Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury

Neurology ◽  
2020 ◽  
Vol 94 (7) ◽  
pp. e667-e677 ◽  
Author(s):  
Chuanjie Wu ◽  
Fang Xue ◽  
Yajun Lian ◽  
Jing Zhang ◽  
Di Wu ◽  
...  

ObjectiveTo investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume.MethodsThis cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score <6.ResultsPlasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 μmol/L; p < 0.001). Every 1–µmol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04–1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41–2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 µmol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748–0.839; p < 0.001), and the optimal cutoff value was 4.95 μmol/L. The sensitivity and specificity of TMAO levels ≥4.95 μmol/L for moderate to severe stroke were 70.2% and 79.9%, respectively.ConclusionsPatients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Esteban Cheng-Ching ◽  
Russell Cerejo ◽  
Ken Uchino ◽  
Muhammad S Hussain ◽  
Gabor Toth

Background and purpose Large vessel occlusion (LVO) in acute ischemic stroke has been reported to be an independent predictor of unfavorable clinical outcome. However, the prognosis and optimal treatment of patients with only mild neurologic deficits due to LVO are not known. Methods We performed a retrospective chart review from a database of stroke patients admitted to our large academic medical center between July 1, 2010 and June 30 , 2011. Inclusion criteria were acute stroke or TIA, presentation within 9 hours from symptom onset, large vessel occlusion as a culprit of ischemic symptoms, and mild stroke severity with initial NIH Stroke Scale (NIHSS) score <8. Results We identified 59 patients with mild ischemic stroke or TIA, who were evaluated within 9 hours from onset. Of these, 13 (22%) had culprit large vessel occlusions. Five were female, 1 had diabetes, 12 had hypertension, 7 had hyperlipidemia, 2 had atrial fibrillation and 7 were smokers. The median NIHSS score was 5. The location of arterial occlusions were 5 in M1 segment of the middle cerebral artery (MCA), 6 in M2 segment of MCA, 1 each in posterior cerebral and vertebral arteries. Two patients received acute therapy, 1 with intravenous thrombolysis and 1 with endovascular therapy. Reasons for withholding thrombolytic therapy were time window in 8, mild stroke severity in 2, and atypical presentations in 2. Reasons for withholding acute endovascular therapy were mild stroke severity in 7, imaging finding in 2, technical considerations in 2, and lack of consent in 1. From hospital admission to discharge, 10 (77%) patients had symptom improvement, 2 had worsening, and one was unchanged. At 30 days, 5 (38%) had good outcome with a modified Rankin Scale (mRS) of 0-1. Three (23%) had mRS of 2, one (8%) patient had mRS of 3. Outcomes for 4 patients were unknown. Conclusions A significant proportion of patients presenting with mild ischemic symptoms has large vessel occlusion. Acute treatment in this population is frequently withheld due to mild severity or thrombolytic time window. Despite mild symptoms at presentation, some patients are left with moderate disability. Optimal treatment options for this population should be further evaluated in a larger group of patients.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 861
Author(s):  
Rikke B. Hansen ◽  
Cathrine C. H. Laursen ◽  
Niala Nawaz ◽  
Jonna S. Madsen ◽  
Helle H. Nielsen ◽  
...  

Tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2) have been found in brain parenchyma of stroke patients, and plasma levels are increased in the acute phase of stroke. We evaluated associations between TNFR1 and TNFR2 plasma levels and stroke severity, infarct size, and functional outcome. Furthermore, we examined cellular expression of TNFR1 and TNFR2 on leukocyte subpopulations to explore the origin of the increased receptor levels. Blood samples were taken from 33 acute ischemic stroke patients and 10 healthy controls. TNFR1 and TNFR2 plasma concentrations were measured and correlated against the Scandinavian Stroke Scale at admission, infarct volume, and the modified Rankin Scale score three months after stroke onset. Classical, intermediate, and non-classical monocytes as well as neutrophils were purified, and cellular expression of TNFR1 and TNFR2 was examined using flow cytometry. TNFR1 and TNFR2 plasma levels were both increased after ischemic stroke, but we found no correlation with patient outcome measurements. Compared to healthy controls, ischemic stroke patients had decreased non-classical monocyte and neutrophil populations expressing TNFR1 and increased neutrophils expressing TNFR2, and decreased non-classical populations co-expressing both TNFR1 and TNFR2. This study supports the hypothesis of an acute immunological response orchestrated by the peripheral immune system following an ischemic stroke. However, the origin of the increased TNFR1 and TNFR2 plasma levels could not be clearly linked to peripheral monocytes or neutrophils. Future studies are needed and will help clarify the potential role as treatment target.


