Network Localisation of White Matter Damage in Cerebral Small Vessel Disease

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

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Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease

Acta Neuropathologica Communications ◽

10.1186/s40478-014-0169-8 ◽

2014 ◽

Vol 2 (1) ◽

Cited By ~ 68

Author(s):

Daniel Kaiser ◽

Gesa Weise ◽

Karoline Möller ◽

Johanna Scheibe ◽

Claudia Pösel ◽

...

Keyword(s):

Animal Model ◽

White Matter ◽

Cognitive Decline ◽

Small Vessel Disease ◽

Early Stage ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Hypertensive Rats ◽

White Matter Damage ◽

Vessel Disease

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Venous disruption affects white matter integrity through increased interstitial fluid in cerebral small vessel disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20904840 ◽

2020 ◽

Vol 41 (1) ◽

pp. 157-165

Author(s):

Ruiting Zhang ◽

Peiyu Huang ◽

Yeerfan Jiaerken ◽

Shuyue Wang ◽

Hui Hong ◽

...

Keyword(s):

White Matter ◽

Interstitial Fluid ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Free Water ◽

Cerebral Small Vessel Disease ◽

White Matter Integrity ◽

Small Vessel ◽

White Matter Damage ◽

Vessel Disease

Deep medullary veins (DMVs) participate in the drainage of surrounding white matter. In cerebral small vessel disease (CSVD), disrupted DMVs were often observed together with damaged white matter, but the phenomenon lacked validation and explanation. We hypothesized that venous disruption might cause white matter damage through increased interstitial fluid resulting from hemodynamic alteration, and we designed a comprehensive multi-modality MRI study to testify our hypothesis. Susceptibility-weighted imaging was used to investigate the characteristics of DMVs and derive DMVs scores. Free water elimination diffusion tensor imaging model was used to analyze interstitial fluid fraction (fraction of free water, fFW) and white matter integrity (tissue fractional anisotropy, FAt). Totally, 104 CSVD patients were included. Total DMVs score was associated with FAt of DMVs drainage area. The effect of total DMVs score on FAt was mediated by fFW, after controlling for age, sex, hypertension, regional cerebral blood flow and lacune numbers. The relationships between DMVs score, fFW and FAt were also significant in most DMVs drainage subregions. Therefore, we discovered the DMVs disruption – increased interstitial fluid – white matter damage link in CSVD patients, which was independent of arterial perfusion variations.

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Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2021.105824 ◽

2021 ◽

Vol 30 (7) ◽

pp. 105824

Author(s):

Salvatore Rudilosso ◽

Luis Mena ◽

Diana Esteller ◽

Marta Olivera ◽

Juan José Mengual ◽

...

Keyword(s):

White Matter ◽

Disease Burden ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

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Cognitive heterogeneity among community-dwelling older adults with Cerebral Small Vessel Disease

10.31234/osf.io/692bf ◽

2018 ◽

Author(s):

Ayan Dey ◽

Vessela Stamenova ◽

Agnes Bacopulos ◽

Nivethika Jeyakumar ◽

Gary R. Turner ◽

...

Keyword(s):

White Matter ◽

Subjective Experience ◽

Small Vessel Disease ◽

Neuropsychological Testing ◽

Cerebral Small Vessel Disease ◽

Community Dwelling ◽

Small Vessel ◽

Vessel Disease ◽

Age Related ◽

Subjective Complaints

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.

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Abstract P369: Cerebral Small Vessel Disease and Enlarged Cardiac Ventricles

Stroke ◽

10.1161/str.52.suppl_1.p369 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Kayla Navarro ◽

Ka-ho Wong ◽

Majd M Ibrahim ◽

Adam H De Havenon ◽

Eric Goldstein

Keyword(s):

White Matter ◽

Ejection Fraction ◽

Right Ventricular ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Right Atrial ◽

