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Stroke constitutes a major cause of functional disability with increasing prevalence among adult individuals. Thus, it is of great importance for both clinicians and stroke survivors to be provided with a timely and accurate prognostication of functional outcome. A great number of biomarkers capable of yielding useful information regarding stroke patients’ recovery propensity have been evaluated so far with leukoaraiosis being among them. Literature research of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of a current leukoaraiosis as a prognostic indicator following stroke. Only full-text articles published in English language were included. Forty-nine articles have been traced and are included in the present review. Our findings highlight the prognostic value of leukoaraiosis in an acute stroke setting. The assessment of leukoaraiosis with visual rating scales in CT/MRI imaging appears to be able to reliably provide important insight into the recovery potential of stroke survivors, thus significantly enhancing stroke management. Yielding additional information regarding both short- and long-term functional outcome, motor recovery capacity, hemorrhagic transformation, as well as early neurological deterioration following stroke, leukoaraiosis may serve as a valuable prognostic marker poststroke. Thus, leukoaraiosis represents a powerful prognostic tool, the clinical implementation of which is expected to significantly facilitate the individualized management of stroke patients.

Sleep is thought to play a major role in brain health and general wellbeing. However, few longitudinal studies have explored the relationship between sleep habits and imaging markers of brain health, particularly markers of brain waste clearance such as perivascular spaces (PVS), of neurodegeneration such as brain atrophy, and of vascular disease, such as white matter hyperintensities (WMH). We explore these associations using data collected over 6 years from a birth cohort of older community-dwelling adults in their 70s. We analysed brain MRI data from ages 73, 76 and 79 years, and self-reported sleep duration, sleep quality and vascular risk factors from community-dwelling participants in the Lothian Birth Cohort 1936 (LBC1936) study. We calculated sleep efficiency (at age 76), quantified PVS burden (at age 73), and WMH and brain volumes (age 73 to 79), calculated the white matter damage metric, and used structural equation modelling (SEM) to explore associations and potential causative pathways between indicators related to brain waste cleaning (i.e., sleep and PVS burden), brain and WMH volume changes during the 8th decade of life. Lower sleep efficiency was associated with a reduction in normal-appearing white matter (NAWM) volume (β = 0.204, P = 0.009) from ages 73 to 79, but not concurrent volume (i.e. age 76). Increased daytime sleep correlated with less night-time sleep (r = −0.20, P < 0.001), and with increasing white matter damage metric (β = −0.122, P = 0.018) and faster WMH growth (β = 0.116, P = 0.026). Shorter night-time sleep duration was associated with steeper 6-year reduction of NAWM volumes (β = 0.160, P = 0.011). High burden of PVS at age 73 (volume, count, and visual scores), was associated with faster deterioration in white matter: reduction of NAWM volume (β = −0.16, P = 0.012) and increasing white matter damage metric (β = 0.37, P < 0.001) between ages 73 and 79. On SEM, centrum semiovale PVS burden mediated 5% of the associations between sleep parameters and brain changes. Sleep impairments, and higher PVS burden, a marker of impaired waste clearance, were associated with faster loss of healthy white matter and increasing WMH in the 8th decade of life. A small percentage of the effect of sleep in white matter health was mediated by the burden of PVS consistent with the proposed role for sleep in brain waste clearance. • Sleep impairments are associated with faster deterioration of white matter health in septuagenarians. • Higher perivascular spaces burden is associated with faster deterioration of white matter health in septuagenarians. • Perivascular spaces partially mediate the effect of sleep on brain health. [ABSTRACT FROM AUTHOR]

Background and objective: The recruitment of collateral circulation correlates with a balance of the microvasculature. Uncertainty remains to be made about the association of leukoaraiosis with leptomeningeal collaterals. To explore the effect of leukoaraiosis on leptomeningeal collaterals in patients treated with endovascular therapy. Methods: Observational studies exploring the correlation between leukoaraiosis and leptomeningeal collaterals in large vessel occlusion treated with endovascular therapy were searched from PubMed, EMBASE, and Cochrane Libraries databases. Two independent reviewers retrieved eligible literature, extracted purpose-related data, and utilized the Newcastle–Ottawa Scale to evaluate the risk of bias. A Mantel–Haenszel method was used to calculate the odds ratio (OR). Meta-regression and subgroup analyses were conducted to clarify heterogeneity. Results: Data from 10 studies with 1606 patients were extracted for pooled analysis. Compared to non-severe leukoaraiosis, patients with severe leukoaraiosis showed significant relevance to poor leptomeningeal collaterals (OR, 2.13; 95% confidence interval [1.27–3.57]; P = 0.004). Meta-regression indicated that sample size (coefficient = -0.007299, P = 0.035) and the number of female patients (coefficient = -0.0174709, P = 0.020) were sources of heterogeneity. Furthermore, all of the countries (USA versus France versus China, Q = 3.67, P = 0.159), various assessment scales of leukoaraiosis (the Fazekas scale versus Non-Fazekas scales, Q = 0.77, P = 0.379), and different imaging methods of leukoaraiosis (computed tomography versus magnetic resonance imaging, Q = 2.12, P = 0.146) and leptomeningeal collaterals (computed tomography angiography versus digital subtraction angiography, Q = 1.21, P = 0.271) showed no contribution to the effect size. Conclusion: Severe leukoaraiosis is associated with poor leptomeningeal collaterals in patients treated with endovascular therapy. Further studies may focus on whether the finding applies to different stroke subtypes. [ABSTRACT FROM AUTHOR]

BackgroundThe relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis.MethodsSixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model.ResultsAfter 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia.DiscussionOur findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Objective To analyze the imaging data of patients with hyperacute hypertensive cerebral hemorrhage with leukoaraiosis (LA), and to evaluate the possibility of unstable CT signs of hematoma as a predictor of hematoma enlargement risk. Methods The imaging data of 95 patients who were admitted to the Department of Emergency of The Affiliated Hospital of Xuzhou Medical University from March to April, 2021 and underwent head CT scan within 6 h of onset were collected, and hematoma volume was obtained by ITK ⁃SNAP software. Unstable CT signs of hematoma including irregular shape sign, mixed density sign, black hole sign, swirl sign, satellite sign, island sign and liquid⁃liquid level sign were recorded. The severity of LA was assessed by the Blennow scale. Univariate and multivariate stepwise Logistic regression analysis were used to screen the risk factors of large volume cerebral hemorrhage (≥30ml). Results According to the hematoma volume of cerebral hemorrhage, 95 cases were divided into＜30ml group (n=53) and ≥30ml group (n=42). Logistic regression analysis showed that severe LA was a risk factor for large volume hematoma in cerebral hemorrhage (OR=6.222, 95%CI: 2.506-15.452; P=0.000). CT showed that the proportions of irregular shape sign (χ2=17.599, P=0.000), mixed density sign (χ2=5.644, P=0.018), black hole sign (χ2=23.161, P=0.000), swirl sign (χ2=26.128, P=0.000), satellite sign (χ2=25.148, P=0.000), island sign (χ2=20.575, P=0.000), ≥2 combined signs (χ2=23.245, P=0.000) and ≥3 combined signs (χ2=58.902, P=0.000) were higher in the hematoma volume ≥30ml group than those in＜30ml group. Severe LA (grade Ⅱ and Ⅲ) group (n=50) showed irregular shape sign (χ2=5.502, P=0.019), black hole sign (χ2=10.715, P=0.001), swirl sign (χ2=7.336, P=0.007), satellite sign (χ2=4.467, P=0.035), island sign (χ2=19.961, P=0.000), ≥2 combined signs (χ2=12.684, P=0.000) and ≥3 combined signs (χ2=17.593, P=0.000) were higher than those in non⁃severe (non and grade Ⅰ) group (n=45). Conclusions Severe LA is an important risk factor for hematoma volume expansion (≥30ml) in hyperacute hypertensive cerebral hemorrhage. The positive rates of unstable CT signs of hematoma in acute stage are higher, suggesting that this indicator can be used as a risk predictor for hematoma expansion after cerebral hemorrhage.

