Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke

2021 ◽  
pp. 1-8
Author(s):  
Sharmila Sagnier ◽  
Gwenaëlle Catheline ◽  
Fanny Munsch ◽  
Antoine Bigourdan ◽  
Mathilde Poli ◽  
...  

<b><i>Objective:</i></b> The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). <b><i>Methods:</i></b> We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo’s cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. <b><i>Results:</i></b> A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (β = −0.16, <i>p</i> = 0.02) and the number of errors to ZCT (β = 0.19, <i>p</i> = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (β = 0.14, <i>p</i> = 0.01) and number of errors (β = 0.17, <i>p</i> = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. <b><i>Conclusion:</i></b> The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hyung-Min Kwon ◽  
Michael J Lynn ◽  
Tanya N Turan ◽  
Colin P Derdeyn ◽  
David Fiorella ◽  
...  

Background: Intracranial atherosclerotic stenosis (ICAS) and small vessel disease (SVD) may coexist. We investigated the frequency and risk factors for SVD in SAMMPRIS patients and the impact of SVD on stroke recurrence in the medical arm of the trial. Methods: Of 451 patients enrolled in SAMMPRIS, 313 had baseline brain MRIs read centrally for SVD. SVD was defined by any of the following: old lacunar infarction, Fazekas score of 2-3 for white matter hyperintensities, or microbleeds. We compared risk factors in patients with vs. without SVD using Fisher’s exact test (for percentages), independent groups t test (for means) or Wilcoxon rank sum test (for medians), and compared the survival curves of patients with vs. without SVD in the medical arm for ischemic stroke in the territory of the stenotic artery and any ischemic stroke using the logrank test. Results: Of the 313 patients, 161 (51.4%) had SVD on the baseline MRI. Variables that were significantly (p<0.05) higher in patients with SVD were age, diabetes, lipid disorder, baseline SBP, coronary disease, and old infarct in the territory. The Kaplan-Meier curves in the figure show that patients with SVD were at significantly higher risk of any ischemic stroke (p = 0.048) but not stroke in the territory (p = 0.10) compared with patients without SVD. Conclusion: SVD in patients with ICAS is common, especially in patients who are older, diabetic, hyperlipidemic, and have higher SBP. Patients with ICAS and coexistent SVD are at higher risk of any ischemic stroke but may not be at higher risk for stroke in the territory.


2021 ◽  
pp. 1-11
Author(s):  
Pi-Shan Sung ◽  
Kang-Po Lee ◽  
Po-Yu Lin ◽  
Hui-Chen Su ◽  
Rwei-Ling Yu ◽  
...  

Background: Differences exist regarding post-stroke cognitive outcomes. Objective: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. Methods: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. Results: A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p <  0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09–6.86). Conclusion: In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.


2021 ◽  
Vol 13 ◽  
Author(s):  
Yangyi Fan ◽  
Ming Shen ◽  
Yang Huo ◽  
Xuguang Gao ◽  
Chun Li ◽  
...  

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P &lt; 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA &lt; 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA &lt; 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Felipe De Los Rios La Rosa ◽  
Jane C Khoury ◽  
Kathleen S Alwell ◽  
Mary Haverbusch ◽  
Daniel Woo ◽  
...  

Introduction: A main goal for hospital admission following acute ischemic stroke (AIS) is to establish the mechanism of stroke (MoS) allowing for patient specific secondary prevention of stroke interventions. We previously reported on diagnostic testing trends and MoS determination from 1993 through 2010. We updated this analysis with 2015 data to better understand the effects of trends in diagnostic testing on MoS determination. Methods: Patients with AIS aged > 20 years from all study time periods (Table) of the population based GCNKSS were included. Charts were abstracted in a systematic way for tests performed during the hospital stay. Only first-ever ischemic stroke cases, evaluated in an emergency department were used for this analysis. Stroke experts reviewed these events and adjudicated the mechanism of stroke according to modified TOAST criteria. We looked at and compared trends for testing and MoS. Results: Our analysis included 7226 patients. Basic patient demographics, MoS categories and tests across study periods are detailed in the Table. There were significant increases in EKG (7%), TTE (35%), TEE (7%), HCT (4%), brain MRI (65%), MRA (30%) and CTA (28%). Across study periods, cardioembolic (4.1%), small vessel disease (3%), large artery disease (0.9%) and other (1.5%) MoS increased while unknown MoS decreased (-9.5%). Discussion: From 1993/1994 to 2015 there has been a significant increase of in-hospital testing in AIS and decreases in undetermined MoS. Cardioembolic and small vessel disease MoS categories increased the most. Despite a significant increase in vessel imaging, large artery disease and “other determined” MoS categories are largely unchanged. Further research is required to elucidate the occult MoS underlying the undetermined category. Based on our analysis it appears unlikely to be significantly associated with our current definition of stroke associated with large artery disease defined as ≥ 50% ipsilateral stenosis.


