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Commonly plaguing in the frigid zone of the world, vitamin D deficiency, as indicated by low levels of 25-hydroxyvitamin D, exacerbated inflammatory responses and impaired endothelial function. Leukoaraiosis (LA) is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses. This study aimed to investigate the impact of vitamin D on the severity of LA. Patients with LA were categorized based on 3.0 T brain MRI findings into mild (N = 43), moderate (N = 40), or severe groups (N = 29) using the Fazekas scale (scoring 1-6). A control group consisting of 41 healthy individuals was included. Serum fibrinogen C, homocysteine, plasma 25-hydroxyvitamin D, and intercellular cell adhesion molecule-1 (ICAM-1) levels were measured using ELISA. All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group, with a more pronounced decrease observed as LA severity increased. Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA (P < 0.05) according to Multiple logistic regression analysis. Additionally, a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1. Disease severity positively correlated with levels of the inflammatory marker ICAM-1, worsening as plasma 25-hydroxyvitamin D concentration decreased. Low 25-hydroxyvitamin D emerged as an independent risk factor for LA, potentially exacerbating the inflammatory response. These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA. [ABSTRACT FROM AUTHOR]

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 (≥ 30 ml). Results According to the hematoma volume of cerebral hemorrhage, 95 cases were divided into < 30 ml group (n = 53) and ≥ 30 ml 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 ≥ 30 ml group than those in < 30 ml 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 (≥ 30 ml) 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. [ABSTRACT FROM AUTHOR]

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Leukoaraiosis (LA) is shown as white matter hyperintensities on T2-weighted magnetic resonance imaging brain scans. Together with candidate gene association studies (CGAS), multiple genome-wide association studies (GWAS) have reported large numbers of single nucleotide polymorphisms (SNPs) to be associated with LA in European populations. To date, no replication studies have been reported in independent Chinese samples. Methods: Here, we performed a candidate gene association study comprising 220 Chinese subjects with LA and 50 controls. Thirty-nine polymorphisms on 32 risk genes were selected from previous studies, and they were genotyped through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genetic association analysis was firstly performed in all subjects with LA. Then, the same analysis was conducted in the six random sampling cohorts of 50 LA patients, respectively. Data analyses on the associations of SNPs with LA risk were evaluated through Pearson's χ2 and multivariate logistic regression tests. Results: We found that eight polymorphisms in six genes (PMF1 , ICAM1 , TRIM65 , AGT , FBF1 , and ACOX1) were significantly associated with LA in the genetic association tests. Except for those eight gene variants, 24 other polymorphisms were not found to be significantly associated with LA in general genetic model, dominant model, recessive model, or multiplicative model. Among those eight polymorphisms, rs2984613 in PMF1 showed significant association with LA in the cohort of 220 LA subjects, and such significant association remained in both general genetic model (OR: 0.262, 95% CI: 0.091–0.752, p adj = 0.030) and recessive model (OR: 0.323, 95% CI: 0.119–0.881, p adj = 0.038) when controlling for clinical variables. Seven other significant variants (rs5498 in ICAM1 , rs699 in AGT , rs2305913 in FBF1 , rs1135640 in ACOX1 , and rs3760128, rs7214628, and rs7222757 in TRIM65) were identified in those six random sampling tests that were conducted in the adjusted cohorts of 50 LA patients. In addition, except for rs699 which showed detrimental effect and represented a risk variant for LA, seven other polymorphisms seemed to exert protective effects on LA and to reduce the risk of LA. It is necessary to confirm these associations in an independent cohort. Conclusions: This first replication study on multiple genes in an independent Chinese population did not replicate any risk polymorphisms for LA other than rs 699 in AGT but revealed the significantly negative associations of PMF1 , ICAM1 , TRIM65 , FBF1 , and ACOX1 polymorphisms with LA. It not only supported the strong ethnic differences in the genetics of LA but also indicated that those six identified genes may be involved in Chinese white matter lesions. Larger scales of CGAS and GWAS are necessary to confirm and decipher those ethnic-Han specific risk genes for LA in China. [ABSTRACT FROM AUTHOR]