Background: Hemorrhagic transformation (HT) is common among acute ischemic stroke patients after treatment with intravenous thrombolysis (IVT). We analyzed potential relationships between markers of cerebral small vessel disease (CSVD) and HT in patients after IVT. Methods: This study retrospectively analyzed computed tomography (CT) data for acute ischemic stroke patients before and after treatment with recombinant tissue plasminogen activator at a large Chinese hospital between July 2014 and June 2021. Total CSVD score were summed by individual CSVD markers including leukoaraiosis, brain atrophy and lacune. Binary regression analysis was used to explore whether CSVD markers were related to HT as the primary outcome or to symptomatic intracranial hemorrhage (sICH) as a secondary outcome. Results: A total of 397 AIS patients treated with IVT were screened for inclusion in this study. Patients with missing laboratory data (n = 37) and patients treated with endovascular therapy (n = 42) were excluded. Of the 318 patients included, 54 (17.0%) developed HT within 24-36 h of IVT, and 14 (4.3%) developed sICH. HT risk was independently associated with severe brain atrophy (OR 3.14, 95%CI 1.43-6.92, P = 0.004) and severe leukoaraiosis (OR 2.41, 95%CI 1.05-5.50, P = 0.036), but not to severe lacune level (OR 0.58, 95%CI 0.23-1.45, P = 0.250). Patients with a total CSVD burden ≥1 were at higher risk of HT (OR 2.87, 95%CI 1.38-5.94, P = 0.005). However, occurrence of sICH was not predicted by CSVD markers or total CSVD burden. Conclusion: In patients with acute ischemic stroke, severe leukoaraiosis, brain atrophy and total CSVD burden may be risk factors for HT after IVT. These findings may help improve efforts to mitigate or even prevent HT in vulnerable patients. [ABSTRACT FROM AUTHOR]

Stroke survivors are at increased risk of developing depression and cognitive decline. Thus, it is crucial for both clinicians and stroke survivors to be provided with timely and accurate prognostication of post-stroke depression (PSD) and post-stroke dementia (PSDem). Several biomarkers regarding stroke patients' propensity to develop PSD and PSDem have been implemented so far, leukoaraiosis (LA) being among them. The purpose of the present study was to review all available work published within the last decade dealing with pre-existing LA as a predictor of depression (PSD) and cognitive dysfunction (cognitive impairment or PSDem) in stroke patients. A literature search of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of preexisting LA as a prognostic indicator of PSD and PSDem/cognitive impairment. Only full-text articles published in the English language were included. Thirty-four articles were traced and are included in the present review. LA burden, serving as a surrogate marker of "brain frailty" among stroke patients, appears to be able to offer significant information about the possibility of developing PSD or cognitive dysfunction. Determining the extent of pre-existing white matter abnormalities can properly guide decision making in acute stroke settings, as a greater degree of such lesioning is usually coupled with neuropsychiatric aftermaths, such as PSD and PSDem. [ABSTRACT FROM AUTHOR]

[Display omitted] • ARWMC-BG score ≥ 2 predicts intraoperative neurologic deficits in CEA with RA. • Higher ARWMC-BG scores correlate with increased prevalence of CKD, CAD, and AF. • No significant differences found in circle of Willis variations between IND and control groups. • CT or MRI scanning recommended pre-CEA for identifying at-risk patients. • Larger studies needed to validate ARWMC-BG score as a predictive tool in CEA. White matter changes (WMC) have been associated with the underlying presence of chronic cerebral ischemia, such as in carotid stenosis and age-related white matter changes (ARWMC). A low attenuation on computed tomography (CT) characterizes these alterations. Patients undergoing carotid endarterectomy (CEA) with severe WMC may be at increased risk of intraoperative neurologic deficits (IND) during carotid clamping. This study aims to determine the potential role of ARWMC as a predictor of IND during CEA with regional anesthesia (RA). Patients undergoing CEA under RA at a tertiary referral center, who presented with IND during CEA were prospectively and consecutively recruited between January 2011 and December 2023. The control group comprised the immediately consecutive patient who underwent the same procedure without IND. From this sample, patients with preoperative CT were selected and compared based on ARWMC score (≤ 1 and 2). Differences in demographics and comorbidities were assessed between the groups. A multivariable logistic regression was performed. One hundred and twenty-one patients were enrolled. Patients with IND had a significantly higher ARWMC score in basal ganglia (ARWMC-BG ≥ 2) and posterior circulation disease was more frequent (27.8 %). No significant differences were observed in anatomical variations of the circle of Willis. For patients with ARWMC-BG ≥ 2, a significant burden of other comorbidities was associated, such as chronic kidney disease, coronary disease, and atrial fibrillation. After multivariable logistic regression analysis, ARWMC-BG score ≥ 2 was an independent risk factor for IND (aOR 3.472). An ARWMC-BG score above 2 predicts positive intraoperative "awake tests" in CEA with RA, constituting a reliable tool to stratify patients according to their risk of adverse events. However, larger prospective cohorts are needed to validate these findings and offer a better selection and management of this subset of patients. [ABSTRACT FROM AUTHOR]

Higher levels of pulse wave velocity (PWV) have been related with the presence of small vessel disease that could damage the brain, in which white matter hyperintensities (WMH) could be presented as consequence. This meta-analysis aims to examine the cross-sectional and longitudinal associations between PWV and the presence of WMH among older adults. We searched PubMed, Scopus, and WOS until June 2024. Pooled Odds Ratio (p-OR) were estimated for the cross-sectional and longitudinal associations between PWV and WMH. In addition, we explored whether this associations could be modified by type of PWV measurement and study and sample characteristics. The p-OR between PWV and WMH was 1.16 (95 % CI, 1.10–1.22) for the cross-sectional and 1.07 (95 %, 1.00–1.15) for the longitudinal association. Similar figures were found by type of PWV measurement and no one of the explored characteristics modified this associations. This meta-analysis revealed that the presence in and the long-term development of WMHs among older adults are more likely among those with elevated PWV. • WMHs are most commonly presented among alder adults with higher levels of PWV. • The development of WMH is most probably among older adults with higher levels of PWV. • The PWV measurement method does not influence theses associations. • Study and sample characteristics do not influence these associations. [ABSTRACT FROM AUTHOR]

