Small Vessel Disease Burden Research Articles

Association between behavioral and psychological symptoms and cerebral small vessel disease MRI findings in memory clinic patients.

Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear. We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments. The CDR was significantly higher in patients with BPS (p = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS (p = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS (p = 0.037). There was no significant difference in total SVD and CAA-SVD score (p = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS (p = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS (p = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity. Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated.

Critical closing pressure as a new hemodynamic marker of cerebral small vessel diseases burden.

To investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO). We recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP. Ninety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17-1.71; P < 0.001] and correlated with CSVD burden [β (95% CI): 0.05 (0.04-0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6-93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [β (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [β (95% CI): 0.61 (0.00-1.22)] and systolic BP [β (95% CI): 0.16 (0.09-0.23); P < 0.001]. CrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.

Changes in CSF sPDGFRβ level and their association with blood–brain barrier breakdown in Alzheimer’s disease with or without small cerebrovascular lesions

BackgroundCSF-soluble platelet-derived growth factor receptor beta (sPDGFRβ) is closely associated with pericyte damage. However, the changes in CSF sPDGFRβ levels and their role in blood–brain barrier (BBB) leakage at different stages of Alzheimer’s disease (AD), with or without cerebral small vessel disease (CSVD) burden, remain unclear.MethodsA total of 158 individuals from the China Aging and Neurodegenerative Disorder Initiative cohort were selected, including 27, 48, and 83 individuals with a clinical dementia rating (CDR) score of 0, 0.5, and 1–2, respectively. CSF total tau, phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured using the Simoa assay. Albumin and CSF sPDGFRβ were measured by commercial assay kits. CSVD burden was assessed by magnetic resonance imaging.ResultsCSF sPDGFRβ was the highest level in the CDR 0.5 group. CSF sPDGFRβ was significantly correlated with the CSF/serum albumin ratio (Q-alb) in the CDR 0–0.5 group (β = 0.314, p = 0.008) but not in the CDR 1–2 group (β = − 0.117, p = 0.317). In the CDR 0–0.5 group, CSF sPDGFRβ exhibited a significant mediating effect between Aβ42/Aβ40 levels and Q-alb (p = 0.038). Q-alb, rather than CSF sPDGFRβ, showed a significant difference between individuals with or without CSVD burden. Furthermore, in the CDR 0.5 group, CSF sPDGFRβ was higher in subjects with progressive mild cognitive impairment than in those with stable mild cognitive impairment subjects (p < 0.001). Meanwhile, CSF sPDGFRβ was significantly associated with yearly changes in MMSE scores in the CDR 0.5 group (β = − 0.400, p = 0.020) and CDR 0.5 (A+) subgroup (β = − 0.542, p = 0.019).ConclusionsWe provide evidence that increased CSF sPDGFRβ is associated with BBB leakage in the early cognitive impairment stage of AD, which may contribute to cognitive impairment in AD progression.

Total Cerebral Small Vessel Disease Burden Predicts the Outcome of Acute Stroke Patients after Intra-Arterial Thrombectomy

Introduction: Various types of cerebral small vessel diseases (cSVD) markers commonly coexist. The neurological function outcome is affected by their combined effect. To investigate the effect of cSVD on intra-arterial thrombectomy (IAT), our study aimed at developing and testing a model with fusing a combination of multiple cSVD markers as total cSVD burden to predict the outcome of acute ischemic stroke (AIS) patients after IAT treatment. Methods: From October 2018 to March 2021, continuous AIS patients with IAT treatment were enrolled. We calculated the cSVD markers identified by magnetic resonance imaging. The outcomes of all patients were assessed according to the modified Rankin Scale (mRS) score at 90 days after stroke. The relationship between total cSVD burden and outcomes was analyzed by logistics regression analysis. Results: A total of 271 AIS patients were included in this study. The proportions of score 0∼4 in the total cSVD burden group (i.e., score 0, 1, 2, 3, and 4 groups) were 9.6%, 19.9%, 23.6%, 32.8%, and 14.0%, respectively. The higher the cSVD score, the more patients with a poor outcome. Heavier total cSVD burden (1.6 [1.01∼2.27]), diabetes mellitus (1.27 [0.28∼2.23]), and higher national institute of health stroke scale (NIHSS) on admission (0.15 [0.07∼0.23]) were associated with poor outcome. In the two Least Absolute Shrinkage and Selection Operator regression models, model 1 using age, duration from onset to reperfusion, Alberta stroke program early CT score (ASPECTS), NIHSS on admission, modified thrombolysis in cerebral infarction (mTICI) and total cSVD burden as variables perform well on predicting short-term outcome in area under curve (AUC) of 0.90. Model 2, including all of the variables above except cSVD, showed less predictive capability than model 1 (AUC 0.90 vs. 0.82, p = 0.045). Conclusions: The total cSVD burden score was independently associated with the clinical outcomes of AIS patients after IAT treatment and it may be a reliable predictor for poor outcomes of AIS patients after IAT treatment.

Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors.

Hypertension is the most important risk factor for cerebral small vessel disease (SVD). In this cross-sectional study, we tested the independent association of cerebral SVD burden with global cognitive function and each cognitive domain in patients with vascular risk factors. The Tokyo Women's Medical University Cerebral Vessel Disease (TWMU CVD) registry is an ongoing prospective, observational registry in which patients with any evidence of CVD in magnetic resonance imaging (MRI) and at least one vascular risk factor were consecutively enrolled. For SVD-related findings, we evaluated white matter hyperintensity, lacunar infarction, cerebral microbleeds, enlarged perivascular space, and medial temporal atrophy. We used the total SVD score as the SVD burden. They underwent the Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests, and each cognitive domain was evaluated. After excluding patients without MRI T2* images and those with MMSE score <24, we analyzed 648 patients. The total SVD score was significantly associated with MMSE and MoCA-J scores. After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and MoCA-J score remained significant. The total SVD score was independently associated with attention. In conclusion, the total SVD score, cerebral SVD burden, was independently association with global cognitive function and attention. A strategy to reduce SVD burden will have the potential to prevent cognitive decline. A total of 648 patients with any evidence of cerebral small vessel disease (SVD) in MRI and at least one vascular risk factor underwent Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests. The total SVD scores count the presence of each SVD-related findings (white matter hyperintensity, Lacunar infarction, cerebral microbleeds and enlarged perivascular space), ranging from 0 to 4, as the SVD burden. Total SVD scores were significantly associated with MoCA-J scores (r = -0.203, P < 0.001). After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and global cognitive scores remained significant.

Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

A neuropsychological profile and its correlation with neuroimaging markers in patients with subcortical ischaemic vascular dementia.

Cognitive and neuroimaging assessments are still the main clinical practice methods for screening and diagnosing vascular dementia (VaD) patients. This study aimed to establish the neuropsychological characteristics of mild-to-moderate subcortical ischaemic vascular dementia (SIVD) patients, find an optimal cognitive marker for differentiating them from Alzheimer's disease (AD) patients, and explore the correlation between cognitive function and total small vessel disease (SVD) burden. SIVD (n=60) and AD (n=30) patients and cognitively unimpaired healthy controls (HCs; n=30) were recruited from our longitudinal MRI AD and SIVD study (ChiCTR1900027943) and received a comprehensive neuropsychological assessment and a multimodal MRI scan. Cognitive performance and MRI SVD markers were compared between groups. Combined cognitive scores were established for differentiating between SIVD and AD patients. Correlations between cognitive function and total SVD scores were analysed in dementia patients. SIVD patients showed poorer performance in information processing speed and better performance in memory, language, and visuospatial function than AD patients, although all cognitive domains were impaired in both groups compared with HCs. Combined cognitive scores showed an area under the curve of 0.727 (95%CI 0.62-0.84, p<0.001) for differentiating SIVD and AD patients. Auditory Verbal Learning Test recognition scores were negatively correlated with total SVD scores in SIVD patients. Our results suggested that neuropsychological assessments, specifically combined tests including episodic memory, information processing speed, language and visuospatial ability, are useful in the clinical differentiation between SIVD and AD patients. Moreover, cognitive dysfunction was partly correlated with MRI SVD burden in SIVD patients.