Ventricular Ejection Fraction ◽

Vessel Disease ◽

Atrial Area

Introduction: White matter hyperintensities (WMH) are a radiographic marker for cerebral small vessel disease (CSVD). Conditions altering cerebral venous outflow such as elevated central venous pressure and right atrial pressure in individuals with cardiac valvular disease have been implicated in the development of WMH. Hypothesis: We hypothesize that increased right-heart chamber size in individuals without significant cardiac valvular disease is associated with worse WMH. Methods: A retrospective chart review of adults with a brain MRI and a 2-dimensional transthoracic echocardiogram (TTE) was performed. Worst burden of WMH by way of Fazekas score, either periventricular or deep white matter, served as the primary outcome. Statistical analysis was performed using a multivariate ordinal logistic regression model. Results: A total of 132 individuals were included. Right atrial area (OR 0.93, 95% CI 0.87 to 1.00, p = 0.0041), right ventricular internal diameter (OR 0.48, 95%CI 0.27 to 0.83, p = 0.008) and left atrial area (OR 0.93, 95%CI 0.88 to 0.98, p = 0.007) was identified as being significant. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (OR 0.99, 95%CI 0.93 to 1.05, p = 0.670), right ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.670) and left ventricular ejection fraction (OR 0.99, 95%CI 0.96 to 1.02, p = 0.567). Analysis of isolated DWM or PVWM Fazekas scores did not find significant predictors in relation to cardiac structure or function. Conclusions: Through non-invasive cardiac imaging, we identified that cardiac structural abnormalities as opposed to functional abnormalities were associated with worse WMH. Mechanistically this may result from altered intracerebral arteriovenous coupling or a shared pathophysiologic pathway between WMH and coronary microvascular disease.

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Abstract TMP119: High Homocysteine Level is not Associated With White Matter Changes, Dementia nor Mortality After Ischemic Stroke

Stroke ◽

10.1161/str.47.suppl_1.tmp119 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Susanna Melkas ◽

Sami Curtze ◽

Gerli Sibolt ◽

Niku K Oksala ◽

Jukka Putaala ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Homocysteine Level ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cross Sectional ◽

White Matter Changes ◽

Vessel Disease

Background: Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up. Methods: A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time. Findings: The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up. Interpretation: In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.

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A Systematic Review of WNT Signaling in Endothelial Cell Oligodendrocyte Interactions: Potential Relevance to Cerebral Small Vessel Disease

Cells ◽

10.3390/cells9061545 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1545

Author(s):

Narek Manukjan ◽

Zubair Ahmed ◽

Daniel Fulton ◽

W. Matthijs Blankesteijn ◽

Sébastien Foulquier

Keyword(s):

White Matter ◽

Small Vessel Disease ◽

Clinical Manifestations ◽

Cell Types ◽

Cerebral Small Vessel Disease ◽

White Matter Injury ◽

Small Vessel ◽

Limited Attention ◽

Vessel Disease

Key pathological features of cerebral small vessel disease (cSVD) include impairment of the blood brain barrier (BBB) and the progression of white matter lesions (WMLs) amongst other structural lesions, leading to the clinical manifestations of cSVD. The function of endothelial cells (ECs) is of major importance to maintain a proper BBB. ECs interact with several cell types to provide structural and functional support to the brain. Oligodendrocytes (OLs) myelinate axons in the central nervous system and are crucial in sustaining the integrity of white matter. The interplay between ECs and OLs and their precursor cells (OPCs) has received limited attention yet seems of relevance for the study of BBB dysfunction and white matter injury in cSVD. Emerging evidence shows a crosstalk between ECs and OPCs/OLs, mediated by signaling through the Wingless and Int-1 (WNT)/β-catenin pathway. As the latter is involved in EC function (e.g., angiogenesis) and oligodendrogenesis, we reviewed the role of WNT/β-catenin signaling for both cell types and performed a systematic search to identify studies describing a WNT-mediated interplay between ECs and OPCs/OLs. Dysregulation of this interaction may limit remyelination of WMLs and render the BBB leaky, thereby initiating a vicious neuroinflammatory cycle. A better understanding of the role of this signaling pathway in EC–OL crosstalk is essential in understanding cSVD development.

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