Total Small Vessel Disease Burden Research Articles

Neuroimaging biomarkers of small vessel disease in cerebral amyloid angiopathy-related intracerebral hemorrhage.

The significance of the correlation of computed tomography (CT)-based cerebral small vessel disease (SVD) markers with the clinical outcomes in patients with cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) remains uncertain. Thus, this study aimed to explore the relationship between SVD markers and short-term outcomes of CAA-ICH. A total of 183 patients with CAA-ICH admitted to the Xuanwu Hospital, and Beijing Fengtai You'anmen Hospital, from 2014 to 2021 were included. The multivariate logistic regression analysis was performed to identify the correlation between SVD markers based on CT and clinical outcomes at 7-day and 90-day. Of the 183 included patients, 66 (36%) were identified with severe SVD burden. The multivariate analysis showed that the total SVD burden, white matter lesion (WML) grade, and brain atrophy indicator were independent risk factors for unfavorable outcomes at 90-day. The brain atrophy indicator was independently associated with mortality at 90-day. Severe cortical atrophy was significantly associated with early neurological deterioration. The neuroimaging profiles of SVD based on CT in patients with CAA-ICH might predict the short-term outcome more effectively. Further studies are required to validate these findings and identify modifiable factors for preventing CAA-ICH development.

Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts

BackgroundAs currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes.MethodsIn a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS).ResultsIn a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21–6.84), multiple lacunes (aOR 3.5, CI 1.29–9.48) and higher total SVD burden (aOR 1.68, CI 1.11–2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up.ConclusionsPatients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation.

Cerebral small vessel disease combined with cerebral collaterals to predict the prognosis of patients with acute large artery atherosclerotic stroke.

Background and purposeBesides cerebral collaterals, few studies have examined other additional factors affecting the prognosis of patients with large artery atherosclerotic (LAA) stroke. Our study aims to explore the effect of the cerebral small vessel disease (SVD) and the effects of its interaction with cerebral collaterals on the prognosis of patients with acute LAA stroke.MethodPatients aged 18 years or older with LAA stroke within 24 h after stroke onset were consecutively enrolled. The functional outcome was determined using the modified Rankin Scale (mRS) at 3 months after stroke onset. Logistic multivariate analyses were used to identify the risk factors for stroke prognosis. Receiver operating characteristic (ROC) curves were constructed to compare the effects of cerebral collaterals and SVD on predicting the prognosis.ResultsOf the 274 enrolled patients, 174 (63.50%) were identified as having a favorable prognosis, and 100 (36.50%) were identified as having an unfavorable prognosis. After adjusting for covariates, the logistic regression analysis identified that unfavorable prognosis was related to the total SVD score (Model 1, adjusted odds ratio = 1.73, 95% CI: 1.15–2.61, P < 0.01; Model 2, adjusted odds ratio = 1.85, 95% CI: 1.23–2.79, P < 0.01) and Tan score (Model 1, adjusted odds ratio = 0.38, 95% CI: 0.23–0.64, P < 0.01; Model 2, adjusted odds ratio = 0.52, 95% CI: 0.33–0.82, P < 0.01). Compared with cerebral collaterals (AUC = 0.59; 95% CI: 0.52–0.67; P < 0.01) or SVD (AUC = 0.62; 95% CI: 0.56–0.69; P < 0.01) alone, the combination of collaterals and SVD (AUC = 0.66; 95% CI: 0.59–0.73; P < 0.01) had higher diagnostic value for an unfavorable prognosis, and the optimal sensitivity and specificity were 77.01 and 53.00%, respectively.ConclusionsThe total SVD burden was related to the prognosis of patients with LAA stroke. Compared with cerebral collaterals or SVD alone, cerebral collaterals combined with total SVD burden are better at predicting the prognosis of patients with acute LAA stroke.

