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ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).MethodsBlinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.ConclusionsNon-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Background: Obstructive sleep apnoea (OSA) is associated with hypertension, nocturnal blood pressure (BP) surges, and increased risk of stroke. It may therefore also be associated with a higher risk of developing leukoaraiosis. Only few data about the prevalence of leukoaraiosis in patients with OSA, and any association between degrees of severity of either condition, exist. Methods: We studied patients who were part of a clinical trial (MOSAIC) in minimally symptomatic OSA. All patients had brain MRI (T2, FLAIR) at baseline. A single observer assessed the images for the presence and severity of leukoaraiosis (ARWMC-score). We related the extent of leukoaraiosis to the severity of OSA (measured by oxygen desaturation index [ODI]) and the presence of other vascular risk factors. Results: 183 patients (156 men, 85.2%; mean age ± SD = 57.7 ± 7.4 years; median oxygen desaturation index = 9.6, interquartile range = 4.6-16.0) took part in the study. Although 135 (74%) patients had some leukoaraiosis, this was generally mild. We confirmed the well-known risk factor associations between leukoaraiosis, increasing age (p < 0.0001) and hypertension (p = 0.003), but we did not find any association between OSA and leukoaraiosis (p = 0.33), despite both conditions being associated with increasing current BP and a history of hypertension. Conclusion: Our data confirm the well-known association between leukoaraiosis, age and increasing BP. However, we found no association between OSA and leukoaraiosis despite some shared risk factor associations. Our findings suggest that OSA is not a strong independent risk factor for leukoaraiosis. Confounding by hypertension may explain any apparent association in previously reported studies of patients with severer OSA.

Background and Aim Leukoaraiosis is a common imaging marker of cerebral small vessel disease. There is now increasing evidence shows the relationship between leukoaraiosis and cognitive impairment, high risk of death after stroke. The aim of this study was to analyze the risk factors clinically associated with the development of leukoaraiosis, and to explore clinical biomarkers that may predict leukoaraiosis. Methods Inpatients were continuously recruited from July 2014 to October 2020. After admission, the cranial MRI examination was evaluated, and the severity of leukoaraiosis were evaluated and graded. Vascular risk factors and relevant clinical data were collected. Univariate analysis was used to analyze the parameters, and multivariate logistic regression analysis was used to analyze the statistically significant parameters. The analysis results were plotted as ROC curve to find out the diagnostic accuracy of the model. Results 1) 327 patients meeting the study criteria were included. Univariate analysis showed that 13 factors were statistically significantly (p < 0.05). 2) Multivariate logistic regression model showed that age (Age 1 [OR, 14.315; 95% CI, 6.662–30.757; p = 0.000], Age 2 [OR, 53.062; 95% CI, 15.661–179.783; p = 0.000]), elevated systolic blood pressure (SBP 1 (OR, 2.927; 95% CI, 1.224–7.003; p = 0.016), SBP 3 (OR, 15.109; 95% CI, 1.380–165.385; p = 0.026)), ischemic stroke (OR, 5.990; 95% CI, 2.594–13.846; p = 0.000), and FT4 (OR, 4.836; 95% CI, 2.086–11.216; p = 0.000) were independent risk factors for leukoaraiosis. 3) The ROC curve indicated the accuracy of diagnosis on leukoaraiosis is 0.906, and the positive rate and negative rate are both 85.2%. Conclusions 1) Our findings support age, systolic blood pressure, ischemic stroke, and FT4 level serving as factors affecting the development of leukoaraiosis. 2) The model of “age, systolic blood pressure, ischemic stroke, FT4” may have relatively ideal sensitivity and specificity in predicting the development of leukoaraiosis. This study was to analyze the risk factors clinically associated with the development of leukoaraiosis, and to explore clinical biomarkers that may predict leukoaraiosis. The results demonstrate that age, systolic blood pressure, ischemic stroke, and FT4 level serving as factors affecting the development of leukoaraiosis.

BackgroundLeukoaraiosis (LA) severity is associated with poor outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion. This meta-analysis aimed to assess the association of LA severity with AIS-related risk factors and outcomes of MT.MethodsPubMed, Web of Science, EMBASE, and Cochrane Collaboration Database was searched for studies on MT for AIS with LA. We conducted a random-effects meta-analysis for the prevalence of stroke risk factors and the MT outcome in the absent to moderate LA and severe LA groups.ResultsWe included seven cohort studies involving 1294 participants (1019 with absent to moderate LA and 275 with severe LA). The absent to moderate LA group had a significantly lower prevalence of coronary artery disease (odds ratio [OR] 0.43; 95% CI 0.29–0.66), atrial fibrillation (OR, 0.26; 95% CI 0.17–0.38), hypertension (OR, 0.39; 95% CI 0.24–0.61), and ischemic stroke (OR, 0.27; 95% CI 0.15–0.50) than the severe LA group. There were no significant between-group differences in symptom onset to recanalization time (364.4 versus 356.2 min, mean difference 19.4; 95% CI − 28.3 to 67.2), final recanalization rate (modified thrombolysis in cerebral infarction score of 2b/3; OR, 0.87; 95% CI 0.55–1.38), and symptomatic intracranial hemorrhage (OR, 0.62; 95% CI 0.34–1.11). The absent to moderate LA group had a higher good functional outcome (modified Rankin Scale score of 0–2 at 90 days; OR, 4.55; 95% CI 3.20–6.47) and a lower mortality rate (179/1019 vs 108/275; OR, 0.28; 95% CI 0.20–0.39).ConclusionThere are unique differences in the characteristics of risk factors and clinical outcomes of ischemic stroke across patients with LA of different severity. Patients with severe LA are more likely to be associated with risk factors for cerebrovascular disease and have a poor post-MT outcome.

