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Background and Objectives: Factors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes., Methods: We recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score., Results: We recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (β 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts., Discussion: In the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.

Objectives: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods., Methods: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis., Results: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (OR ivw  = 1.08, 95% CI: 1.03-1.16, p ivw  = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses., Discussion: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.

Introduction: This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI)., Method: Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0-50% EPVS progression), and Group 3 (≥ 50% EPVS progression). Multiple logistic regression analysis was used to analyze the risk of occurrence of SLI., Results: The EPVS scores and ΔEPVS scores were not significantly different between the EL and EOL groups (p > 0.05). EPVS volumes and their progression were significantly higher in EL compared with EOL (p < 0.001). The incidence of SLI was increased in Groups 2 and 3 compared with those in Group 1, and the trend test showed statistically significant (p = 0.032). Multiple logistic regression analysis showed that the risk of occurrence of SLI was significantly increased in Group 2 (OR 2.24; p = 0.024) and Group 3 (OR 3.31; p = 0.037) versus that in Group 1., Conclusion: 3D volume quantification allows for a more sensitive assessment of EPVS changes, and the progression of EPVS volume may contribute to the occurrence of SLI., (© 2023. Fondazione Società Italiana di Neurologia.)

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 (β=0.142, P =0.032), executive function (β=0.287, P =0.027), and long-term memory (β=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., Competing Interests: Disclosures Dr Tozer was funded by the Medical Research Council. H.S. Markus discloses grant support from the British Heart Foundation. The other author reports no conflict.

Despite the enormous health burden of lacunar stroke, data from low- and middle-income countries on lacunar stroke characteristics and its comparison with that of high-income countries are scarce. Thus, we aimed to investigate and compare the variable characteristics and vascular status in patients from Egypt and Germany suffering lacunar stroke. Two cohorts of lacunar stroke patients from Ain Shams University Hospital, Egypt and Goethe University Hospital Frankfurt, Germany were retrospectively collected between January 2019 and December 2020 and analyzed for demographics, risk factors, mode of presentation, neuroimaging features, treatment protocols and outcomes. MRI showed a different distribution pattern of lacunar strokes between cohorts, detecting posterior circulation lacunar infarctions preponderantly in patients from Egypt and anterior circulation lacunar infarctions preponderantly in patients from Germany. Complementary MR/CT angiography revealed a significantly higher proportion of intracranial and combined intracranial and extracranial arterial stenosis in patients from Egypt than in patients from Germany, suggesting differences in pathological processes. Younger age, higher NIHSS on admission, and posterior circulation lacunar infarction were predictors of Egyptian origin, whereas hypertension was a predictor of German origin. Our results support the idea of clinical and neuroimaging phenotype variations in lacunar stroke, including different sources of lacunar stroke in patients of different populations and geographical regions. This implies that guidelines for management of lacunar stroke might be tailored to these differences accordingly., (© 2023. The Author(s).)

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.

Background: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke., Methods: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding., Results: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81])., Conclusions: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

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.

Cerebral small vessel disease (SVD) causes lacunar stroke and intracerebral hemorrhage, and is the most common pathology underlying vascular cognitive impairment. Increasingly, the importance of other clinical features of SVD is being recognized including motor impairment, (vascular) parkinsonism, impaired balance, falls, and behavioral symptoms, such as depression, apathy, and personality change. Epidemiological data show a high prevalence of the characteristic magnetic resonance imaging (MRI) features of white matter hyperintensities and lacunar infarcts in community studies, and recent data suggest that it is also a major health burden in low- and middle-income countries. In this review, we cover advances in diagnosis, imaging, clinical presentations, pathogenesis, and treatment.The two most common pathologies underlying SVD are arteriolosclerosis caused by aging, hypertension, and other conventional vascular risk factors, and cerebral amyloid angiopathy (CAA) caused by vascular deposition of β-amyloid. We discuss the revised Boston criteria of CAA based on MRI features, which have been recently validated. Imaging is providing important insights into pathogenesis, including improved detection of tissue damage using diffusion tensor imaging (DTI) leading to its use to monitor progression and surrogate endpoints in clinical trials. Advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, while the high spatial resolution provided by ultrahigh field MRI at 7 T allows imaging of individual perforating arteries for the first time, and the measurement of flow velocity and pulsatility within these arteries. DTI and structural network analysis have highlighted the importance of network disruption in mediating the effect of different SVD pathologies in causing a number of symptoms, including cognitive impairment, apathy, and gait disturbance.Despite the public health importance of SVD, there are few proven treatments. We review the evidence for primary prevention, and recent data showing how intensive blood pressure lowering reduces white matter hyperintensities (WMH) progression and delays the onset of cognitive impairment. There are few treatments for secondary prevention, but a number of trials are currently evaluating novel treatment approaches. Recent advances have implicated molecular processes related to endothelial dysfunction, nitric oxide synthesis, blood-brain barrier integrity, maintenance and repair of the extracellular matrix, and inflammation. Novel treatment approaches are being developed to a number of these targets. Finally, we highlight the importance of large International collaborative initiatives in SVD to address important research questions and cover a number which have recently been established.

Objectives: To report the prevalence and distribution of lacunar stroke in different regions of China, as well as the demographical characteristics of symptomatic and asymptomatic lacunar stroke., Design: Cross-sectional study., Setting: Data were derived from NESS-China Study that was conducted in 157 sites covering all 31 provinces, including 64 urban and 93 rural areas in mainland China between 1 September 2013 and 31 December 2013. Lacunar stroke was defined as being previously diagnosed according to the participants' medical history. Patients were further divided into symptomatic or asymptomatic groups, depending on whether they were initially diagnosed with neurological symptoms., Participants: 458 833 participants aged ≥20 years were enrolled in this study., Results: A total of 7520 participants (1.63%) were diagnosed with lacunar stroke. The peak rate of diagnosis was between the ages of 70 and 79 years in both men and women. Geographically, the age-standardised and sex-standardised prevalence was highest in Northeast China (2495.3/100 000 persons) and lowest in Southeast China (599.7/100 000 persons), showing a geographical disparity. Over 90% of patients with lacunar stroke were diagnosed in secondary or tertiary hospitals. Patients with symptomatic lacunar stroke had significantly different demographic characteristics in age, sex and geographical regions compared with those who were asymptomatic., Conclusions: In this study, the prevalence and distribution of lacunar stroke were reported at population level across China. Special attention and prevention should be given to the age, sex and geographical groups that are vulnerable to lacunar stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ambient air pollution is one of the most important global health issues. Although several studies have been reported the associations between air pollution and brain function or structure, impact of the air pollution on cerebral small vessel disease (cSVD) have rarely been explored in Asian adult population. We evaluated the association between exposure to air pollutants and cSVD in Korean asymptomatic adults. This cross-sectional study included 3257 participants of a health screening program from January 2006 to December 2013. All participants performed brain magnetic resonance imaging. To assess the cSVD, we considered three features such as white matter hyperintensities (WMH), silent lacunar infarction (SLI), and cerebral microbleeds (CMBs). The annual average exposure to air pollutants [particulate matter ≤ 10 μm in aerodynamic diameter (PM 10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and carbon monoxide (CO)] was generated. The mean [standard deviation (SD)] age of the total 3257 participants was 56.5 (9.5) years, and 54.0% of them were male. Among all the included participants, 273 (8.4%) had SLI and 135 (4.1%) had CMBs. The mean volume (± SD) of WMH was 2.72 ± 6.57 mL. In result of linear regression analysis, the volume of WMH was associated with various potential factors including age, height, weight, smoking and alcohol consumption status, blood pressure (BP), hypertension, and diabetes mellitus. SLI-positive group, compared to the SLI-negative group, was older, shorter, and had higher BP as well as higher frequency of hypertension and diabetes mellitus. After adjusting for covariates, the annual average concentration of PM 10 was significantly associated with the volume of WMH [β (95% CI) for Model 1 = 0.082 (0.038- 0.125), p < 0.001; β (95% CI) for Model 2 = 0.060 (0.013, 0.107), p = 0.013]. CMBs were not associated with the annual average concentration of PM 10 . No significant associations of NO 2 , SO 2 , and CO with cSVD were observed. In conclusion, PM 10 exposure is associated with significant increases in brain WMH' volume and silent lacunar infarcts in asymptomatic adults., (© 2022. The Author(s).)

