Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease.

BACKGROUND: Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia. METHODS: In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years. We determined associations between DTI-ALPS and PVS volume with cerebral small vessel disease imaging markers (white matter hyperintensity volume, lacunes, and microbleeds) at baseline and with changes in imaging markers. We determined whether DTI-ALPS and PVS volume at baseline and change over 3 years predicted incident dementia. Analyses were controlled for conventional diffusion tensor image metrics using 2 markers (median mean diffusivity [MD] and peak width of skeletonized MD) and adjusted for age, sex, and vascular risk factors. RESULTS: A total of 120 patients, mean age 70.0 years and 65.0% male, were included. DTI-ALPS declined over 3 years, while no change in PVS volume was found. Neither DTI-ALPS nor PVS volume was associated with cerebral small vessel disease imaging marker progression. Baseline DTI-ALPS was associated with changes in global cognition (ß=0.142, P=0.032), executive function (ß=0.287, P=0.027), and long-term memory (ß=0.228, P=0.027). Higher DTI-ALPS at baseline predicted a lower risk of dementia (hazard ratio, 0.328 [0.183-0.588]; P<0.001), and this remained significant after including median MD as a covariate (hazard ratio, 0.290 [0.139-0.602]; P<0.001). Change in DTI-ALPS predicted dementia conversion (hazard ratio, 0.630 [0.428-0.964]; P=0.048), but when peak width of skeletonized MD and median MD were entered as covariates, the association was not significant. There was no association between baseline PVS volume, or PVS change over 3 years, and conversion to dementia. CONCLUSIONS: DTI-ALPS predicts future dementia risk in patients with lacunar strokes and confluent white matter hyperintensities. However, the weakening of the association between change in DTI-ALPS and incident dementia after controlling for peak width of skeletonized MD and median MD suggests part of the signal may represent conventional diffusion tensor image metrics. PVS volume is not a predictor of future dementia risk.

Does Thrombosis Play a Causal Role in Lacunar Stroke and Cerebral Small Vessel Disease?

BACKGROUND: The importance of thromboembolism in the pathogenesis of lacunar stroke (LS), resulting from cerebral small vessel disease (cSVD), is debated, and although antiplatelets are widely used in secondary prevention after LS, there is limited trial evidence from well-subtyped patients to support this approach. We sought to evaluate whether altered anticoagulation plays a causal role in LS and cSVD using 2-sample Mendelian randomization. METHODS: From a recent genome-wide association study (n=81 190), we used 119 genetic variants associated with venous thrombosis at genome-wide significance (P<5*10-8) and with a linkage disequilibrium r2<0.001 as instrumental variables. We also used genetic associations with stroke from the GIGASTROKE consortium (62 100 ischemic stroke cases: 10 804 cardioembolic stroke, 6399 large-artery stroke, and 6811 LS). In view of the lower specificity for LS with the CT-based phenotyping mainly used in GIGASTROKE, we also used data from patients with magnetic resonance imaging-confirmed LS (n=3199). We also investigated associations with more chronic magnetic resonance imaging features of cSVD, namely, white matter hyperintensities (n=37 355) and diffusion tensor imaging metrics (n=36 533). RESULTS: Mendelian randomization analyses showed that genetic predisposition to venous thrombosis was associated with an increased odds of any ischemic stroke (odds ratio [OR], 1.19 [95% CI, 1.13-1.26]), cardioembolic stroke (OR, 1.32 [95% CI, 1.21-1.45]), and large-artery stroke (OR, 1.41 [95% CI, 1.26-1.57]) but not with LS (OR, 1.07 [95% CI, 0.99-1.17]) in GIGASTROKE. Similar results were found for magnetic resonance imaging-confirmed LS (OR, 0.94 [95% CI, 0.81-1.09]). Genetically predicted risk of venous thrombosis was not associated with imaging markers of cSVD. CONCLUSIONS: These findings suggest that altered thrombosis plays a role in the risk of cardioembolic and large-artery stroke but is not a causal risk factor for LS or imaging markers of cSVD. This raises the possibility that antithrombotic medication may be less effective in cSVD and underscores the necessity for further trials in well-subtyped cohorts with LS to evaluate the efficacy of different antithrombotic regimens in LS.

Incidence and influencing factors of urinary incontinence in stroke patients: A meta-analysis.