We aimed to study the impact of leukoaraiosis (LA) and blood pressure (BP) on clinical outcome, mortality and symptomatic intracerebral hemorrhage (sICH) in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). We analyzed data retrospectively from 521 patients with anterior large vessel occlusion treated with MT. LA was dichotomized in 0–2 (absent-to-moderate) versus 3–4 (moderate-to-severe) according to the van Swieten scale. Various systolic (SBP) and diastolic (DBP) BP parameters during the first 24 h were collected. Multivariable logistic regressions were performed to identify predictors of a poor 90-day outcome, mortality and sICH. LA was significantly associated with poor outcome (OR 3.2; p < 0.001) and mortality (OR 3.19; p = 0.008), but not sICH (p = 0.19). Higher maximum SBP was significantly associated with poor outcome (OR per 10 mmHg increase = 1.21; p = 0.009) and lower mean DBP was a predictor of mortality (OR per 10 mmHg increase = 0.53; p < 0.001). In the univariate analysis high SBP variability was associated with poor outcome, mortality and sICH, but not in the multivariate model. There was no association between BP and sICH. Severity of LA, SBP variability, high maximum SBP and low DBP are associated with either poor outcome or mortality in AIS patients undergoing MT. However, neither LA nor BP were associated with sICH in our cohort. Thus, mechanisms of the negative impact on outcome remain unclear. Further studies on impact of BP course and its mechanisms and interventions are needed to improve outcome in patients undergoing MT. [ABSTRACT FROM AUTHOR]

Leukoaraiosis, a common ischaemic lesion diagnosed using magnetic resonance imaging (MRI), can influence driving safety performance (DSP). Most older drivers with leukoaraiosis are unaware of their affliction. Japan is a super-aged country, where preventing accidents caused by older drivers is an urgent national issue. We investigated the subcortical and periventricular leukoaraiosis regions that were most involved in DSP decline. The driving skills of 101 drivers (49 men, 52 women; mean age, 77.88 ± 3.77 years) without dementia were assessed by official driving instructors, using actual vehicles on a closed-circuit course. Parietal and occipital (but not frontal or temporal) leukoaraiosis volumes were significantly correlated with decreased DSP scores regardless of age, especially when turning right at intersections, which needs more attention than turning left because left-side driving is legally enforced in Japan. Occipital leukoaraiosis was also involved via a decline in dynamic visual cognitive function. MRI-based assessment of leukoaraiosis volume and localisation may enable the identification of older drivers prone to DSP deterioration. Risk factors for leukoaraiosis include smoking and lifestyle-related diseases such as hypertension. Thus, brain healthcare in patients with MRI-diagnosed leukoaraiosis may be particularly useful for the risk management of traffic accidents caused by the elderly in Japan. [ABSTRACT FROM AUTHOR]

Understanding the relationship between white matter hyperintensities (WMHs) and cognitive and physical decline in people with dementia will assist in determining potential treatment strategies. Currently there is conflicting evidence describing the association between WMHs and cognitive decline and, WMHs association with declines in objective measures of physical function have not been examined. We examined the relationship between baseline WMH volume and physical/cognitive decline over one-year in older people with dementia. Twenty-six community-dwelling older people with dementia (mean age = 81 ± 8 years; 35% female) were assessed at baseline and follow-up (one-year) using the Addenbrooke's Cognitive Examination-Revised (including verbal fluency), Trail Making Test A, the Physiological Profile Assessment (PPA), timed-up-and-go (TUG) and gait speed. WMH volumes were quantified using a fully automated segmentation toolbox, UBO Detector. In analyses adjusted for baseline performance, higher baseline WMH volume was associated with decline in executive function (verbal fluency), sensorimotor function (PPA) and mobility (TUG). Executive function (semantic/category fluency) was the only domain association that withstood adjustment for age, and additionally hippocampal volume. In unadjusted analyses, WMH volume was associated with one-year declines in cognitive and physical function in older people with dementia. The association with executive function decline withstood adjustment for age. More research is needed to confirm these findings and explore whether vascular risk reduction strategies can reduce WMH volume and associated cognitive and physical impairments in this group. [ABSTRACT FROM AUTHOR]

Stroke constitutes a major cause of functional disability with increasing prevalence among adult individuals. Thus, it is of great importance for both clinicians and stroke survivors to be provided with a timely and accurate prognostication of functional outcome. A great number of biomarkers capable of yielding useful information regarding stroke patients' recovery propensity have been evaluated so far with leukoaraiosis being among them. Literature research of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 25 June 2022 that dealt with the clinical utility of a current leukoaraiosis as a prognostic indicator following stroke. Only full-text articles published in English language were included. Forty-nine articles have been traced and are included in the present review. Our findings highlight the prognostic value of leukoaraiosis in an acute stroke setting. The assessment of leukoaraiosis with visual rating scales in CT/MRI imaging appears to be able to reliably provide important insight into the recovery potential of stroke survivors, thus significantly enhancing stroke management. Yielding additional information regarding both short- and long-term functional outcome, motor recovery capacity, hemorrhagic transformation, as well as early neurological deterioration following stroke, leukoaraiosis may serve as a valuable prognostic marker poststroke. Thus, leukoaraiosis represents a powerful prognostic tool, the clinical implementation of which is expected to significantly facilitate the individualized management of stroke patients. [ABSTRACT FROM AUTHOR]

Stroke stands as a major cause of death and disability with increasing prevalence. The absence of clinical improvement after either intravenous thrombolysis (IVT) or mechanical thrombectomy (MT) represents a frequent concern in the setting of acute ischemic stroke (AIS). In an attempt to optimize overall stroke management, it is clinically valuable to provide important insight into functional outcomes after reperfusion therapy among patients presenting with AIS. The aim of the present review is to explore the predictive value of leukoaraiosis (LA) in terms of clinical response to revascularization poststroke. A literature research of two databases (MEDLINE and Scopus) was conducted in order to trace all relevant studies published between 1 January 2012 and 1 November 2022 that focused on the potential utility of LA severity regarding reperfusion status and clinical outcome after revascularization. A total of 37 articles have been traced and included in this review. LA burden assessment is indicative of functional outcome post-intervention and may be associated with hemorrhagic events' incidence among stroke individuals. Nevertheless, LA may not solely guide decision-making about treatment strategy poststroke. Overall, the evaluation of LA upon admission seems to have interesting prognostic potential and may substantially enhance individualized stroke care. [ABSTRACT FROM AUTHOR]

Background and purpose: As a part of the natural course of ischemic stroke, hemorrhagic transformation (HT) is a serious complication after reperfusion treatment, which may affect the prognosis of patients with ischemic stroke. White matter lesions (WMLs) refer to focal lesions on neuroimaging and have been suggested to indicate a high risk of HT. This systematic review and meta-analysis aimed to summarize current evidence on the relation between WML and HT. Methods: This systematic review was prepared with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for publications on WML and HT in patients with ischemic stroke. Odds ratios (ORs) and 95% confidence intervals (CIs) from eligible studies were combined to quantify the association between the severity of WML and the risk of HT. In addition, the descriptive analysis was adopted to evaluate the influence of different WML distributions on predicting HT. Results: A total of 2,303 articles were identified after removing duplicates through database searching, and 41 studies were included in our final analysis. The meta-analysis showed that the presence of WML was associated with HT (OR = 1.62, 95%CI 1.08–2.43, p = 0.019) and symptomatic intracerebral hemorrhage (sICH) (OR = 1.64, 95%CI 1.17–2.30, p = 0.004), and moderate-to-severe WML indicated a high risk of HT (OR = 2.03, 95%CI 1.33–3.12, p = 0.001) and sICH (OR = 1.92, 95%CI 1.31–2.81, p < 0.001). The dose–response meta-analysis revealed risk effects of increasing the severity of WML on both HT and ICH. In addition, both periventricular WML (PWML) (five of seven articles) and deep WML (DWML) (five of six articles) were shown to be associated with HT. Conclusions: White matter lesions are associated with overall HT and sICH in patients with ischemic stroke, and more severe WMLs indicate a high risk of HT and sICH. In addition, both PWML and DWMLs could be risk factors for HT. [ABSTRACT FROM AUTHOR]