Retinal and cerebral arterioles have similar characteristics. Silent infarcts are associated with a risk of incident lacunar stroke and dementia. The objective of our study was to determine the correlation between silent lacunar strokes and retinopathy in patients hospitalized in our department for lacunar strokes. This is an observational, retrospective study, from July 2018 to December 2019, of patients diagnosed with lacunar stroke at the neurology department of Befelatanana Hospital, Antananarivo. Stroke was diagnosed with brain CT scan and retinopathy was classified according to fundus examination. The correlation between the presence of silent lacunar stroke and different types and stages of retinopathy was studied. Silent lacunar lesions were discovered on imaging in 70.59% of patients with lacunar strokes. All patients with symptomatic lacunar stroke, with or without associated silent lacunar lesions, were hypertensives. No statistical difference was found between patients with or without associated silent lacunar lesions according to age and gender. Among patients with silent lacunar lesions, dysexecutive syndrome was more prevalent as compared to patients without silent lesions (52.63% vs. 47.36%, P=0.03). Arteriolopathy was more prevalent in patients with silent lacunar lesions (85.71% vs. 14.28%, P=0.047). Silent lacunar lesions were unique in 72% of cases (P=0.022). The presence of stage II hypertensive retinopathy was significantly correlated with the presence of silent lacunar lesions (OR 5.20 [1.02-267] [1.02-26.47], P=0.018). Upon discovery of stage II hypertensive retinopathy on fundus examination, brain imaging should be performed for silent lacunar stroke screening to optimize hypertension management. This management is expected to prevent the incidence of lacunar stroke and vascular dementia., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Purpose: The aim of this study is to explore the factors associated with the fall risk in type 2 diabetes (T2D) patients with a lacunar stroke., Materials and Methods: We compiled data of 146 T2D patients (mean age 68 years), including the Morse fall scale data (MFS), nutrition score, self-care scale, laboratory data, and data from continuous glucose monitoring system (CGMS) from 2019 to 2021 in Shanghai Pudong Hospital. Thereby, we evaluated the associations between MFS and other clinical parameters., Results: The analyses showed that there were significantly increased size and numbers of lacunar infarction (p < 0.05). Furthermore, the greater risk group had an older mean age (p < 0.05), and significant decreased estimated glomerular filtration rate (eGFR), total triglyceride (TG), while increased microalbuminuria, magnesium, lipoprotein A (LP(a)), anti-thyroid peroxidase antibody (TPOAb) (p < 0.05). However, the time in range (TIR) was very comparable (p > 0.05). The correlational study revealed the higher score of MFS was associated with the age (r = 0.41), number of lacunar infarction (r = 0.18), nutrition score (r = 0.20), self-care score (r = - 0.43), serum creatine level (r = 0.19), eGFR (r = - 0.26) (p < 0.05). The total numbers of lacunar infarction were associated with age (r = 0.36), eGFR (r = - 0.40), homocysteine level (r = 0.33) (p < 0.05)., Conclusions: Age, nutrition, self-care ability, and renal function are all critical factors associated with the risk of fall in T2D with lacunar infarction. The age, eGFR, and homocysteine are closely associated with lacunar infarction, suggesting that in T2D, evaluation of kidney dysfunction, homocysteine level in the elderly can predict lacunar infarcts and falls., (© 2022. The Author(s).)

Objective: Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK)., Methods: An observational study was conducted in which two groups of patients were compared. Group I (N = 242) comprised of asymptomatic subjects with arterial hypertension and/or diabetes or with a history of transient ischemic attacks, and Group II (N = 382) comprised patients with lacunar stroke or deep hemispheric intracerebral hemorrhage (ICH) of hypertensive origin. Serum levels of sTWEAK were analyzed and correlated with prevalence and intensity of LA according to the Fazekas scale., Results: The prevalence of LA was higher in symptomatic (85.1%) versus asymptomatic patients (62.0%). Logistic regression model showed a significant relation of LA with neurovascular pathologies (OR: 2.69, IC 95%: 1.10-6.59, p = 0.003). When stratified according to the Fazekas scale, LA of grade II (OR: 3.53, IC 95%: 1.10-6.59, p = 0.003) and specially grade III (OR: 4.66, 95% CI: 1.09-19.84, p = 0.037) showed correlation with neurovascular pathologies. Increased sTWEAK levels were found in the symptomatic group in all LA grades (p < 0.0001), and associated with 5.06 times more risk of presenting clinical symptoms (OR: 5.06, 95% CI: 2.66-9.75, p < 0.0001)., Interpretation: LA showed a higher prevalence in patients with symptomatic lacunar stroke or deep hemispheric ICH. There is an association between sTWEAK levels and LA degree., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65-84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94-2.48], Low; 1.86 [1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98-2.02], Low; 1.49 [1.04-2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64-11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk., (© 2021. The Author(s).)