Influence of Pre-Existing Cerebral Small Vessel Disease on the Outcome of Acute Cardioembolic Stroke: A Retrospective Study

PurposeThis study was to explore the role of pre-existing small vessel disease (SVD) on the 3-month outcomes of acute cardioembolic stroke (CES) patients.Patients and MethodsData of 189 consecutive acute CES patients at a single center were retrospectively enrolled. SVD imaging markers of lacunes, white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) were evaluated and their total burden score (0–3 points) was calculated. Patients were divided into the good functional outcome group (modified Rankin scale, mRS ≤ 2) and the poor functional outcome group (mRS ≥ 3) at 3 months after stroke onset. The effect of each single SVD marker and its total burden score on the outcome was identified using binary logistic regression.ResultsOverall, 100 (52.9%), 52 (27.1%), 28 (14.8%) and 9 (4.8%) patients had 0, 1, 2 and 3 SVD imaging markers. Patients with a total SVD burden score of 2 and 3 were significantly older and had higher baseline National Institutes of Health Stroke Scale (NIHSS) score than those with a score of 0 and 1 (P<0.01). Forty-seven (24.9%) patients had a poor outcome. Patients in the poor outcome group had significantly higher baseline NIHSS score, increased incidence of stroke associated pneumonia, and heavier burden of lacunes, WMH and EPVS, and thus had elevated total SVD burden score than those in good outcome group (P<0.05). After adjusting for potential confounders, the WMH (odds ratio [OR] = 2.6777, 95% confidence interval [CI] = 1.052–6.812, P = 0.039) and the total SVD burden score (OR = 1.717, 95% CI = 1.072–2.749, P = 0.024) were, respectively, independent risk factors for a poor outcome.ConclusionThe pre-existing SVD may be associated with the 3-month prognosis of CES.

Lacunes and type 2 diabetes mellitus have a joint effect on cognitive impairment: a retrospective study.

ObjectiveTo evaluate the joint effects of cerebral small vessel disease (CSVD)-related imaging biomarkers in patients of type 2 diabetes mellitus (T2DM) with cognitive impairment.MethodsThis study is a retrospective cohort study. A total of 227 participants (115 patients with T2DM and 112 healthy control subjects) were enrolled in this study. Cognitive function assessments were evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. The burden of CSVD markers, including the lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), and enlarged perivascular spaces (PVS), was identified by magnetic resonance imaging and evaluated using small vessel disease (SVD) scores (0–4). The subjects were divided into two groups based on the results of the cognitive function assessments. The synergy index was used to estimate the biological interactions between T2DM and lacunes.ResultsThere was a significant correlation between T2DM and cognitive impairment (p < 0.001, χ2 test). In patients with diabetes, cognitive impairment was significantly associated with both the presence of lacunes (p < 0.01, χ2 test) and increased total SVD burden scores (p < 0.01, χ2 test). Regarding CMBs, only the existence of lobar CMBs was correlated with cognitive impairment (p < 0.05, χ2 test). The joint effect tended to be larger than the independent effects of T2DM and lacunes on cognitive impairment (adjusted odds ratio [OR]: 7.084, 95% CI [2.836–17.698]; synergy index: 10.018, 95% CI [0.344–291.414]).ConclusionsT2DM and the presence of lacunes are significantly correlated with cognitive impairment. There was a joint effect of T2DM and lacunes on cognitive impairment.

Total magnetic resonance imaging of cerebral small vessel disease burden predicts dysphagia in patients with a single recent small subcortical infarct

BackgroundThis study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI).MethodsWe retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4.ResultsIn total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level.ConclusionsDysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies.

