Stroke最新文献

Background: We aimed to develop and validate a protein risk score for ischemic stroke (IS) risk prediction and to compare its predictive capability with IS clinical risk factors and IS polygenic risk score.

Methods: The prospective cohort study included 53 029 participants from UKB-PPP (UK Biobank Pharmaceutical Proteomics Project). IS protein risk score was calculated as the weighted sum of proteins selected by the least absolute shrinkage and selection operator regression. The discrimination ability of models was assessed by C statistic. IS risk factors included age, sex, smoking, waist-to-hip ratio, antihypertensive medication use, systolic and diastolic blood pressure, coronary heart disease, diabetes, total cholesterol/high-density lipoprotein cholesterol ratio, and estimated glomerular filtration rate. Polygenic risk score was computed using identified susceptibility variants.

Results: After exclusions, 38 060 participants from England were randomly divided into the training set and the internal validation set in a 7:3 ratio, and 4970 participants from Scotland/Wales were assigned as the external validation set. Of 43 030 participants included (mean age, 59.0 years; 54.0% female), 989 incident IS occurred during a median follow-up of 13.6 years. In the training set, IS protein risk score was constructed using 17 out of 2911 proteins. In the internal validation set, compared with the basic model (age and sex: C statistic,0.720 [95% CI, 0.691-0.749]), IS protein risk score had the highest predictive performance for IS risk (C statistic, 0.765 [95% CI, 0.736-0.793]), followed by clinical risk factors of IS (C statistic, 0.753 [95% CI, 0.725-0.781]), and IS polygenic risk score (C statistic, 0.730 [95% CI, 0.701-0.759]). The top 5 proteins with the largest absolute coefficients in the IS protein risk score, including GDF15 (growth/differentiation factor 15), PLAUR (urokinase plasminogen activator surface receptor), NT-proBNP (N-terminal pro-B-type natriuretic peptide), IGFBP4 (insulin-like growth factor-binding protein 4), and BCAN (brevican core protein), contributed most of the predictive ability of the IS protein risk score, with a cumulative C statistic of 0.761 (95% CI, 0.733-0.790). These results were verified in the external validation cohort.

Conclusions: A simple model, including age, sex, and the IS protein risk score (or only the top 5 proteins) had a good predictive performance for IS risk.

Background: Mechanical thrombectomy is the treatment of choice for ischemic strokes of the anterior circulation with proximal occlusion. Mechanical thrombectomy can be performed under sedation, which can lead to episodes of periprocedural agitation. The aim of this study is to describe the prevalence of agitation and determine the consequences during and after mechanical thrombectomy.

Methods: This is an ancillary study to the AMETIS study (Anesthesia Management in Endovascular Therapy for Ischemic Stroke). We evaluated the patients from the sedation group of this randomized trial; some patients presented at least 1 episode of agitation during the procedure (determined by a Richmond Agitation-Sedation Scale score >1) prospectively collected. We explored the association between agitation and a composite outcome (Thrombolysis in Cerebral Infarction score <2b and/or arterial perforation) through univariate and multivariate analyses, accounting for confounders (agitation, age, National Institutes of Health Stroke Scale score, local thrombus) identified a priori by the acyclic diagram method.

Results: Among the 138 participants (average age, 71±14 years; 72 [52%] male; average National Institutes of Health Stroke Scale score, 15±6), 53 (38%) experienced at least 1 agitation episode. Agitation was neither a risk factor of Thrombolysis in Cerebral Infarction score <2b and/or arterial perforation in univariate and multivariate analyses (adjusted odds ratio, 1.29 [0.57-2.92]; P=0.5), nor a risk of unfavorable outcome (adjusted OR, 0.7 [0.18-2.56]; P=0.56). Although, agitated patients had a higher incidence of conversion with intubation (21% versus 5%; OR, 5.3 [1.7-20]; P<0.01) and significantly worse radiological image quality (62% versus 17%; OR, 8.37 [3.9-19.1]; P<0.01).

Conclusions: Our study found a high frequency of agitation during mechanical thrombectomy under sedation. Despite the absence of any significant link with prognosis, Thrombolysis in Cerebral Infarction score, and perforations, there is more conversion to general anesthesia with intubation and poorer quality images.

Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis. DNase-I, which degrades neutrophil extracellular traps, could improve thrombolytic efficacy. However, more studies are needed to understand the impact of DNase-I in tPA-sensitive stroke models, the safety of coadministering DNase-I and tPA regarding hemorrhagic transformation (HT), optimal timing for use, and effects on aspirin-treated animals.