Objectives: Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood., Materials and Methods: This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography., Results: In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated., Conclusions: Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions)., Competing Interests: Declaration of Competing Interest none., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: This study aimed to assess the effect of folic acid combined with pravastatin on atherosclerosis-related indexes in elderly patients with hypertension complicated with lacunar cerebral infarction.A total of 134 elderly hypertensive patients with lacunar cerebral infarction were randomly divided into 3 groups using the random number table method. Group A, the folic acid group, had 45 cases and received low-dose folic acid (0.8 mg/d) treatment on the basis of antihypertensive treatment. Group B, the pravastatin group, had 45 cases and received pravastatin (20 mg/d) treatment on the basis of antihypertensive treatment. Group C, the folic acid combined with the pravastatin group, had 44 cases. Members of this group received pravastatin (20 mg/d) and low-dose folic acid (0.8 mg/d) based on antihypertensive treatment. Levels of folic acid, homocysteine (Hcy), tumor necrosis factor alpha (TNF-a), matrix metallopeptidase 9 (MMP-9), cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were measured by ELISA before treatment in all 3 groups. Carotid intima-media thickness (IMT) was measured using ultrasound, and systolic and diastolic blood pressure were measured with a mercury column. After 8 weeks of treatment, the levels of folic acid, Hcy, TNF-a, MMP-9, TC, LDL-C, and systolic and diastolic blood pressure were compared among the 3 groups. IMT levels were measured at 12 weeks of treatment.After 8 weeks of treatment, compared with group B, patients in groups A and C had folic acid levels significantly higher than baseline levels, with significantly lower Hcy levels (both P < .05). Patients in group C presented significantly decreased TNF-a, MMP-9, TC, and LDL-C levels and systolic and diastolic blood pressure after 8 weeks of treatment, compared with those in groups A and B (both P < .05). These patients also showed significantly decreased IMT levels compared with those in the other groups (P < .05).Low-dose folic acid combined with pravastatin in elderly patients with lacunar cerebral infarction can reduce the level of homocysteine, improve the degree of carotid atherosclerosis, protect vascular endothelium, and reduce blood lipids and blood pressure, presenting better benefits than pravastatin alone., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease., Methods: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation., Findings: Our meta-analysis comprised studies from Europe, the USA, and Australia, including 7338 cases and 254 798 controls, of which 2987 cases (matched with 29 540 controls) were confirmed using MRI. Five loci (ICA1L-WDR12-CARF-NBEAL1, ULK4, SPI1-SLC39A13-PSMC3-RAPSN, ZCCHC14, ZBTB14-EPB41L3) were found to be associated with lacunar stroke in the European or transethnic meta-analyses. A further seven loci (SLC25A44-PMF1-BGLAP, LOX-ZNF474-LOC100505841, FOXF2-FOXQ1, VTA1-GPR126, SH3PXD2A, HTRA1-ARMS2, COL4A2) were found to be associated in the multi-trait analysis with cerebral white matter hyperintensities (n=42 310). Two of the identified loci contain genes (COL4A2 and HTRA1) that are involved in monogenic lacunar stroke. The TWAS identified associations between the expression of six genes (SCL25A44, ULK4, CARF, FAM117B, ICA1L, NBEAL1) and lacunar stroke. Pathway analyses implicated disruption of the extracellular matrix, phosphatidylinositol 5 phosphate binding, and roundabout binding (false discovery rate <0·05). Mendelian randomisation analyses identified positive associations of elevated blood pressure, history of smoking, and type 2 diabetes with lacunar stroke., Interpretation: Lacunar stroke has a substantial heritable component, with 12 loci now identified that could represent future treatment targets. These loci provide insights into lacunar stroke pathogenesis, highlighting disruption of the vascular extracellular matrix (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1), pericyte differentiation (FOXF2, GPR126), TGF-β signalling (HTRA1), and myelination (ULK4, GPR126) in disease risk., Funding: British Heart Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the relationship of lacunes with cortical cerebral microinfarcts (CMIs), to assess their association with vascular dysfunction, and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA)., Methods: The count and topography of lacunes (deep/lobar), CMIs, and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time to peak (TTP) of blood oxygen level-dependent signal, an established measure of vascular dysfunction, was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH., Results: The cohort consisted of 122 patients with probable CAA without dementia (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%); all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume ( p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox regression models ( p = 0.048 and p = 0.026, respectively)., Conclusions: Our findings show a high prevalence of lobar lacunes, frequently coexisting with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism., (© 2021 American Academy of Neurology.)

Aim: To reveal the correlation between total cerebrovascular disease load and primary lacunar infarction., Background: Cerebral small vessel disease (CSVD) is the lack of specific clinical manifestations, whose clinical diagnoses are highly dependent on neuroimaging results. Total CSVD load scores may be more suitable for the assessment of overall brain function damage caused by CSVD. Little is known about whether the association between imaging markers of CSVD and CSVD total load scores at the time of first-ever lacunar infarction (LI)., Methods: clinical data of 396 patients hospitalised from September 2016 to May 2018 due to a first-ever LI (case group), along with patients diagnosed with CSVD based on imaging alone and those with no abnormalities (control group) based on magnetic resonance imaging (MRI). Binary logistic regression and multiple ordered logistic regression were used to analyse the characteristics of imaging markers of CSVD in patients with first-ever LI, including different total score burden and distribution, and the relationship between different markers., Results: In 396 patients, smoking, cholesterol level and total small vessel disease (SVD) score were all significantly associated with the first-ever LI. There were more LI, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and moderate to severe enlarged perivascular spaces (EPVS) in the first-ever LI group, relative to controls (p < 0.01). The Fazekas scores for periventricular WMH, deep WMH, and total Fazekas score were all significantly higher in patients with first-ever LI relative to those with no cerebral abnormalities (p < 0.01). An analysis of various imaging markers of CSVD revealed a significant correlation between the presence and degree of any marker and the severity of other markers, even after adjusting for the presence of other markers (p < 0.05)., Conclusions: The first-ever LI group exhibited higher total CSVD score loads, a greater number of lacunae, CMB, severe WMH and moderate to severe EPVS. Smoking is an independent risk factor in patients with first-ever LI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population., Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression., Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors., Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

Background and Purpose: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing., Methods: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance., Results: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3-63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05-1.15], P <0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01-1.09], P =0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07-9.16], P =0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain., Conclusions: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

Background and Purpose: Previous studies have revealed a relationship between chronic kidney disease (CKD) and white matter hyperintensities (WMH). However, studies on the WMH and CKD in acute stroke patients are rare, and the conclusion is consistent. Our study aimed to investigate the relationship between the severity of WMH and CKD in acute lacunar infarction patients., Methods: Consecutive acute lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to the severity of periventricular WMH (PVWMH) and deep WMH (DWMH). We dichotomized the severity of WMH (PVWMH and DWMH, separately) into mild group (Fazekas scores 0-1) and moderate-severe group (Fazekas scores 2-3). Estimated glomerular filtration rate (eGFR), proteinuria, vascular risk factors, and clinical features were compared between these two groups. Multivariable logistic regression analysis was used to investigate the association between the severity of WMH and risk factors., Results: A total of 993 acute lacunar infarction patients aged 25-95 years were enrolled. The proportions of participants presenting moderate-severe group PVWMH and DWMH were 46.6% and 38.6%, respectively. Patients with moderate-severe PVWMH had higher age (P < 0.001) and higher incidence of stroke history (P < 0.001) than those in mild group. The level of serum creatinine and the presence of CKD were significantly higher while the eGFR was significantly lower in patients with moderate-severe PVWMH than those with mild PVWMH. Patients with moderate-severe DWMH (n = 383) also had higher age (P < 0.001) and often had a history of stroke (P < 0.001). But the association between the severity of DWMH and eGFR was not found. Multivariable logistic regression analyses showed stage 2 CKD and stage 3 CKD were independently associated with moderate-severe PVWMH, but not DWMH., Conclusions: Our study demonstrates that CKD was independently associated with moderate-severe PVWMH in patients with acute lacunar infarction, but not DWMH. PVWMH and DWMH may have distinct pathophysiology.

