A Mouse Model of Small-Vessel Disease that Produces Brain-Wide-Identified Microocclusions and Regionally Selective Neuronal Injury

We developed a mouse model of small-vessel disease where occlusions are produced through endovascular injection of fluorescent microspheres that target ~12 μm diameter penetrating arterioles and can be localized in histology. Using Thy1-GFP transgenic mice, we visualized the impact of microocclusions on neuronal structure. Microocclusions in the hippocampus produce cell loss or neuronal atrophy (~7% of lodged microspheres led to microinfarcts), while axons within white matter tracts, as well as the striatum and thalamus became blebbed or disrupted. Although the neocortex contained more occlusions than other structures, labeled layer 5 neurons were relatively resistant to structural damage, with <2% of the lodged microspheres producing obvious neuronal damage.

Download Full-text

Cerebral Small Vessel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21249729 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9729

Author(s):

Jakub Litak ◽

Marek Mazurek ◽

Bartłomiej Kulesza ◽

Paweł Szmygin ◽

Joanna Litak ◽

...

Keyword(s):

Small Vessel Disease ◽

Current Knowledge ◽

Cerebral Small Vessel Disease ◽

Cerebral Vessels ◽

Small Vessel ◽

Epithelial Layer ◽

Small Arteries ◽

Vessel Disease ◽

The Impact ◽

Cerebral Small Vessel Diseases

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger’s disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.

Download Full-text

Abstract T MP35: Frequency, Risk Factors, and Impact of Coexistent Small Vessel Disease in the SAMMPRIS Trial

Stroke ◽

10.1161/str.46.suppl_1.tmp35 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Hyung-Min Kwon ◽

Michael J Lynn ◽

Tanya N Turan ◽

Colin P Derdeyn ◽

David Fiorella ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Small Vessel Disease ◽

Small Vessel ◽

Stroke Recurrence ◽

Logrank Test ◽

Exact Test ◽

Vessel Disease ◽

Atherosclerotic Stenosis ◽

The Impact

Background: Intracranial atherosclerotic stenosis (ICAS) and small vessel disease (SVD) may coexist. We investigated the frequency and risk factors for SVD in SAMMPRIS patients and the impact of SVD on stroke recurrence in the medical arm of the trial. Methods: Of 451 patients enrolled in SAMMPRIS, 313 had baseline brain MRIs read centrally for SVD. SVD was defined by any of the following: old lacunar infarction, Fazekas score of 2-3 for white matter hyperintensities, or microbleeds. We compared risk factors in patients with vs. without SVD using Fisher’s exact test (for percentages), independent groups t test (for means) or Wilcoxon rank sum test (for medians), and compared the survival curves of patients with vs. without SVD in the medical arm for ischemic stroke in the territory of the stenotic artery and any ischemic stroke using the logrank test. Results: Of the 313 patients, 161 (51.4%) had SVD on the baseline MRI. Variables that were significantly (p<0.05) higher in patients with SVD were age, diabetes, lipid disorder, baseline SBP, coronary disease, and old infarct in the territory. The Kaplan-Meier curves in the figure show that patients with SVD were at significantly higher risk of any ischemic stroke (p = 0.048) but not stroke in the territory (p = 0.10) compared with patients without SVD. Conclusion: SVD in patients with ICAS is common, especially in patients who are older, diabetic, hyperlipidemic, and have higher SBP. Patients with ICAS and coexistent SVD are at higher risk of any ischemic stroke but may not be at higher risk for stroke in the territory.

Download Full-text

Contributions of Aging to Cerebral Small Vessel Disease

Annual Review of Physiology ◽

10.1146/annurev-physiol-021119-034338 ◽

2020 ◽

Vol 82 (1) ◽

pp. 275-295 ◽

Cited By ~ 2

Author(s):

T. Michael De Silva ◽

Frank M. Faraci

Keyword(s):

Recent Progress ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Brain Health ◽

Vessel Disease ◽

Age Related ◽

The Face ◽

Basic Biology ◽

The Impact

Cerebral small vessel disease (SVD) is characterized by changes in the pial and parenchymal microcirculations. SVD produces reductions in cerebral blood flow and impaired blood-brain barrier function, which are leading contributors to age-related reductions in brain health. End-organ effects are diverse, resulting in both cognitive and noncognitive deficits. Underlying phenotypes and mechanisms are multifactorial, with no specific treatments at this time. Despite consequences that are already considerable, the impact of SVD is predicted to increase substantially with the growing aging population. In the face of this health challenge, the basic biology, pathogenesis, and determinants of SVD are poorly defined. This review summarizes recent progress and concepts in this area, highlighting key findings and some major unanswered questions. We focus on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.

