The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. Methods: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. Results: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, p = 0.395). Conclusion: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

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Serum Homocysteine as One of the Risk Factors of Cerebral Small Vessel Disease in Chinese Patients

Journal of Modern Neurology ◽

10.36922//jmn.v5i1.898 ◽

2019 ◽

pp. 1-7

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Logistic Regression ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Chinese Patients ◽

Multivariate Logistic Regression ◽

Vessel Disease ◽

Serum Homocysteine

Objective: This study aimed to determine the risk factors of cerebral small vessel disease (CSVD) from different variables including serum homocysteine (Hcy) in a group of Chinese patients. Methods: A total of 139 patients with CSVD admitted to the affiliated hospital of Xuzhou Medical University from July 2017 to July 2018 were enrolled. Fifty healthy individuals were selected as controls. According to the diagnostic criteria, the CSVD patients were divided into three groups, namely, lacunar infarction (LI) group (n=59), white matter lesion (WML) group (n=46), and LI+WML group (n=34). The serum Hcy levels of the three groups were observed and compared. Multivariate logistic regression was performed to determine whether a number of variables including serum Hcy level are the risk factors of CSVD. Results: Hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), fasting blood glucose (FBG), and Hcy were significantly higher in CSVD group than the control group (P < 0.05). The age, gender, SBP, platelet, TG, and Hcy were significantly different between the LI group, WML group, and LI+WML groups (P<0.05). The age and Hcy level of patients in LI+WML group were higher than those of the LI group and WML group, and the difference was statistically significant (P < 0.05). The level of SBP was higher in the LI group than the WML group (P < 0.05). The Hcy level of patients in the LI group was higher than that in the WML group, but there was no significant difference (P > 0.05). The platelet and TG were significantly higher in WML group than LI group and LI+WML group (P < 0.05). Controlling the influence of sex and age, multivariate logistic regression analysis revealed that the Hcy levels were correlated with the incidence of the CSVD. Conclusion: Serum Hcy level is a risk factor for CSVD. Regular detection of serum Hcy level and timely intervention may effectively prevent and control the occurrence and development of CSVD.

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Enlarged Perivascular Spaces and Cerebral Small Vessel Disease in Spontaneous Intracerebral Hemorrhage Patients

Frontiers in Neurology ◽

10.3389/fneur.2019.00881 ◽

2019 ◽

Vol 10 ◽

Author(s):

Xin Wang ◽

Hao Feng ◽

Yu Wang ◽

Jian Zhou ◽

Xingquan Zhao

Keyword(s):

Intracerebral Hemorrhage ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Spontaneous Intracerebral Hemorrhage ◽

Vessel Disease

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Enlarged perivascular spaces and cognitive impairment after stroke and transient ischemic attack

International Journal of Stroke ◽

10.1177/1747493016666091 ◽

2016 ◽

Vol 13 (1) ◽

pp. 47-56 ◽

Cited By ~ 35

Author(s):

Francesco Arba ◽

Terence J Quinn ◽

Graeme J Hankey ◽

Kennedy R Lees ◽

Joanna M Wardlaw ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Cognitive Impairment ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

One Year

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03–2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

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Coagulation Factor XIII VaI34Leu Polymorphism in Patients with Small Vessel Disease or Primary Intracerebral Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000083251 ◽

2005 ◽

Vol 19 (3) ◽

pp. 165-170 ◽

Cited By ~ 17

Author(s):

Agnieszka Slowik ◽

Tomasz Dziedzic ◽

Joanna Pera ◽

Denise A. Figlewicz ◽

Andrzej Szczudlik

Keyword(s):

Intracerebral Hemorrhage ◽

Factor Xiii ◽

Small Vessel Disease ◽

Coagulation Factor ◽

Small Vessel ◽

Vessel Disease ◽

Coagulation Factor Xiii

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Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.116 ◽

2015 ◽

Vol 36 (1) ◽

pp. 72-94 ◽

Cited By ~ 98

Author(s):

Anna Poggesi ◽

Marco Pasi ◽

Francesca Pescini ◽

Leonardo Pantoni ◽

Domenico Inzitari

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

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Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Neurology ◽

10.1212/wnl.0000000000013077 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013077

Author(s):

Corey W Bown ◽

Roxana O Carare ◽

Matthew S Schrag ◽

Angela L Jefferson

Keyword(s):

Fluid Transport ◽

Small Vessel Disease ◽

Treatment Strategies ◽

Small Vessel ◽

Aging Brain ◽

Perivascular Spaces ◽

Vessel Disease ◽

Clinical Consequences ◽

The Brain

Perivascular spaces (PVS) are fluid filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on magnetic resonance imaging. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as two possible mechanisms that drive ePVS formation. In this review, we describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the two most prominent theoretical views and review ePVS associations with other common small vessel disease markers. As ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer’s disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

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Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions

Stroke ◽

10.1161/str.52.suppl_1.p332 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Dorothee Schoemaker ◽

Yesica Zuluaga ◽

Lina Velilla ◽

Carolina Ospina ◽

Francisco Lopera ◽

...

Keyword(s):

Small Vessel Disease ◽

Structural Mri ◽

Vascular Cognitive Impairment ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Perivascular Spaces ◽

Cerebrovascular Injury ◽

Vessel Disease ◽

History Of

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.

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Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders

Frontiers in Neurology ◽

10.3389/fneur.2021.747115 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yangyi Fan ◽

Yicheng Xu ◽

Ming Shen ◽

Huailian Guo ◽

Zhaoxu Zhang

Keyword(s):

Linear Regression ◽

Regression Model ◽

Linear Regression Model ◽

Small Vessel Disease ◽

Multiple Linear Regression Model ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Perivascular Spaces ◽

Vessel Disease ◽

Moca Score

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P < 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.

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