Development of cerebral small vessel disease, a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socio-economic status or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, socio-economic status), adult small vessel disease, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n = 1080; mean age = 59 years); the Dutch Famine Birth Cohort (n = 118; mean age = 68 years); the Lothian Birth Cohort 1936 (LBC1936; n = 617; mean age = 73 years), and the Simpson’s cohort (n = 110; mean age = 78 years). We analysed each small vessel disease feature individually and summed to give a total small vessel disease score (range 1–4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult socio-economic status.Higher birth weight was associated with fewer lacunes [odds ratio (OR) per 100 g = 0.93, 95% confidence interval (CI) = 0.88 to 0.99], fewer infarcts (OR = 0.94, 95% CI = 0.89 to 0.99), and fewer perivascular spaces (OR = 0.95, 95% CI = 0.91 to 0.99). Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point = 0.99, 95% CI 0.98 to 0.998), fewer infarcts (OR = 0.98, 95% CI = 0.97 to 0.998), fewer lacunes (OR = 0.98, 95% CI = 0.97 to 0.999), and lower total small vessel disease burden (OR = 0.98, 95% CI = 0.96 to 0.999). Low education was associated with more microbleeds (OR = 1.90, 95% CI = 1.33 to 2.72) and lower total brain volume (mean difference = −178.86 cm3, 95% CI = −325.07 to −32.66). Low childhood socio-economic status was associated with fewer lacunes (OR = 0.62, 95% CI = 0.40 to 0.95).Early life factors are associated with worse small vessel disease in later life, independent of each other, vascular risk factors and adult socio-economic status. Risk for small vessel disease may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may improve lifelong brain health and contribute to the prevention of dementia and stroke in older age.

Increased Levels of Circulating Angiogenic Cells and Signaling Proteins in Older Adults With Cerebral Small Vessel Disease.

Background: Cerebral small vessel disease (SVD) is associated with increased risk of stroke and dementia. Progressive damage to the cerebral microvasculature may also trigger angiogenic processes to promote vessel repair. Elevated levels of circulating endothelial progenitor cells (EPCs) and pro-angiogenic signaling proteins are observed in response to vascular injury. We aimed to examine circulating levels of EPCs and proangiogenic proteins in older adults with evidence of SVD.Methods: Older adults (ages 55–90) free of dementia or stroke underwent venipuncture and brain magnetic resonance imaging (MRI). Flow cytometry quantified circulating EPCs as the number of cells in the lymphocyte gate positively expressing EPC surface markers (CD34+CD133+CD309+). Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, and Flt-1). Total SVD burden score was determined based on MRI markers, including white matter hyperintensities, cerebral microbleeds and lacunes.Results: Sixty-four older adults were included. Linear regression revealed that older adults with higher circulating EPC levels exhibited greater total SVD burden [β = 1.0 × 105, 95% CI (0.2, 1.9), p = 0.019], after accounting for age and sex. Similarly, a positive relationship between circulating VEGF-D and total SVD score was observed, controlling for age and sex [β = 0.001, 95% CI (0.000, 0.001), p = 0.048].Conclusion: These findings suggest that elevated levels of circulating EPCs and VEGF-D correspond with greater cerebral SVD burden in older adults. Additional studies are warranted to determine whether activation of systemic angiogenic growth factors and EPCs represents an early attempt to rescue the vascular endothelium and repair damage in SVD.

Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. Methods: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. Results: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, p = 0.395). Conclusion: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian Birth Cohort 1936 (n = 540; age: 72.6 ± 0.7 years). We found negative associations between total SVD burden and general cognitive ability (standardized β: -0.363; 95%CI: [-0.49, -0.23]; p(FDR) < 0.001), processing speed (-0.371 [-0.50, -0.24]; p(FDR) < 0.001), verbal memory (-0.265; [-0.42, -0.11]; p(FDR) = 0.002), and visuospatial ability (-0.170; [-0.32, -0.02]; p(FDR) = 0.029). Only the association between SVD burden and processing speed remained after accounting for covariance with general cognitive ability (-0.325; [-0.61, -0.04]; p(FDR) = 0.029). This suggests that SVD's association with poorer processing speed is not driven by, but is independent of its association with poorer general cognitive ability. Tests of processing speed may be particularly sensitive to the cognitive impact of SVD, but all major cognitive domains should be tested to determine the full range of SVD-related cognitive characteristics.

