Higher Cerebral Small Vessel Disease Research Articles

Small vessel disease burden and prognosis of recent subcortical ischaemic stroke differ by parent artery atherosclerosis.

Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion-weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high-resolution magnetic resonance imaging (HR-MRI); (2) low-grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR-MRI); (3) steno-occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90-day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. A total of 239 patients (median age 60.0 [52.0-67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low-grade MCA atherosclerosis and 35 with steno-occlusive MCA atherosclerosis. Patients with steno-occlusive MCA atherosclerosis had the largest infarct volume. Low-grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low-grade MCA atherosclerosis was an independent determinant of 90-day functional dependence (odds ratio 3.897; 95% confidence interval 1.309-11.604). Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low-grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis.

Analysis of gait pattern related to high cerebral small vessel disease burden using quantitative gait data from wearable sensors

Background and ObjectivesSensor-based wearable devices help to obtain a wide range of quantitative gait parameters, which provides sufficient data to investigate disease-specific gait patterns. Although cerebral small vessel disease (CSVD) plays a significant role in gait impairment, the specific gait pattern associated with a high burden of CSVD remains to be explored. MethodsWe analyzed the gait pattern related to high CSVD burden from 720 participants (aged 55–65 years, 42.5 % male) free of neurological disease in the Taizhou Imaging Study. All participants underwent detailed quantitative gait assessments (obtained from an insole-like wearable gait tracking device) and brain magnetic resonance imaging examinations. Thirty-three gait parameters were summarized into five gait domains. Sparse sliced inverse regression was developed to extract the gait pattern related to high CSVD burden. ResultsThe specific gait pattern derived from several gait domains (i.e., angles, phases, variability, and spatio-temporal) was significantly associated with the CSVD burden (OR=1.250, 95 % CI: 1.011–1.546). The gait pattern indicates that people with a high CSVD burden were prone to have smaller gait angles, more stance time, more double support time, larger gait variability, and slower gait velocity. Furthermore, people with this gait pattern had a 25 % higher risk of a high CSVD burden. ConclusionsWe established a more stable and disease-specific quantitative gait pattern related to high CSVD burden, which is prone to facilitate the identification of individuals with high CSVD burden among the community residents or the general population.

Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort.

While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. Using a Singapore-based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH- group (β=0.383; P<0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH- group (area under the curve [AUC]=0.896) than in the WMH+ group (AUC=0.712, P=0.008). The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.

Abstract WMP22: Higher Burden of Cerebral Small Vessel Disease is Associated With Risk of Incident Stroke in Community-Dwelling Individuals

Background: Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple CSVD markers may better identify a person’s risk, but it remains unclear if they offer benefit beyond tools based on clinical factors alone such as the revised Framingham Stroke Risk Profile (FSRP). Therefore, we related a multi-marker CSVD score to risk of incident stroke and compared the findings with the FSRP in community-dwelling individuals. Methods: Framingham Heart Study (FHS) participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging (MRI) ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used (one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis, ranging 0-5). Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Results: Among 1,154 participants (46% male, mean age 70.9±8.7), 590 (51%) had score 0, 352 (31%) had score 1, 164 (14%) had score 2, and 48 (4%) had score ≥ 3. Over a median follow-up of 8.2 years (Q1-Q3: 5.1-12.5) from the time of MRI, 92 (8%) developed stroke. In models adjusting for time interval between clinic exam and MRI, FHS cohort, and FSRP score, number of CSVD manifestations was associated with increased risk of stroke in a dose-dependent manner: score 1 (HR: 1.73; 95% CI 1.05-2.84), score 2 (HR 1.83; 95% CI: 1.01-3.30), and score ≥ 3 (HR: 3.31; 95% CI: 1.50-7.28) in relation to participants with no CSVD markers. In comparison, a 5-percent increase in FSRP alone was associated with increased risk of stroke (HR: 1.25; 95% CI 1.15-1.36). Interpretation: Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals.

Quantitative Analysis of Multimodal MRI Markers and Clinical Risk Factors for Cerebral Small Vessel Disease Based on Deep Learning.

Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors. We recruited 211 lacunar stroke patients and 83 control patients. The patients' cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC>0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P<0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P<0.05). Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.

The effects of P2 segment of posterior cerebral artery to thalamus blood supply pattern on gait in cerebral small vessel disease: A 7 T MRI based study

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

Effect of Cerebral Small Vessel Disease Burden on Infarct Growth Rate and Stroke Outcomes in Large Vessel Occlusion Stroke Receiving Endovascular Treatment.

This study aimed to investigate the association between cerebral small vessel disease (CSVD) burden and infarct growth rate (IGR) in patients with large vessel occlusion (LVO) stroke who underwent endovascular treatment (EVT). A retrospective analysis was conducted on a cohort of 495 patients with anterior circulation stroke who received EVT. CSVD burden was assessed using a CSVD score based on neuroimaging features. IGR was calculated from diffusion-weighted imaging (DWI) lesion volumes divided by the time from stroke onset to imaging. Clinical outcomes included stroke progression and functional outcomes at 3 months. Multivariate analyses were performed to assess the relationship between CSVD burden, IGR, and clinical outcomes. The fast IGR group had a higher proportion of high CSVD scores than the slow IGR group (24.4% vs. 0.8%, p < 0.001). High CSVD burden was significantly associated with a faster IGR (odds ratio [95% confidence interval], 26.26 [6.26-110.14], p < 0.001) after adjusting for confounding factors. High CSVD burden also independently predicted stroke progression and poor functional outcomes. This study highlights a significant relationship between CSVD burden and IGR in LVO stroke patients undergoing EVT. High CSVD burden was associated with faster infarct growth and worse clinical outcomes.

The impact of cerebral small vessel disease burden and its imaging markers on gait, postural control, and cognition in Parkinson's disease.

This study aimed to investigate how cerebral small vessel disease (CSVD) burden and its imaging markers are related to alterations in different gait parameters in Parkinson's disease (PD) and whether they affect attention, information processing speed, and executive function when global mental status is relatively intact. Sixty-five PD patients were divided into the low CSVD burden group (n = 43) and the high CSVD burden group (n = 22). All patients underwent brain magnetic resonance imaging scans, clinical scale evaluations, and neuropsychological tests, as well as quantitative evaluation of gait and postural control. Multivariable linear regression models were conducted to investigate associations between CSVD burden and PD symptoms. Between-group analysis showed that the high CSVD group had worse attention, executive dysfunction, information processing speed, gait, balance, and postural control than the low CSVD group. Regression analysis revealed that greater CSVD burden was associated with poor attention, impaired executive function, and slow gait speed; white matter hyperintensity was associated with slow gait speed, decreased cadence, increased stride time, and increased stance phase time; the presence of lacune was associated only with poor attention and impaired executive function; enlarged perivascular space in the basal ganglia was associated with gait speed. CSVD burden may worsen gait, postural control, attention, and executive function in patients with PD, and different imaging markers play different roles. Early management of vascular risks and treatment of vascular diseases provide an alternate way to mitigate some motor and cognitive dysfunction in PD.

