scholarly journals Topological relationships between perivascular spaces and progression of white matter hyperintensities: a pilot study in a sample of the Lothian Birth Cohort 1936

Author(s):  
Abbie N Barnes ◽  
Lucia Ballerini ◽  
Maria Del Carmen Valdes Hernandez ◽  
Francesca M Chappell ◽  
Susana Munoz Maniega ◽  
...  

Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesised to also have topological proximity. However, this, and the influence of their spatial proximity on WMH progression are unknown. We analysed longitudinal MRI data from 29/32 participants (mean age at baseline = 71.9 years) in a longitudinal study of cognitive ageing, from three waves of data collection at 3-year intervals, alongside semi-automatic segmentation masks for PVS and WMH, to assess relationships. The majority of deep WMH clusters were found adjacent to or enclosing PVS (Wave 1: 77%; 2: 76%; 3: 69%), especially in frontal, parietal and temporal regions. Of the WMH clusters in the deep white matter that increased between waves, most increased around PVS (Waves 1-2: 73%; 2-3: 72%). Formal statistical comparisons of severity of each if these two SVD markers yielded no associations between deep WMH progression and PVS proximity. These findings may suggest deep WMH clusters preferentially form and grow around PVS, possibly reflecting the consequences of impaired interstitial fluid drainage via PVS. The utility of these relationships as predictors of WMH progression remains unclear.

Author(s):  
Xuemei Qi ◽  
Huidong Tang ◽  
Qi Luo ◽  
Bei Ding ◽  
Jie Chen ◽  
...  

ABSTRACT:Introduction: White matter hyperintensities (WMHs) were commonly seen in brain magnetic resonance imaging (MRI) of the elderly. Many studies found that WMHs were associated with cognitive decline and dementia. However, the association between WMHs in different brain regions and cognitive decline remains debated. Methods: We explored the association of the severity of WMHs and cognitive decline in 115 non-demented elderly (≥50 years old) sampled from the Wuliqiao Community located in urban area of Shanghai. MRI scans were done during 2009–2011 at the beginning of the study. Severity of WMHs in different brain regions was scored by Improved Scheltens Scale and Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated by Mini-Mental State Examination (MMSE) every 2 to 4 years during 2009–2018. Results: After adjusting for confounding factors including age, gender, education level, smoking status, alcohol consumption, depression, hypertension, diabetes, hyperlipidemia, brain infarcts, brain atrophy, apoE4 status, and baseline MMSE score, periventricular and subcortical WMH lesions as well as WMHs in cholinergic pathways were significantly associated with annual MMSE decline ( p < 0.05), in which the severity of periventricular WMHs predicted a faster MMSE decline (–0.187 points/year, 95% confidence interval: –0.349, –0.026, p = 0.024). Conclusions: The severity of WMHs at baseline was associated with cognitive decline in the non-demented elderly over time. Interventions on WMH lesions may offer some benefits for cognitive deterioration.


Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
Michelle P. Lin ◽  
Thomas G. Brott ◽  
David S. Liebeskind ◽  
James F. Meschia ◽  
Kevin Sam ◽  
...  

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.


2020 ◽  
Vol 75 (8) ◽  
pp. 1545-1550
Author(s):  
Timothy P Siejka ◽  
Velandai K Srikanth ◽  
Ruth E Hubbard ◽  
Chris Moran ◽  
Richard Beare ◽  
...  

Abstract Background The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people. Methods People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume. Results At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty. Conclusions We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty.


2021 ◽  
pp. 088307382110279
Author(s):  
Salman Rashid ◽  
Samantha Weaver ◽  
Khaled Al-Robaidi ◽  
Leon Dure ◽  
Sumit Singh

Background: Cyclic vomiting syndrome is classified as a possible subset of migraine. Brain magnetic resonance imaging (MRI) findings of white matter hyperintensities are well documented in migraineurs, but not in patients with cyclic vomiting syndrome. This study focuses on white matter hyperintensities in children with cyclic vomiting syndrome. Methods: We investigated our database of outpatient medical records for the diagnosis codes associated with cyclic vomiting syndrome from January 2008 to October 2018. Results: Brain MRIs were obtained in 31 of 185 patients (∼17%) with a diagnosis code related to cyclic vomiting syndrome. We excluded 13 of 31 patients because of the inaccessibility of images or a confounding diagnosis. Remaining patients were divided into 2 groups: 13 of 18 cyclic vomiting syndrome with migraine (CVS+M), and 5 of 18 cyclic vomiting syndrome without migraine (CVS-M). We found that 3 of the 13 patients in the CVS +M group had migraine-like white matter hyperintensities compared to 0 of the 5 in the CVS-M group. Conclusion: This small study suggests a possible relationship between white matter hyperintensities and CVS+M. A larger study is required to validate these findings.


2021 ◽  
pp. 028418512110665
Author(s):  
Meimei Wang ◽  
Yunfei Li ◽  
Yingjie Song ◽  
Yingyu Zhao ◽  
Xiaohu Zhao

Background Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. Purpose To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. Material and Methods We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2–30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Results Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden ( P  = 0.005) and infarct diameter ( P  = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3–4) at baseline was independently related to cavitation ( P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1–3) at baseline to 3 (IQR=2–4) at follow-up. The extent of the increase in total burden was correlated with cavitation ( r = 0.201; P = 0.004). Conclusion Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.


