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Hypertension is confirmed to be one of the major risk factors of leukoaraiosis (LA). However, the pathogenesis of LA is not completely understood and there is no reliable indicator for the early diagnosis of LA in the hypertensive population. This study was designed to explore the potential biomarker for LA diagnosis in patients with hypertension. And it serves as the basis for the further study of LA mechanism. In this study, This study included 110 subjects, including 50 in the LA group and 60 in the control group. First, we performed transcriptome sequencing and quantitative PCR (qPCR) in four samples from the LA group, and three from the control group (seven people) to identify relevant long non-coding RNAs (long ncRNAs or lncRNA). The 103 samples were used for qPCR validation of relevant lncRNAs and the results were consistent with the sequencing. In-depth bioinformatics analysis were performed on differentially expressed (DE) lncRNAs and mRNAs. Go-functional enrichment analysis was performed on DE mRNAs. Some DE mRNA were enriched to biological processes associated with LA, And some lncRNAs related to DE mRNAs were traceable through cis/trans analysis, suggesting that they might be regulated in some way. Additionally, potential biomarkers for LA diagnosis in the hypertension population were identified via RT-qPCR and receive operating characteristic curve (ROC) analysis of lncRNA. One lncRNA, AC020928.1, has been demonstrated to be potential biomarkers for LA diagnosis in the hypertension population. The results of the present study indicated that the lncRNA may have an important role in the pathogenesis of LA and may be a novel target for further research. As the relationship between lncRNAs and LA is just beginning to be unraveled, their specific mechanisms require further investigation.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.

White matter hyperintensities (WMH), also known as leukoaraïosis are very common neuroradiological manifestations in the elderly. The main risk factors for WMH are age and high blood pressure. The vascular origin of these lesions is classically accepted and WMH are considered as one feature of the small vessel disease. WMH may be associated with clinical symptoms, depending notably on their importance according to age. They are associated with increased mortality, strokes and changes in cognition with a higher risk of dementia (vascular dementia or Alzheimer's disease). Modification of vascular risk factors could have a beneficial effect, but few evidences from controlled trials are available., (Copyright © 2020 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Objective: The progression of white matter hyperintensities (WMH) varies considerably in adults. In this study, we aimed to predict the progression and related risk factors of WMH based on the radiomics of whole-brain white matter (WBWM)., Methods: A retrospective analysis was conducted on 141 patients with WMH who underwent two consecutive brain magnetic resonance (MR) imaging sessions from March 2014 to May 2018. The WBWM was segmented to extract and score the radiomics features at baseline. Follow-up images were evaluated using the modified Fazekas scale, with progression indicated by scores ≥ 1. Patients were divided into progressive (n = 65) and non-progressive (n = 76) groups. The progressive group was subdivided into any WMH (AWMH), periventricular WMH (PWMH), and deep WMH (DWMH). Independent risk factors were identified using logistic regression., Results: The area under the curve (AUC) values for the radiomics signatures of the training sets were 0.758, 0.749, and 0.775 for AWMH, PWMH, and DWMH, respectively. The AUC values of the validation set were 0.714, 0.697, and 0.717, respectively. Age and hyperlipidemia were independent predictors of progression for AWMH. Age and body mass index (BMI) were independent predictors of progression for DWMH, while hyperlipidemia was an independent predictor of progression for PWMH. After combining clinical factors and radiomics signatures, the AUC values were 0.848, 0.863, and 0.861, respectively, for the training set, and 0.824, 0.818, and 0.833, respectively, for the validation set., Conclusions: MRI-based radiomics of WBWM, along with specific risk factors, may allow physicians to predict the progression of WMH., Key Points: • Radiomics features detected by magnetic resonance imaging may be used to predict the progression of white matter hyperintensities. • Radiomics may be used to identify risk factors associated with the progression of white matter hyperintensities. • Radiomics may serve as non-invasive biomarkers to monitor white matter status.