Background and Purpose: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities)., Methods: Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease., Results: At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94])., Conclusions: Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

Objectives: We aimed to study the value of ambulatory blood pressure monitoring (ABPM) in predicting the global progression of cerebral small vessel disease (cSVD)., Design: Longitudinal cohort study., Setting: Data from the population-based Investigating Silent Strokes in Hypertensives study., Participants: Individuals with hypertension who were 50 to 70 years of age and stroke free at baseline. In baseline and follow-up visits, patients underwent magnetic resonance imaging and ABPM., Measurements: Ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were studied as continuous variables and dichotomized according to good or poor control on the basis of 125/75 (24 hours), 130/80 (day), and 110/65 (night) mm Hg cutoff values. Whole cSVD progression was qualitatively scored with 1 point when an incident lesion (incident lacunar infarcts, deep cerebral microbleeds, white matter hyperintensities, and basal ganglia enlarged perivascular spaces) was detected. The score ranged from 0 to 4., Results: We followed up 233 participants with a median age of 65 years within 4 years. A total of 61 (26.2%) and 23 (9.9%) subjects showed cSVD progression in one and two or more markers, respectively. Baseline ambulatory SBP and DBP and nighttime pulse pressure (PP) values were positively correlated with the number of incident cSVD lesions. Interestingly, patients without incident lesions showed greater differences between office and ambulatory BP, thus suggesting an increased white coat effect. Poor DBP control, nighttime PP, and DBP white coat effect were independently associated with cSVD progression. The inclusion of these metrics in a clinical model resulted in a significant increase in the prediction of incident lesions (integrated discrimination improvement = 9.09%; P value <.001)., Conclusion: ABPM may help assess cSVD risk of progression, especially by the identification of poor BP control, masked hypertension, and increased nighttime PP. J Am Geriatr Soc 68:2232-2239, 2020., (© 2020 The American Geriatrics Society.)

Objective: Autonomic instability during sleep can influence the risk of cerebrovascular diseases. In this study, we performed a polygraphy to evaluate, heart rate variability (HRV) in a group of patients with lacunar stroke that is a condition at high risk of recurrence., Methods: Twenty-one lacunar stroke patients were enrolled one month after stroke occurrence. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The presence of common sleep disorders and autonomic changes during the night was investigated by a polygraphy monitoring. Results were compared with those obtained in a group of 21 healthy subjects., Results: Patients and controls were similar for age, sex distribution and main cardiovascular risk factors with the exception of the body mass index. Significant differences were detected for all polysomnographic (PSG) parameters and for the PSQI score. By considering HRV values, patients with pathologic values (12 patients, HRV>2) showed significantly higher values in BMI (31 ± 2.9 vs. 26.6 ± 3.6, p = 0.006) and PSQI scores (7.9 ± 2.6 vs. 4.2 ± 1.9) with respect to patients with normal HRV values (nine patients, HRV≤2)., Conclusions: The results of this study suggest that the prevalence of nocturnal autonomic dysfunction is high in lacunar stroke patients even in the absence of the commonest sleep-related disorders. An abnormal HRV may contribute to increase the risk of stroke recurrence. Based on our results, the indication to polygraphy in patients with lacunar stroke should be carefully considered., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke., Methods: Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living)., Results: One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events)., Conclusion: There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events., Trial Registration: Clinicaltrials.gov Identifier: NCT00059306.

Aims: To understand the different influences of statins on the incidence rate of each stroke subtype in association with low-density lipoprotein (LDL) cholesterol levels, we performed a post hoc analysis on the data from the Japan Statin Treatment Against Recurrent Stroke (J-STARS) study., Methods: Subjects (n=1,578) were divided into three groups according to their mean postrandomized LDL cholesterol level (＜100, 100-120, and ≥ 120 mg/dL) until the last observation before the event or the end of follow-up. A Cox proportional hazard model for time to events was used for calculating adjusted hazard ratios, 95% confidence intervals, and the trend tests., Results: The event rates for atherothrombotic stroke did not decrease in accordance with the postrandomized LDL cholesterol level subgroups of either the control or the pravastatin group (p=0.15 and 0.33 for the trend, respectively). In the control group, however, no atherothrombotic stroke event was observed in the subgroup of the low postrandomized LDL cholesterol level (less than 100 mg/dL). The event rates for atherothrombotic stroke were lower in the middle postrandomized LDL cholesterol level subgroup (100-120 mg/dL) of the pravastatin group than that of the control group. The event rates for lacunar stroke decreased in the lower postrandomized LDL cholesterol level subgroup of the control group but not of the pravastatin group (p=0.004 and 0.06 for the trend, respectively)., Conclusions: Statins showed different influences on the risks of atherothromobotic and lacunar stroke according to postrandomized LDL cholesterol levels.

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients. Methods: Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors. Results: A total of 587 participants aged 60-95 years were enrolled. Patients with severe PVWMH ( n  = 178) had higher age ( p  = 0.030) and higher incidence of stroke history ( p <0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH ( p ＝ 0.002). Patients with severe DWMH ( n  = 142) had higher age ( p <0.001) and often had a history of stroke ( p <0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance ( p ＝ 0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors ( p ＝ 0.014). Conclusions: Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

This study aimed to explore the risk factors for severity of white matter lesions and its correlation with in the elderly with lacunar infarction.Patients (range, 70-85 years) with lacunar infarction treated in a hospital in China from 2016 to 2017were enrolled. Fazekas rating scale (0-6 points) was used to assess severity of white matter lesions. Risk factors for the severity of white matter lesions and correlation between cerebral microbleeds and white matter lesions in the elderly with lacunar infarction were studied.The elderly (81-85 years' old, odds ratio [OR]: 2.423, 95% confidence interval [CI]: 1.795-3.271, P = .018; 76∼80 years' old, OR: 3.113, 95% CI: 1.723-5.625, P = .043), carotid atherosclerosis (OR: 3.062, 95% CI:1.715-5.468, P < .001), history of hypertension (OR: 3.694, 95% CI: 2.031-6.717, P < .001) were risk factors for the severity of white matter lesions. The white matter lesions score increased corresponding to increase in the cerebral microbleeds grade (P < .001). The white matter lesions score was higher in the cerebral microbleeds combined with the white matter lesions group than in the white matter lesions group (P < .01). After correcting the effects of age, there was a correlation between white matter lesions and cerebral microbleeds (P < .001). Logistic analysis revealed that the patients' age (81-85 years' old, OR: 2.722, 95% CI: 1.985-3.734, P = .019; 76∼80 years' old, OR: 1.857, 95% CI: 1.075-3.207, P = .031), history of hypertension (OR: 2.931, 95% CI: 1.136-7.567, P = 0.0.036), systolic blood pressure (OR: 1.049, 95% CI: 1.015-1.084, P = .007), high-sensitivity C-reactive protein (OR: 1.504, 95% CI: 1.254-1.803, P < .001), homocysteine (OR: 1.076, 95% CI: 1.020-1.136, P = .009), and carotid atherosclerosis (OR: 1.389, 95% CI: 1.103-1.748, P = .010) were significant risk factors for combined cerebral microbleeds with white matter lesions in patients with lacunar infarction.The elderly, carotid atherosclerosis, history of hypertension were risk factors for the severity of white matter lesions. Cerebral microbleeds were positively correlated with the severity of white matter lesions.