BACKGROUND: The incidence of stroke in China ranks first in the world and is the leading cause of death and disability in adults. Urinary incontinence is an independent risk factor leading to poor prognosis of stroke. However, studies on the incidence of urinary incontinence in stroke patients and its influencing factors are different, fluctuate greatly, and there is no unified basis. OBJECTIVE: To quantitatively analyze the incidence of urinary incontinence in stroke patients and its related influencing factors, and further make public health strategic decisions to reduce the occurrence of adverse outcomes. METHODS: Computer searches were conducted in PubMed, Medline, Web of Science, Cochrane Library, Embase, CLNAHL Complete, China National Knowledge Infrastructure (CNKI), Chinese Biomedical database(CBM), Wan Fang Database, VIP Database, observational studies such as cohort studies, case-control studies or cross-sectional studies on the incidence or influencing factors of urinary incontinence in stroke patients from the establishment of the database to the publication in August 2023. Studies selection, quality evaluation and data extraction were conducted independently by two researchers according to the established search strategy. Stata 14.0 statistical software was used for meta-analysis. RESULTS: A total of 21 manuscripts were included, with a cumulative sample size of 7327 cases, including 2887 patients with urinary incontinence. Meta-analysis results showed that the incidence of urinary incontinence in stroke patients was 38% [95% confidence interval (34%, 41%)], including married patients and lacunar infarction were the protective factors for urinary incontinence in stroke patients, while age, chaperone, low educational level, chronic cough, lesion sites (parietal lobe, frontal lobe, and temporal lobe), stroke type (cerebral hemorrhage, subarachnoid hemorrhage and cerebral hemorrhage complicated with subarachnoid hemorrhage), dysfunction (aphasia dyslexia, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, the higher the NIHSS score, the lower the Bachmann index (BI) score, OCSP classification (total anterior circulation infarction) and other 11 items were risk factors for urinary incontinence in stroke patients. CONCLUSION: The incidence of urinary incontinence in stroke patients is 38%. Marriage and lacunar infarction are the protective factors of urinary incontinence. Age, carer, low educational level, chronic cough, lesion site (parietal, frontal and temporal lobes), stroke type (cerebral hemorrhage, subarachnoid hemorrhage, cerebral hemorrhage combined with subarachnoid hemorrhage), dysfunction (aphasia and dysarthria syndrome, dysphagia, eye movement abnormalities, leg muscle disorders), post-stroke depression, and higher NIHSS score, Lower BI score and OCSP classification (total anterior circulation infarction) were risk factors for urinary incontinence in stroke patients.

Deep Resequencing of the 1q22 Locus in Non-Lobar Intracerebral Hemorrhage.

OBJECTIVE: Genome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. METHODS: A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired-end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. RESULTS: Common and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired-end tag data analysis highlighted the presence of long-range interactions between the SEMA4A-promoter and PMF1-enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. INTERPRETATION: Altered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325-337.

Posterior reversible encephalopathy syndrome and acute ischemic stroke: an underreported association.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported. METHODS: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES. DISCUSSION: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one. CONCLUSIONS: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES.

Causal Effect of the 25-Hydroxyvitamin D Concentration on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Previous observational studies reported that a lower serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with a higher burden of cerebral small vessel disease (cSVD). The causality of this association is uncertain, but it would be clinically important, given that 25(OH)D can be a target for intervention. We tried to examine the causal effect of 25(OH)D concentration on cSVD-related phenotypes using a Mendelian randomization approach. METHODS: Genetic instruments for each serum 25(OH)D concentration and cSVD-related phenotypes (lacunar stroke, white matter hyperintensity, cerebral microbleeds, and perivascular spaces) were derived from large-scale genome-wide association studies. We performed 2-sample Mendelian randomization analyses with multiple post hoc sensitivity analyses. A bidirectional Mendelian randomization approach was also used to explore the possibility of reverse causation. RESULTS: We failed to find any significant causal effect of 25(OH)D concentration on cSVD-related phenotypes (odds ratio [95% CI], 1.00 [0.87-1.16], 1.01 [0.96-1.07], 1.06 [0.85-1.33], 1.00 [0.97-1.03], 1.02 [0.99-1.04], 1.01 [0.99-1.04] for lacunar stroke, white matter hyperintensity, cerebral microbleeds, and white matter, basal ganglia, hippocampal perivascular spaces, respectively). These results were reproduced in the sensitivity analyses accounting for genetic pleiotropy. Conversely, when we examined the effects of cSVD phenotypes on 25(OH)D concentration, cerebral microbleeds were negatively associated with 25(OH)D concentration (0.94 [0.92-0.96]). CONCLUSIONS: Given the adequate statistical power (>0.8) of the analyses, our findings suggest that the previously reported association between 25(OH)D concentration and cSVD phenotypes might not be causal and partly attributed to reverse causation.