2010 ◽  
Vol 56 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Raf Brouns ◽  
Bart De Vil ◽  
Patrick Cras ◽  
Didier De Surgeloose ◽  
Peter Mariën ◽  
...  

Abstract Background: Ischemic injury to the central nervous system causes cellular activation and disintegration, leading to release of cell-type–specific proteins into the cerebrospinal fluid (CSF). We investigated CSF concentrations of myelin basic protein (MBP), glial fibrillary astrocytic protein (GFAP), the calcium-binding protein S100B, and neuron-specific enolase (NSE) in acute ischemic stroke patients and their relation to initial stroke severity, stroke location, and long-term stroke outcome. Methods: CSF concentrations of MBP, GFAP, S100B, and NSE were assessed in 89 stroke patients on admission (mean 8.7 h after stroke onset) and in 35 controls. We evaluated the relation between CSF concentrations and (a) stroke severity (NIH Stroke Scale [NIHSS] score on admission, infarct volume), (b) stroke location, and (c) stroke outcome (modified Rankin Scale [mRS] score at month 3). Results: MBP concentration was significantly higher in subcortical than in cortical infarcts (median MBP, 1.18 vs 0.66 μg/L, P &lt; 0.001). GFAP and S100B concentrations correlated with the NIHSS score on admission (GFAP, R = 0.35, P = 0.001; S100B, R = 0.29, P = 0.006), infarct volume (GFAP, R = 0.34, P = 0.001; S100B, R = 0.28, P = 0.008), and mRS score at month 3 (R = 0.42, P &lt; 0.001 and R = 0.28, P = 0.007). Concentrations of NSE did not correlate with stroke characteristics. Conclusions: MBP, GFAP, S100B, and NSE display relevant differences in cellular and subcellular origins, which are reflected in their relation to stroke characteristics. MBP is a marker for infarct location. GFAP and S100B correlate with stroke severity and outcome.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Manuel Murie-Fernández ◽  
Mercedes Molleda Marzo

Background. Improving our knowledge about the impact of restorative therapies employed in the rehabilitation of a stroke patient may help guide practitioners in prescribing treatment regimen that may lead to better post-stroke recovery and quality of life. Aims. To evaluate the neurological and functional recovery for 3 months after an acute ischemic stroke occurred within previous 3 months. To determine predictors of recovery. Design. Prospective observational registry. Population. Patients having suffered acute moderate to severe ischemic stroke of moderate to severe intensity within the previous 3 months with National Institutes of Health Stroke Scale (NIHSS) score from 10 to 20, 24 hours after arrival at emergency room (ER). Methods. All prespecified variables (sociodemographic and clinical data, lifestyle recommendations, rehabilitation prescription, and neurological assessments) were assessed at three visits, i.e., baseline (D0), one month (M1), and three months (M3). Results. Out of 143 recruited patients, 131 could be analysed at study entry within 3 months after stroke onset with a mean acute NIHSS score of 14.05, decreased to 10.8 at study baseline. Study sample was aged 64.9±13.8 years, with 49.2% of women. Neurorehabilitation treatment was applied to 9 of 10 patients from the acute phase and for three months with different intensities depending on the centre. A large proportion of patients recovered from severe dependency on activities of daily living (ADL) at D0 to a mild or moderate disability requiring some help at M3: mean NIHSS=10.8 to 5.7; median modified Rankin Scale mRS=4 to 3; Barthel index BI=40 to 70; all p values<0.001. Multivariate analyses integrating other regression variables showed a trend in favour of rehabilitation and revascularization therapies on recovery although did not reach statistical significance and that the positive predictors of recovery improvement were baseline BI score, time to treatment, and dietary supplement MLC901 (NurAiD™II). A larger percentage of patients with more severe stroke (NIHSS>14) who received MLC901 showed above median improvements on mRS compared to control group at M1 (71.4% vs. 29.4%; p=0.032) and M3 (85.7% vs. 50%; p=0.058). Older subjects and women tend to have less improvement by M3. Conclusions. Our study in patients with moderate to severe stroke shows overall recovery on neurological and functional assessments during the 3 months of study observation. Apart from demonstrating traditional “non-modifiable” predictors of outcome after stroke, like age, sex, and stroke severity, we also detected association between the use of dietary supplement MLC901 and recovery.