Background and Objective The aim of this study was to evaluate the impact of radiographic cerebral small vessel disease (CSVD) on the severity of acute intracerebral hemorrhage (ICH) as measured by: ICH volume, hematoma expansion, and extension of intraventricular hemorrhage (IVH). Methods CSVD was determined on baseline computed tomography (CT) scans of patients from the Ethnic and Racial Variations of Intracerebral Hemorrhage study through the extent of leukoaraiosis and cerebral atrophy using visual rating scales. The associations of leukoaraiosis and atrophy with ICH volume, hematoma expansion, IVH presence, and severity of IVH were tested using multivariable regression models. Secondary analyses were stratified by hemorrhage location. Bonferroni correction was applied to correct for multiple testing. Results A total of 2579 patients (mean age 61.7 years, 59% male) met inclusion criteria. Median ICH volume was 10.5 (Interquartile range [IQR] 4.0–25.3) mL. IVH was detected in 971 patients (38%). Neither leukoaraiosis nor atrophy was associated with hematoma expansion. Increasing grades of leukoaraiosis were associated with increased risk of IVH in a dose-dependent manner, while cerebral atrophy was inversely associated with IVH (both P for trend < 0.001). Increasing grades of global atrophy were dose-dependently associated with lower ICH volumes (ß (95% Confidence Interval [CI]) − 0.30[− 0.46, − 0.14], − 0.33[− 0.49, − 0.17], − 0.40[− 0.60, − 0.20], and − 0.54[− 0.76, − 0.32], for grades 1, 2, 3 and 4 compared to 0; all P  < 0.001). The associations of leukoaraiosis with ICH volume were consistent with those of atrophy, albeit not meeting statistical significance. Conclusions Leukoaraiosis and cerebral atrophy appear to have opposing associations with ICH severity. Cerebral atrophy correlates with smaller ICH volume and decreased risk and severity of IVH, while leukoaraiosis is associated with increased risk of IVH. Whether these observations reflect overlapping or divergent underlying mechanisms requires further study.

Background: The mechanisms of cerebral small vessel disease (SVD) are unclear. Both atherosclerosis and a non-atherosclerotic diffuse arteriopathy have been reported pathologically. Two pathological and radiological subtypes have been suggested: localised atherosclerotic disease in larger perforating arteries causing larger lacunar infarcts without leukoaraiosis, and diffuse disease in smaller arterioles causing multiple smaller lacunar infarcts with leukoaraiosis. If atherosclerosis were important in SVD as a whole or in one particular subtype, one would expect the risk factor profile to be similar to that of cerebral large vessel disease (LVD). Methods: Risk factor profiles were compared in Caucasian stroke patients with SVD (n = 414), LVD (n = 471) and 734 stroke-free Caucasian population controls. Patients with SVD were subdivided according to the presence or absence of confluent leukoaraiosis, into isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). Results: Hypertension was commoner in SVD than LVD (odds ratio (OR) 3.43 (2.32 to 5.07); p<0.001) whereas hypercholesterolaemia (OR 0.34 (0.24 to 0.48); p<0.001), smoking (OR 0.63 (0.44 to 0.91); p = 0.012), myocardial infarction (OR 0.35 (0.20 to 0.59); p<0.001) and peripheral vascular disease (OR 0.32 (0.20 to 0.50); p<0.001) were commoner in LVD. Among SVD patients, age (OR 1.11 (1.09 to 1.14); p<0.001) and hypertension (OR 3.32 (1.56 to 7.07); p = 0.002) were associated with ILA and hypercholesterolaemia (OR 0.45 (0.28 to 0.74); p = 0.002), diabetes (OR 0.42 (0.21 to 0.84); p = 0.014) and myocardial infarction (OR 0.18 (0.06 to 0.52); p = 0.001) with ILI. Conclusion: SVD has a different risk factor profile from the typical atherosclerotic profile found in LVD, with hypertension being important. There are differences in the risk factor profile between the SVD subtypes; the association of ILI with hypercholesterolaemia, diabetes and myocardial infarction may be consistent with a more atherosclerotic aetiology.

