Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial

Arba, Francesco; Mair, Grant; Carpenter, Trevor; Sakka, Eleni; Sandercock, Peter; Lindley, Richard I.; Inzitari, Domenico; Wardlaw, Joanna M.

doi:10.1016/j.jstrokecerebrovasdis.2017.03.002

Cited by 57 publications

(71 citation statements)

References 31 publications

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“…Apart from BBB permeability change, we also found that participants with higher total MRI cSVD burden had a lower fractional blood plasma volume in the NAWM, CGM, and DGM. As blood plasma volume is related to the CBF, this finding is in line with a previous study ( 29 ), further illustrating the association between the cSVD and reduced CBF. A meta-analysis of 4 longitudinal and 34 cross-sectional CBF studies also showed that CBF was lower in subjects with more WMH, and most CBF data were from gray matter, which was consistent with our study ( 30 ).…”

Section: Discussionsupporting

confidence: 92%

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Zuo

et al. 2018

Front. Neurol.

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ObjectiveSeveral studies have demonstrated that compromised blood–brain barrier (BBB) integrity may play a pivotal role in the pathogenesis of individual cerebral small vessel disease (cSVD) markers, but the association between BBB permeability and total magnetic resonance imaging (MRI) cSVD burden remains unclear. This study aimed to investigate the relationship between BBB permeability and total MRI cSVD burden.MethodsConsecutive participants without symptomatic stroke history presented for physical examination were enrolled in this cross-sectional study. The presence of lacunes, white matter hyperintensities (WMH), cerebral microbleeds, and enlarged perivascular spaces was recorded in an ordinal score (range 0–4). We used dynamic contrast-enhanced-MRI and Patlak pharmacokinetic model to quantify BBB permeability in the normal-appearing white matter (NAWM), WMH, cortical gray matter (CGM), and deep gray matter (DGM).ResultsAll 99 participants averaged 70.33 years old (49–90 years). Multivariable linear regression analyses adjusted for age, sex, and vascular risk factors showed that leakage rate and area under the leakage curve in the NAWM, WMH, CGM, and DGM were positively associated with total MRI cSVD burden (all P < 0.01). Moreover, fractional blood plasma volumes in the NAWM, CGM, and DGM were negatively associated with total MRI cSVD burden (all P < 0.05).ConclusionThis study verified that compromised BBB integrity is associated with total MRI cSVD burden, suggesting that BBB dysfunction may be a critical contributor to the pathogenesis of cSVD. Longitudinal studies are required to determine whether there is a causal relationship between BBB permeability and total MRI cSVD burden.

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Section: Discussionsupporting

confidence: 92%

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Zuo

et al. 2018

Front. Neurol.

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“…29,30 Seven of the 27 new cross-sectional studies reported only the results of association analyses, and did not provide quantitative data for CBF or WMH measurements. Patient groups in these studies included patients with acute stroke, 12,31 MCI, 32 vascular depression 33 , individuals at varying risk of cerebrovascular disease 34 and older individuals with WMH. 17,35 The three newly identified longitudinal studies (n=440) investigated baseline CBF and WMH progression in older individuals with WMH (Table 1) over follow-up periods ranging from two 36 to five 37 years.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…While 2 studies investigated associations between baseline WMH volume and change in either subregional 15 or global 37 CBF, one study considered associations between change in WMH volume and change in cortical grey matter CBF. 36 Fifteen studies used ASL 6-8, 10, 14, 15, 19, 20, 25, 27, 30, 32, 34-36 , 3 used CT perfusion 18,28,29 , 2 used dynamic susceptibility contrast (DSC) MRI 9,37 , one study each used SPECT 21 , phase contrast MRI 22 , CT angiography/digital subtraction angiography, 31 PET, 23 and a combination of CT and DSC MRI 12 . Five studies used transcranial Doppler ultrasound 16,17,24,26,33 .…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated meta-analysis

Stewart

Stringer

Shi

et al. 2020

Preprint

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Cerebral small vessel disease is a major contributor to stroke and dementia, characterised by white matter hyperintensities (WMH) on neuroimaging. WMH are associated with reduced cerebral blood flow (CBF) cross-sectionally, though longitudinal associations remain unclear. We updated a 2016 meta-analysis, identifying 30 studies, 27 cross-sectional (n=2956) and 3 longitudinal (n=440), published since 2016. Cross-sectionally, we meta-analysed 10 new studies with 24 previously reported studies, total 34 (n=2180), finding lower CBF to be associated with worse WMH burden (mean global CBF: standardised mean difference: -0.45, 95% confidence interval (CI): -0.64,-0.27). Longitudinally, the association of baseline CBF with WMH progression varied: the largest study (5 years, n=252) found no associations, while another small study (4.5 years, n=52) found that low CBF in the periventricular WMH penumbra predicted WMH progression. We could not meta-analyse longitudinal studies due to different statistical and methodological approaches. We found lower CBF within WMH compared to normal appearing white matter (novel meta-analysis; 5 cross-sectional studies; n=295; SMD: -1.51, 95% CI: -1.94,-1.07). These findings highlight that relationships between resting CBF and WMH are complex and that more longitudinal studies analysing regional CBF and subsequent WMH change are required to determine the role of CBF in small vessel disease progression.

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“…SVD lesions reduce the brain’s ‘reserve’ against vascular insults and its plasticity ( Mok et al, 2017 ). Stroke patients with more severe SVD are prone to have larger infarct volume ( Helenius et al, 2016 ), impaired reperfusion ( Arba et al, 2017b ), and recurrent stroke ( Lau et al, 2017 ). Consequently, disability and cognitive decline were more likely to occur among stroke survivors with severe SVD burden ( Huijts et al, 2013 ; Arba et al, 2017a ).…”

Section: Discussionmentioning

confidence: 99%

Cerebral Small Vessel Disease Burden Is Associated With Poststroke Depressive Symptoms: A 15-Month Prospective Study

Liang

Chen

Mok

et al. 2018

Front. Aging Neurosci.

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Objective: All types of cerebral small vessel disease (SVD) markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds, and perivascular spaces were found to be associated with poststroke depressive symptoms (PDS). This study explored whether the combination of the four markers constituting an overall SVD burden was associated with PDS.Methods: A cohort of 563 patients with acute ischemic stroke were followed over a 15-month period after the index stroke. A score of ≥7 on the 15-item Geriatric Depression Scale was defined as clinically significant PDS. Scores of the four SVD markers ascertained on magnetic resonance imaging were summed up to represent total SVD burden. The association between SVD burden and PDS was assessed with generalized estimating equation models.Results: The study sample had a mean age of 67.0 ± 10.2 years and mild-moderate stroke [National Institutes of Health Stroke Scale score: 3, interquartile, 1–5]. PDS were found in 18.3%, 11.6%, and 12.3% of the sample at 3, 9, and 15 months after stroke, respectively. After adjusting for demographic characteristics, vascular risk factors, social support, stroke severity, physical and cognitive functions, and size and locations of stroke, the SVD burden was associated with an increased risk of PDS [odds ratio = 1.30; 95% confidence interval = 1.07–1.58; p = 0.010]. Other significant predictors of PDS were time of assessment, female sex, smoking, number of acute infarcts, functional independence, and social support.Conclusion: SVD burden was associated with PDS examined over a 15-month follow-up in patients with mild to moderate acute ischemic stroke.

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Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial

Abstract: The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.

Cited by 57 publications

References 31 publications

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated meta-analysis

Cerebral Small Vessel Disease Burden Is Associated With Poststroke Depressive Symptoms: A 15-Month Prospective Study

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