Abstract P549: Total Small Vessel Disease Burden Not Associated With Functional Independence After Endovascular Treatment in Acute Ischemic Stroke Patients

Background: Individual small vessel disease (SVD) markers had been associated with outcomes of endovascular treatment (EVT) in acute stroke patients. We aimed to investigate the associations between total SVD burden and outcomes in such patients. Methods: In a nation-wide multicenter registration study, we enrolled stroke patients with anterior circulation large vessel occlusion (LVO) receiving EVT, who had undergone 3T MRI. Presence of lacunes, white matter hyperintensities, cerebral microbleeds and perivascular spaces in both hemispheres were assessed in MRI and each marker was assigned a score of 0 or 1 by presence. A total SVD burden score (0-4) was calculated by summing up the individual scores, which was dichotomized as none-to-mild (score 0-2) and moderate-to-severe (score 3-4). The primary outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) of 0-2. Secondary outcomes included change in NIHSS from baseline to 7 days, early neurological deterioration (END), symptomatic intracranial hemorrhage and 90-day mortality. We investigated the associations of dichotomized total SVD burden score with the outcomes using binary logistic regression analyses. Results: Of the 202 patients (65.38% male; mean age 65.54 ± 11.93 years) enrolled, 176 patients had none-to-mild and 26 had moderate-to-severe total SVD burden. Those with moderate-to-severe SVD were older (mean age 69.8 versus 64.7; P=0.043) and more of them had a prior stroke (42.31% versus 23.3%; P=0.039), compared with otherwise. Dichotomized total SVD burden was not significantly associated with the primary outcome, 90-day functional independence (moderate-to-severe versus none-to-mild SVD burden: 53.85% versus 47.13%; OR 0.76, 95% CI 0.33-1.75; P=0.523). Although moderate-to-severe total SVD burden was associated with a higher rate of END (15.38% versus 3.43%; OR 5.12; 95% CI 1.34-19.58; P=0.017), no significant association was detected between the total SVD burden and other secondary outcomes. Conclusions: The total SVD burden as assessed in MRI was not significantly associated with the chance of obtaining functional independence at 90 days in LVO-stroke patients receiving EVT. A higher total SVD burden may not be an exclusion criteria for clinical decision for EVT.

Abstract P73: Imaging Markers of Brain Frailty and Outcome in Patients With Acute Ischemic Stroke

Background and purpose: Functional outcome after stroke may be related to preexisting brain health. Several imaging markers of brain frailty have been described including brain atrophy and markers of small vessel disease. We investigated the association of these imaging markers with functional outcome after acute ischemic stroke. Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial, an international, multicenter, randomized controlled clinical trial of Granulocyte Colony Stimulating Factor versus placebo. We assessed the ratio of brain parenchymal volume to total intracerebral volumes (i.e., the brain parenchymal fraction [BPF]) and total brain volumes from routine baseline MRI data obtained within 9 hours of symptom onset using the unified segmentation algorithm in SPM12. Enlarged perivascular spaces (EPVS), white matter hyperintensities (WMH), lacunes as well as a small vessel disease (SVD) burden were rated visually. Functional outcomes (modified Rankin Scale [mRS] score) at day 90 were determined. Logistic regression was used to test associations between brain imaging features and functional outcomes. As there was no significant effect of G-CSF on any outcomes in AXIS-2, placebo and active groups were combined for these analyses. Results: We enrolled 259 patients with a mean age of 69±12 years and 46 % were female. Increased BPF was associated with higher odds of excellent outcome (OR per percent increase: 1.081, 95%CI: 1.012-1.155). Total brain volumes and SVD burden were not associated with functional outcome. An interaction between BPF and large vessel occlusion on excellent outcome was not observed. Conclusions: Global brain health, as assessed by brain parenchymal fraction on magnetic resonance imaging, is associated with excellent functional outcome after ischemic stroke. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00927836.

Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3-Tesla magnetic resonance imaging.