Background/aim: Leukoaraiosis produces white matter lesions (WML) similar to multiple sclerosis (MS) on brain magnetic resonance imaging (MRI), and the distinction between these two conditions is difficult radiologically. This study aimed to investigate the role of the central vein sign (CVS) in susceptibility-weighted imaging (SWI) sequence in distinguishing MS lesions from leukoaraiosis lesions in Turkish population. Materials and methods: In this prospective study, axial SWI and sagittal three-dimensional fluid-attenuated inversion recovery (3DFLAIR) were obtained in 374 consecutive patients. The study consisted of 169 (89 MS patients, 80 patients with leukoaraiosis) patients according to the inclusion and exclusion criteria. Two observers evaluated MR images by consensus, and observers were unaware of the patient's clinical findings. Locations (periventricular, juxtacortical, and deep white matter) and the presence of CVS were investigated for each of the lesions. Differences between patients in the leukoaraiosis and MS groups were investigated using the Mann-Whitney U test or chi-square analysis. In addition, receiver operating characteristic (ROC) analysis was used to analyze the diagnostic performance of CVS. Results: A total of 1908 WMLs (1265 MS lesions, 643 leukoaraiosis) were detected in 169 patients. The CVS was significantly higher in the MS lesions (p < 0.001). The CVS positivity rate in periventricular WMLs was higher than in juxtacortical WMLs or deep WMLs, both for all patients and for patients with MS (p < 0.001). The area under the curve (AUC) of the ROC analysis was 0.88 (95% confidence interval 0.83-0.93) for CVS in the distinction of MS lesions and leukoaraiosis. Conclusion: The presence of CVS in the SWI sequence can be used as an auxiliary finding for the diagnosis of MS in the differentiation of MS and leukoaraiosis lesions. [ABSTRACT FROM AUTHOR]

Background: Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion.Purpose: To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis.Material and Methods: Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume.Results: Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age (P < 0.001), lacunes (P = 0.022), and cerebral microbleeds (P = 0.010). A statistical association was found between both age (P < 0.001) and lacunes (P = 0.047) and leukoaraiosis T2 values.Conclusion: Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds. [ABSTRACT FROM AUTHOR]

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Leukoaraiosis (LA) results from ischemic injury in small cerebral vessels, which may be attributable to decreased vascular density, reduced cerebrovascular angiogenesis, decreased cerebral blood flow, or microcirculatory dysfunction in the brain. In this study, we enrolled 357 patients with mild intracerebral hemorrhage (ICH) from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission, neurological function prognosis at 3 months, and 1-year stroke recurrence. Patients were divided into groups based on Fazekas scale scores: no LA (n = 83), mild LA (n = 64), moderate LA (n = 98) and severe LA (n = 112). More severe LA, larger hematoma volume, and higher blood glucose level at admission were associated with more severe neurological deficit. More severe LA, older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months. In addition, moderate-to-severe LA, admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence. These findings suggest that LA severity may be a potential marker of individual ICH vulnerability, which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH. Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols. This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University (approval No. 12) on March 10, 2011.

Yikun Guo,1 Min Zhang,1 Yan Su,2 Jianfang Liu,1 Hongran Fu,1 Qian Wang,1 Yun Chen1 1Department of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Radiology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yikun GuoDepartment of Neurology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, 68# Middle Gehu Road, Changzhou, 213000, Jiangsu Province, People’s Republic of ChinaTel +86-519-81087079Fax +86-519-81087711Email guoyikun000@163.comPurpose: Few clinical indicators of a poor outcome have been defined in acute cardioembolic stroke (CES) patients. We would like to explore practical clinical factors that can predict poor outcomes of CES in the early stage.Patients and Methods: In this single-center, retrospective, observational study, 251 consecutive patients with acute CES who did not undergo reperfusion therapy were evaluated. On the basis of the modified Rankin Scale (mRS) score at 3 months, patients were divided into the good functional outcome group (mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3). Risk factors were analyzed and the independent indicators for a poor outcome were identified using a binary logistic regression model.Results: One hundred (39.8%) patients had a poor outcome. Patients in the poor outcome group were significantly older (P = 0.002) and had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) score compared with those with a good outcome (P < 0.001). After adjusting for potential confounders, the baseline NIHSS score (P < 0.001), moderate to severe leukoaraiosis (P = 0.011), non-symptomatic intracranial hemorrhage (P = 0.019), stroke-associated pneumonia (P = 0.001), and fasting glucose (P = 0.040) were independent risk factors for a poor outcome.Conclusion: The short-term outcome in acute CES patients without reperfusion therapy can be predicted by using five practical clinical factors. These indicators should attract more attention.Keywords: acute cardioembolic stroke, risk factor, functional outcome, reperfusion therapy, leukoaraiosis

Background: The relationship of global white matter microstructural integrity and ischemic stroke outcomes is not well understood. Aims: To investigate the relationship of global white matter microstructural integrity with clinical variables and functional outcomes after acute ischemic stroke. Methods: A retrospective analysis of neuroimaging data from 300 acute ischemic stroke patients with magnetic resonance imaging brain obtained within 48 hours of stroke onset and long-term functional outcomes (modified Rankin, mRS) was performed. Peak width of skeletonized mean diffusivity (PSMD), as a measure of global white matter microstructural injury, was calculated in the hemisphere contralateral to the acute infarct. Multivariable linear and logistic regression analyses were performed to identify variables associated with PSMD and excellent functional outcome (mRS < 2) at 90 days, respectively. Mediation analysis was then pursued to characterize how PSMD mediates the effect of age on acute ischemic stroke functional outcomes. Results: White matter hyperintensity volume, age, pre-stroke disability, and normal-appearing white matter mean diffusivity were independently associated with increased PSMD. In logistic regression analysis, increased infarct volume and PSMD were independent predictors of excellent functional outcome. Additionally, the effect of age on functional outcomes was indirectly mediated by PSMD (P < 0.001). Conclusions: As a marker of global white matter microstructural injury, increased PSMD mediates the effect of increased age to contribute to poor acute ischemic stroke functional outcomes. PSMD could serve as a putative radiographic marker of brain age for stroke outcomes prognostication. [ABSTRACT FROM AUTHOR]