Background and Purpose: In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large- and small-vessel diseases (cLVD and cSVD) in a healthy population, METHODS: We assessed consecutive health check-up volunteers from 2006 to 2013. We calculated the estimated 10-year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at P < 0.10 in univariate analysis were included for further multivariable linear or regression analyses., Results: A total of 2720 participants were evaluated (mean age, 57 years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [β = 0.361; 95% confidence interval (CI), 0.320-0.402, P < 0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29-2.16, P < 0.001], lacunes (aOR, 1.80; 95% CI, 1.52-2.14, P < 0.001) and CMBs (aOR, 1.75; 95% CI, 1.40-2.19, P < 0.001). Furthermore, PCR score also showed dose-response tendencies according to the burden of cLVD, WMH, lacunes and CMB., Conclusions: A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD., (© 2020 European Academy of Neurology.)

Binswanger disease (BD) involves injuries to the brain small vessels, resulting to gradually progressive subcortical ischemia. This disorder manifests with dementia, gait abnormalities, upper motor signs and parkinsonism, and presents as extensive, confluent, bilateral cerebral white matter hyperintensities in the MRI. Cases of BD typically manifests with vascular risk factors, such as hypertension and multiple strokes. We report a unique case of a Filipino patient whom we have diagnosed with BD presenting with no cardinal signs of parkinsonism, but with generalized choreiform movement disorder and without a history of hypertension and symptomatic strokes. To our knowledge, this is the first report presenting an adult patient with subcortical leukoaraiosis of Binswanger type associated with a hyperkinetic movement disorder.

Introduction: T1- and T2-weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1-weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM-hyper) volume from FLAIR and white matter hypointensity (WM-hypo) volume from T1-weighted images and compared their associations with age and cerebrospinal fluid (CSF) β-amyloid and tau., Methods: A total of 56 nondemented participants (68-94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM-hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM-hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2-FLAIR., Results: WM-hyper and WM-hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p < .0001). Age was significantly associated with both WM-hyper (r = .31, p.e. 0.078 ± 0.030, p = .013) and WM-hypo (r = .42, p.e. 0.055 ± 0.015, p < .001). CSF β-amyloid levels were predicted by WM-hyper (r = .33, p.e. -0.11 ± 0.044, p = .013) and WM-hypo (r = .42, p.e. -0.24 ± 0.073, p = .002). CSF tau levels were not correlated with either WM-hyper (p = .9) or WM-hypo (p = .99)., Conclusions: Strong correlations between WM-hyper and WM-hypo, and similar associations with age, abnormal β-amyloid, and tau suggest a general equivalence between these two imaging markers. Our work supports the equivalence of white matter hypointensity volumes derived from FreeSurfer for evaluating leukoaraiosis. This may have particular utility when T2-FLAIR is low in quality or absent, enabling analysis of older imaging data sets., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objectives: Although white matter hyperintensities (WMHs) are quite commonly found incidentally, their aetiology, structural characteristics, and functional consequences are not entirely known. The purpose of this study was to quantify WMHs in a sample of young, neurologically asymptomatic adults and evaluate the structural and functional correlations of lesion load with changes in brain volume, diffusivity, and functional connectivity., Methods: MRI brain scan using multimodal protocol was performed in 60 neurologically asymptomatic volunteers (21 men, 39 women, mean age 34.5 years). WMHs were manually segmented in 3D FLAIR images and counted automatically. The number and volume of WMHs were correlated with brain volume, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) data. Diffusion parameters measured within WMHs and normally appearing white matter (NAWM) were compared., Results: At least 1 lesion was found in 40 (67%) subjects, median incidence was 1 lesion (interquartile range [IQR] = 4.5), and median volume was 86.82 (IQR = 227.23) mm 3 . Neither number nor volume of WMHs correlated significantly with total brain volume or volumes of white and grey matter. Mean diffusivity values within WMHs were significantly higher compared with those for NAWM, but none of the diffusion parameters of NAWM were significantly correlated with WMH load. Both the number and volume of WMHs were correlated with the changes of functional connectivity between several regions of the brain, mostly decreased connectivity of the cerebellum., Conclusions: WMHs are commonly found even in young, neurologically asymptomatic adults. Their presence is not associated with brain atrophy or global changes of diffusivity, but the increasing number and volume of these lesions correlate with changes of brain connectivity, and especially that of the cerebellum., Key Points: • White matter hyperintensities (WMHs) are commonly found in young, neurologically asymptomatic adults. • The presence of WMHs is not associated with brain atrophy or global changes of white matter diffusivity. • The increasing number and volume of WMHs correlate with changes of brain connectivity, and especially with that of the cerebellum.