2019 ◽  
Vol 32 (6) ◽  
pp. 438-444
Author(s):  
Adrien Villain ◽  
Grégoire Boulouis ◽  
Wagih Ben Hassen ◽  
Christine Rodriguez-Regent ◽  
Denis Trystram ◽  
...  

Purpose Investigating the associations between cerebral small vessel disease (cSVD) burden and cerebral vasospasm (CVS), delayed cerebral ischemia (DCI) and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods Consecutive aSAH patients with initial (<7 days after onset) and 3-month follow-up brain magnetic resonance imaging (MRI) and clinical evaluation at 6 months were included. The cSVD burden score was built using MRI criteria. CVS was defined according to transcranial Doppler examination and computed tomography (CT) or digital subtraction angiography. DCI was defined by the appearance of hyperintense fluid-attenuated inversion recovery lesions, with territorial or cortico-subcortical distribution, between initial MRI and 3-month MRI. The modified Rankin scale of ≤2 at 6 months was considered a favorable outcome. Using univariate and multivariable analyses, we investigated the associations between cSVD and CVS, DCI and clinical outcome. Results A total of 113 patients were included in the study sample (median age 49.1 years (IQR 42.1–60.8), 70/113 females). The burden of cSVD was mild with a median of 0 (IQR 0–1). When comparing patients with no/mild versus those with moderate/severe cSVD burden, we did not find a univariable difference regarding vasospasm occurrence (60% versus 46.1%, p = 0.54), DCI (20.2% versus 23%, p = 0.66) or favorable outcome at 3 months (94% versus 83.3%, p = 0.20). There was a univariable trend towards more frequent favorable outcome in patients with no/milde white matter hyperintensities versus those with moderate/severe white matter hyperintensities (92% versus 85%, p = 0.09). In multivariable models, cSVD markers were not associated with CVS occurrence and severity, DCI or clinical outcome. Conclusions In patients with mild aSAH, the burden of cSVD as assessed by MRI is minimal and is not associated with CVS, DCI or clinical outcome.


2017 ◽  
Vol 38 (9) ◽  
pp. 1654-1663 ◽  
Author(s):  
François De Guio ◽  
Alexandre Vignaud ◽  
Hugues Chabriat ◽  
Eric Jouvent

In Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), by contrast to sporadic cerebral small vessel disease related to age and hypertension, white matter hyperintensities (WMH) are frequently observed in the white matter of anterior temporal poles, external capsules, and superior frontal regions. Whether these WMH (specific WMH) differ from those observed in other white matter areas (nonspecific WMH) remains unknown. Twenty patients were scanned to compare specific and nonspecific WMH using high-resolution images and analyses of relaxation times (T1R: longitudinal relaxation time and T2*R: effective transversal relaxation time). Specific WMH were characterized by significantly longer T1R and T2*R (T1R: 2309 ± 120 ms versus 2145 ± 138 ms; T2*R: 40 ± 5 ms versus 35 ± 5 ms, p < 0.001). These results were not explained by the presence of dilated perivascular spaces found in the close vicinity of specific WMH. They were not either explained by the normal regional variability of T1R and T2*R in the white matter nor by systematic imaging artifacts as shown by the study of 17 age- and sex-matched healthy controls. Our results suggest large differences in water content between specific and nonspecific WMH in CADASIL, supporting that mechanisms underlying WMH may differ according to their location.


Stroke ◽  
2021 ◽  
Author(s):  
Mozhu Ding ◽  
Rui Wang ◽  
Grégoria Kalpouzos ◽  
Erika J. Laukka ◽  
Yuanjing Li ◽  
...  

Background and Purpose: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Methods: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001–2004) and follow-ups (2004–2007 and 2007–2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. Results: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04–0.86]) and lateral ventricular volume (0.58 [0.13–1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Conclusions: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.


2021 ◽  
Vol 13 ◽  
Author(s):  
Shanshan Cao ◽  
Jiajia Nie ◽  
Jun Zhang ◽  
Chen Chen ◽  
Xiaojing Wang ◽  
...  

ObjectiveWhite matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances.MethodsA total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored.ResultsThe analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs.ConclusionOur study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.


Author(s):  
Emilia Salvadori ◽  
Fabio Fierini ◽  
Leonardo Pantoni

Cerebral small vessel disease (SVD) is well recognized as a highly prevalent disorder that plays an important role in stroke and cognitive impairment. This chapter deals with the relationship between SVD and cognition in longitudinal studies and aims at clarifying the role of SVD as a marker and determinant of neurocognitive impairment. This chapter discusses the prognostic role of magnetic resonance imaging (MRI)-based SVD features (i.e., white matter hyperintensities, small lacunar infarcts, microbleeds, and perivascular spaces) as predictors of dementia or cognitive decline. The evidence reviewed in this chapter provides strong supports for the impact of white matter hyperintensities and small lacunar infarcts in increasing the risk of dementia and cognitive decline. Microbleeds and perivascular spaces have been more recently targeted as MRI features of SVD, and this chapter will review the increasing evidence of their role in cognitive decline.


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