Background: Lesion-related factors are associated with severity of language impairment in persons with aphasia. The extent to which demographic and health factors predict language impairment beyond traditional cortical measures remains unknown. Identifying and understanding the contributions of factors to predictive models of severity constitutes critical knowledge for clinicians interested in charting the likely course of aphasia in their patients and designing effective treatment approaches in light of those predictions.Methods: Utilizing neuroimaging and language testing from our cohort of 224 individuals in the chronic stage of recovery from a left-hemisphere stroke in a cross-sectional study, we first conducted a lesion symptom mapping (LSM) analysis to identify regions associated with aphasia severity scores. After controlling for lesion volume and damage to pre-identified areas, three models were created to predict severity scores: 1) Demographic Model (N = 147); 2) Health Model (N = 106); and 3) Overall Model (N = 106). Finally, all identified factors were entered into a Final Model to predict raw severity scores.Results: Two areas were associated with aphasia severity-left posterior insula and left arcuate fasciculus. The results from the Demographic Model revealed non-linguistic cognitive ability, age at stroke, and time post-stroke as significant predictors of severity (P = .005; P = .02; P = .001, respectively), and results from the Health Model suggested the extent of leukoaraiosis is associated with severity (P = .0004). The Overall Model showed a relationship between aphasia severity and cognitive ability (P = .01), time post-stroke (P = .002), and leukoaraiosis (P = .01). In the Final Model, which aimed to predict raw severity scores, demographic, health, and lesion factors explained 55% of the variance in severity, with health and demographic factors uniquely explaining nearly half of performance variance.Conclusions: Results from this study add to the literature suggesting patient-specific variables can shed light on individual differences in severity beyond lesion factors. Additionally, our results emphasize the importance of non-linguistic cognitive ability and brain health in aphasia recovery. [ABSTRACT FROM AUTHOR]

Purpose: Leukoaraiosis (LA) is a major public issue that affects elderly adults. However, the underlying neuropathological mechanism of LA without cognitive impairment requires examination. The present study aimed to explore the dynamic functional network connectivity (dFNC) in LA patients without cognitive impairment. Methods: Twenty-three patients with LA and 20 well-matched healthy controls were recruited for the present study. Each subject underwent magnetic resonance imaging (MRI) scanning and cognition evaluations. Spatial independent component analysis was conducted to evaluate dynamic functional connectivity. The differences in dFNC were determined and correlated with cognitive performance. Results: Compared with controls, LA without cognitive impairment showed aberrant dFNC in State 1, involving increased connectivity in the default mode network (DMN) with the executive control network (ECN). In addition, decreased connectivity in the DMN with the salience network (SN) was found in State 3. Furthermore, the decreased number of transitions between states was positively associated with the visuospatial/executive score (Spearman's rho = 0.452, p = 0.031), and the longer mean dwell time in State 1 was negatively associated with the Montreal Cognitive Assessment (MoCA) score (Spearman's rho = - 0.420, p = 0.046). Conclusion: These findings enrich our understanding of the neural mechanisms underlying LA and may serve as a potential imaging biomarker for investigating and recognizing the LA at an early stage. [ABSTRACT FROM AUTHOR]

Leukoaraiosis is a common imaging marker of cerebral small vessel disease. In recent years, with the continuous advances in brain imaging technology, the detection rate of leukoaraiosis is higher and its clinical subtypes are gradually gaining attention. Although leukoaraiosis has long been considered an incidental finding with no therapeutic necessity, there is now growing evidence linking it to, among other things, cognitive impairment and a high risk of death after stroke. Due to dierent research methods, some of the findings are inconsistent and even contradictory. Therefore, a comprehensive and indepth study of risk factors for leukoaraiosis is of great clinical significance. In this review, we summarize the literature on leukoaraiosis in recent years with the aim of elucidating the disease in terms of various aspects (including pathogenesis, imaging features, and clinical features, etc.) [ABSTRACT FROM AUTHOR]

Background and aimsAortic atherosclerosis is an aggregate marker of vascular risk factor exposure and has been associated with intracranial atherosclerosis and stroke. We hypothesized that atherosclerosis of the descending aorta (DAo) could be a risk marker for brain aging and injury.MethodsWe evaluated 1527 participants (mean age 59.9 years, 53.5% women) in the Framingham Offspring cohort who underwent both aortic and brain MRI. Participants were free of clinical stroke, dementia, or other neurological illness at the time of axial MRI of the thoracic and abdominal DAo and subsequent brain MRI. We related the prevalence and burden of aortic plaque to total cerebral brain volume (TCBV) and white matter hyperintensity volume (WMHV). An additional analysis compared incidence of stroke or TIA in participants with and without DAo plaques.ResultsPresence of thoracic DAo plaque (8%) was associated with decreased TCBV in sex-pooled analysis (-0.77, SE 0.25, p = 0.002, equivalent to 4.5 years of aging) and with increased WMHV only in men (0.26, SE 0.12, p = 0.032, equivalent to 6.5 years aging). We observed similar associations of DAo plaque burden with TCBV and WMHV. There were 43 strokes and 11 TIAs in prospective follow-up (median 7 years). Presence of DAo plaque was not associated with subsequent stroke or TIA.ConclusionsIn this cross-sectional community-based study, we found DAo plaque is associated with accelerated brain aging. These data underscore the potential implications of incidentally identified subclinical aortic atherosclerosis and question whether targeted intervention in these high risk individuals can modulate cognitive decline.

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV-; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV- groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV- group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.

Abstract Background There are numerous barriers to identifying patients with silent brain infarcts (SBIs) and white matter disease (WMD) in routine clinical care. A natural language processing (NLP) algorithm may identify patients from neuroimaging reports, but it is unclear if these reports contain reliable information on these findings. Methods Four radiology residents reviewed 1000 neuroimaging reports (RI) of patients age > 50 years without clinical histories of stroke, TIA, or dementia for the presence, acuity, and location of SBIs, and the presence and severity of WMD. Four neuroradiologists directly reviewed a subsample of 182 images (DR). An NLP algorithm was developed to identify findings in reports. We assessed interrater reliability for DR and RI, and agreement between these two and with NLP. Results For DR, interrater reliability was moderate for the presence of SBIs (k = 0.58, 95 % CI 0.46–0.69) and WMD (k = 0.49, 95 % CI 0.35–0.63), and moderate to substantial for characteristics of SBI and WMD. Agreement between DR and RI was substantial for the presence of SBIs and WMD, and fair to substantial for characteristics of SBIs and WMD. Agreement between NLP and DR was substantial for the presence of SBIs (k = 0.64, 95 % CI 0.53–0.76) and moderate (k = 0.52, 95 % CI 0.39–0.65) for the presence of WMD. Conclusions Neuroimaging reports in routine care capture the presence of SBIs and WMD. An NLP can identify these findings (comparable to direct imaging review) and can likely be used for cohort identification.