White matter hyperintensity (WMH) in the general population has clinical importance. However, MRI (magnetic resonance imaging) is not suitable for screening purposes due to high cost and restricted availability. We hypothesized that performance on the trail making test black & white (TMT-B&W) may correlate with WMH and provide a screening tool for patients with WMH. Intergroup comparisons between WMH (+) (a Fazekas score of ≥2) and WMH (-) (<2) were performed for time variables in type A, B, B-A, B/A, B*A and errors in type A and B. To determine an ideal cutoff value and confirm the diagnostic performance of TMT-B&W on the presence of WMH (+), the area under the receiver operating characteristics curve (AUC) was analyzed. Multiple linear regression analysis was used, adjusting for age and education, to correlate the normalized WMH volumes and TMT-B&W performance. We show that higher WMH correlates with a significant increase in completion time for type A (p < 0.001) and B (p = 0.006) TMT-B&W. In AUC analysis, the optimal cutoff time to complete type A was 75 s [sensitivity, 66.7%; specificity, 67.2%; %; p = 0.001; AUC, 0.729; 95% confidence interval (CI), 0.600-0.858]. Additionally, there were significant correlations between normalized WMH volume and TOTAL-A (B = 0.233, p = 0.016) and errors in type A (B = 0.353, p < 0.001). We identified the correlation between the performance in TMT-B&W and WMH burden, and propose its potential clinical utility in predicting brain WMH burden., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hypothesis: We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort., Methods: PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors., Results: Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 μV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 μV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts., Conclusion: Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following possible competing interests: Dr. Elkind has the following financial disclosures: Boehringer-Ingelheim, Inc.; BMS-Pfizer Alliance; BioTelemetry/Cardionet. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective This study was performed to evaluate the potential predictors of poor outcomes associated with diabetes-specific microvascular pathologies and to analyze their influence on clinical outcomes by adjusting for other well-known prognostic factors in patients with acute ischemic stroke. Methods We analyzed 1389 consecutive adult patients with acute ischemic stroke and explored the relationship among clinical characteristics, laboratory measurements, imaging findings, and 6-month functional outcomes. Results The final study population comprised 216 patients with both acute ischemic stroke and diabetes mellitus who were followed up for 6 months. A multiple logistic regression analysis of poor outcomes revealed the following independent predictors: leukoaraiosis severity [odds ratio (OR), 7.38; 95% confidence interval (CI), 1.40-38.86, per 1-point increase), diabetic nephropathy (OR, 10.66; 95% CI, 1.10-103.43), and the admission National Institutes of Health stroke scale score (OR, 2.58; 95% CI, 1.36-4.92 per 1-point increase). In this model, admission hyperglycemia and intracerebral hemorrhagic transformation were not independent prognostic predictors. Conclusion Microvascular complications (such as nephropathy) caused by diabetes mellitus predict an unfavorable clinical outcome after acute ischemic stroke. Diabetic nephropathy may partly affect post-stroke prognosis by means of exacerbating leukoaraiosis.