Preliminary study of the interactive effects of coronary heart disease and lacunar infarction on renal function in patients with type 2 diabetes mellitus by gender.

BACKGROUND: Coronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR). METHODS: We conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination. RESULTS: In this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06-32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37-3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61-2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = -0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = -0.229, P = 0.001). CONCLUSION: This study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.

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.

Impact of total cerebral small vessel disease score on ophthalmic artery morphologies and hemodynamics.

BACKGROUND: Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score. METHODS: This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations. RESULTS: The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (ß = - 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001). CONCLUSIONS: The decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA.

Intracranial carotid artery calcification morphology differs in patients with lacunar and nonlacunar acute ischemic strokes.

BACKGROUND AND PURPOSE: Intracranial carotid artery calcifications (ICACs) are a common finding on noncontrast computed tomography (NCCT) and have been associated with an increased risk of ischemic stroke. However, no data are available about the association between ICAC patterns and stroke etiology. We investigated the association between ICAC patterns and etiological subtypes of ischemic stroke. METHODS: We retrospectively analyzed a single center cohort of patients admitted for ischemic stroke with known etiology. Each carotid artery was evaluated separately on NCCT scans to define the ICAC pattern (intimal, medial, mixed). The association between ICAC patterns and stroke etiology was investigated using logistic regression models adjusting for relevant confounders. RESULTS: A total of 485 patients were included (median age = 78 [interquartile range (IQR) = 70-85] years, 243 [50%] female, median National Institutes of Health Stroke Scale = 6 [IQR = 3-12]). Frequencies of ICAC patterns were: intimal, n = 96 (20%); medial, n = 273 (56%); mixed, n = 51 (11%), indistinct/absent, n = 65 (13%) patients. Intimal pattern was more frequent in lacunar compared with nonlacunar (33% vs. 16%, p < 0.001) stroke etiology, whereas medial pattern was less frequent in lacunar compared with nonlacunar stroke (36% vs. 62%, p < 0.001). After adjustment for confounders, intimal ICAC predominant pattern remained associated with lacunar stroke etiology in two multivariate models (Model 1: adjusted odds ratio [aOR] = 2.08, 95% confidence interval [CI] = 1.20-3.56; Model 2: aOR = 2.01, 95% CI = 1.16-3.46). CONCLUSIONS: Our study suggests that intimal ICAC pattern is associated with lacunar stroke and may serve as a marker for lacunar stroke etiology, possibly strengthening the relation between endothelial dysfunction and lacunar stroke.

Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients.

PURPOSE: Sarcopenia is associated with poor outcomes, and evidence suggests an inverse relationship between skeletal muscle mass and cardiovascular risk. Sarcopenia has been studied after stroke, but its value as a risk factor for stroke has not been examined. This prospective cohort study measured sarcopenia in stroke/TIA patients at baseline to explore its role in predicting recurrent events. METHOD: The Arterial Stiffness In lacunar Stroke and TIA (ASIST) study included 96 patients with TIA/lacunar stroke, of which 82 patients (mean age 71.2±10.8 years) had bioimpedance analysis to assess body composition. Skeletal Mass Index (SMI) was calculated and parameters of sarcopenia assessed using Davison (1) and Janssen (2) criteria. Recurrent cerebrovascular events were monitored over 5 years. RESULTS: Eighteen patients had recurrent events. On independent samples t test there were significantly more participants with sarcopenia in the recurrent events group (89% vs 56%, p<0.001) using Davison (1) criteria, as well as lower mean SMI, significantly more participants with diabetes and higher arterial stiffness. On binary logistic regression, the only significant predictors of recurrent events were SMI (p=0.036, hazard ratio=0.414, 95% confidence interval 0.195-0.948) and diabetes (p=0.004, hazard ratio=9.06, 95% confidence interval 2.009-40.860) when corrected for age, sex and cardiovascular risk factors. Using Janssen (2) criteria in the regression, severe sarcopenia was a significant predictor of recurrent events (p=0.028). There was a significant association between sarcopenia and recurrent events on Chi square based on Davison (p=0.02) and Janssen (p=0.034) definitions. CONCLUSIONS: The presence of baseline sarcopenia in stroke and TIA patients is an independent predictor of recurrent events.