Background and Objective: Microvascular failure might result in the collapse of cerebral collaterals. However, controversy remains regarding the role of leukoaraiosis (LA) in collateral recruitment. We, therefore, performed a systematic review and meta-analysis of the association between LA and cerebral collaterals. Methods: Ovid Medline, PubMed, Embase, Web of Science, and three Chinese databases were searched from inception to August 2021. Two types of cerebral collaterals, including Circle of Willis (CoW) and leptomeningeal collaterals (LC), were investigated separately. Random effect models were used to calculate the pooled odds ratio (OR). Meta-regression and subgroup analyses were performed to explore the potential sources of heterogeneity. Results: From 14 studies (n = 2,451) that fulfilled our inclusion criteria, data from 13 could be pooled for analysis. Overall, there was a significant association between severe LA and incomplete CoW (pooled OR 1.66, 95% CI 1.18–2.32, p = 0.003), with low heterogeneity (I 2 = 5.9%). This association remained significant in deep LA (pooled OR 1.48, 95% CI 1.04–2.11, p = 0.029, I 2 = 0), but not periventricular LA. Similarly, there was a significant association between LA and LC (pooled OR 1.73, 95% CI 1.03–2.90, p = 0.037), but with high heterogeneity (I 2 = 67.2%). Meta-regression indicated a negative association of sample size with the effect sizes (p = 0.029). In addition, most of the studies (7/9) included into the analysis of the relationship of severe LA with poor LC enrolled subjects with large vessel occlusion stroke, and this relationship remained significant when pooling the seven studies, but with high heterogeneity. Conclusion: Severe LA is associated with a higher prevalence of poor collaterals. This association is robust for CoW but weak for LC. Further studies are required to explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Leukoaraiosis (LA) is commonly found in aging healthy people but its pathophysiological mechanism is not entirely known. Furthermore, there is still a lack of effective pathological biomarkers that can be used to identify the early stage of LA. Our aim was to investigate the white matter structural network in asymptomatic patients with the early stage of LA. Tractography data of 35 asymptomatic patients and 20 matched healthy controls (HCs) based on diffusion kurtosis imaging (DKI) were analysed by using graph theory approaches and tract-based spatial statistics (TBSS). Diffusion parameters measured within the ALAs and HCs were compared. Decreased clustering coefficient and local efficiency values of the overall topological white matter network were observed in the ALAs compared with those of the HCs. Participants in the asymptomatic group also had lower nodal efficiency in the left triangular part of the inferior frontal gyrus, left parahippocampal gyrus, right calcarine fissure and surrounding cortex, right temporal pole of the superior temporal gyrus and left middle temporal gyrus compared to the ALAs. Moreover, similar hub distributions were found within participants in the two groups. In this study, our data demonstrated a topologic efficiency abnormalities of the structural network in asymptomatic patients with leukoaraiosis. The structural connectome provides potential connectome-based measures that may be helpful for detecting leukoaraiosis before clinical symptoms evolve. [ABSTRACT FROM AUTHOR]

Background: Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. Aim: We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. Methods: This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. Results: In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. Conclusion: The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack. [ABSTRACT FROM AUTHOR]

Many patients with acute ischemic stroke (AIS) are found to accompany with leukoaraiosis (LA) in brain imaging. The risk factors of LA in patients with AIS were examined in this study. Patients with AIS were recruited and underwent head magnetic resonance imaging. According to Fazekas scores, patients were divided into LA group and non-LA group. We compared demographic and laboratory characteristics in two groups. Multivariate logistic regression analysis demonstrated that high-density lipoprotein (HDL), age, stroke history, admission SBP, and homocysteine were independent risk factors for LA in patients with AIS (P < 0.05). Multinomial logistic regression analysis demonstrated that HDL was an independent risk factor for moderate LA (OR 4.151, 95% CI 1.898–9.078, P < 0.001) and severe LA (OR 3.151, 95% CI 1.350–7.358, P = 0.008). In order to further explore the correlation between HDL level and the severity of LA, HDL was categorized in quartiles and multinomial logistic regression analysis was presented. Regression analysis showed that HDL ≥ 1.34 mmol/L was correlated with moderate and severe LA after adjusting for corresponding confounding factors in different models. After 1-year follow-up, patients were divided into regular statin therapy group and irregular statin therapy group. There was no significant difference in HDL level between two groups; however, the proportion of patients with increased Fazekas scores in regular statin therapy group was significantly less than that in the irregular statin therapy group (P < 0.05). In conclusion, HDL was an independent risk factor for LA and associated with the severity of LA in patients with AIS; regular statin therapy may be negatively related with the progress of LA. These results provide more evidences for controlling risk factors and severity of LA in patient with AIS. [ABSTRACT FROM AUTHOR]

Malignant infarction of the middle cerebral artery (m-MCA) is a complication of ischemic stroke. Since hyperthermia is a predictor of poor outcome, and antihyperthermic treatment is well tolerated, our main aim was to analyze whether the systemic temperature decrease within the first 24 h was associated with a better outcome. Furthermore, we studied potential biochemical and neuroimaging biomarkers. This is a retrospective observational analysis that included 119 patients. The temperature variations within the first 24 h were recorded. Biochemical laboratory parameters and neuroimaging variables were also analyzed. The temperature increase at the first 24 h (OR: 158.97; CI 95%: 7.29–3465.61; p < 0.001) was independently associated with a higher mortality. Moreover, antihyperthermic treatment (OR: 0.08; CI 95%: 0.02–0.38; p = 0.002) was significantly associated with a good outcome at 3 months. Importantly, antihyperthermic treatment was associated with higher survival at 3 months (78% vs. 50%, p = 0.003). Significant independently associations between the development of m-MCA and both microalbuminuria (OR: 1.01; CI 95%: 1.00–1.02; p = 0.005) and leukoaraiosis (OR: 3.07; CI 1.84–5.13–1.02; p < 0.0001) were observed. Thus, antihyperthermic treatment within the first 24 h was associated with both a better outcome and higher survival. An increased risk of developing m-MCA was associated with leukoaraiosis and an elevated level of microalbuminuria. [ABSTRACT FROM AUTHOR]

The vascular depression hypothesis posits that cerebrovascular diseases are a major risk factor for emotional and behavioral disorders (EBD). Arterial hypertension (AH) is one of the main causes of cerebrovascular diseases.Objective: to assess the relationship between anxiety, depression and apathy in the patients with AH with case history, clinical features and neuroimaging.Patients and methods. 65 hypertensive outpatient were examined (mean age – 57.17±10.76 years). Cognitive status was evaluated with MiniMental State Examination, Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery. EBD was assessed with Beck Depression Scale, Spielberger Anxiety Questionnaire, and Robert's Apathy Scale. The Fazekas scale was used to determine the severity of leukoaraiosis. Results and discussion. Significant depression was present in 66.2%, anxiety – in 41.5%, and apathy – in 80% of hypertensive patients. Blood pressure level (p

To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients.

Background and ObjectiveMicrovascular failure might result in the collapse of cerebral collaterals. However, controversy remains regarding the role of leukoaraiosis (LA) in collateral recruitment. We, therefore, performed a systematic review and meta-analysis of the association between LA and cerebral collaterals.MethodsOvid Medline, PubMed, Embase, Web of Science, and three Chinese databases were searched from inception to August 2021. Two types of cerebral collaterals, including Circle of Willis (CoW) and leptomeningeal collaterals (LC), were investigated separately. Random effect models were used to calculate the pooled odds ratio (OR). Meta-regression and subgroup analyses were performed to explore the potential sources of heterogeneity.ResultsFrom 14 studies (n = 2,451) that fulfilled our inclusion criteria, data from 13 could be pooled for analysis. Overall, there was a significant association between severe LA and incomplete CoW (pooled OR 1.66, 95% CI 1.18–2.32, p = 0.003), with low heterogeneity (I2 = 5.9%). This association remained significant in deep LA (pooled OR 1.48, 95% CI 1.04–2.11, p = 0.029, I2 = 0), but not periventricular LA. Similarly, there was a significant association between LA and LC (pooled OR 1.73, 95% CI 1.03–2.90, p = 0.037), but with high heterogeneity (I2 = 67.2%). Meta-regression indicated a negative association of sample size with the effect sizes (p = 0.029). In addition, most of the studies (7/9) included into the analysis of the relationship of severe LA with poor LC enrolled subjects with large vessel occlusion stroke, and this relationship remained significant when pooling the seven studies, but with high heterogeneity.ConclusionSevere LA is associated with a higher prevalence of poor collaterals. This association is robust for CoW but weak for LC. Further studies are required to explore the underlying mechanisms.