Leukoaraiosis (LA) is common in elderly patients with ischemic stroke on magnetic resonance imaging. In this study, we investigate whether the degree of LA is associated with clinical outcomes and prognosis of patients with middle cerebral artery occlusion following intravenous thrombolytic. Ninety-seven patients were recruited and divided into three groups based on the degree of LA (no, mild and moderate to severe LA) by the Fazekas scale. Clinical outcomes, recurrent stroke, Fugl-Meyer rating scale (FMS) and complications of intravenous thrombolysis were assessed. The association between the degree of LA and functional outcomes was analyzed by multivariable logistic regression model. Patients enrolled were divided into three groups: 26 patients with no LA, 43 patients with mild LA and 28 patients with moderate to severe LA. Impressively, the patients with mild LA were better in early neurological recovery and 90-day FMS score than patients in the other two groups. Multivariate logistic analysis revealed that moderate to severe LA was an independent predictor of poor functional outcome (OR: 10.482; 95% CI: 1.442-76.181; P = .020). Moreover, the patients with moderate to severe LA have a higher rate of hemorrhagic transformation and recurrent stroke as compared with two other groups during 90-day follow-up. Different degrees of LA differentially affect clinical outcome and prognosis in patients with middle cerebral artery occlusion following intravenous thrombolytic. Moderate to severe LA is a risk factor of poor prognosis. Mild LA is associated with early neurological recovery and good motor functional outcome., (Copyright © 2017. Published by Elsevier B.V.)

Background: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A)., Methods: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques., Results: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one., Conclusion: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Futile recanalization occurs when successful recanalization fails to improve clinical outcome in acute ischemic stroke patients. Predictors of futile recanalization are still debated and may help in selecting patients for reperfusion strategies. We aim to determine whether leukoaraiosis may be useful in predicting futile recanalization in acute ischemic stroke patients treated by endovascular mechanical thrombectomy. We included in the analysis patients with acute ischemic stroke due to anterior circulation large vessel occlusion undergoing endovascular mechanical thrombectomy obtaining complete vessel recanalization. Demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale score, time from symptoms onset to recanalization, Alberta Stroke Program Early CT Score, and leukoaraiosis graded on a 4-point van Swieten scale were collected. We dichotomized patients into those with moderate-severe leukoaraiosis (2-4) versus those with absent-slight leukoaraiosis (0, 1). Outcome measures were symptomatic intracranial hemorrhage, and modified Rankin scale score at 90 days. The relationships among radiological parameters and clinical data with outcome measures were studied with univariate and multivariable analyses. Sixty-eight patients were identified. Recanalization was futile in 32.4% of cases. On multivariable logistic regression analysis, the presence of moderate-severe LA was independent predictors of FR (P = 0.01). Furthermore, higher NIHSS score at baseline (P < 0.01) end endovascular mechanical thrombectomy alone treatment (P < 0.01) resulted associated with futile recanalization. Our results showed that the presence of moderate-severe leukoaraiosis is associated with poor outcome in recanalized patients.

Objective To explore the possible correlation between uric acid levels and leukoaraiosis (LA). Methods This cross-sectional study enrolled patients who presented with some neurological discomfort (e.g. dizziness, headache, mild cognitive impairment). Potential demographic and clinical risk factors associated with LA, including sex, age, hypertension, diabetes mellitus, smoking, alcohol consumption, dyslipidaemia, plasma fibrinogen, D-dimer, uric acid, and homocysteine, were investigated using univariate and multivariate logistic regression analyses. Results A total of 268 patients were enrolled in the study and divided into the LA group ( n = 164) and the non-LA group ( n = 104). Compared with the non-LA group, uric acid was significantly higher in the LA group (mean ± SD: 356.49 ± 121.85 µmol/l versus 289.96 ± 102.98 µmol/l). Multivariate logistic regression analyses showed that uric acid was an independent risk factor for LA (odds ratio 1.285; 95% confidence interval 1.062, 1.556). Conclusion Hyperuricaemia was an independent risk factor for leukoaraiosis in Chinese patients.

