Gray and white matter changes linking cerebral small vessel disease to gait disturbances

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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White matter changes and gait decline in cerebral small vessel disease

NeuroImage Clinical ◽

10.1016/j.nicl.2017.12.007 ◽

2018 ◽

Vol 17 ◽

pp. 731-738 ◽

Cited By ~ 22

Author(s):

H.M. van der Holst ◽

A.M. Tuladhar ◽

V. Zerbi ◽

I.W.M. van Uden ◽

K.F. de Laat ◽

...

Keyword(s):

White Matter ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Changes ◽

Vessel Disease

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Affective status in cerebral small vessel disease

Medicinski pregled ◽

10.2298/mpns1910280s ◽

2019 ◽

Vol 72 (9-10) ◽

pp. 280-285

Author(s):

Aleksandar Stevanovic ◽

Anja Stefanovic ◽

Natasa Stojanovski ◽

Gordana Tomic ◽

Jasna Zidverc-Trajkovic ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Affective Disorders ◽

Small Vessel Disease ◽

Statistical Tests ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Screening Tests ◽

White Matter Changes ◽

Vessel Disease

Introduction. Cerebral small vessel disease is a neurological condition characterized by motor, cognitive and affective disorders, often found on brain magnetic resonance imaging scans in patients with vascular risk factors. Affective disorders may have a major impact on patients? quality of life, although they are often ignored as an entity in cerebrovascular pathology. Material and Methods. This prospective study included 80 patients with the diagnosis of cerebral small vessel disease admitted at the Clinic of Neurology, Clinical Center of Serbia in the period from January 1, 2017 to January 1, 2019. Baseline demographic data and brain magnetic resonance findings were obtained along with the results of cognitive function and affective status tests. Data were analyzed using standard statistical tests. Results. Standard screening tests revealed that 51.25% and 33.75% of our patients with cerebral small vessel disease suffer from apathy and depression, respectively. A significant correlation was found between the severity of white matter changes on magnetic resonance scans and apathy (p = 0.0092). Additionally, white matter changes were also significantly associated with depression (p = 0.021). Conclusion. Affective disorders are not uncommon in cerebral small vessel disease and apathy was the leading phenomenon among our patients. Since a strong correlation was detected between affective disorders and severity of vascular changes on magnetic resonance scans, we may conclude that both apathy and depression are key features of an underlying brain injury, rather than just comorbidity.

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Magnetic resonance white matter changes in patients with obstructive sleep apnoea. The subset of the PURE-MIND (Prospective Urban and Rural Epidemiological) cohort study

Archives of Medical Science ◽

10.5114/aoms/125400 ◽

2021 ◽

Author(s):

Katarzyna Postrzech-Adamczyk ◽

Artur Nahorecki ◽

Jagoda Jacków-Nowicka ◽

Maria Wołyniec ◽

Maciej Karczewski ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Small Vessel Disease ◽

Sleep Apnoea ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Study Group ◽

White Matter Changes ◽

Vessel Disease ◽

Obstructive Sleep

IntroductionChanges typical for cerebral small vessel disease (i.a. white matter hyperintensities – WMHs) are often found accidentally in neuroimaging studies. Although asymptomatic, this condition increases the risk of future ischaemic incidents and neurodegenerative disorders. Sleep apnoea is a recognised risk factor for vascular diseases. The aim of our study was to assess the prevalence of, and association between, obstructive sleep apnea (OSA) and cerebral small vessel disease in the studied population.Material and methodsTwo hundred and seven patients (participants of Prospective Urban Rural Epidemiology Study) took part in our study. The study group consisted of 31 patients with OSA (11 women and 20 men). Nine of them were diagnosed with mild OSA, nine with moderate OSA, and 13 with severe OSA. The control group consisted of 176 patients (133 women and 43 men) who scored 0–2 points in the STOP-BANG questionnaire. All patients underwent brain magnetic resonance imaging. We evaluated the occurrence and severity of WMHs.ResultsSignificantly higher incidence of WMHs was found in the study group compared to controls. In univariate analyses, age was a significant predictor of periventricular white matter changes. For subcortical area, age and waist-to-hip ratio were significant predictors.ConclusionsSignificantly higher incidence of WMHs in the studied group suggests that patients with OSA may have a higher risk of neurodegeneration.

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Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Stroke ◽

10.1161/strokeaha.121.035766 ◽

2021 ◽

Author(s):

Byeong C. Kim ◽

Young Chul Youn ◽

Jee Hyang Jeong ◽

Hyun Jeong Han ◽

Jong Hun Kim ◽

...

Keyword(s):

Randomized Controlled Trial ◽

White Matter ◽

Small Vessel Disease ◽

Controlled Trial ◽

Mean Diffusivity ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Changes ◽

Vessel Disease ◽

Randomized Controlled

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02–0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01932203.

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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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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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