2018 ◽  
Vol 16 (12) ◽  
pp. 931-941
Author(s):  
Orapen SUKHAVULLI ◽  
Siriorn SINDHU ◽  
Wanpen PINYOPASSAKUL ◽  
Chukiat VIWATWONGKASEM

The purposes of this cross-sectional descriptive study were to describe early neurological recovery in patients with acute ischemic stroke and to identify the statistical predictors of early neurological recovery at 24 h and 3 days after admission. A purposive random sampling was employed to recruit 220 AIS patients from 8 hospitals in the southern region of Thailand from January to May 2016, and the data was analyzed by using multivariate logistic regression analysis. The results revealed that moderate and severe stroke severity decreased neurological recovery at 24 h (OR = .095, p < .001, and OR = .126, p < .01, respectively), compared with mild stroke severity. In addition, onset time to rt-PA within 3 h and 3.0 - 4.5 h increased the neurological recovery at 24 h (OR = 22.22, P < .001, and OR = 17.28, P < .01, respectively), compared with those who did not receive rt-PA treatment. Lastly, age > 80 years decreased neurological recovery at 24 h after admission (OR=.361, P < .05). Neurological recovery at 3 days showed that moderate and severe stroke severity decreased neurological recovery (OR = .10, p < .001, and OR = .09, p < .001, respectively), compared with mild stroke severity. Stroke patients who had onset time to rt-PA within 3 h and within 3.0 - 4.5 h increased neurological recovery at 3 days (OR=16.95, P < .05, and OR = 14.43, P < .01, respectively), compared with those who did not receive rt-PA treatment. The findings of this study show that stroke severity and onset time to rt-PA influence early neurological recovery in AIS patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Fang Yu ◽  
Xi Li ◽  
Xianjing Feng ◽  
Minping Wei ◽  
Yunfang Luo ◽  
...  

Background: To discover novel metabolic biomarkers of ischemic stroke (IS), we carried out a two-stage metabolomic profiling of IS patients and healthy controls using untargeted and targeted metabolomic approaches.Methods: We applied untargeted liquid chromatography-mass spectrometry (LC-MS) to detect the plasma metabolomic profiles of 150 acute IS patients and 50 healthy controls. The candidate differential microbiota-derived metabolite phenylacetylglutamine (PAGln) was validated in 751 patients with IS and 200 healthy controls. We evaluated the associations between PAGln levels and the severity and functional outcomes of patients with IS. Clinical mild stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score 0–5, and moderate-severe stroke as NIHSS score &gt;5. A favorable outcome at 3 months after IS was defined as the modified Rankin Scale (mRS) score 0–2, and unfavorable outcome as mRS score 3–6.Results: In untargeted metabolomic analysis, we detected 120 differential metabolites between patients with IS and healthy controls. Significantly altered metabolic pathways were purine metabolism, TCA cycle, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. Elevated plasma PAGln levels in IS patients, compared with healthy controls, were observed in untargeted LC-MS analysis and confirmed by targeted quantification (median 2.0 vs. 1.0 μmol/L; p &lt; 0.001). Patients with moderate-severe stroke symptoms and unfavorable short-term outcomes also had higher levels of PAGln both in discovery and validation stage. After adjusting for potential confounders, high PAGln levels were independently associated with IS (OR = 3.183, 95% CI 1.671–6.066 for the middle tertile and OR = 9.362, 95% CI 3.797–23.083 for the highest tertile, compared with the lowest tertile) and the risk of unfavorable short-term outcomes (OR = 2.286, 95% CI 1.188–4.401 for the highest tertile).Conclusions: IS patients had higher plasma levels of PAGln than healthy controls. PAGln might be a potential biomarker for IS and unfavorable functional outcomes in patients with IS.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
H. B Brouwers ◽  
Svetlana Lorenzano ◽  
Lyndsey H Starks ◽  
David M Greer ◽  
Steven K Feske ◽  
...  

