scholarly journals Intracranial pulsatility in patients with cerebral small vessel disease: a systematic review

2018 ◽  
Vol 132 (1) ◽  
pp. 157-171 ◽  
Author(s):  
Yulu Shi ◽  
Michael J. Thrippleton ◽  
Ian Marshall ◽  
Joanna M. Wardlaw

Growing evidence suggests that increased intracranial pulsatility is associated with cerebral small vessel disease (SVD). We systematically reviewed papers that assessed intracranial pulsatility in subjects with SVD. We included 27 cross-sectional studies (n=3356): 20 used Doppler ultrasound and 7 used phase-contrast MRI. Most studies measured pulsatility in the internal carotid or middle cerebral arteries (ICA, MCA), whereas few assessed veins or cerebrospinal fluid (CSF). Methods to reduce bias and risk factor adjustment were poorly reported. Substantial variation between studies in assessment of SVD and of pulsatility indices precluded a formal meta-analysis. Eight studies compared pulsatility by SVD severity (n=26–159, median = 74.5): arterial pulsatility index was generally higher in more severe SVD (e.g. MCA: standardized mean difference = 3.24, 95% confidence interval [2.40, 4.07]), although most did not match for age. Seventeen studies (n=9–700; median = 110) performed regression or correlation analysis, of which most showed that increased pulsatility was associated with SVD after adjustment for age. In conclusion, most studies support a cross-sectional association between higher pulsatility in large intracranial arteries and SVD. Future studies should minimize bias, adjust for potential confounders, include pulsatility in veins and CSF, and examine longitudinal relationship between pulsatility and SVD. Agreement on reliable measures of intracranial pulsatility would be helpful.

2015 ◽  
Vol 6 (03) ◽  
pp. 336-338 ◽  
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mería ◽  
María de la Luz Andrade ◽  
Pablo R. Castillo ◽  
Mauricio Zambrano ◽  
...  

ABSTRACT Background: Diagnosis of cerebral small vessel disease (SVD) is a challenge in remote areas where magnetic resonance imaging (MRI) is not available. Hospital-based studies in high-risk or stroke patients have found an association between the pulsatility index (PI) of intracranial arteries - as derived from transcranial Doppler (TCD) - and white matter hyperintensities (WMH) of presumed vascular origin. We aimed to assess the reliability of cerebral pulsatility indices to identify candidates for MRI screening in population-based studies assessing prevalence of SVD. Methods: A representative sample of stroke-free Atahualpa residents aged ≥65 years investigated with MRI underwent TCD. Using generalized linear models, we evaluated whether the PI of major intracranial arteries correlate with WMH (used as a proxy of diffuse SVD), after adjusting for demographics and cardiovascular risk factors. Results: Out of 70 participants (mean age 70.6 ± 4.6 years, 57% women), 28 (40%) had moderate-to-severe WMH. In multivariate models, there were no differences across categories of WMH in the mean PI of middle cerebral arteries (1.10 ± 0.16 vs. 1.22 ± 0.24, β: 0.065, 95% confidence interval (CI): −0.084-0.177, P = 0.474) or vertebrobasilar arteries (1.11 ± 0.16 vs. 1.29 ± 0.27, β: 0.066, 95% CI: −0.0024-0.156, P = 0.146). Conclusions: Cerebral PI should not be used to identify candidates for MRI screening in population-based studies assessing the burden of SVD.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susanna Melkas ◽  
Sami Curtze ◽  
Gerli Sibolt ◽  
Niku K Oksala ◽  
Jukka Putaala ◽  
...  

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.


2018 ◽  
Vol 314 (6) ◽  
pp. H1117-H1136 ◽  
Author(s):  
Dana R. Jorgensen ◽  
C. Elizabeth Shaaban ◽  
Clayton A. Wiley ◽  
Peter J. Gianaros ◽  
Joseph Mettenburg ◽  
...  

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.


2016 ◽  
Vol 36 (10) ◽  
pp. 1653-1667 ◽  
Author(s):  
Yulu Shi ◽  
Michael J Thrippleton ◽  
Stephen D Makin ◽  
Ian Marshall ◽  
Mirjam I Geerlings ◽  
...  

White matter hyperintensities are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease. They are commonly attributed to chronic hypoperfusion, although whether low cerebral blood flow is cause or effect is unclear. We systematically reviewed studies that assessed cerebral blood flow in small vessel disease patients, performed meta-analysis and sensitivity analysis of potential confounders. Thirty-eight studies ( n = 4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most cerebral blood flow data were from grey matter. Twenty-four cross-sectional studies ( n = 1161) were meta-analysed, showing that cerebral blood flow was lower in subjects with more white matter hyperintensity, globally and in most grey and white matter regions (e.g. mean global cerebral blood flow: standardised mean difference−0.71, 95% CI −1.12, −0.30). These cerebral blood flow differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies ( n = 1079) gave differing results, e.g., more baseline white matter hyperintensity predated falling cerebral blood flow (3.9 years, n = 575); cerebral blood flow was low in regions that developed white matter hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with more white matter hyperintensity cross-sectionally, but evidence for falling cerebral blood flow predating increasing white matter hyperintensity is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.


Stroke ◽  
2020 ◽  
Vol 51 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Yuan Ma ◽  
Alex Song ◽  
Anand Viswanathan ◽  
Deborah Blacker ◽  
Meike W. Vernooij ◽  
...  

Background and Purpose— Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia. Methods— A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models. Results— These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06–1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74–1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89–1.44]) were not statistically significant. Conclusions— A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.


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