Risk factors related to early neurological deterioration in lacunar stroke and its influence on functional outcome.

OBJECTIVE: To identify risk factors for early neurological deterioration (END) in acute lacunar stroke patients and its influence on functional outcome. METHODS: Consecutive acute lacunar stroke patients defined by magnetic resonance imaging (MRI) between January 2018 and June 2020 were included in the study. END was defined as any persisting increase in National Institutes of Health Stroke Scale (NIHSS) score of ⩾ 2 points post admission, and favorable outcome was defined as a modified Rankin Scale (mRS) of 0-2 at discharge. Univariable and multivariable logistic regression were performed to identify risk factors related to END, as well as the influence of END on functional outcome. RESULTS: Among a total of 638 lacunar stroke patients (420 males (65.8%), median age 66 years (interquartile range (IQR): 56-74)), 108 (16.9%) developed END, and 94.4% (102/108) of the END occurred within 72 h post admission. Admission NIHSS score (adjusted odds ratio (aOR) 1.132, 95% confidence interval (CI) 1.046-1.225, p = 0.002), female (aOR 2.752, 95% CI 1.277-5.933, p = 0.010), admission systolic blood pressure (SBP) (160-179 mm Hg) (aOR 9.395, 95% CI 4.310-20.479, p < 0.001) and admission SBP (⩾180 mm Hg) (aOR 16.030, 95% CI 5.991-42.891, p < 0.001) were significantly associated with END. Delay time from onset to admission (aOR 0.995, 95% CI 0.990-1.000, p = 0.031), SBP dropping (⩾20 mm Hg) within 3 days or when END occurred (aOR 0.037, 95% CI 0.016-0.086, p < 0.001) and thalamic lacunar infarction (aOR 0.098, 95% CI 0.012-0.827, p = 0.033) were inversely associated with END. END (aOR 12.374, 95% CI 6.881-22.254, p < 0.001) and higher admission NIHSS score (aOR 1.488, 95% CI 1.359-1.629, p < 0.001) predicted unfavorable outcome at discharge. CONCLUSION: END in lacunar stroke patients is common and is associated with unfavorable outcome. Admission high SBP is a potentially modifiable risk factor for prevention of END, but this needs further investigation.

Prevalence of, and risk factors for, cognitive impairment in lacunar stroke.

BACKGROUND: Small vessel disease (SVD) is associated with vascular cognitive impairment (VCI) but why VCI occurs in some, but not other patients, is uncertain. We determined the prevalence of, and risk factors for, VCI in a large cohort of patients with lacunar stroke. METHODS: Participants with magnetic resonance imaging (MRI)-confirmed lacunar stroke were recruited in the multicenter DNA Lacunar 2 study and compared with healthy controls. A logistic regression model was used to determine which vascular risk factors and MRI parameters were independent predictors of VCI, assessed using the Brief Memory and Executive Test (BMET). RESULTS: A total of 912 lacunar stroke patients and 425 controls were included, with mean (SD) age of 64.6 (12.26) and 64.7 (12.29) years, respectively. VCI was detected in 38.8% lacunar patients and 13.4% controls. In a logistic regression model, diabetes mellitus (odds ratio (OR) = 1.98 (95% confidence interval (CI) = 1.40-2.80), p < 0.001) and higher body mass index (BMI) (OR = 1.03 (95% CI = 1.00-1.05), p = 0.029) were independently associated with increased risk of VCI, and years of full-time education with lower risk (OR = 0.92 (95% CI = 0.86-0.99), p = 0.018). When entering both lacune count and white matter hyperintensity (WMH) in the same logistic regression model, only WMH grade was significantly associated with VCI (OR = 1.46 (95% CI = 1.24-1.72), p < 0.001). CONCLUSION: VCI is common in lacunar stroke patients, affecting almost 40%. This prevalence suggests that it should be routinely screened for in clinical practice. Risk factors for VCI in patients with lacunar stroke include diabetes mellitus, depressive symptoms, higher BMI, and WMH severity, while education is protective.