Background: Recent prospective registration studies of transient ischemic attack in Western countries demonstrated that large artery atherosclerosis is the highest risk etiology for early stroke recurrence under urgent evaluation and treatment. On the other hand, some limited transient ischemic attack studies from East Asian countries showed transient ischemic attack patients due to small vessel occlusion were at a higher early stroke risk., Aims: We aimed to assess the risk for early stroke in small vessel occlusion-transient ischemic attack patients in a Japanese large transient ischemic attack registry., Methods: We analyzed the data of a prospective Japanese transient ischemic attack registry including 1320 transient ischemic attack patients within seven days after onset. Small vessel occlusion-transient ischemic attack was defined as the presence of lacunar transient ischemic attack syndrome, without other etiologies. The outcome measure was recurrent stroke within 30 days after transient ischemic attack. The predictors of 30-day recurrent stroke were estimated using the Cox proportional hazards model., Results: The study population had a mean age of 69 ± 12 years and 470 were women. Recurrent stroke was observed in 61 patients (4.6%), and the highest rate was observed with small vessel occlusion-transient ischemic attack (7.8%), followed by large artery atherosclerosis (5.4%). In multivariate analysis, recurrent stroke was independently associated with small vessel occlusion-transient ischemic attack (hazard ratio (HR): 2.01, 95% confidence interval (CI): 1.19-3.35), higher systolic blood pressure (HR: 1.18, 95% CI: 1.08-1.28), and presentation within 3 h after onset (HR: 2.21, 95% CI: 1.27-4.04). Furthermore, small vessel occlusion-transient ischemic attack with acute small deep infarct on diffusion-weighted imaging was a stronger predictor of recurrent stroke (HR: 4.87, 95% CI: 2.09-10.0)., Conclusion: Small vessel occlusion-transient ischemic attack, especially with acute small deep infarct, had a higher early stroke risk compared with other etiologies in Japanese transient ischemic attack patients who received early management.

Objective: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs)., Methods: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test. The odds ratios for recurrent strokes were derived using multivariate logistic regression models, adjusted for risk factors., Results: We evaluated the stroke recurrence rate in 362 ATI patients and 309 LI patients. The log-rank test and multivariate analyses revealed that the incidence of recurrent stroke was significantly higher in ATI patients with mean IMT greater than or equal to 1.1 mm, asymptomatic ICHs, or lobar MBs than in those without. The incidence was significantly higher in LI patients with asymptomatic ICHs, asymptomatic LIs, and severe WMLs than in those without. In ATI patients, those with strictly lobar MBs or mixed MBs (deep and lobar MBs) had significantly higher recurrence rates than those without MB. In LI patients, those with strictly deep MBs or mixed MBs had higher recurrence rates than those without MB, and the incidences of those with mixed MBs was larger than those with strictly deep MBs., Conclusions: There were differences between ATI and LI patients in terms of the association of MRI and ultrasonography findings, in particularly strictly lobar or deep MBs, with the incidence of stroke recurrence., (Copyright © 2019. Published by Elsevier Inc.)

Background and Aims: The association between carotid wall shear stress (WSS) and cerebral small vessel disease has yet to be fully elucidated. The major purpose of this study was to investigate this association in older subjects., Methods: Common carotid artery WSS, endothelial function, white matter hyperintensities (WMH), lacunes, and microbleeds were assessed in 1396 older adults. Participants were followed-up for an average of 69.7 months., Results: Mean (M) and peak (P) WSS and changes in endothelial function were independently associated with changes in WMH volume and fraction, lacune counts, and microbleed counts (all p < 0.05). The risks of new-incident Fazekas scale ≥2 [hazard ratio (HR) with 95% confidence interval (CI): 2.141 (1.469-3.119), p = 0.005 and 1.731 (1.197-2.505), p = 0.004, respectively], lacunes [HR (95% CI): 2.034 (1.369-3.022), p < 0.001 and 1.693 (1.151-2.490), p = 0.003, respectively], and microbleeds [HR (95% CI): 2.311 (1.509-3.541), p < 0.001 and 2.208 (1.299-3.751), p < 0.001, respectively] were significantly higher in the lowest quartile group than in the higher quartile group, as classified by either MWSS or PWSS, after adjustment for confounders., Conclusions: Low carotid WSS is an independent risk factor for the progression of cerebral small vessel disease in older adults., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background We conducted a post hoc analysis of the SPS3 (Secondary Prevention of Small Subcortical Strokes) Trial to examine the association of chronic kidney disease (CKD) with recurrent stroke, and to assess whether baseline renal function modifies the effects of intensive systolic blood pressure control in patients with previous stroke. Methods and Results A total of 3020 patients with recent magnetic resonance imaging-defined symptomatic lacunar infarctions were randomized to a systolic blood pressure target of <130 mm Hg versus 130 to 149 mm Hg. Predefined primary outcomes were (all-recurrent) stroke and a composite of stroke, acute myocardial infarction, or all-cause death; secondary outcomes were acute myocardial infarction, all-cause death, and intracerebral hemorrhage individually. Among 3017 patients with baseline estimated glomerular filtration rate measurements, we evaluated, using Cox proportional hazards models, the association of CKD with recurrent stroke and effects of the blood pressure targets on outcomes using baseline estimated glomerular filtration rate both as a categorical and linear variable. Regardless of the randomized treatment, CKD at baseline was significantly associated with an increased risk of the primary cardiovascular composite outcome (hazard ratio, 1.7; 95% CI, 1.4-2.1), and all-recurrent stroke (1.5; 1.1-2.0). However, the effects of the lower systolic blood pressure intervention on the primary outcome were not influenced by baseline CKD status (P for interaction=0.62). Conclusions CKD increases the risk of recurrent stroke by 50% in patients with previous lacunar stroke. We found no definitive evidence that renal dysfunction modifies the effects of systolic blood pressure control in patients with previous stroke. Conclusive evidence for this will require adequately powered studies with moderate-to-advanced CKD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Background Homeless and vulnerably housed individuals are at increased risk for multimorbidity compared with the general population. We assessed prevalence of brain infarcts on neuroimaging and associations with vascular risk factors and cognitive performance in a prospective study of residents living in marginal housing. Methods and Results Two hundred twenty-eight participants underwent structured clinical interviews, targeted clinical, laboratory, and neuropsychological assessments, and magnetic resonance imaging with T 1 , T 2 -fluid-attenuated inversion recovery and susceptibility-weighted images. Subjects underwent cognitive testing to assess premorbid IQ , verbal learning and memory, inhibition, sustained attention, mental flexibility, and decision making. In this sample (mean age 44.0 years [ SD 9.4], 77% male), prevalence of conventional vascular risk factors was lower than in the general population apart from tobacco use (94%). Ten-year Framingham risk for any cardiovascular event was 11.4%±9.2%. Brain infarcts were present in 25/228 (11%). All were ischemic (40% cortical, 56% lacunar, 4% both). Participants with infarcts were older than those without (48.9±9.4 versus 43.4±9.2, P=0.006). In a multivariable regression analysis, only age remained a significant predictor of brain infarcts (odds ratio 1.08, 95% CI 1.02-1.14, P=0.004). After controlling for age and education, the presence of infarct was a significant predictor of impaired decision making on the Iowa Gambling Task of decision making (β -28.2, 95% CI -42.7 to -14.1, P<0.001). Conclusions Prevalence of infarcts on neuroimaging in this disadvantaged, community-dwelling cohort was much higher than expected for age and was associated with impaired decision making. Further research is needed to identify individuals at highest risk who may benefit from targeted preventative strategies.