Download Full-text

[P2-219]: INFLAMMATION MEDIATES THE IMPACT OF SMALL-VESSEL DISEASE ON COGNITION IN ALZHEIMER'S DISEASE: EVIDENCE FROM A MULTIMODAL STRATIFIED COHORT STUDY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.06.871 ◽

2017 ◽

Vol 13 (7S_Part_14) ◽

pp. P693-P694

Author(s):

Di Yu ◽

Joel Ramirez ◽

Hugo Cogo-Moreira ◽

Gustavo Scola ◽

Pak Cheung Chan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

The Impact

Download Full-text

Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.698035 ◽

2021 ◽

Vol 13 ◽

Author(s):

Yangyi Fan ◽

Ming Shen ◽

Yang Huo ◽

Xuguang Gao ◽

Chun Li ◽

...

Keyword(s):

Risk Factors ◽

Small Vessel Disease ◽

Brain Mri ◽

Cognitive Status ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Memory Clinic ◽

Vessel Disease ◽

Mri Features ◽

The Impact

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.

Download Full-text

The impact of cerebral small vessel disease on cognitive impairment and rehabilitation

Cognitive Neurorehabilitation ◽

10.1017/cbo9781316529898.026 ◽

2015 ◽

pp. 360-375 ◽

Cited By ~ 1

Author(s):

Harry V. Vinters ◽

S. Thomas Carmichael

Keyword(s):

Cognitive Impairment ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease ◽

The Impact

Download Full-text

Lesion location and cognitive impact of cerebral small vessel disease

Clinical Science ◽

10.1042/cs20160452 ◽

2017 ◽

Vol 131 (8) ◽

pp. 715-728 ◽

Cited By ~ 59

Author(s):

J. Matthijs Biesbroek ◽

Nick A. Weaver ◽

Geert Jan Biessels

Keyword(s):

Image Analysis ◽

Cognitive Impairment ◽

White Matter ◽

Small Vessel Disease ◽

Case Series ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Lesion Location ◽

Vessel Disease ◽

The Impact

Cerebral small vessel disease (SVD) is an important cause of cognitive impairment. Important MRI manifestations of SVD include white matter hyperintensities (WMH) and lacunes. This narrative review addresses the role of anatomical lesion location in the impact of SVD on cognition, integrating findings from early autopsy studies with emerging findings from recent studies with advanced image analysis techniques. Early autopsy and imaging studies of small case series indicate that single lacunar infarcts in, for example the thalamus, caudate nucleus or internal capsule can cause marked cognitive impairment. However, the findings of such case studies may not be generalizable. Emerging location-based image analysis approaches are now being applied to large cohorts. Recent studies show that WMH burden in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation (ATR), is more relevant in explaining variance in cognitive functioning than global WMH volume. These findings suggest that the future diagnostic work-up of memory clinic patients could potentially be improved by shifting from a global assessment of WMH and lacune burden towards a quantitative assessment of lesion volumes within strategic brain regions. In this review, a summary of currently known strategic regions for SVD-related cognitive impairment is provided, highlighting recent technical developments in SVD research. The potential and challenges of location-based approaches for diagnostic purposes in clinical practice are discussed, along with their potential prognostic and therapeutic applications.

Download Full-text

Comparison Study of ASCO and TOAST Classification System in Chinese Minor Stroke Patients

Cerebrovascular Diseases ◽

10.1159/000497478 ◽

2019 ◽

Vol 47 (1-2) ◽

pp. 95-100 ◽

Cited By ~ 3

Author(s):

Xiao-Yu Xin ◽

Lin Cheng ◽

Zhao Yang ◽

Yu Zhang ◽

Li-Li Zeng ◽

...

Keyword(s):

Classification System ◽

Small Vessel Disease ◽

Small Vessel ◽

Minor Stroke ◽

Large Artery ◽

Stroke Patients ◽

Vessel Disease ◽

Small Artery Occlusion ◽

Toast Classification ◽

The Impact

Background: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Methods: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively. Results: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719–0.832) except cause undetermined category (κ = 0.470). Conclusion: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future.

Download Full-text