[Ischaemic or transient attack? Magnetic resonance imaging in transient ischaemic attack: a review of 106 cases]. / Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.

INTRODUCTION: Transient ischaemic attack (TIA) has classically been defined as an episode of self-limited focal neurological deficit lasting up to 24 hours, with no neuroimaging evidence of established acute ischaemic injury. However, the definition of this entity is changing, and is adapting to new times and new diagnostic techniques, including magnetic resonance imaging (MRI) with diffusion sequences. An early and comprehensive approach to TIA, including MRI, is important to rule out clinically recovered established ischaemic strokes, in order to optimise the diagnostic and therapeutic management of patients. PATIENTS AND METHODS: Patients admitted to our stroke unit over a six-month period with suspected TIA were identified, and the definitive diagnosis and approach was studied based on the tests performed. RESULTS: A sample of 106 suspected cases of TIA were studied, in which early MRI was performed. Of these, 42 (39.62%) were clinically recovered ischaemic strokes (CRIS); 32 (30.18%), other pathologies (six epileptic seizures, five migraine auras, nine functional disorders, two amyloid spells and nine other causes, totalling 31); 26 (24.52%), TIAs; and six (5.66%), haemorrhagic stroke. Of 43 CRIS, eight (18.6%) were cardioembolic; eight (18.6%), atherothrombotic; eight (18.6%), embolic stroke of unknown origin; six (13.95%), lacunar stroke; five (11.62%) of infrequent cause; and four (9.3%), totalling 39, of undetermined cause. CRIS patients received significantly more individualised therapeutic management than TIA patients. CONCLUSIONS: The early use of MRI in the clinical suspicion of TIA makes it possible to gather evidence of CRIS and optimises the diagnostic and therapeutic approach for patients.

TITLE: Accidente isquémico y ¿transitorio? Resonancia magnética en el AIT: experiencia de 106 casos.Introducción. El accidente isquémico transitorio (AIT) clásicamente se ha definido como un episodio de déficit focal neurológico autolimitado con duración máxima de 24 horas, sin evidencia en la neuroimagen de lesión isquémica aguda establecida. Sin embargo, la definición de esta entidad está variando y se está adaptando a los nuevos tiempos y técnicas diagnósticas, incluida la resonancia magnética (RM) con secuencias en difusión. Es importante un abordaje íntegro y precoz del AIT, con RM cerebral, para descartar ictus isquémicos establecidos recuperados clínicamente, y así optimizar el manejo diagnóstico y terapéutico de los pacientes. Pacientes y métodos. Se identificó a los pacientes ingresados en un período de seis meses como sospecha de AIT en nuestra unidad de ictus, y se estudió el diagnóstico definitivo y su abordaje basándose en las pruebas realizadas. Resultados. Se estudiaron 106 sospechas de AIT en las que se realizó una RM precoz. De ellas, 43 (40,57%) fueron ictus isquémicos clínicamente recuperados (IICR); 31 (29,24%), otras patologías (nueve trastornos funcionales, seis crisis epilépticas, cinco auras migrañosas, dos amyloid spells y nueve otras causas); 26 (24,52%), AIT; y seis (5,66%), ictus hemorrágicos. De 43 IICR, ocho (18,6%) fueron cardioembólicos; ocho (18,6%), aterotrombóticos; ocho (18,6%), ictus embólico de origen desconocido; seis (13,95%), lacunares; cinco (11,62%) de causa infrecuente; cuatro (9,3%) microangiopáticos y cuatro (9,3%), de causa indeterminada. Los IICR recibieron un manejo terapéutico significativamente más individualizado respecto a los pacientes con AIT. Conclusiones. El uso de RM precoz en la sospecha clínica de AIT permite evidenciar la existencia de IICR y optimizar el abordaje diagnóstico y terapéutico de los pacientes.

Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes COL4A1/COL4A2 encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats. METHODS: We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates (M mulatta) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months). RESULTS: Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, P=0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD (P<0.017), including age as a covariate and either clinical hypertension (P<0.030) or neuropathological SVD diagnosis (P<0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals (P=0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV. CONCLUSIONS: Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV.

Systolic blood pressure and recurrent stroke in patients with different lesion patterns on diffusion weighted imaging.

Little is known about the relationship between baseline systolic blood pressure (SBP) and subsequent clinical events in patients with different lesion patterns on diffusion weighted imaging (DWI). We analyzed the Acute Non-disabling Cerebrovascular Events (CHANCE) trial dataset. Patients were categorized into negative DW imaging (no detectable lesions), lacunar infarction (single lesion ≤15 mm) and non-lacunar infarction (single lesion >15 mm or multiple lesions) based on lesion patterns on DWI. The primary outcome was recurrent stroke within 90 days. Cox proportional hazards models were used to assess the association between SBP levels and stroke outcomes in patients with different lesion patterns. A total of 1089 patients were analyzed. We found 258 cases (23.7%) with negative DW imaging, 392 (36.0%) with lacunar infarction and 439 (40.3%) with non-lacunar infarction. Patients with non-lacunar infarction had the highest incidence of stroke at 90-day (P < .001). In non-lacunar infarction group, compared with SBP < 160 mmHg, patients with SBP ≥ 160 mmHg had significantly higher risk of 90-day recurrent stroke (20.3% vs. 10.7%; adjusted hazard ratio 1.81, 95% confidence interval 1.09-3.00). No significant association was found between SBP and clinical outcomes in patients with negative DWI and lacunar stroke groups. The result at 1 year was similar as at 90-day. Therefore, non-lacunar infarction, the most common lesion pattern in CHANCE study, had the highest risk of recurrent stroke and combined vascular events both in 90 days and 1 year. High baseline SBP was significantly associated with increased risk of short- and long-term recurrent strokes in patients with non-lacunar infarction.

Association between frailty index based on routine laboratory tests and risk of cerebral small vessel disease in elderly patients: a hospital-based observational study.

BACKGROUND: The association between frailty and cerebral small vessel disease (CSVD) remains controversial due to the use of different methods to assess frailty, including physical frailty phenotype and frailty scores containing measures of cognition. A frailty index based on laboratory tests (FI-Lab), which assesses frailty by the combination of routine laboratory measures and several vital signs, is independent of cognition and function status. We aimed to evaluate the association of FI-Lab with CSVD. METHODS: An observational study was carried out in a hospitalized cohort of older patients with minor ischemic stroke or TIA. The FI-Lab was constructed by 20 routine laboratory tests, plus systolic blood pressure, diastolic blood pressure, and pulse pressure. Manifestations of CSVD including white matter hyperintensity (WMH), silent lacunar infarcts, microbleed, enlarged perivascular spaces (EPVS), as well as deep brain atrophy, were measured on magnetic resonance imaging (MRI). An ordinal score system constructed by WMH, EPVS, silent lacunar infarcts, and microbleed was used to reflect the total burden of CSVD. The associations between FI-lab and CSVD were examined by logistic regression analysis and ordinal regression. RESULTS: A total of 398 patients were recruited from January 2016 to December 2018. The mean FI-Lab value was 0.26 ± 0.11. The prevalence of extensive periventricular WMH, extensive deep WMH, extensive basal ganglia EPVS, extensive centrum semiovale EPVS, silent lacunar infarcts, and deep microbleed was 26.1, 66.6, 68.6, 80.7, 32.9, and 6.5%, respectively. A higher FI-Lab value was associated with increased risks of extensive deep WMH (OR = 1.622; 95% CI, 1.253 ~ 2.100), extensive basal ganglia EPVS (OR = 1.535; 95% CI, 1.187 ~ 1.985), extensive centrum semiovale EPVS (OR = 1.584; 95% CI, 1.167 ~ 2.151), silent lacunar infarcts (OR = 1.273; 95% CI, 1.007 ~ 1.608), and higher total burden of CSVD. These associations remained after the adjustment of potential confounding factors. CONCLUSION: This study demonstrated that a higher FI-Lab score might be associated with the presence of WMH, EPVS, silent lacunar infarcts, as well as severe total CSVD burden in older patients with minor stroke or TIA. The FI-Lab provides a basis for the prediction of CSVD.