Cortical microinfarcts (CMIs) are frequently found in the brains of patients with advanced cerebral amyloid angiopathy (CAA) at autopsy. The small vessel disease (SVD) score for CAA (i.e., the CAA-SVD score) has been proposed to evaluate the severity of CAA-associated vasculopathic changes by a combination of magnetic resonance imaging (MRI) markers. The aim of this study was to examine the association between total CAA-SVD score and features of CMIs on in vivo 3-Tesla MRI. Eighty patients with probable CAA were retrospectively analyzed. Lobar cerebral microbleeds, cortical superficial siderosis, enlargement of perivascular space in the centrum semiovale and white matter hyperintensity were collectively assessed, and the total CAA-SVD score was calculated. The presence of CMI was also examined. Of the 80 patients, 13 (16.25%) had CMIs. CMIs were detected more frequently in the parietal and occipital lobes. A positive correlation was found between total CAA-SVD score and prevalence of CMI (ρ=0.943; p=0.005). Total CAA-SVD score was significantly higher in patients with CMIs than in those without (p=0.009). In a multivariable logistic regression analysis, the presence of CMIs was significantly associated with total CAA-SVD score (odds ratio 2.318 [95% confidence interval 1.228-4.376]; p=0.01, per each additional point). The presence of CMIs with a high CAA-SVD score could be an indicator of more severe amyloid-associated vasculopathic changes in patients with probable CAA.

Total small vessel disease burden and functional outcome in patients with ischemic stroke.

Cerebral small vessel disease (SVD) is comprised of lacunes, cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and enlarged perivascular space (EPVS). We investigated the cumulative effect of SVD on 3-month functional outcome following ischemic stroke using the total SVD score. The total SVD score of 477 acute ischemic stroke patients with adequate brain MRI was analyzed. We used multivariable ordinal logistic regression analysis to investigate the independent impact of total SVD score on ordinal modified Rankin Scale (mRS) score at 3-month after ischemic stroke. Mean age was 66±14 years, and 61% were men. The distribution of the total SVD score from 0 to 4 was 27%, 24%, 26%, 16%, and 7%, respectively. The proportion of mRS scores 2 or greater was 16% and 47% in total SVD score 0 and 4, respectively. Multivariable ordinal logistic regression analysis results showed that compared with the total SVD score of 0, total SVD scores of 2, 3, and 4 were independently associated with higher mRS scores with adjusted odds ratios (95% confidence intervals) of 1.68 (1.02-2.76), 2.24 (1.25-4.00), and 2.00 (1.02-4.29). Lacunes, CMBs, WMHs but not EPVS were associated with mRS scores at 3 months. However, the impact of each SVD marker on stroke outcome was smaller than that of the total SVD score. We found an independent association between total SVD scores and functional outcome at 3 months following ischemic stroke. The total SVD score may be useful for stratification of patients who are at a high-risk of unfavorable outcomes.

Abstract TP194: Relation Between Lipoprotein (a) and Cerebral Arteriosclerosis

Background: Lipoprotein(a) is known to be associated with increased atherosclerotic burden and vascular event. We investigated the relationship between lipoprotein(a) level and cerebral arteriosclerosis burden, including both atherosclerosis and small vessel disease. Methods: Consecutive patients with acute cerebral infarction or transient ischemic attack who had been through both brain imaging and serum lipoprotein a level analysis were included in the study. For cerebral atherosclerosis, intracranial arterial calcification status at cavernous portion of internal carotid artery and cerebral atherosclerosis score as the sum of major cerebral arterial stenosis were measured from brain CT angiography. Assessed cerebral small vessel disease phenotype included white matter hyperintensities, old lacune, cerebral microbleeds and extensive perivascular space. The patients were categorized into four groups according to the predefined cut-off values of lipoprotein(a) (15, 30, 50mg/dL). Results: A total of 990 patients were included with 457 female patients (mean age = 68.2 ± 12.8 years). Overall cerebral atherosclerosis score or total small vessel disease burden was not increased according to increased lipoprotein(a) group, although the proportion of the patients with severe calcification showed increasing tendency. Multivariable logistic regression analysis revealed that increased lipoprotein(a) was independently associated with severe calcification (group 4, odds ratio = 1.68, confidence interval = 1.01 – 2.80). Increased lipoprotein(a) was associated with the presence of white matter hyperintensities and extensive perivascular space, but not associated with old lacune or cerebral microbleed. Conclusion: Lipoprotein(a) is independently associated with severe calcification of intracranial artery. The impact of elevated lipoprotein(a) toward small vessel disease burden seems to be different according to its phenotype.