Abstract TP185: Cardiac Gadolinium Enhancement And Cerebral Small Vessel Disease

Background: Accumulation of cerebral small vessel disease (CSVD) leads to various well described detrimental clinical consequences. Similar to CSVD, the development of coronary microvascular disease (CMD) yields end-organ dysfunction, namely myocardial ischemia and chamber dilation. We aimed to investigate the relationship between cardiac gadolinium enhancements (CGE), a marker for CMD, on CSVD burden on brain MRI. Methods: We performed a retrospective cross-sectional analysis of adults between January 2014 and December 2019 who completed a cardiac and brain MRI within one year of each other. The ordinal total small vessel disease score (tSVD) was used to quantify CSVD with two cohorts being created: tSVD 0 to 1 (low CSVD) and tSVD 2 to 4 (high CSVD). Cardiac MRI data was obtained under the guidance of an experienced cardiologist with advanced cardiac imaging training. Chi-squared or Fisher’s, Wilcoxon rank-sum analyses were performed for binary and ordinal variables, respectively. Adjusted multivariate logistic regression models were used to calculate odds ratios. Statistical significance was defined as &lt; 0.05. Results: A total of 259 individuals were included with 140 and 119 in the low and high CSVD groups, respectively. Those with low CSVD were significantly lower in age, predominately female and had lower rates of hypertension, hyperlipidemia, diabetes mellitus and congestive heart failure. CGE was more common in those with higher burdens of CSVD (23.2% vs 47.2%, p&lt;0.001). CGE increased the odds of being within the high CSVD group despite adjustment for significant clinical and demographic factors (OR 2.1, 95% CI 1.1 - 4.0). Discussion: In those with CMD as identified by CGE, there was a 2 fold increase in being within the high burden of CSVD cohort likely as a result of similar intrinsic pathological processes. Further studies are needed to determine whether CGE predates development of CSVD, its association with development of acute cerebrovascular diseases and its influence on specific subtypes of CSVD.

Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment.

ObjectiveTo evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance.MethodsWe recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4.ResultsIn total, 158 participants were included in this study with a mean age of 60.5 (56.0–66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively.ConclusionsSerum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.

Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis.

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p > 0.05).Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed-location intracerebral hemorrhage.

To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30ml vs. <30ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p<.001). Higher WMH score was associated with lower risk of hematoma volume ≥30ml (adjusted OR 0.521, 95% CI 0.299-0.908, p=.021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (β=-0.349, p=.019 for CMB≥5; β=-0.183, p<.001 for WMH score; β=-0.456, p=.002 for EPVS>20 in basal ganglia and/or centrum semiovale; β=-0.256, p=.002 for CSVD score), while these relationships were not observed in non-mixed ICH. Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.

Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease (CSVD). We assessed whether the topography of RSSI was related to CSVD markers on magnetic resonance imaging (MRI). We screened the local registries of two independent stroke centers in Catalonia and selected patients with a symptomatic RSSI on MRI performed during admission. RSSI location was classified into brainstem, supratentorial subcortical structures (SSS), and centrum semiovale (CSO) regions. Clinical variables, including vascular risk factors, were collected. Radiological markers of CSVD on MRI were evaluated individually and by means of the global CSVD burden score. The associations between each RSSI location and CSVD markers were studied in uni- and multivariate logistic regression analysis. Among 475 patients with RSSI, 152 (32%) had an infarct in the brainstem, 227 (48%) in SSS, and 96 (20%) in CSO region. The median CSVD burden score was 2 (IQR, 1-3). After adjusting for confounding factors, a RSSI in CSO was associated with higher periventricular and deep white matter hyperintensity scores [OR 1.64 (95% CI, 1.16-2.33), and OR 1.44 (95% CI, 1.07-1.93), respectively]. Higher CSVD burden score was positively associated with CSO [OR 1.48 (95% CI, 1.22-1.81)] and inversely associated with SSS [0.85 (95% CI, 0.72-0.99)] location after adjusting for relevant confounders. CSO RSSI were related to a higher burden of CSVD, particularly to white matter hyperintensities, compared to other RSSI locations. The pathophysiological significance of such findings should be investigated in the future with advanced neuroimaging techniques.

Left ventricular ejection fraction and right atrial diameter are associated with deep regional CBF in arteriosclerotic cerebral small vessel disease

BackgroundSystemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development.MethodsThis retrospective study identified 103 arteriosclerotic CSVD (aCSVD) patients (CSVD burdenlow 0 ~ 1, n = 61 and CSVD burdenhigh 2 ~ 4, n = 42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n = 81), structural magnetic resonance imaging and arterial spin labelling (ASL). Total CSVD burden was graded according to the ordinal “small vessel disease” rating score (0–4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh.ResultsRight atrial diameter (B coefficient, − 0.289; 95% CI, − 0.578 to − 0.001; P = 0.049) and left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P = 0.012) were independently associated with deep regional CBF in aCSVD patients. Binary logistic regression analysis demonstrated decreased deep regional CBF (OR 0.894; 95% CI 0.811–0.985; P = 0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve integrating clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve = 84.25, 95% CI 74.86–93.65%, P < 0.0001).ConclusionThe interrelationship of “cardiac -deep regional CBF-neuroimaging burden” reinforces the importance and prognostic significance of echocardiographic and cerebral hemodynamic assessment in CSVD early-warning.