Cerebral Small Vessel Disease Progression Increases Risk of Incident Parkinsonism.

Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross-sectionally, however, there are little longitudinal data on whether SVD increases risk of incident parkinsonism itself. We investigated the relation between baseline SVD severity as well as SVD progression, and incident parkinsonism over a follow-up of 14 years. This study included 503 participants with SVD, and without parkinsonism at baseline, from the RUN DMC prospective cohort study. Baseline inclusion was performed in 2006 and follow-up took place in 2011, 2015, and 2020, including magnetic resonance imaging (MRI) and motor assessments. Parkinsonism was diagnosed according to the UK Brain Bank criteria, and stratified into vascular parkinsonism (VaP) and idiopathic Parkinson's disease (IPD). Linear mixed-effect models were constructed to estimate individual rate changes of MRI-characteristics. Follow-up for incident parkinsonism was near-complete (99%). In total, 51 (10.2%) participants developed parkinsonism (33 VaP, 17 IPD, and 1 progressive supranuclear palsy). Patients with incident VaP had higher SVD burden compared with patients with IPD. Higher baseline white matter hyperintensities (hazard ratio [HR]=1.46 per 1-SD increase, 95% confidence interval [CI]=1.21-1.78), peak width of skeletonized mean diffusivity (HR=1.66 per 1-SD increase, 95% CI=1.34-2.05), and presence of lacunes (HR=1.84, 95% CI=0.99-3.42) were associated with increased risk of all-cause parkinsonism. Incident lacunes were associated with incident VaP (HR=4.64, 95% CI=1.32-16.32). Both baseline SVD severity and SVD progression are independently associated with long-term parkinsonism. Our findings indicate a causal role of SVD in parkinsonism. Future studies are needed to examine the underlying pathophysiology of this relation. ANN NEUROL 2023;93:1130-1141.

Clinical features and FLAIR radiomics nomogram for predicting functional outcomes after thrombolysis in ischaemic stroke.

We explored whether radiomics features extracted from diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images can predict the clinical outcome of patients with acute ischaemic stroke. This study was conducted to investigate and validate a radiomics nomogram for predicting acute ischaemic stroke prognosis. A total of 257 patients with acute ischaemic stroke from three clinical centres were retrospectively assessed from February 2019 to July 2022. According to the modified Rankin scale (mRS) at 3 months, the patients were divided into a favourable outcome group (mRS of 0-2) and an unfavourable outcome group (mRS of 3-6). The high-throughput features from the regions of interest (ROIs) within the radiologist-drawn contour by AK software were extracted. We used two feature selection methods, minimum redundancy and maximum (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO), to select the features. Three radiomics models (DWI, FLAIR, and DWI-FLAIR) were established. A radiomics nomogram with patient characteristics and radiomics signature was built using a multivariate logistic regression model. The performance of the nomogram was evaluated in the test and validation sets. Ultimately, decision curve analysis was implemented to assess the clinical value of the nomogram. The FLAIR, DWI, and DWI-FLAIR radiomics model exhibited good prediction performance, with area under the curve (AUCs) of 0.922 (95% CI: 0.876-0.968), 0.875 (95% CI: 0.815-0.935), and 0.895 (95% CI: 0.840-0.950). The radiomics nomogram with clinical characteristics including the overall cerebral small vessel disease (CSVD) burden score, hemorrhagic transformation (HT) and admission National Institutes of Health Stroke Scale score (NIHSS) score and the FLAIR Radscore presented good discriminatory potential in the training set (AUC = 0.94; 95% CI: 0.90-0.98) and test set (AUC = 0.94; 95% CI: 0.87-1), which was validated in the validation set 1 (AUC = 0.95; 95% CI: 0.88-1) and validation set 2 (AUC = 0.90; 95% CI: 0.768-1). In addition, it demonstrated good calibration, and decision curve analysis confirmed the clinical value of this nomogram. This non-invasive clinical-FLIAR radiomics nomogram shows good performance in predicting ischaemic stroke prognosis after thrombolysis.

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.

Systemic Immune-Inflammation Index is Associated with Cerebral Small Vessel Disease Burden and Cognitive Impairment.