Background: Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH., Methods: In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years., Results: Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality., Conclusions: The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P < 1 × 10(-7)), and significant grey matter loss and whole brain atrophy occurs annually (P < 0.05). Additionally, the rate of white matter hyperintensity growth was heterogeneous, occurring more rapidly within long association fasciculi. Using voxel-based quantification (family-wise error corrected P < 0.05), we show the rate of white matter hyperintensity progression is associated with increases in cortical grey matter atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities with increasing rates of regional grey matter atrophy, and demonstrate that grey matter atrophy is the major contributor to whole brain atrophy in symptomatic cerebral small vessel disease. These measures provide novel insights into the longitudinal pathogenesis of small vessel disease, and imply that therapies aimed at reducing progression of white matter hyperintensities via end-arteriole damage may protect against secondary brain atrophy and consequent functional morbidity., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) awards higher deficit scores for infarcts in the dominant hemisphere when compared with otherwise similar infarcts in the nondominant hemisphere. This has been shown to adversely affect stroke recognition, therapeutic decisions, and outcome. However, factors modifying the association between infarct side and deficit severity are incompletely understood. Thus, we sought to determine whether age and age-related leukoaraiosis alter the relation between NIHSS deficit score and the side and volume of infarction., Methods: We studied 238 patients with supratentorial, nonlacunar ischemic infarcts prospectively included in our stroke registry between January 2013 and January 2014. NIHSS deficit severity was assessed at the time of presentation. Infarct volumes were assessed by manual planimetry on diffusion-weighted imaging. Leukoaraiosis burden was graded on fluid-attenuated inversion recovery images according to the Fazekas scale and dichotomized to none-to-mild (0-2) versus severe (3-6). Multivariable linear regression with backward elimination was used to identify independent predictors of the admission NIHSS., Results: Left-hemispheric infarction (P<0.001), severe leukoaraiosis (P=0.001), their interaction term (P=0.005), infarct volume (P<0.001), and sex (P=0.013) were independently associated with the NIHSS deficit. Analysis of the individual NIHSS components showed that severe leukoaraiosis was associated with an increase of the lateralizing components of the NIHSS in patients with right-hemispheric infarction (P<0.05)., Conclusions: Severe leukoaraiosis substantially attenuates the classic hemispheric lateralization of the NIHSS deficit by relating to greater NIHSS scores of components that are typically assigned to left hemisphere function., (© 2015 American Heart Association, Inc.)

Background: The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood., Aim: We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis., Methods: We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes. We dichotomized the burden of small vessel disease to "absent or moderate" and "severe." Clinical outcomes at 90 days included excellent outcome (mRS = 0-1), good outcome (mRS = 0-2), and the occurrence of symptomatic intracerebral hemorrhage. Sensitivity analysis was performed on two age groups (≤80 versus >80). We ran logistic regression adjusting for confounders to evaluate independent effect of small vessel disease on outcomes., Results: There were 820 patients with available brain computer tomography with mean age (±SD) of 71.3 (±13.2), 455 (55.5%) were male. Of these, 123 (15%) patients had severe small vessel disease at baseline. Age group analysis revealed significant associations of small vessel disease only in patients aged ≤80. After adjustment for confounders, presence of severe small vessel disease reduced the chances of both excellent (OR = 0.42, 95% CI = 0.24-0.74) and good outcome (OR = 0.35, 95% CI = 0.21-0.58) and with an increased risk of symptomatic intracerebral hemorrhage (OR = 5.91; 95% CI = 2.40-14.57)., Conclusion: When considered together as radiological expressions of small vessel disease, presence and severity of severe leukoaraiosis and lacunes on baseline computer tomography scan are associated with poor clinical outcomes in patients treated with i.v. thrombolysis., (© 2016 World Stroke Organization.)

Background: The association between edentulism and cerebral small vessel disease is controversial. We aimed to assess this relationship in community-dwelling older adults living in rural Ecuador., Methods: MRI was performed in 311 (81%) of 385 individuals ≥60 years enrolled in the Atahualpa Project. Participants were classified in 2 groups according to whether they have severe edentulism (<10 remaining teeth) or not. Using multivariate logistic regression and exposure effect models, we assessed whether edentulism correlated with severity of white matter hyperintensities (WMHs), after adjusting for relevant confounders., Results: Mean age of participants was 70 ± 8 years (57% women). Severe edentulism was noticed in 152 (49%) individuals and moderate-to-severe WMHs in 81 (26%). In univariate analyses, moderate-to-severe WMHs were more common among edentulous individuals (OR 1.88, 95% CI 1.13-3.16, p = 0.015). Such difference became non-significant in the logistic regression model (OR 1.65, 95% CI 0.91-2.99, p = 0.098); in this model, the single relevant covariate was age. A weighted exposure effect model revealed no association of severe edentulism with moderate-to-severe WMH (average exposure effect: 0.73, 95% CI -0.01 to 0.16, p = 0.10)., Conclusion: The relationship between edentulism and diffuse subcortical damage of vascular might be explained by the high prevalence of both variables in older adults., (© 2016 S. Karger AG, Basel.)