Objectives: The effects of increased intracranial pulsatility on the severity of white matter hyperintensities (WMH) in participants with asymptomatic intracranial arterial stenosis (aICAS) remain uncertain. We aimed to investigate whether an increased pulsatility index (PI) is associated with WMH volume (WMHV) in individuals with aICAS., Materials and Methods: All participants were recruited from the Kongcun Town aICAS Study, including a total of 103 participants with aICAS and 98 healthy controls (age- and sex-matched). PI was assessed using transcranial Doppler ultrasound. The WMHV was calculated through the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging. The association between PI and lnWMHV was analyzed by linear regression models adjusting for demographics, lifestyle, and vascular risk factors., Results: The lnWMHV and PI between the aICAS and control groups showed no significant differences (P = 0.171 and 0.287, respectively). In a multivariable model, age ≥ 60 years and male sex (P = 0.000 and 0.006, respectively) were significant predictors of lnWMHV in the aICAS group. In sex-stratified analyses, there was a significant association between PI and lnWMHV in males with aICAS (P = 0.038)., Conclusions: This study suggest there might be a likely association between increased intracranial pulsatility and WMH burden in males with aICAS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: The aim of the study was to evaluate whether leukoaraiosis (LA) severity is associated with earlier neurological outcome in acute stroke patients undergoing mechanical thrombectomy., Materials and Methods: In this retrospective multicenter study, we evaluated 273 acute stroke patients treated with mechanical thrombectomy. LA severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of early neurological improvement and early neurological deterioration. Early neurological improvement was defined as a decrease of≥4 points on the NIHSS, or an NIHSS score of zero 24hours after baseline assessment. Early neurological deterioration was defined as an increase of≥4 points on the NIHSS 24hours after baseline assessment., Results: There was a significantly lower early neurological improvement rate (17.1% versus 39.2%; P=0.006) and non-significantly higher early neurological deterioration rate (29.3% versus 17.7%; P=0.084) in patients with severe LA (sLA) compared with patients with absent-to-moderate LA. In multivariable analysis, sLA was inversely associated with early neurological improvement (OR, 0.31; 95% CI, 0.13-0.78; P=0.012). There was no significant association of sLA with early neurological deterioration. However, in patients without symptomatic intracranial hemorrhage, sLA was an independent predictor of early neurological deterioration (OR, 2.65; 95% CI, 1.09-6.45; P=0.032)., Conclusions: sLA is a significant negative predictor of early neurological improvement and is an independent predictor of early neurological deterioration in patients without symptomatic intracranial hemorrhage., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: Blood-brain barrier (BBB) disruption is the primary initiating cause of cerebral small-vessel diseases including leukoaraiosis (LA). β-Catenin is a key regulator of the BBB and plays an important role in cell-cell adhesion at adherens junctions by interacting with cadherin molecules. Thus, β-Catenin may be a good candidate gene for LA. We performed a genetic analyses to investigate the association between β-catenin alleles and LA. Materials and Methods: A total of 339 LA cases and 203 controls were enrolled from individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of β-catenin single nucleotide polymorphisms (SNPs), including rs1880481 C > A, rs13072632 C > T, and rs4135385 A > G, was performed by real-time polymerase chain reaction using a LightCycler 2.0. Results: Two SNPs, rs188048 1 and rs4135385 , showed significant differences in their allelic frequencies between the control and LA groups and the combinatorial effects of the risk alleles for these two SNPs also significantly increased the risk of LA. The G-T-A, A-T-A, and A-T-G haplotypes for the three SNPs showed significant differences in both types of LA: LA-periventricular white matter and LA-deep white matter. However, the C-T-G haplotype was only significantly different for LA-PVWM, while the A-C-A was only significantly different for LA-DWM. The combination of diabetes mellitis, hypertension, and these risk alleles increased the likelihood of both types of LA. Conclusion: This study provides evidence that β-catenin polymorphisms and their associated haplotypes are associated with susceptibility to LA.