Objectives : To investigate the prevalence and risk factors for microalbuminuria in patients with lacunar infarction. Methods : 702 lacunar infarction patients and 234 controls were recruited in this study, the concentration of urinary albumin and clinical characteristics were collected for each participant. We analyzed the prevalence of microalbuminuria in lacunar infarction patients, as well as the risk factors of microalbuminuria in patients with lacunar infarction. Results : The prevalence of microalbuminuria in patients with lacunar infarction was 32.8%, which was significantly higher than that in controls (9.8%, P ＜0.001). Multiple linear regression analysis indicated that age, alcohol abuse, fasting blood glucose, systolic blood pressure, and triglyceride were positively associated with albumin/creatinine ratio levels. Multiple logistic regression analysis indicated that age (odds ratio [OR] = 1.067, 95% confidence interval [CI] = 1.029 to 1.105), alcohol abuse (OR = 3.001, 95% CI = 1.668 to 5.398), fasting blood glucose (OR = 2.014, 95% CI = 1.794 to 2.260), and systolic blood pressure (OR = 1.033, 95% CI = 1.010 to 1.056) were the independent risk factors for microalbuminuria in acute lacunar infarction patients, with high sensitivity, specificity, positive predictive value, and negative predictive value. Receiver operating characteristic curve analysis showed that the area under the curve for age, systolic blood pressure, and fasting blood glucose were 0.618 (cutoff value, 63.5 years; sensitivity, 54.8%; and specificity, 62.9%), 0.736 (cutoff level, 149.5 mmHg; sensitivity, 78.3%; and specificity, 61.2%) and 0.893 (cutoff value, 7 mmol/L; sensitivity, 92.2%; and specificity, 86%), respectively. Conclusion : Lacunar infarction was associated with higher microalbuminuria prevalence. Age, alcohol abuse, fasting blood glucose, and systolic blood pressure were individually significant and correlated factors of microalbuminuria in patients with lacunar infarction. More attention should be provided to this group of patients.

Chronic oral infections (gingivitis/periodontitis) have been associated with age-related diseases such as diabetes, coronary heart disease, and acute ischemic stroke. In addition, imaging surrogates of cerebrovascular ischemia beyond acute ischemic stroke (i.e., silent strokes and brain white matter hyperintensities) may also be associated with chronic oral infections. The pathology underlying lacunar strokes and brain white matter hyperintensities (WMH) relates to small vessel disease in the brain. In this review, we highlight recent progress in exploring potential associations of oral infections with cerebral small vessel disease and its surrogates (silent strokes, white matter hyperintensities) and clinical sequelae (i.e., vascular dementia). Recent evidence suggests that periodontitis aggravates cerebral small vessel disease and increases lacunar stroke risk. Moreover, periodontitis interacts with Alzheimer's disease to increase the severity of clinical dementia and to accelerate its manifestations. The results suggest that periodontitis may be an emerging risk factor of small vessel disease-associated cerebrovascular disorders and that the risk increase may be mediated by the systemic inflammation resulting from chronic oral infections. Large cohort studies employing state-of-the-art magnetic resonance techniques to identify specific cerebral pathologies as a function of time, oral health status, and systemic inflammation are needed to further substantiate the hypothesis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: Presumed microvascular ischemia is the most frequent cause of ocular motor palsy (OMP). Ischemic stroke incidence after an episode of microvascular OMP (mOMP) is not established, contrasting with other common vascular conditions, such as lacunar ischemic stroke (LS). We sought to compare the incidence of subsequent ischemic stroke between mOMP and LS populations., Methods: A retrospective observational analysis was conducted on acute patients presenting with either mOMP or LS. A propensity score match was applied to ensure a balance between groups. We compared the incidence of subsequent ischemic stroke during an 80-month follow-up., Results: A total of 110 patients were included in the study (57, mOMPs; 53, LS). During follow-up, the annual occurrence rate of ischemic stroke was 2.1% per year in mOMP group and 0.6% per year in the LS group. After performing Cox regression, we found no statistical significance difference between groups in the incidence of subsequent ischemic stroke (P=0.801)., Conclusions: Patients with presumed mOCP seem to share similar incidence of subsequent ischemic stroke with patients with LS. Presumed mOCP may be an underrecognized independent risk factor for ischemic stroke.

Background We aimed to determine whether cerebral white matter hyperintensities ( WMHs ) can distinguish stroke survivors susceptible to rapid kidney function decline from intensive blood pressure ( BP ) lowering. Methods and Results The SPS3 (Secondary Prevention of Small Subcortical Strokes) trial randomized participants with recent lacunar stroke to systolic BP targets of 130 to 149 and <130 mm Hg. We included 2454 participants with WMH measured by clinical magnetic resonance imaging at baseline and serum creatinine measured during follow-up. We tested interactions between BP target and WMH burden on the incidence of rapid kidney function decline (≥30% decrease from baseline estimated glomerular filtration rate at 1-year follow-up) and recurrent stroke. Rapid kidney function decline incidence was 11.0% in the lower- BP -target arm and 8.1% in the higher-target arm (odds ratio=1.40; 95% CI=1.07-1.84). Odds ratio for rapid kidney function decline between lower- and higher-target groups ranged from 1.26 in the lowest WMH tertile (95% CI , 0.80-1.98) to 1.71 in the highest tertile (95% CI , 1.05-2.80; P for interaction=0.65). Overall incidence of recurrent stroke was 7.9% in the lower-target arm and 9.6% in the higher-target arm (hazard ratio=0.80; 95% CI , 0.63-1.03). Hazard ratio for recurrent stroke in the lower-target group was 1.13 (95% CI , 0.73-1.75) within the lowest WMH tertile compared with 0.73 (95% CI , 0.49-1.09) within the highest WMH tertile ( P for interaction=0.04). Conclusions Participants with higher WMH burden appeared to experience greater benefit from intensive BP lowering in prevention of recurrent stroke. By contrast, intensive BP lowering increased the odds of kidney function decline, but WMH burden did not significantly distinguish this risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00059306.