Background: Carotid artery plaque, white matter disease (WMD), and silent lacunae infarcts (initial indicators) are associated with symptomatic cerebral infarction (CI) caused by atherosclerosis. We retrospectively examined the association between the initial indicators and risk factors for cerebrovascular disease, considering the primary prevention of symptomatic CI. Methods: We divided 1503 individuals who were neurologically healthy and enrolled in a brain screening program (brain dock) at our institution, into three initial plaque grades (grade 0, 1, and 2) based on having no plaques, having plaques on the right or left carotid artery, or having plaques on both carotid arteries, respectively. We analyzed the risk factors according to the presence/absence of the initial indicators. Results: WMD and the risk factors (low-density lipoprotein [LDL], hemoglobin A1c, systolic blood pressure [BP], and smoking cigarettes) were positively correlated with the initial plaque grades, even when their laboratory values were within normal ranges. Systolic BP (116.5 ± 14.0 mmHg) was significantly lower in group 00 (without carotid plaque and WMD) than that in age-adjusted others (with carotid plaque or WMD). In young participants aged between 40 and 52 years, LDL (132.8 ± 24.5 mg/dl) was significantly higher in subgroup ++ (with carotid plaque and WMD) compared to others (without carotid plaque or WMD). Conclusion: Initial plaque grade and WMD grade as clinical initial indicators of symptomatic CI are associated with risk factors. To avoid deterioration of the initial indicators, it was suggested that the risk factors should be maintained at the lower ends of normal ranges and smoking cessation should be recommended.