This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment. We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment. After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577-6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342-5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = -0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359-5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315-24.145) for cognitive impairment and 4.945 (2.063-11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden. Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.

Abstract TMP51: A Big-data Neuro-informatics Infrastructure To Support Research Pipelines For Cerebrovascular Disease

Background: Cerebrovascular disease has significant gaps in translational and outcomes research. We provide the framework for a neuro-informatics pipeline, “Registry for Neurological Endpoints Assessment Among Patients with Ischemic and Hemorrhagic Stroke (REINAH)”, aimed at harnessing ‘big data’ across a 7-hospital certified stroke healthcare system. Methods: An automated extract, transform, load (ETL) process imports all clinical inpatient and outpatient data for patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), transient ischemic attack (TIA), subarachnoid hemorrhage (SAH), cerebral amyloid angiopathy (CAA) and matched controls. Following validation, a 2 nd stage ETL merges geocoding data for area deprivation index and generates domain specific dashboards. Neuroimaging and physiological wave form data are imported and analyzed for infarct / hemorrhage characteristics, cerebral small vessel disease burden, and hemodynamic variability. Cross linkages between REINAH and Medicare claims data have been established with &gt; 98% overlap. Functional, cognitive, and quality of life outcomes are collected up till 365-days after discharge. Results: As of August 5, 2022, REINAH hosts data on 18,746 patients, including primary encounters for 1,863 ICH, 13,964 AIS, 1,264 SAH, and 3,307 TIA patients. Median (IQR) age for patients is 69 [58-79] years, including 51.7% Female, 15.6% Hispanic, 64.4% White, 24.6% Black, 5.4% Asian. Median Glasgow Coma Scale scores for AIS and ICH are 15 [14-15] and 13.5 [7-15], respectively. The successful contact rate for outcomes assessment is 70.9%, with 69.8% of responders providing consent for follow up. REINAH layout and demographics are shown in Figure. Conclusions: Mature data pipelines are needed to support validated and rapid evidence synthesis. REINAH provides a highly curated, clinically focused platform for stroke research that may impact patient care and post-stroke outcomes.

Abstract 3: Cerebral Small Vessel Disease Burden For Bleeding Risk During Antithrombotic Therapy -BAT2-

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models. Results: Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P&lt;0.001 for each). A unit increase of SVD score was associated with a higher risk of major bleeding (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.29-1.85) and intracranial hemorrhage (adjusted HR 1.61, 95% CI 1.28-2.03). With SVD score 4 compared to score 0, extracranial major bleeding (adjusted HR 3.37, 95% CI 1.12-10.15) and gastrointestinal bleeding (adjusted HR 2.54, 95% CI 1.02-6.35) were also significantly increased. A higher SVD score was associated with a mild but significant elevation of ischemic event risk (adjusted HR per unit increase 1.17, 95% CI 1.06-1.29). Conclusions: The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.

Small vessel disease burden predicts functional outcomes in patients with acute ischemic stroke using machine learning.

Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS). We enrolled 398 small-vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis. In the feature evaluation of SVO-AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO-AIS, SVD performed better than regular clinical data, which is the opposite of LAA-AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO-AIS. [0.91 (0.84-0.97)]. Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO-AIS patients' prognosis.

Association of deep medullary veins with the neuroimaging burden of cerebral small vessel disease

This study aimed to explore the association between deep medullary veins (DMVs) and the neuroimaging burden of cerebral small vessel disease (CSVD). In this cross-sectional study based on a retrospective analysis, a total of 248 patients (183 males and 65 females; mean age ± standard deviation, 69.5±14.8 years) diagnosed with CSVD with complete imaging and clinical data were enrolled. Neuroimaging markers of CSVD, including white matter hyperintensities, lacunes, prominent perivascular spaces (PVSs), and cerebral microbleeds (CMBs), were identified, and the total burden of CSVD was scored. Both DMV number and DMV score were used for assessment using susceptibility-weighted imaging (SWI). With the exception of perivascular spaces, more severe neuroimaging markers were observed in patients with a higher DMV score. After adjustments were made for age and body mass index (BMI), a higher DMV score (β=1.39; P<0.001) and smaller DMV number (β=-2.55; P=0.001) were associated with an increased CSVD burden. The degree of CMBs was independently correlated with both DMV score (β=1.60; P<0.001) and DMV number (β=-2.27; P=0.009). The association between lacunes and DMV score was also significant (β=0.97; P=0.026). Both DMV score and DMV number are potential imaging indicators of CSVD.