ASSOCIATION BETWEEN CEREBRAL SMALL VESSEL DISEASE AND MILD MOTOR PARKINSONIAN SIGNS IN PATIENTS WITH LACUNAR STROKES AND TRANSIENT ISCHEMIC ATTACKS

Background: Both cerebral small vessel disease (SVD) and Mild Parkinsonian signs (MPS) are serious conditions affecting elderly patient, but, the association between them remain unclear. Objective: Examine the association between SVD, Total SVD burden and MPS in patients with Transient Ischemic Attacks (TIA) and Lacunar Strokes. Patients and Methods: We performed a cross-sectional study among 36 patients admitted with either TIA or Lacunar Stroke, but not known to have Parkinson’s disease or Parkinsonism. Patients were recruited from Al-Azhar University Hospitals during the period from June, 2016 to May 2018. Mean age was 73.38 ± 8.3 years, 58.3% males. MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (lacunar infarctions [LIs], white matter hyperintensities [WMH], cerebral microbleeds [CMBs], and Enlarged Perivascular spaces [EPVSs]). Total SVD score was calculated based upon presence/absence of these four SVD markers. Results: In a multivariate analysis, we found that the presence of LIs, WMHs, CMBs, and total SVD score were significantly associated with MPS, whereas EPVSs were not. We found a strong correlation between SVD score & MPS score. We also found a significant association between total SVD score and Rigidity & Bradykinesia. GFR was found to significantly correlate with SVD score & MPS score. Conclusion: Our results provided additional evidence that SVD and especially total SVD burden, might be a surrogate marker for MPS and support the support the hypothesis of a vascular contribution to MPS in older adults.

ASSOCIATION BETWEEN CEREBRAL SMALL VESSEL DISEASE AND MILD MOTOR PARKINSONIAN SIGNS IN PATIENTS WITH LACUNAR STROKES AND TRANSIENT ISCHEMIC ATTACKS

Background: Both cerebral small vessel disease (SVD) and Mild Parkinsonian signs (MPS) are serious conditions affecting elderly patient, but, the association between them remain unclear. Objective: Examine the association between SVD, Total SVD burden and MPS in patients with Transient Ischemic Attacks (TIA) and Lacunar Strokes. Patients and Methods: We performed a cross-sectional study among 36 patients admitted with either TIA or Lacunar Stroke, but not known to have Parkinson’s disease or Parkinsonism. Patients were recruited from Al-Azhar University Hospitals during the period from June, 2016 to May 2018. Mean age was 73.38 ± 8.3 years, 58.3% males. MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (lacunar infarctions [LIs], white matter hyperintensities [WMH], cerebral microbleeds [CMBs], and Enlarged Perivascular spaces [EPVSs]). Total SVD score was calculated based upon presence/absence of these four SVD markers. Results: In a multivariate analysis, we found that the presence of LIs, WMHs, CMBs, and total SVD score were significantly associated with MPS, whereas EPVSs were not. We found a strong correlation between SVD score & MPS score. We also found a significant association between total SVD score and Rigidity & Bradykinesia. GFR was found to significantly correlate with SVD score & MPS score. Conclusion: Our results provided additional evidence that SVD and especially total SVD burden, might be a surrogate marker for MPS and support the support the hypothesis of a vascular contribution to MPS in older adults.