Association between large artery stenosis, cerebral small vessel disease and risk of ischemic stroke.

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

Cerebral small vessel disease is associated with gait disturbance among community-dwelling elderly individuals: the Taizhou imaging study.

Gait disturbance is considered to be a significant clinical manifestation of cerebral small vessel disease (CSVD). We aimed to investigate the association between different imaging markers of CSVD or total CSVD burden and gait disturbance in a community-dwelling population. In the cross-sectional Taizhou Imaging Study (TIS), 314 participants free of neurological disorders underwent MRI scanning and gait assessment with quantitative wearable devices as well as clinical rating scales. In linear regression, after adjustment for demographics and vascular risks, total CSVD burden was associated with prolonged 3-m walking (β=0.118, P=0.035), shorter stride length (β=-0.106, P=0.042), and poorer Timed-Up-and-Go (TUG) performance (β=0.146, P=0.009). Lacunes were positively associated with 3-m walking (β=0.118, P=0.037) and duration of TUG test (β=0.112, P=0.047). White matter hyperintensities and cerebral microbleeds were associated with prolonged stride time (β=0.134, P=0.024) and increased stance phase time percentage (β=0.115, P=0.038), respectively. Logistic regression revealed that participants with high CSVD burden or more lacunes were more likely to have an impaired gait velocity and an impaired TUG test. These results suggest that total CSVD burden and CSVD imaging markers are associated with gait disturbance among community-dwelling elderly people. Different CSVD imaging markers may cause gait disturbance through different pathways.

Total Burden of Cerebral Small Vessel Disease in Recurrent ICH versus First-ever ICH.

The relationship between recurrent intracerebral hemorrhage (ICH) and total burden of cerebral small vessel disease (CSVD) is not completely investigated. We aimed to study whether recurrent intracerebral hemorrhage (ICH) had higher CSVD score than first-ever ICH. Lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), cortical superficial siderosis (cSS) and CSVD score were rated on brain magnetic resonance imaging (MRI) in primary ICH patients. Recurrent ICHs were confirmed by reviewing the medical records and MRI scans. Mixed hematomas were defined as follows: deep + lobar, deep + cerebellar, or deep + lobar + cerebellar. Of the 184 patients with primary ICH enrolled (mean age, 61.0 years; 75.5% men), recurrent ICH was present in 45 (24.5%) patients; 26.1% (48/184) had ≥2 hematomas, 93.8% (45/48) of which exhibited recurrent ICH. Mixed hematomas were identified in 8.7% (16/184) of patients and bilateral hematomas in 17.9% (33/184). All mixed hematomas and bilateral hematomas were from cases of recurrent ICH. Patients with mixed etiology-ICH were more likely to have recurrent ICH than patients with cerebral amyloid angiopathy (CAA) or hypertensive angiopathy (HA)-related ICH (36.8% vs17.8%, p=0.008). Multivariate ordinal regression analysis showed that the presence of recurrent ICH (p=0.001), ≥2 hematomas (p=0.002), mixed hematomas (p<0.00001), and bilateral hematomas (p=0.002) were separately significantly associated with a high CSVD score. Recurrent ICH occurs mostly among patients with mixed etiology-ICH and is associated with a higher CSVD burden than first-ever ICH, which needs to be verified by future larger studies.