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.

The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.

Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. This study aims to systematically review the prevalence of cSVD in LMICs. Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

Overall cerebral small vessel disease burden is associated with outcome of acute ischemic stroke after mechanical thrombectomy.

To investigate the association between the overall cerebral small vessel disease (CSVD) burden and the therapeutic outcome of mechanical thrombectomy (MT) in patients with acute anterior circulation large-vessel occlusion stroke. Data of patients who achieved successful revascularization after MT for acute anterior circulation large-vessel occlusion stroke in the Ningbo Medical Center Lihuili Hospital between April 2017 and January 2022 were retrospectively analyzed. The overall CSVD burden was evaluated by total CSVD score based on MRI images. According to the 90-day modified Rankin Scale (mRS) score, the participants were divided into the Good outcome group (mRS score 0-2) and Poor outcome group (mRS score 3-6). Multivariate Logistic regression was applied to assess the relationship between the overal CSVD burdern and 90-day outcome. In total, 145 eligible patients were included and classified into the Good outcome group (n = 77, 62.3% males, mean age: 64.92 ± 13.67 years) and Poor outcome group (n = 68, 50% males, mean age: 69.76 ± 10.88 years). Symptomatic intracranial hemorrhage (OR = 2.788, 95%CI: 1.143-8.745, P = 0.048), poor preoperative collateral status (OR = 3.619, 95%CI: 1.670-7.844, P = 0.001), and high total CSVD score (score 2: OR = 3.800, 95%CI: 1.173 = 12.311, P = 0.026; score 3: OR = 7.529, 95%CI: 1.555-36.460, P = 0.012) were independently prognostic for poor 90-day outcome in patients receiving MT. This study identified that the overall CSVD burden was independently associated with the prognosis of patients receiving MT for acute anterior circulation large-vessel occlusion stroke.

Cerebral Small Vessel Disease Burden and Futile Reperfusion after Endovascular Treatment for Patients with Acute Ischemic Stroke

Introduction: Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). Methods: Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b–3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3–6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. Results: Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12 h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602–9.619; p = 0.003). Conclusions: We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD.

Association between Twenty-Four-Hour Ambulatory Blood Pressure Variability and Cerebral Small Vessel Disease Burden in Acute Ischemic Stroke.

Objective This study is aimed at investigating the association between the twenty-four-hour ambulatory blood pressure variability monitoring (ABPM) and cerebral small vessel disease (cSVD) burden in acute ischemic stroke (AIS) patients. Methods 115 AIS patients with demographics, vascular risk factors, 24 h ABPM, and brain magnetic resonance imaging (MRI) were retrospectively enrolled. 3.0 T MRI was used to assess cSVD burden by combining four MRI markers including white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), perivascular spaces (PVS), and lacunes. Correlation analysis was conducted to detect whether ABPM was associated with cSVD burden in AIS patients. Results 115 AIS patients with mean age 68.77 ± 10.26 years and 75.7% male were enrolled in this study. 112 AIS patients (97.4%) had at least one cSVD marker. Spearman correlation analysis indicated that hypertension was positively correlated with cSVD burden (ρ = 0.21, P = 0.07). High-density lipoprotein (HDL) was negatively correlated with cSVD burden (ρ = −0.21, P = 0.02). Blood pressure variability such as 24 h mean SBP (ρ = 0.23, P = 0.01), day mean SBP (ρ = 0.23, P = 0.01), and night mean SBP (ρ = 0.20, P = 0.04) was positively correlated with higher cSVD burden. Ordinal logistic regression analysis demonstrated that higher 24 h SBP SD and day mean SBP were independent risk factors for cSVD after controlling for other confounders. Conclusions Higher BPV was significantly related to total cSVD burden in AIS patients. 24 h SBP SD and day mean SBP were independent risk factors for cSVD burden in AIS patients but not DBP or DBP variability.