Background and Purpose: Cerebral small vessel disease (CSVD) markers have not been widely studied in relation to hematoma volume and growth in hypertensive intracerebral hemorrhage (ICH). The objectives to assess the relationship of white matter hyperintense lesions (WMHL), microbleeds (MBs), and cortical siderosis (CSS) with hematoma volume, hematoma expansion (HE), and 3 months outcome in patients with hypertensive ICH. Methods: All consecutive acute hypertensive supratentorial ICH presenting to the emergency were prospectively recruited. Baseline and 24 hours computed tomography (CT) to assess hematoma volume and magnetic resonance imaging (MRI) for CSVD markers were performed in all subjects. WMHL (graded using Fazekas's scale), MBs, and CSS were assessed and compared with baseline variables and outcomes. All the images were assessed by an experienced stroke neurologist/neuroradiologist. Results: One hundred and fifty-seven patients were screened and 60 were included. Mean age was 54.08 ± 11.57 years and 47 (78%) were males. Of 60, 19 (28.1%) had HE, 31 (51.6%) had major bleed (>30 ml), and 28 (47.46%) had poor 3 month outcome (mRS 4-6). On univariate analysis, high grade WMHL was associated with greater HE [odds ratio (OR): 2.65, confidence interval (CI) 1.48–4.72, P = 0.001), greater proportion with volume >30 ml (OR: 7.16, CI: 1.09–47.13, P = 0.001) and poor outcome (OR: 2.1, CI: 0.05–3.27, P = 0.001). MBs were associated with poor outcome (P = 0.029) but not with HE/volume. CSS was related to HE (P = 0.031), a large volume bleed (P = 0.023), and poor outcome (P = 0.021). On multivariate model, only WMHL independently predicted HE (P = 0.034), greater proportion with bleed volume >30 ml (P = 0.041), and poor outcome (P = 0.042). Conclusions: WMHL in MRI serves as a predictor of hematoma expansion, a large volume bleed, and poor outcome in hypertensive ICH and may be incorporated into existing prediction models.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal–Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Background and aim: Whether cerebral microbleeds cause cognitive impairment remains uncertain. We analyzed whether cerebral microbleeds are associated with cognitive dysfunction in patients with symptomatic cerebral small vessel disease, and whether this association is independent of other neuroimaging markers of cerebral small vessel disease. Methods: We analyzed consecutive patients with MRI-confirmed lacunar stroke included in DNA-Lacunar-2 multicenter study. Cerebral microbleeds were graded using the Brain Observer Microbleed Rating Scale (BOMBS). Neuropsychological assessment was performed using the Brief Memory and Executive Test (BMET). We analyzed the association between cerebral microbleeds, BMET, and the following subdomains: executive function/processing speed and orientation/memory. We also searched for an independent association between cerebral microbleeds and vascular cognitive impairment, defined as BMET ≤ 13. Results: Out of 688 included patients, cerebral microbleeds were detected in 192 (27.9%). After adjusting for white matter hyperintensities severity, lacune count, and other confounders, both the presence and the number of cerebral microbleeds were significantly associated with impaired cognitive performance [β = −13.0; 95% CI = (−25.3, −0.6) and β = −13.1; 95% CI = (−19.8, −6.4), respectively]. On analysis of specific cognitive domains, associations were present for executive function/processing speed [β = −5.8; 95% CI = (−9.3, −2.2) and β = −4.3; 95% CI = (−6.2, −2.4), respectively] but not for orientation/memory [β = −0.4; 95% CI = (−4.0, 3.2) and β = −2.1; 95% CI = (−4.0, 0.1), respectively]. We also found an independent association between the presence and the number of cerebral microbleeds and vascular cognitive impairment [adjusted OR = 1.48; 95% CI = (1.01, 2.18) and OR = 1.43; 95% CI = (1.15, 1.79), respectively]. Conclusion: In a large cohort of symptomatic cerebral small vessel disease patients, after controlling for other neuroimaging markers of cerebral small vessel disease severity, cerebral microbleeds were associated with cognitive dysfunction. Executive function and processing speed were predominantly impaired. This might suggest a causal role of cerebral microbleeds in determining vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: Novel coronavirus disease 2019 (COVID‐19) has been found to be associated with encephalopathy and brain imaging abnormalities. The identification of incident white matter lesions, known to be associated with cerebral microcirculatory failure and cerebrovascular disease, in COVID‐19 patients is of clinical and scientific interest. We performed a meta‐analysis to investigate the incidence of white matter lesions (WMLs) in hospitalized COVID‐19 patients. Methods: PubMed, EMBASE, and the Cochrane Library were searched for studies on brain imaging abnormalities in hospitalized COVID‐19 patients. The terms used included "white matter lesions," "white matter hyperintensity," "COVID‐19," "coronavirus," and "SARS‐CoV‐2." A random‐effects meta‐analysis was conducted to obtain a pooled estimate of WML prevalence in hospitalized COVID‐19 patients. Results: A total of 4 eligible studies involving 362 patients (144 with WMLs and 218 without) were included in the meta‐analysis. We found the pooled estimate of WML prevalence to be 20% (ES 0.20; 95% CI 0.00–0.54; p =.03). Conclusions: The estimated pooled prevalence rate of WMLs was approximately 20% in hospitalized COVID‐19 patients, albeit lower than the crude prevalence rate (39.8%). [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the relationship between diffusion tensor imaging (DTI) quantification and cerebrospinal fluid r (Tau) protein expression in leukoaraiosis patients. Inpatients who attended the Department of Neurology of our hospital from January 2018 to December 2018 were selected as study subjects, with 58 patients with leukoarais as the experimental group, and 60 patients without leukoarais in the same period as the control group. ELISA was used to detect r (Tau) protein expression level in the cerebrospinal fluid of the two groups. DTI technique was taken to compare DTI anisotropic diffusion coefficients of the two groups. According to our results there was a statistically significant difference in cerebrospinal fluid Tau protein concentration between the experimental group and the control group (P<0.05), and there was no statistically significant difference in CSF IgG index between the experimental group and the control group (P>0.05). DTI was used to process diffusion tensor data and visually and clearly display the distribution and metastasis of brain nerve fibers or white matter. In terms of leukoaraiosis degree, FA decreased. Where, DR increased, AMO decreased, Dave and DAx remained unchanged. Most FA reduction observed in white matter was observed in the corpus callosum. In the end we concluded r protein expression in cerebrospinal fluid can enable identification of the occurrence of LA symptoms to a certain extent. Its combined use with DTI, an important tool for non-invasive analysis of the internal brain structure, is playing an increasingly important role in medical clinical and basic research. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between smoking habit and the serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), in relation with the functional outcome of patients with acute ischemic stroke undergoing reperfusion treatment. Methods: Observational and retrospective study of a series of patients with acute ischemic stroke subjected to reperfusion treatments. Clinical, analytical, and neuroimaging parameters were analyzed. The main endpoint was the functional outcome at 3 months, measured by the modified Ranking Scale (mRS). Logistic regression models were used to analyze the association between smoking and sTWEAK levels with functional outcome and leukoaraiosis. Results: The results showed that smoking habit was associated with a good functional outcome at 3 months in patients with stroke (OR: 3.52; 95% CI: 1.03–11.9; p = 0.044). However, this independent association was lost after adjusting by sTWEAK levels (OR 1.73; 95% CI: 0.86–13.28; p = 0.116). sTWEAK levels were significantly lower in smoker patients [4015.5 (973.66–7921.83) pg/ml vs. 5,628 (2,848–10,202) pg/ml, p < 0.0001], while sTWEAK levels were significantly higher in patients with poor functional outcomes at 3 months [10,284 (7,388–13.247) pg/ml vs. 3,405 (2,329–6,629) pg/ml, p < 0.0001]. Conclusion: The decrease in sTWEAK levels was associated with a good functional outcome in smoker patients with stroke undergoing reperfusion therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to analyze the patient characteristics in accordance with white matter lesions and confirm whether white matter lesions affect final treatment outcomes in idiopathic sudden sensorineural hearing loss. METHODS: Medical records of 126 patients treated for unilateral idiopathic sudden sensorineural hearing loss and who underwent magnetic resonance imaging of the brain at an otology clinic in a university hospital from 2013 to June 2019 were reviewed. The Fazekas scale was used to evaluate the severity of white matter lesions. Complete recovery was defined if final hearing at 3 months did not exceed 25 dB. RESULTS: Overall, 107 patients were enrolled in this study. A score of 0 on the Fazekas scale was most frequent (n = 78, 72.9%), followed by 1 (n = 17, 15.9%), and 2 (n = 12, 11.2%). Prevalence of diabetes (P = .032) and/or hypertension (P = .006) and distribution of age (P < .001) were different according to Fazekas scale scores. Hearing level in the affected side was significantly different between those with scores of 1 and 2 (P = .009). Contralateral hearing thresholds were not different according to Fazekas scale scores, but hearing on the contralateral side was significantly poorer in patients with hypertension than those without hypertension (P < .001). Regression analysis revealed that Fazekas scale score and initial hearing thresholds of the affected side were significant prognostic factors for complete recovery. CONCLUSION: Although the prevalence of white matter lesions in idiopathic sudden sensorineural hearing loss was not high, severe white matter lesions and accompanying cardiovascular risk factors may increase the possibility of initially worse hearing and decrease response to treatment in idiopathic sudden sensorineural hearing loss. Therefore, it might be important to control cardiovascular abnormalities in idiopathic sudden sensorineural hearing loss to achieve a better prognosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Leukoaraiosis is thought to be related to long-standing microvascular ischemia. The pathogenic mechanisms and hemodynamic changes could be different for periventricular and deep white matter leukoaraiosis. In this cross-sectional study, we examined whether the Pulsatility Index (PI) in Transcranial Doppler ultrasonography (TCD), which can give indirect information regarding downstream microvascular resistance and compliance, is different for leukoaraiosis in periventricular and deep locations. Correlation between presence of leukoaraiosis and PI was also studied since it was not studied in South-Asian patients before.Methods: Consecutive patients with suspected lacunar stroke or white-matter disease, undergoing MR brain imaging were included. Vascular imaging was done with CT or MR Angiography to rule out significant (>50%) stenosis. Fazeka's grading was done for severity of leukoaraiosis and mean PI in the middle cerebral artery (MCA) was obtained with trans-temporal TCD.Results: Ninety patients (Mean age 61 ± 10.9 years, 29% females) were available for final analysis. Age, hypertension, diabetes mellitus, CAD, and presence of leukoaraiosis were strongly associated with elevated mean PI in univariate analysis. In multivariate analysis, presence of leukoaraiosis was significantly associated with higher mean PI after adjusting for other variables. Mean PI strongly correlated with both periventricular (Spearman's correlation coefficient 0.56, P = 0.01) and deep white matter (Spearman's correlation coefficient 0.63, P = 0.01) leukoaraiosis.Conclusions: Our study confirms the correlation of Pulsatility Index with leukoaraiosis in South-Asian patients. Interestingly, changes in microvascular resistance appeared to be similar for both periventricular and deep white matter leukoaraiosis in spite of potential differences in etiopathogenesis. [ABSTRACT FROM AUTHOR]

Background and Purpose: The inflammatory response could play a key role in cognitive impairment. However, there has been limited research into the association between total white blood cell (WBC) count and post-stroke cognitive impairment (PSCI), and the significance of leukoaraiosis (LA) in this relationship is unknown. We aimed to examine the total WBC count in relation to PSCI and whether this association was mediated by LA. Methods: Consecutive patients with first-ever ischemic stroke were prospectively enrolled from October 2020 to June 2021. The total WBC count was measured after admission. Cognitive function evaluations were performed at the 3-month follow-up using Mini-mental State Examination (MMSE). We defined the PSCI as an MMSE score <27. Results: A total of 276 patients (mean age, 66.5 years; 54.7% male) were included in this analysis. Among them, 137 (49.6%) patients experienced PSCI. After adjustment for potential confounders, higher total WBC count was significantly correlated with an increased risk of LA [per 1-SD increase, odds ratio (OR), 1.39; 95% CI 1.06–1.82; p = 0.017] and PSCI (per 1-SD increase, OR , 1.51; 95% CI 1.12–2.04; p = 0.006). Furthermore, mediation analysis demonstrated that the association between total WBC count and PSCI was partly mediated by LA (the regression coefficient was changed by 9.7% for PSCI, and 12.4% for PSCI severity, respectively). Conclusion: Increased total WBC count is a risk factor for PSCI. The presence of LA was partially responsible for the PSCI in patients who had a higher total WBC count. [ABSTRACT FROM AUTHOR]