A relationship between the integrated assessment of magnetic resonance imaging markers for cerebral small vessel disease and the clinical and functional status in the acute period of ischemic stroke

Cerebral small vessel disease (CSVD) is the most common neurological pathological process and contributes to the process of aging and to the development of dementia and stroke. At the same time, the role of CSVD as a factor influencing the course of acute ischemic stroke (IS) has been little studied. There is no generally accepted magnetic resonance imaging (MRI) scale for the integrated assessment of CSVD markers. Objective : to carry out an integrated assessment of the MRI manifestations of CSVD in acute ischemic stroke and to analyze a correlation of both individual markers and the final indicator with the clinical and functional status of patients. Patients and methods. 100 patients with acute IS were examined. All patients underwent standard clinical, laboratory and instrumental examinations, as well as brain MRI estimating the number of lacunae, visible perivascular spaces (PVSs) and leukoaraiosis. The number of cerebral microbleeds (CMBs) was additionally calculated in 57 patients. Integral scale scores were calculated by gradation and summation of four MRI markers of CSVD. Results . The patients with acute IS showed the high representativeness of individual markers for CSVD. The values of MRI markers for CSVD correlated with age, education level, and cardiovascular parameters in patients. An integrated CSVD severity assessment scale was developed. The overall manifestations of CSVD, which were assessed using this scale, were associated with the severity of a stenotic process in the brachycephalic arteries, with BP levels at admission, ejection fraction, hyperglycemia, and atherogenic index of blood lipids. The high CSVD score was also correlated with low mobility and more severe disability in patients being discharged from hospital. The high severity of CSVD was associated with lower neurological deficit regression during inpatient treatment. Subgroup analysis showed the greatest negative impact of CSVD on the severity of stroke in female patients, young and middle-aged ones, diabetics, as well as in patients with noncardioembolic stroke, a smallsized focus, and intima-media thickening. Conclusion . The overall manifestations of CSVD calculated using the original scale based on the analysis of the degree of lacunae, PVSs, leukoaraiosis, and CMBs are associated with premorbid cardiovascular parameters in a patient and are important indicators for the neurological, cognitive, and functional outcomes of acute IS.

Abstract WP336: Cerebral Small Vessel Disease Burden, Functional Outcome and Hematoma Expansion in Intracerebral Hemorrhage

Background: Older age, larger hematoma volume, and intraventricular hemorrhage (IVH) are established predictors of poor prognosis after intracerebral hemorrhage (ICH). We hypothesized that higher cerebral small vessel disease (CSVD) burden substantially affects functional outcome and its detailed characterization in addition to already established predictors will enhance our prognostic accuracy. Methods: We studied consecutive patients with spontaneous supratentorial ICH, functionally independent at baseline (modified Rankin Scale (mRS) ≤2), with brain MRI within 1 month of ICH and known 3-month functional status. We collected clinical and imaging data and data on: Cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS) severity, white matter disease (WMD) (Fazekas scale), chronic lacunar and non-lacunar infarcts, cerebral atrophy. Functional endpoints were (a) 3-month functional independence (mRS ≤2) (b) independent ambulation at 3 months. Hematoma expansion was defined as relative increase of ≥ 33% or absolute increase of &gt;6ml. Results: 111 patients (70.7±13.9 years, 40% female) met our inclusion criteria. 43(38%) achieved functional independence,71(64%) independent ambulation. In univariate analyses, older age, hematoma volume, IVH, cerebral atrophy, severe WMD but not EPVS severity or chronic infarcts were associated with worse functional and ambulatory outcome. CMBs presence was associated with poor functional outcome but not ambulation status. In multivariable logistic regression, volume, IVH, CMBs (OR 3.95, CI: 1.4-12.1, p=0.009), brain atrophy (OR 3.99, CI: 1.1-16.2 p=0.03) but not age or WMD severity remained associated with functional independence (model p&lt;0.0001, ROC=0.92). Hematoma volume and brain atrophy but not age, IVH or WMD severity were associated with independent ambulation. We found no association between CSVD markers and hematoma expansion. Conclusion: CMBs presence and cerebral atrophy conferred a 4-fold higher risk of functional dependence after ICH. The effect of hematoma size remained very robust but addition of CSVD markers and brain atrophy neutralized the previously observed effect of age. This observation merits further exploration and validation in a larger, prospective cohort.