even after recanalizing therapy. Potential reasons include mechanisms that relate directly to the extent of brain tissue damage, but also age-dependent factors which are not, or only indirectly, stroke-related, such as pre-existing functional deficits, comorbidities, and post-stroke complications (eg, infections).ObjectiveTo compare early neurological course with subsequent functional outcome in older (≥80 years) and younger stroke patients in order to estimate the relative impact of these factors. Specifically, to examine if the strong age-dependency of modified Rankin Scale (mRS) outcome scores in stroke patients after mechanical thrombectomy is paralleled by a similar age dependency of early postinterventional National Institute of Health Stroke Scale (NIHSS) scores—a more specific measure of stroke-induced brain damage.MethodsWe evaluated technical results, pre- and postinterventional NIHSS scores, mid-term mRS scores and early and overall mortality and their relation to age in 125 patients, 40 of them ≥80 years, with acute middle cerebral artery occlusion, treated by mechanical thrombectomy.ResultsTechnical success, pre- and postinterventional NIHSS scores and early mortality were age-independent. Early neurological improvement depended on successful recanalization, but not on age. Nevertheless, good mRS outcome (mRS 0–2) was much rarer, and overall mortality almost threefold higher in aged patients.ConclusionsOlder patients exhibit a similar early neurological course and responsiveness to mechanical thrombectomy as younger patients, but this is not reflected in mid-term functional outcome scores. This indicates that post-stroke complications and other factors that are not, or only indirectly, related to the brain tissue damage induced by the incident stroke have a dominant role in their poor prognosis.


Author(s):  
Wouter B L van den Bossche ◽  
Arnaud J P E Vincent ◽  
Cristina Teodosio ◽  
Jeroen Koets ◽  
Aladdin Taha ◽  
...  

Abstract Diagnosis and monitoring of primary brain tumours, brain metastasis and acute ischemic stroke all require invasive, burdensome and costly diagnostics, frequently lacking adequate sensitivity, particularly during disease monitoring. Monocytes are known to migrate to damaged tissues, where they act as tissue macrophages, continuously scavenging, phagocytizing, and digesting apoptotic cells and other tissue debris. We hypothesize that upon completion of their tissue-cleaning task, these tissue macrophages might migrate via the lymph system to the bloodstream, where they can be detected and evaluated for their phagolysosomal contents. We discovered a blood monocyte subpopulation carrying the brain-specific glial fibrillary acidic protein (GFAP) in glioma patients and in patients with brain metastasis and evaluated the diagnostic potential of this finding. Blood samples were collected in a cross-sectional study before or during surgery from adult patients with brain lesions suspected of glioma. Together with blood samples from healthy controls, these samples were flow cytometrically evaluated for intracellular GFAP in monocyte subsets. Acute ischemic stroke patients were tested at multiple time points after onset to evaluate the presence of GFAP-carrying monocytes in other forms of brain-tissue damage. Clinical data was collected retrospectively. High-grade gliomas (N = 145), brain metastasis (N = 21) and large stroke patients (&gt;100cm3)(N = 3 vs. 6; multiple time points) had significantly increased frequencies of GFAP+CD16+ monocytes compared to healthy controls. Based on both a training and validation set, a cut-off value of 0.6% GFAP+CD16+ monocytes was established, with 81% sensitivity (95%CI 75%-87%) and 85% specificity (95%CI 80%-90%) for brain lesion detection. Acute ischemic strokes of &gt; 100 cm3 reached &gt;0.6% of GFAP+CD16+ monocytes within the first 2-8 hours after hospitalisation and subsided within 48 hours. Glioblastoma patients with &gt;20% GFAP+CD16+ non-classical monocytes had a significantly shorter median overall survival (8.1 vs 12.1 months). Our results and the available literature, support the hypothesis of a tissue-origin of these GFAP-carrying monocytes. Blood monocytes carrying GFAP have a high sensitivity and specificity for detection of brain lesions and for glioblastoma patients with a decreased overall survival. Furthermore, their very rapid response to acute tissue damage identifies large areas of ischemic tissue damage within 8 hours after an ischemic event. These studies are the first to report the clinical applicability for brain tissue damage detection through a minimal invasive diagnostic method, based on blood monocytes and not serum markers, with direct consequences for disease monitoring in future (therapeutic) studies and clinical decision making in glioma and acute ischemic stroke patients.


e-CliniC ◽  
2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Glen Y. C. R. Kabi ◽  
Rizal Tumewah ◽  
Mieke A. H. N. Kembuan