Total Small Vessel Disease Burden Predicts Functional Outcome in Patients With Acute Ischemic Stroke.

Background: Cerebral small vessel disease (SVD) is generally considered as a cause of stroke, disability, gait disturbances, vascular cognitive impairment, and dementia. The aim of this study was to investigate whether the total SVD burden can be used to predict functional outcome in patients with acute ischemic stroke.Methods: From April 2017 to January 2018, consecutive patients with acute ischemic stroke who underwent baseline MRI scan were evaluated. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days and defined as i) excellent outcome (mRS ≤ 1) and ii) good outcome (mRS ≤ 2). Brain MRI was performed and assessed for lacunes, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The total SVD burden was calculated based on lacunes, WMH, and EPVS and then summed up to generate an ordinal “total SVD burden” (range 0–3). Bivariate logistic regression models were used to identify the association between SVD and functional outcome.Results: A total of 416 patients were included in the final analysis; 44.0, 33.4, 19.2, and 3.4% of the patients had 0, 1, 2, and 3 features of SVD, respectively. In regard to individual SVD feature, lacunes (OR: 0.48, 95% CI: 0.32–0.71; OR: 0.49, 95% CI: 0.31–0.77) and WMH (OR: 0.53, 95% CI: 0.34–0.82; OR: 0.53, 95% CI: 0.33–0.85) were negatively associated with excellent outcome and good outcome. As to the total burden of SVD, three SVD features had strongest negative associations with functional outcomes (excellent outcome, OR: 0.13, 95% CI: 0.03–0.48; good outcome, OR: 0.18, 95% CI: 0.06–0.54). After adjustment for potential confounders, a high SVD burden (3 features, OR: 0.07, 95% CI: 0.01–0.41) and the score of total SVD burden (OR: 0.64, 95% CI: 0.44–0.93) remained negatively associated with excellent outcome.Conclusion: Total SVD burden negatively associated with functional outcome at 3 months in patients with acute ischemic stroke and is superior to individual SVD feature in prediction of functional outcome. MRI-based assessment of total SVD burden is highly valuable in clinical management of stroke victims and could help guide the allocation of resources to improve outcome.

A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease.

Background: Previous studies have investigated the association between a single marker of cerebral small vessel disease (SVD) and hemorrhagic transformation (HT). However, the effect of the total SVD burden on HT has not been evaluated yet. We aimed to investigate the association between the total SVD score and HT in ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD).Methods: Ischemic stroke patients with AF and/or RHD admitted within 7 days after onset were enrolled at two hospitals in China. The total SVD score was based on the presence of lacunes, extensive white matter hyperintensities, cerebral microbleeds, and moderate to severe enlarged perivascular spaces in the basal ganglia. One point was awarded for the presence of each marker, with the total SVD score ranging from 0 to 4 points. HT was assessed based on follow-up imaging scans during hospitalization and was classified according to the radiographic appearance and associated neurological deterioration.Results: Of 207 enrolled patients (mean age, 67.79 years; 58.9% female), 89 (43.0%) developed HT. The distribution of the total SVD score was significantly different between patients with and without HT in the univariate analysis (p = 0.04). After adjustment for confounders, a SVD score of 1 was independently associated with an increased risk of HT [odds ratio (OR), 3.23; 95% confidence interval (CI), 1.48–7.04; p = 0.003], while a SVD score ≥2 was inversely related to the occurrence of HT (OR, 0.41; 95% CI, 0.19–0.91; p = 0.03). These independent associations remained significant in the subgroups of hemorrhagic infarction and asymptomatic HT (all p < 0.05).Conclusions: In our study, the relationship between the total SVD score and HT was not linear, since the presence of only one marker of SVD was associated with an increased risk of HT, while the presence of two or more markers of SVD was a potential protective factor for HT. These results indicate the need to take the total SVD score into account, not only a single SVD marker, when assessing the risk of HT. Further studies with larger samples are required to validate these findings.