Background and Purpose: We aimed to evaluate factors associated with neurological worsening among patients with lacunar or non-lacunar infarction admitted within 3 hours and between 3 and 24 hours after stroke onset., Methods: All patients admitted to Haukeland university hospital between 2006 and 2016 with acute cerebral infarction on MRI and admission within 24 hours were included. Repeated National Institute of Health Stroke Scale (NIHSS) scoring was performed in all patients whenever possible. Neurological worsening during the hospital stay was defined as NIHSS score increase ≥3 compared to NIHSS score on admission., Results: In patients with lacunar infarction admitted within 3 hours of onset, neurological worsening was associated with low NIHSS score on admission, low body temperature, and leukoaraiosis, whereas only internal carotid artery stenosis or occlusion was associated with neurological worsening in non-lacunar infraction. For patients admitted 3-24 hours after onset, neurological worsening was associated with low body temperature, high systolic blood pressure, and short time from onset to admission in patients with lacunar infarction, whereas high systolic blood pressure, high NIHSS score on admission, middle cerebral artery occlusion, and high blood glucose were associated with neurological worsening in patients with non-lacunar infarction (all P < 0.05)., Conclusions: Lacunar infarctions with minor neurological deficits within 3 hours of stroke onset are at high risk of neurological worsening especially if concomitant low body temperature and leukoaraiosis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: White matter hyperintensities (WMH) is identified as a marker of cerebral small vessel diseases and is a major contributor to cognitive impairment, depression, gait disturbance, and urinary incontinence. However, the risk factors for WMH in patients with type 2 diabetes mellitus (T2DM) has not been well explored. Thus, in this study, we aimed to investigate the relationship between the severity of WMH and vascular risk factors in lacunar infarction patients with T2DM., Methods: Consecutive lacunar infarction patients with T2DM were recruited in this cross-sectional study. Paraventricular WMH (P-WMH) and deep WMH (D-WMH) were separately scored by the Fazekas scale, and classified into two categories by the severity. Vascular risk factors and clinical features were compared between the mild and severe WMH. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors., Results: A total of 327 participants aged 34-91 years were enrolled in this study. Compared with the patients with mild P-WMH, the patients with severe P-WMH had higher age ( P =0.031), higher proportion of hypertension ( P =0.042) and stroke ( P <0.001). Levels of TG, LDL, and HbA1c were significantly higher in patients with mild P-WMH. Compared with the patients with mild D-WMH the patients with severe D-WMH had higher age and hyperhomocysteinemia (HCY) level ( P <0.001), higher proportion of hyperlipidemia ( P =0.008), and stroke ( P <0.001). Multivariable logistic regression analyses showed that higher age and recurrent stroke were independently related to severe P-WMH and D-WMH in lacunar infarction patients with T2DM., Conclusions: Age and recurrent stroke are related to the severity of P-WMH and D-WMH in lacunar infarction patients with T2DM., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background and Purpose- Since cerebral small vessel disease (SVD) is associated with cognitive and motor impairment and both might ultimately lead to nursing home admission, our objective was to investigate the association of SVD markers with nursing home admission. Methods- The RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort) is a prospective cohort of 503 independent living individuals with SVD. Date of nursing home admission was retrieved from the Dutch municipal personal records database. Risk of nursing home admission was calculated using a competing risk analysis, with mortality as a competing risk. Results- During follow-up (median 8.7 years, interquartile range 8.5-8.9), 31 participants moved to a nursing home. Before nursing home admission, 19 participants were diagnosed with dementia, 6 with parkinsonism, and 10 with stroke. Participants with the lowest white matter volume had an 8-year risk of nursing home admission of 13.3% (95% CI, 8.6-18.9), which was significantly different from participants with middle or highest white matter volume (respectively, 4.8% [95% CI, 2.3-8.8] and 0%; P<0.001). After adjusting for baseline age and living condition, the association of white matter volume and total brain volume with nursing home admission was significant, with, respectively, hazard ratios of 0.88 [95% CI, 0.84-0.95] ( P value 0.025) and 0.92 [95% CI, 0.85-0.98] ( P<0.001) per 10 mL. The association of white matter hyperintensities and lacunes with nursing home admission was not significant. Conclusions- This study demonstrates that in SVD patients, independent from age and living condition, a lower white matter volume and a lower total brain volume is associated with an increased risk of nursing home admission. Nursing home admission is a relevant outcome in SVD research since it might be able to combine both cognitive and functional consequences of SVD in 1 outcome.

Objectives: We evaluated a prospective cohort of 150 patients under observation in our centre for lacunar strokes. The purpose of this study was to evaluate the outcome at time of discharge and 6 months after lacunar stroke, as well as the correlation with cardiovascular risk factors and selected biochemical parameters already evaluated on admission. Focus was to identify possible prognostic factors, which might be targeted through appropriate intervention concentrating on reduction in the incidence and impact of early clinical deterioration., Methods: 150 patients with a lacunar stroke were included in the present study. A clinical 6-month follow-up was available for 98.7% of the patients. Infarcts were classified by size, shape and location., Results: The most important predictors of high NIHSS score at time of discharge resulted NIHSS on admission (P < .001), leukocytosis (P = .013), in-hospital infections (P = .016) and size of lacunae (P = .005). Similarly, the most important predictors of poor outcome 6 months later were NIHSS on admission (P = .01), leukocytosis (P = .014), elevated CRP (P = .019), in addition to pre-admission Rankin (P < .001)., Conclusion: Although infections are not causatively related to lacunar strokes, their prompt recognition and early treatment, control of inflammatory markers and fever are most important in influencing functional outcome in lacunar stroke., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Plasma brain natriuretic peptide (BNP), a diagnostic marker of cardiovascular diseases, has been previously linked to cerebrovascular diseases. Our goal was to determine whether plasma BNP level is helpful for identifying high-risk individuals who are likely to present with the 3 main subtypes of cerebral small vessel diseases (CSVDs), namely, white matter lesions, lacunar infarcts, and cerebral microbleeds, on magnetic resonance imaging (MRI) in patients with hypertension.Three hundred forty-six consecutive hypertensive patients presenting at our cardiology or neurology clinic were investigated. Plasma BNP level was measured by chemiluminescent microparticle immunoassay. The presence of CSVD was assessed by 1.5-T brain MRI. Multivariate linear regression was used to determine whether individual or combined MRI-defined CSVD subtypes were associated with BNP level, after adjustment for several covariates.The mean age of patients was 69.1 ± 9.8 years, and 44.2% were female. The highest quartile BNP group was positively associated with advanced age, female sex, clinically manifesting cardiac diseases, and ischemic CSVD (white matter lesions and lacunar infarcts) and no association with cerebral microbleeds. According to multivariate linear regression, white matter lesions [β = 0.722; 95% confidence interval (95% CI), 0.624-0.819] and lacunar infarcts (β = 0.635; 95% CI, 0.508-0.762) were independently associated with BNP level, even after controlling for vascular risk factors and clinically manifesting cardiac diseases. Combined white matter lesions and lacunar infarcts were more strongly associated with BNP level than each subtype alone. With the cutoff value of 106.4 pg/mL, BNP level had a sensitivity, a specificity, and an area under the curve of 95.2%, 64.9%, and 0.799, respectively, for white matter lesions, whereas the values were 143.0 pg/mL, 81.6%, 73.5%, and 0.848, respectively, for lacunar infarcts.Plasma BNP level, which is independently correlated with individual or combined white matter lesions and lacunar infarcts, is a useful molecular marker for identifying ischemic CSVD in patients with hypertension.