Abstract: Ischemic stroke is a clinical sign of dysfunction or brain tissue damage caused by lack of blood flow to the brain that disrupts the need for blood and oxygen to the brain. WHO defines stroke as a rapidly developing clinical signs of focal brain due to interference (or global) with symptoms - that last for 24 hours or more- and can cause death without any other obvious cause other than vascular. This study aimed to obtain an overview of risk factors in ischemic stroke patients in the Inpatient Neurology Department of Prof. Dr. R. D. Kandou Hospital Manado period July 2012 - June 2013. Data were taken by collecting data of ischemic stroke patients medical records. There were 60 patients during that period. Patients affected by stroke were aged between 51 - 65 years and had histories of hypertension.Keywords: risk factors, ischemic stroke.Abstrak: Stroke iskemik adalah tanda klinis disfungsi atau kerusakan jaringan otak yang disebabkan kurangnya aliran darah ke otak sehingga mengganggu kebutuhan darah dan oksigen di otak. WHO mendefiniskan stroke merupakan suatu tanda klinis yang berkembang cepat akibat gangguan otak fokal (atau global) dengan gejala - gejala yang berlangsung selama 24 jam atau lebih dan dapat menyebabkan kematian tanpa adanya penyebab lain yang jelas selain vaskuler. Penelitian ini bertujuan untuk mendapatkan gambaran tentang faktor resiko pada pasien stroke iskemik di rawat inap Neurologi RSUP Prof. Dr. R. D. Kandou Manado periode Juli 2012 - Juni 2013. Penelitian dilakukan dengan cara mengumpulkan data pasien yang terkena stroke iskemik di bagian rekam medik RSUP Prof. Dr. R. D. Kandou Manado. Didapatkan 60 pasiem selama periode Juli 2012 – Juni 2013. Berdasarkan hasil yang didapat maka disimpulkan bahwa pasien yang sering terkena stroke adalah pasien yang berumur antara 51-65 tahun, dan pasien yang memiliki riwayat hipertensi.Kata kunci: faktor risiko, stroke iskemik


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tae-Jin Song ◽  
Jinkwon Kim ◽  
Dongbeom Song ◽  
Yong-Jae Kim ◽  
Hyo Suk Nam ◽  
...  

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p<0.1), multiple CMBs (≥5) were the independent predictor for all-cause, cardiovascular and ischemic stroke mortalities. The strictly lobar CMBs were associated with hemorrhagic stroke mortality in multivariate Cox regression analysis (HR 4.776, p=0.032) (Figure 1). Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.


2018 ◽  
Vol 243 (15-16) ◽  
pp. 1207-1211 ◽  
Author(s):  
Martin Pedard ◽  
Céline Brenière ◽  
Nicolas Pernet ◽  
Catherine Vergely ◽  
Yannick Béjot ◽  
...  

Stroke outcome is dependent on brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity. As peripheral blood mononuclear cells (PBMC) contain BDNF, diapedesis of these cells might be followed by BDNF delivery to the ischemic brain. To test this hypothesis, we investigated the association between BDNF levels in PBMC and functional outcome in patients with ischemic stroke. BDNF was measured in PBMC that were isolated from ischemic stroke patients ( n = 40) just before (day 0) and after (days 1 and 3) fibrinolysis. Three months after stroke, patients were stratified using the modified Rankin Scale (mRS) according to the unfavorable (mRS scores 3–6) and favorable (mRS scores 0–2) functional outcome. We used univariate and multivariate logistic regressions to assess the relationship between BDNF levels in PBMC and functional outcome. BDNF levels in PBMC decreased from day 0 to day 3 in patients with unfavorable outcome, while they remained stable in patients with favorable outcome. Patients with favorable outcome exhibited at day 3 higher PBMC-BDNF levels than patients with unfavorable outcome and the levels were associated with good outcome (odd ratio: 12.0; 95% confidence interval, 1.4–106.2, P = 0.023). PBMC-BDNF levels remained a predictor of stroke outcome after adjusting from cardiovascular risk, interval between admission and fibrinolysis, stroke severity from hospital admission to discharge, lymphocytes count, neutrophils/lymphocytes ratio at admission. Favorable functional outcome in ischemic stroke patients that benefited from fibrinolysis was predicted by a high BDNF level in PBMC, suggesting that PBMC might serve as a cellular vector to deliver BDNF to the ischemic brain. Impact statement There are a great number of arguments suggesting that BDNF could be involved in stroke recovery dependent of neuroplasticity. Methods that can enhance BDNF levels in the ischemic brain could therefore have great clinical value. Peripheral blood mononuclear cells (PBMC) that contain BDNF and infiltrate early and sustainably the ischemic brain might be used as a cellular vector to deliver BDNF to the ischemic brain and consequently promote recovery. This work is important in this field to show if this BDNF derived from BDNF could exert a positive action on stroke recovery. Our main results showed that a high BDNF level at day 3 after hospital admission was associated with a 12.4 fold increase in favorable outcome after adjusting for still recognized prognostic markers. The new information in this field is this finding identifies PBMC as an attractive cellular vector to deliver BDNF to the ischemic brain.