Methods: We used in situ thromboembolic stroke, a tPA-sensitive model, where late tPA administration causes HT. Middle cerebral artery occlusion was induced at different zeitgeber times (ZT) to study the optimal timing for administration. DNase-I, tPA, and aspirin were administered at various times to evaluate their effects.

Results: DNase-I reduced infarct volume and improved functional outcomes 24 hours post-middle cerebral artery occlusion by decreasing plasma and cortical neutrophil extracellular trap levels. DNase-I caused no bleeding or impact on HT induced by late tPA. Its protective effect was only seen when given during the daytime (rodent inactive phase; ZT4-7), not overnight (active phase; ZT13-16). Chronic aspirin pretreatment increased tPA-induced HT but did not change the protective effects of DNase-I, with or without tPA.

Conclusions: Our study demonstrates that daytime (inactive phase) DNase-I administration is a safe and effective treatment for experimental stroke. This is particularly important given the 2 ongoing clinical trials for stroke patients.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05203224 and NCT05880524.

Background: Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Methods: We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.5±5.1 years, 59.0% female and 22.2% Black). Olfaction was assessed by the 12-item Sniffin' Sticks odor identification test and defined as poor (number correct ≤8), moderate (9-10), or good (11-12). Participants were followed from baseline to the date of the first stroke, death, last contact, or December 31, 2020, whichever occurred first. We used the discrete-time subdistribution hazard model to estimate the marginal cumulative incidence of stroke across olfactory statuses and adjusted risk ratios, accounting for covariates and competing risk of death.

Results: After up to 9.6 years of follow-up, we identified 332 incident stroke events. The adjusted marginal cumulative incidence of stroke at 9.6-year follow-up was 5.3% (95% CI, 4.2%-6.3%), 5.9% (95% CI, 4.8%-7.1%), and 7.7% (95% CI, 6.5%-9.1%) for good, moderate, and poor olfaction, respectively. Compared with good olfaction, poor olfaction was significantly associated with higher stroke risk throughout follow-up, albeit the association modestly attenuated after 6 years. Specifically, the adjusted risk ratios were 2.14 (95% CI, 1.22-3.94) at year 2, 1.98 (95% CI, 1.43-3.02) at year 4, 1.91 (95% CI, 1.43-2.77) at year 6, 1.49 (95% CI, 1.17-2.00) at year 8, and 1.45 (95% CI, 1.16-1.95) at year 9.6. Results were robust in multiple subgroup and sensitivity analyses.

Conclusions: In older adults, poor olfaction assessed by a single olfaction test was associated with the higher risk of stroke in the next 10 years.

Background: How cerebral microbleeds (CMBs) are formed, and how they cause tissue damage is not fully understood, but it has been suggested they are associated with inflammation, and they could also be related to increased blood-brain barrier (BBB) leakage. We investigated the relationship of CMBs with inflammation and BBB leakage in cerebral small vessel disease, and in particular, whether these 2 processes were increased in the vicinity of CMBs.

Methods: In 54 patients with sporadic cerebral small vessel disease presenting with lacunar stroke, we simultaneously assessed microglial activation using the positron emission tomography ligand [11C]PK11195 and BBB leakage using dynamic contrast enhanced magnetic resonance imaging, on a positron emission tomography-magnetic resonance imaging system. To assess local inflammation and BBB leakage, 3 one-voxel concentric shells were generated around each CMB on susceptibility-weighted imaging and resampled to positron emission tomography and T1 mapping images, respectively. In these 3 shells, we calculated the mean of PK11195 nondisplaceable binding potential (BPND) as a marker of microglial activation, as well as the mean influx rate as a marker of BBB leakage. In addition, 93 blood biomarkers related to cardiovascular disease, inflammation, and endothelial activation were measured to quantify systemic inflammation.

Results: No significant associations were found between the number of CMBs and the measures for microglial activation (β=2.6×10^-5, P=0.050) and BBB leakage (β=-0.0001, P=0.400) in the white matter. There was no difference in measures of microglial activation (P=0.403) or BBB leakage (P=0.423) across the 3 shells surrounding the CMBs. Furthermore, after correcting for multiple comparisons, no associations were observed between systemic inflammation biomarkers and the number of CMBs.

Conclusions: We found no evidence that CMBs are associated with either microglial activation assessed by [11]CPK11195 positron emission tomography or BBB leakage assessed by dynamic contrast enhanced magnetic resonance imaging, either globally or locally, in sporadic cerebral small vessel disease. There was also no association with markers of systemic inflammation.