Red blood cell distribution width (RDW) is one of the routine hematologic parameters reported in the complete blood count test, which has been recognized as strong prognostic marker for various medical conditions, especially cardiovascular disease. We evaluated that RDW was also associated with the leukoaraiosis; common radiological finding of brain and that has been strongly associated with risk of stroke and dementia. In the present study, we included 1006 non-stroke individuals who underwent brain MRI and routine complete blood count test including RDW. Fazekas scale was used to measure the severity of leukoaraiosis based on fluid-attenuated inversion recovery image, and the severity was dichotomized to mild-degree (Fazekas scale: 0-1) and severe-degree leukoaraiosis (Fazekas scale: 2-3). Univariate and multivariate logistic regression models were constructed to evaluate independent risk factor for severe-degree of leukoaraiosis. Mean age of 1006 subjects was 64.34 ± 9.11 year, and mean of RDW was 12.97 ± 0.86%. The severe-degree of leukoaraiosis (Fazekas scale ≥ 2) was found in 28.83%. In the multivariate logistic regression, 4th quartile of RDW (> 13.3%) were significantly associated with the presence of severe-degree of leukoaraiosis (adjusted odds ratio, 1.87; 95% confidence interval, 1.20-2.92) compared to the 1st quartile of RDW (< 12.5%). The significance was not changed after adjustments for hemoglobin and other hematologic indices. These findings suggest that RDW is independently associated with severity of leukoaraiosis.

Objective Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. Methods BIOCARD Study participants were cognitively normal and primarily middle‐aged (M = 57 years) at baseline and have been followed with annual cognitive and clinical assessments (M = 13 years). Baseline cognitive reserve was indexed with a composite score combining education with reading and vocabulary scores. Baseline vascular risk (N = 229) was assessed with a composite risk score reflecting five vascular risk factors. Baseline white matter hyperintensity load (N = 271) was measured with FLAIR magnetic resonance imaging. Cox regression models assessed risk of progression from normal cognition to onset of clinical symptoms of Mild Cognitive Impairment. Longitudinal mixed effects models measured the relationship of these variables to cognitive decline, using a global composite score, and executive function and episodic memory sub‐scores. Results Both vascular risk and white matter hyperintensities were associated with cognitive decline, particularly in executive function. Higher vascular risk, but not white matter hyperintensity burden, was associated with an increased risk of progression to Mild Cognitive Impairment. Higher cognitive reserve was associated with a reduced risk of symptom onset and higher levels of baseline cognition but did not modify the associations between the vascular risk score and white matter hyperintensities with clinical progression or cognitive decline. Interpretation Although cognitive reserve has protective effects on clinical and cognitive outcomes, it does not mitigate the negative impact of vascular risk and small vessel cerebrovascular disease on these same outcomes.

Background Stroke-associated pneumonia (SAP) is common in patients with acute ischemic stroke, and several risk factors have been reported. However, the relationship between underlying leukoaraiosis (LA) and SAP has not been addressed. Methods We collected consecutive patients with acute ischemic stroke within 24 h of symptom onset. SAP was defined as the lower respiratory tract infection within the first 7 days after stroke onset, according to the modified Centers for Disease Control and Prevention criteria. LA was graded using the Fazekas scale in both the periventricular and subcortical areas. We evaluated LA burden by summing the grade and dichotomized into mild LA (0–2) or severe LA (3–6). Relationship between LA and SAP was analyzed by binary logistic regression analysis with variables of P  < 0.05 in univariate analysis. Results Three hundred eight consecutive patients were enrolled, and SAP developed in 44 patients (14%). Univariate analysis revealed that SAP correlated with age, initial NIHSS score, atrial fibrillation, impaired consciousness, dysphagia, severe LA and hyperlipidemia. On multivariate analysis, severe LA [adjusted OR (aOR) = 4.41, 95% CI = 2.04–9.55, P  < 0.001 remained independent predictors of SAP after adjusted confounders. Conclusions In this study, LA was an independent predictor of SAP. This observation needs to be confirmed in suitably-designed, prospective studies.

The embolization of cancer cells to cerebral vessels occurs early in the multi-step metastatic process. We aimed to determine whether the presence of leukoaraiosis (LA) before treatment would predict the development of brain metastases (BM) in patients with lung cancer. Between January 2014 and June 2015, 1007 patients underwent initial (i.e., prior to any chemotherapy) or routine magnetic resonance (MR) imaging of the brain and exhibited no evidence of BM. Of these, 189 underwent repeat MR imaging; 34 of 189 patients (18%) developed new BM, whereas 155 patients did not. LA was retrospectively evaluated according to Fazekas scale on the initial screening MR images of these 189 patients. The frequency of grade 0 periventricular hyperintensity (PVH) was greater among patients with BM, compared to those without BM (p = 0.001). In a multivariate analysis, patients with adenocarcinoma (95% confidence interval [CI] 1.8–171.8) and small cell carcinoma (95% CI 1.4–172.4) respectively developed BM at 9.3- and 8.8-fold higher rates than those with squamous cell carcinoma. Patients with grade 0 PVH developed BM at a rate 3.5-, 8.6-, and 3.6-fold higher rates than those with grade 1 (95% CI 1.4–9.0), 2 (95% CI 2.4–41.9), and 3 (95% CI 1.02–15.0), respectively. Lung cancer patients with grade 0 PVH on initial MR images have a high subsequent incidence of BM. PVH is a useful method for evaluating risk of BM.