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

Stroke ◽  
2021 ◽  
Author(s):  
Byeong C. Kim ◽  
Young Chul Youn ◽  
Jee Hyang Jeong ◽  
Hyun Jeong Han ◽  
Jong Hun Kim ◽  
...  

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.

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 17 ◽  
pp. 731-738 ◽  
Author(s):  
H.M. van der Holst ◽  
A.M. Tuladhar ◽  
V. Zerbi ◽  
I.W.M. van Uden ◽  
K.F. de Laat ◽  
...  

2019 ◽  
Vol 72 (9-10) ◽  
pp. 280-285
Author(s):  
Aleksandar Stevanovic ◽  
Anja Stefanovic ◽  
Natasa Stojanovski ◽  
Gordana Tomic ◽  
Jasna Zidverc-Trajkovic ◽  
...  

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.


2017 ◽  
Vol 131 (12) ◽  
pp. 1361-1373 ◽  
Author(s):  
Iain D. Croall ◽  
Valerie Lohner ◽  
Barry Moynihan ◽  
Usman Khan ◽  
Ahamad Hassan ◽  
...  

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.


2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  

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.


Neurology ◽  
2016 ◽  
Vol 86 (13) ◽  
pp. 1199-1207 ◽  
Author(s):  
Yeo Jin Kim ◽  
Hun Ki Kwon ◽  
Jong Min Lee ◽  
Hanna Cho ◽  
Hee Jin Kim ◽  
...  

Author(s):  
Katarzyna Postrzech-Adamczyk ◽  
Artur Nahorecki ◽  
Jagoda Jacków-Nowicka ◽  
Maria Wołyniec ◽  
Maciej Karczewski ◽  
...  

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.


Author(s):  
Salvatore Rudilosso ◽  
Luis Mena ◽  
Diana Esteller ◽  
Marta Olivera ◽  
Juan José Mengual ◽  
...  

2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  

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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