Background/aims: Lacunar infarct, a small subcortical ischaemic lesion, is a known risk factor for future cognitive impairment, dementia and stroke. We evaluated the relationship between fatty liver disease (FLD) and lacunar infarct in a healthy general population., Methods: Subjects who underwent brain magnetic resonance imaging (MRI) and abdominal ultrasonography (US) during health check-ups from 2007 to 2009 were included. FLD was diagnosed by US. Subjects with a history of cerebrovascular disease, radiological findings consistent with cerebrovascular stenosis or cerebral small vessel disease were excluded., Results: Of the 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had FLD. Subjects with lacunar infarct had a higher prevalence of FLD (59.3% vs 39.4%, P = .004). There was significant interaction between obesity (BMI < 25 kg/m 2 vs ≥ 25 kg/m 2 ) and FLD for lacunar infarct (P for interaction = .024). Subgroup analysis revealed that non-obese FLD was more common in the subjects with lacunar infarct than those without (51.7% vs 23.5%, P = .001). However, there was no significant difference in the obese FLD prevalence between these 2 groups. In multivariate models adjusted by age, sex, smoking, alcohol, hypertension and diabetes, FLD was significantly associated with lacunar infarct (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.08-3.58; P = .027). Non-obese FLD was associated with lacunar infarct (OR 3.58; 95% CI 1.63-7.89; P = .002); however, this association remained insignificant in obese FLD. Instead, ageing and hypertension were independent risk factors for lacunar infarct in the obese population., Conclusions: FLD is significantly associated with lacunar infarct, independent of traditional risk factors. This association was prominent in the non-obese population., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine the age-specific temporal trends in blood pressure (BP) before acute lacunar vs nonlacunar TIA and stroke., Methods: In a population-based study of TIA/ischemic stroke (Oxford Vascular Study), we studied 15-year premorbid BP readings from primary care records in patients with lacunar vs nonlacunar events (Trial of Org 10172 in Acute Stroke Treatment [TOAST]) stratified by age (<65, ≥65 years)., Results: Of 2,085 patients (1,250 with stroke, 835 with TIA), 309 had lacunar events. In 493 patients <65 years of age, the prevalence of diagnosed hypertension did not differ between lacunar and nonlacunar events (46 [48.4%] vs 164 [41.2%], p = 0.20), but mean/SD premorbid BP (44,496 BP readings) was higher in patients with lacunar events (15-year records: systolic BP [SBP] 138.5/17.7 vs 133.3/15.0 mm Hg, p = 0.004; diastolic BP [DBP] 84.1/9.6 vs 80.9/8.4 mm Hg, p = 0.001), mainly because of higher mean BP during the 5 years before the event (SBP 142.6/18.8 vs 134.6/16.6 mm Hg, p = 0.0001; DBP 85.2/9.7 vs 80.6/9.0 mm Hg, p < 0.0001), with a rising trend ( p trend = 0.006) toward higher BP leading up to the event (<30-day pre-event SBP: 152.7/16.1 vs 135.3/23.1 mm Hg, p = 0.009; DBP 87.9/9.4 vs 80.8/12.8 mm Hg, p = 0.05; mean BP ≤1 year before the event 145.8/22.0 vs 134.7/16.1 mm Hg, p = 0.001; 86.1/10.7 vs 80.4/9.8 mm Hg, p = 0.0001). Maximum BP in the 5 years before the event was also higher in patients with lacunar events (SBP 173.7/26.6 vs 158.6/23.2 mm Hg, p = 0.0001; DBP 102.3/12.9 vs 94.2/11.2 mm Hg, p < 0.0001), as was persistently elevated BP (≥50% SBP >160 mm Hg, odd ratio 4.95, 95% confidence interval 1.99-12.31, p = 0.0002). However, no similar differences in BP were observed in patients ≥65 years of age., Conclusion: Recent premorbid BP control is strongly temporarily related to acute lacunar events at younger ages, suggesting a direct role of BP in accelerating causal pathology and highlighting the need to control hypertension quickly., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Purpose: It has been hypothesized that cerebral small vessel disease (SVD) and chronic renal impairment may be part of a multisystem small-vessel disorder, but their association may simply be as a result of shared risk factors (eg, hypertension) rather than to a systemic susceptibility to premature SVD. However, most previous studies were hospital based, most had inadequate adjustment for hypertension, many were confined to patients with lacunar stroke, and none stratified by age., Methods: In a population-based study of transient ischemic attack and ischemic stroke (OXVASC [Oxford Vascular Study]), we evaluated the magnetic resonance imaging markers of cerebral SVD, including lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular space. We studied the age-specific associations of renal impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and total SVD burden (total SVD score) adjusting for age, sex, vascular risk factors, and premorbid blood pressure (mean blood pressure during 15 years preevent)., Results: Of 1080 consecutive patients, 1028 (95.2%) had complete magnetic resonance imaging protocol and creatinine measured at baseline. Renal impairment was associated with total SVD score (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.69-2.75; P <0.001), but only at age <60 years (<60 years: OR, 3.97; 95% CI, 1.69-9.32; P =0.002; 60-79 years: OR, 1.01; 95% CI, 0.72-1.41; P =0.963; ≥80 years: OR, 0.95; 95% CI, 0.59-1.54; P =0.832). The overall association of renal impairment and total SVD score was also attenuated after adjustment for age, sex, history of hypertension, diabetes mellitus, and premorbid average systolic blood pressure (adjusted OR, 0.76; 95% CI, 0.56-1.02; P =0.067), but the independent association of renal impairment and total SVD score at age <60 years was maintained (adjusted OR, 3.11; 95% CI, 1.21-7.98; P =0.018). Associations of renal impairment and SVD were consistent for each SVD marker at age <60 years but were strongest for cerebral microbleeds (OR, 5.84; 95% CI, 1.45-23.53; P =0.013) and moderate-severe periventricular white matter hyperintensities (OR, 6.28; 95% CI, 1.54-25.63; P =0.010)., Conclusions: The association of renal impairment and cerebral SVD was attenuated with adjustment for shared risk factors at older ages, but remained at younger ages, consistent with a shared susceptibility to premature disease., (© 2018 The Authors.)