Objective: To explore related factors affecting evolution of recent small subcortical infarct (RSSI) with small-artery occlusion. Methods: A total of 96 RSSI patients with RSSI were admitted from Shanghai Tongji Hospital between January 2015 and December 2018. The age of patients containing 60 men was 64.5 (58-73) years, and MRI follow-up time was 11.6 (6.3-11.8) months. Clinical information of patients, images data at baseline head MRI and evolution outcomes at follow-up MRI were collected. All patients were divided into cavitation group (lacunes) and no cavitation group (white matter hyperintensities (WMH) and disappearance) to analyze related factors. Results: Fifty-nine cases (61.5%) developed to cavities, 32 cases (33.3%) were focal WMH, and 5 cases (5.2%) disappeared.In the univariate analysis, RSSI maximum diameter on the DWI or T(2)WI sequence of cavitation group was significantly higher than non-cavitation group, but male proportion was lower (11.6 (9.9-16.6) vs 8.6 (6.9-13.0) mm, 11.8 (9.7-16.2) vs 8.8 (6.7-13.1) mm, 54.2% vs 75.7%, all P< 0.05). In Logistic regression analysis,the maximum diameter on DWI sequence was an independent predictor of cavity formation ( P= 0.022, OR= 1.138).When conducting quantitative analysis of infarct diameter and taking infarct maximum diameter ≤10 mm group as reference, the cavitation risk of maximum diameter > 15 mm group was about 7.5 times higher ( P= 0.010, OR= 7.464). The maximum diameter of 10-15 mm lost predictive value for cavity formation ( P= 0.129, OR= 2.444). Conclusions: About 61.5% of RSSI develop to cavitation and 38.5% to WMH or disappear. The RSSI showing larger diameter on DWI has a greater possibility of cavitation.

Objectives: The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer's disease, Parkinson's disease (PD) and frontotemporal dementia, in European populations. This study aims to assess the genetic association of the variant rs75932628-T with PD and leucoaraiosis (LA) in a Han Chinese population., Setting: This population-based study was conducted in China by Xiamen University and its affiliated hospital., Participants: 308 patients with LA, 342 patients with PD and 198 healthy blood donors were recruited from the First Affiliated Hospital of Xiamen University., Outcome Measures: Genotyping was performed by molecular beacon real-time PCR and Sanger sequencing., Results: None of our participants carried the rs75932628-T mutation., Conclusions: Our results corroborate and extend previous findings, concluding that the variant rs75932628-T (p.R47H) in TREM2 is not a risk factor for LA or PD in the Han Chinese population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke., Methods: A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA., Results: A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA., Conclusions: LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: There are some controversial results on the relationship between cerebral atherosclerosis and leukoaraiosis in the published papers, where cerebral atherosclerosis was often evaluated by ultrasonography, CTA or MRA. We analyzed data in which patients underwent both MRI and DSA to explore the above relationship in the aged people., Methods: Three hundred and thirty-three patients were enrolled in the study from the Nanjing Stroke Registry. They underwent both cerebral DSA and MRI. Age, sex, and vascular risk factors were collected. Atherosclerosis was scored from grade 0 to 4. Leukoaraiosis was scored from grade 0 to 3., Results: Cerebral artery stenosis was not correlated with the presence of leukoaraiosis. There were no correlations between the number of cerebral moderately or more severely stenotic arteries and the severity of leukoaraiosis in periventricular, deep, or whole white matter (P = .747, .268, and .608, respectively). Old age (odds ratio = 1.103, P = .027) and hypertension (odds ratio = 2.748, P = .003) were correlated with leukoaraiosis in the periventricular white matter. Old age (odds ratio = 1.073, P = .031) and prior stroke (odds ratio = 2.678, P = .002) were correlated with leukoaraiosis in the deep white matter., Conclusions: No apparent correlation exists between cerebral artery stenosis and the presence and severity of leukoaraiosis., (Copyright © 2013 by the American Society of Neuroimaging.)