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1866 ◽  
Author(s):  
Yu-Chin Su ◽  
Kuo-Feng Huang ◽  
Fu-Yi Yang ◽  
Shinn-Kuang Lin

Background. Cardiac morbidities account for 20% of deaths after ischemic stroke and is the second commonest cause of death in acute stroke population. Elevation of cardiac troponin has been regarded as a prognostic biomarker of poor outcome in patients with acute stroke.Methods. This retrospective study enrolled 871 patients with acute ischemic stroke from August 2010 to March 2015. Data included vital signs, laboratory parameters collected in the emergency department, and clinical features during hospitalization. National Institutes of Health Stroke Scale (NIHSS), Barthel index, and modified Rankin Scale (mRS) were used to assess stroke severity and outcome.Results.Elevated troponin I (TnI) > 0.01 µg/L was observed in 146 (16.8%) patients. Comparing to patients with normal TnI, patients with elevated TnI were older (median age 77.6 years vs. 73.8 years), had higher median heart rates (80 bpm vs. 78 bpm), higher median white blood cells (8.40 vs. 7.50 1,000/m3) and creatinine levels (1.40 mg/dL vs. 1.10 mg/dL), lower median hemoglobin (13.0 g/dL vs. 13.7 g/dL) and hematocrit (39% vs. 40%) levels, higher median NIHSS scores on admission (11 vs. 4) and at discharge (8 vs. 3), higher median mRS scores (4 vs3) but lower Barthel index scores (20 vs. 75) at discharge (p< 0.001). Multivariate analysis revealed that age ≥ 76 years (OR 2.25, CI [1.59–3.18]), heart rate ≥ 82 bpm (OR 1.47, CI [1.05–2.05]), evidence of clinical deterioration (OR 9.45, CI [4.27–20.94]), NIHSS score ≥ 12 on admission (OR 19.52, CI [9.59–39.73]), and abnormal TnI (OR 1.98, CI [1.18–3.33]) were associated with poor outcome. Significant factors for in-hospital mortality included male gender (OR 3.69, CI [1.45–9.44]), evidence of clinical deterioration (OR 10.78, CI [4.59–25.33]), NIHSS score ≥ 12 on admission (OR 8.08, CI [3.04–21.48]), and elevated TnI level (OR 5.59, CI [2.36–13.27]).C-statistics revealed that abnormal TnI improved the predictive power of both poor outcome and in-hospital mortality. Addition of TnI > 0.01 ug/L or TnI > 0.1 ug/L to the model-fitting significantly improvedc-statistics for in-hospital mortality from 0.887 to 0.926 (p= 0.019) and 0.927 (p= 0.028), respectively.Discussion.Elevation of TnI during acute stroke is a strong independent predictor for both poor outcome and in-hospital mortality. Careful investigation of possible concomitant cardiac disorders is warranted for patients with abnormal troponin levels.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ki Woong Nam ◽  
Chi Kyung Kim ◽  
Tae Jung Kim ◽  
Sang Joon An ◽  
Kyungmi Oh ◽  
...  

Background: Stroke in cancer patients is not rare, but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. Methods: We included 210 ischemic stroke patients with active cancer. The data of 30-day mortality were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. Results: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS score, D-dimer levels, CRP levels, frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. Initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independently from D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease of D-dimer levels, despite treatment, while the survivor group showed opposite responses. Conclusions: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.


2018 ◽  
Vol 39 (11) ◽  
pp. 2277-2285 ◽  
Author(s):  
Angela SM Salinet ◽  
Nathália CC Silva ◽  
Juliana Caldas ◽  
Daniel S de Azevedo ◽  
Marcelo de-Lima-Oliveira ◽  
...  

We aimed to assess cerebral autoregulation (CA) and neurovascular coupling (NVC) in stroke patients of differing severity comparing responses to healthy controls and explore the association between CA and NVC with functional outcome. Patients admitted with middle cerebral artery (MCA) stroke and healthy controls were recruited. Stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS) scores: ≤4 mild, 5–15 moderate and ≥16 severe. Transcranial Doppler ultrasound and Finometer recorded MCA cerebral blood flow velocity (CBFv) and blood pressure, respectively, over 5 min baseline and 1 min passive movement of the elbow to calculate the autoregulation index (ARI) and CBFv amplitude responses to movement. All participants were followed up for three months. A total of 87 participants enrolled in the study, including 15 mild, 27 moderate and 13 severe stroke patients, and 32 control subjects. ARI was lower in the affected hemisphere (AH) of moderate and severe stroke groups. Decreased NVC was seen bilaterally in all stroke groups. CA and NVC correlated with stroke severity and functional outcome. CBFv regulation is significantly impaired in acute stroke, and further compromised with increasing stroke severity. Preserved CA and NVC in the acute period were associated with improved three-month functional outcome.


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