Author(s):  
H. M. Eldeeb ◽  
D. H. Elsalamawy ◽  
A. M. Elabd ◽  
H. S. Abdelraheem

Abstract Background About 6.2 million individuals worldwide and approximately 200 Egyptians/100,000 citizens have cerebrovascular stroke annually, and only less than 1% of stroke patients received intravenous (IV) thrombolysis in 2014. Outcome of the ischemic stroke after IV thrombolysis varies, and there is lack of data about the predicting factors that contributes to the outcome of ischemic strokes after IV thrombolysis in Egypt. Objective The aim of this work is to study the predictors of the functional outcome of ischemic cerebrovascular stroke after IV thrombolysis in Egyptian patients. Patients and methods This is a prospective study that includes acute ischemic stroke patients who received IV thrombolysis at the Alexandria University Hospital during the year from February 2017 to February 2018, and they were evaluated initially by Rapid Arterial Occlusion Evaluation (RACE) scale and followed-up serially for 6 months after thrombolysis using the National Institutes of Health Stroke Scale (NIHSS) and modified ranking score (mRS). Results Forty-five patients are included; 56% had favorable functional outcome (mRS 0–2) after 6 months, 68% had ≥ 4 points improvement in NIHSS after 6 months, and 13% had hemorrhagic conversion with 18% mortality rate. High initial RACE scale and long hospital stay are associated with poor functional outcome 6 months after thrombolysis. Conclusion Stroke severity demonstrated by high initial RACE and the duration of hospital stay are the two most significant predictors with an impact on the functional outcome of ischemic cerebrovascular stroke after thrombolysis.


2020 ◽  
Vol 1 (2) ◽  
pp. 49
Author(s):  
Hijriyah Putri Tarmizi Hasibuan ◽  
Isra Thristy

Background: Stroke is the second largest cause of death in the world. Stroke is classified based on its etiology as ischemic stroke and hemorrhagic stroke. Most large-scale studies on the risk of total cholesterol and triglyceride levels in stroke are not distinguished between ischemic and hemorrhagic strokes. Purposes: The purpose of this study was to determine the comparison of triglyceride and total cholesterol levels in ischemic stroke patients with hemorrhagic stroke. Method: Descriptive analytic study using medical records of patients at Medan Haji General Hospital in 2018-2019. The number of ischemic stroke patients is 28 patients and hemorrhagic stroke 28 patients with a total sample of 56 patients. Results: In ischemic stroke patients, the average value of triglyceride levels was 144.75 mg/dL and the average value of total cholesterol was 250.93 mg/dL. In hemorrhagic stroke patients, the average value of triglyceride levels is 126.93 mg/dL and the average total cholesterol level is 174.25 mg/dL. Conclusion: From this study we found a significant difference in total cholesterol between ischemic and hemorrhagic strokes. No significant difference was found in triglycerides between ischemic and hemorrhagic strokes.


2019 ◽  
Author(s):  
Leah Wormack ◽  
Brice Blum ◽  
Benjamin Bailes ◽  
Thomas Nathaniel

Abstract Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.


2009 ◽  
Vol 32 (2) ◽  
pp. 151 ◽  
Author(s):  
Ning Wang ◽  
Dawei Qiao ◽  
Weijun Tong ◽  
Fengshan Zhang ◽  
Zhong Ju ◽  
...  

Purpose: There is still controversy about the association between admission blood glucose concentration and outcome of acute stroke. We studied the association between admission blood glucose and in-hospital death / dependency among acute stroke patients in Inner Mongolia, China. Methods: 2,178 acute ischemic and 1,760 hemorrhagic stroke patients in six hospitals were included in the study. Blood glucose and other study variables were collected within the first 24-hr of hospital admission. Clinical outcomes were evaluated by neurologists during hospitalization. The associations between admission blood glucose and the risk of in-hospital death/dependency were analyzed using a multiple logistic model. Results: There were associations between admission blood glucose and in-hospital death/dependency among patients with acute ischemic or hemorrhagic stroke. Compared with patients with blood glucose < 6.1mmol/L, multivariate-adjusted odds ratio (95% confidence interval) of death/dependency were 0.53 (0.23, 1.27), 2.22 (1.21, 4.11), 1.92 (1.12, 3.33) and 1.91 (1.00, 3.64) for ischemic stroke patients, and 0.93 (0.44, 1.96), 1.42 (0.65, 3.10), 1.98 (1.10, 3.55) and 2.93 (1.40, 6.11) for hemorrhagic stroke patients, with blood glucose 6.1-6.9, 7.0-7.7, 7.8-11.0 and ?11.1mmol/L, respectively. Conclusion: Increased admission blood glucose was associated with death/dependency among patients with acute hemorrhagic and ischemic stroke.


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