Author(s):  
Dwi Retno Hastani ◽  
Aldy S. Rambe ◽  
Kiki M. Iqbal

Background: ASCO Phenotype classification is a new classification of stroke based on phenotypic system. ASCO classification can evaluate the etiology of ischemic stroke comprehensively to characterize patients using different grade of evidence for the subtype of ischemic stroke. ASCO classification can predict post ischemic stroke cognitive decline. This Study purpose to evaluate the association between ASCO classification with the executive function in post ischemic stroke patients.Methods: This cross sectional study followed by 28 post ischemic stroke patients (men 16, women 12) over 3 months. Mean age 52.82±8.66. Cognitive function was assessed by Montreal Cognitive Assessment Indonesia (MoCA INA).Results: There were 17 patients with grade 1 atherosclerosis (ASCO A1), ten patients with grade 1 small vessel disease (ASCO S1), one patient with grade 1 cardioembolism (ASCO C1) in post ischemic stroke. Grade 1 atherosclerosis (ASCO A1) was significantly associated with executive function decline (p=0.002), naming decline (p=0.05), abstraction decline (p=0.001), memory decline (p=0.002) and orientation decline (p=0.016)). Grade 1 small vessel disease (ASCO S1) was significantly associated with executive function decline (p=0.001) and memory decline (p = 0.001) and abstraction (p=0.001). Grade 1 cardioembolism 1 (ASCO C1) was not significantly associated with cognitive decline.Conclusions: There was significant association between ASCO classification with the executive function of Montreal Cognitive Assestment Indonesia (MoCA INA) in post ischemic stroke patients.


Neurology ◽  
2017 ◽  
Vol 88 (24) ◽  
pp. 2260-2267 ◽  
Author(s):  
Kui Kai Lau ◽  
Linxin Li ◽  
Ursula Schulz ◽  
Michela Simoni ◽  
Koon Ho Chan ◽  
...  

Objective:In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke.Methods:Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered.Results:In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16–1.51, p < 0.0001; c statistic 0.61, 0.56–0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11–2.13, p = 0.009; c statistic 0.65, 0.54–0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59–0.74, p < 0.0001 and 0.60, 0.55–0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60–0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56–0.65, phet = 0.76) on internal validation.Conclusions:The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yousef Hannawi ◽  
Eder Caceres ◽  
Mohamed G. Ewees ◽  
Kimerly A. Powell ◽  
Anna Bratasz ◽  
...  

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.


2019 ◽  
Vol 32 (6) ◽  
pp. 336-343 ◽  
Author(s):  
Yan Liang ◽  
Yang-Kun Chen ◽  
Yong-Lin Liu ◽  
Vincent C. T. Mok ◽  
Gabor S. Ungvari ◽  
...  

Objective: This study investigated the association between small vessel disease (SVD) burden, a combination of multiple SVD markers and cognitive dysfunction after stroke. Methods: The study sample comprised 451 patients with first-ever acute ischemic stroke. Cognitive functions were assessed with the Mini-Mental State Examination (MMSE) at 3, 9, and 15 months after the index stroke. Cognitive impairment was defined as an MMSE score of ≤26. A total SVD score, indicating SVD burden, was constructed by summing the scores of the 4 SVD markers (white matter hyperintensities [WMHs], lacunes, cerebral microbleeds, and perivascular spaces) ascertained by magnetic resonance imaging (range: 0-4). The association between SVD burden and cognitive dysfunction was assessed with linear mixed models or generalized estimating equation models, as appropriate. Results: The majority of patients had mild-to-moderate stroke and at least one identifiable SVD marker. Cognitive impairment was found in about one-third of patients. After adjusting for confounding factors, the SVD burden was associated with MMSE scores (β = −0.37, P = .003) and cognitive impairment (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42). SVD burden was specifically associated with the performance of MMSE subscores including orientation to place and time, calculation, and word recall. Of the SVD markers, WMHs was the most robust predictor of decrease in MMSE scores (β = −0.25, P = .01) and cognitive impairment (OR = 1.14, 95% CI = 1.01-1.29). Conclusion: Cerebral SVD burden is associated with decreased MMSE scores, suggesting cognitive dysfunction during the first year after mild-to-moderate acute ischemic stroke.


2016 ◽  
Vol 36 (10) ◽  
pp. 1708-1717 ◽  
Author(s):  
Willem H Bouvy ◽  
Jaco JM Zwanenburg ◽  
Rik Reinink ◽  
Laura EM Wisse ◽  
Peter R Luijten ◽  
...  

Cerebral perivascular spaces (PVS) are small physiological structures around blood vessels in the brain. MRI visible PVS are associated with ageing and cerebral small vessel disease (SVD). 7 Tesla (7T) MRI improves PVS detection. We investigated the association of age, vascular risk factors, and imaging markers of SVD with PVS counts on 7 T MRI, in 50 persons aged ≥ 40. The average PVS count ± SD in the right hemisphere was 17 ± 6 in the basal ganglia and 71 ± 28 in the semioval centre. We observed no relation between age or vascular risk factors and PVS counts. The presence of microbleeds was related to more PVS in the basal ganglia (standardized beta 0.32; p = 0.04) and semioval centre (standardized beta 0.39; p = 0.01), and white matter hyperintensity volume to more PVS in the basal ganglia (standardized beta 0.41; p = 0.02). We conclude that PVS counts on 7T MRI are high and are related SVD markers, but not to age and vascular risk factors. This latter finding may indicate that due to the high sensitivity of 7T MRI, the correlation of PVS counts with age or vascular risk factors may be attenuated by the detection of “normal”, non-pathological PVS.


2020 ◽  
Vol 21 (24) ◽  
pp. 9729
Author(s):  
Jakub Litak ◽  
Marek Mazurek ◽  
Bartłomiej Kulesza ◽  
Paweł Szmygin ◽  
Joanna Litak ◽  
...  

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger’s disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.


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