Objective: Pontine infarction is a common type of brain stem infarction and early neurological deterioration (END). We evaluated the possibility of severe white matter hyperintensity (WMH) as a predictor of END in isolated pontine infarction., Methods: We recruited 2 types of patients with isolated pontine infarction within 24 h from symptom onset. END was defined as an increase of ≥1 point on the motor National Institutes of Health Stroke Scale (NIHSS) or ≥2 points on the total NIHSS score within 72 h from admission. We graded WMH using Fazekas scale, which is dichotomized into mild (grades 0-1) and moderate to severe (grades 2-3) on fluid-attenuated inversion recovery images., Results: A total of 82 patients with an isolated pontine infarction were selected. END was detected in 23 patients (28%). Severe periventricular and subcortical WMH (PVWMH and SCWMH, respectively) were more frequent in deteriorating patients (p = 0.001 and p = 0.019, respectively). A logistic regression analysis revealed that both severe PVWMH (OR 6.17; 95% CI 1.93-19.75, p = 0.002) and SCWMH (OR 3.19; 95% CI 1.10-9.23, p = 0.032) remained independent predictors of END., Conclusions: Both severe PVWMH and SCWMH were useful to predict END in patients with isolated pontine infarction., (© 2016 S. Karger AG, Basel.)

Background and Purpose: We investigated the factors influencing inpatient convalescent rehabilitation outcomes in patients with ischemic stroke, particularly severity of leukoaraiosis on magnetic resonance imaging., Methods: Participants included 520 patients with ischemic stroke (317 men and 203 women; mean age, 72.8±8.4 years) who were transferred from acute care hospitals for inpatient convalescent rehabilitation. Ischemic stroke subtypes included lacunar infarction (n=41), atherothrombosis (n=223), artery-to-artery embolism (n=67), cardiogenic embolism (n=97), undetermined embolism (n=76), and uncategorized ischemic stroke (n=16). Leukoaraiosis was graded according to periventricular hyperintensity (PVH) and deep white matter hyperintensity on magnetic resonance imaging. Functional Independence Measure scores were assessed on admission and at discharge., Results: Multiple regression analysis revealed that rehabilitation outcomes, measured as total Functional Independence Measure scores, were significantly associated with leukoaraiosis estimated by PVH grade. This association was observed after adjustment for factors such as severity, age, and poststroke history. In all patients, PVH grades were associated with Functional Independence Measure motor scores (P<0.001), whereas in patients with artery-to-artery embolism or cardiogenic embolism and deep white matter hyperintensity grades were associated with Functional Independence Measure cognitive scores (P<0.05)., Conclusions: Our study revealed that the degree of leukoaraiosis was associated with inpatient convalescent rehabilitation outcome in patients with ischemic stroke. Furthermore, the PVH grade was associated with motor function outcome, whereas the deep white matter hyperintensity grade correlated with cognitive function outcome, likely because the progression patterns and anatomic backgrounds of PVH and deep white matter hyperintensity differ according to ischemic stroke subtype., (© 2015 American Heart Association, Inc.)

Aims: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up., Methods: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed., Results: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (β = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up., Conclusion: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years., (© 2016 S. Karger AG, Basel.)

Background and Aims: Ischemic stroke remains a leading cause of disability, particularly among the elderly, but this association has not been consistently noted among patients with minor stroke. We sought to determine the association of chronological age and leukoaraiosis, which is considered a marker of biological age, with the degree of neurological deficit recovery and 90-day disability after minor ischemic stroke., Methods: We retrospectively analyzed 185 patients with a minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤ 5). Leukoaraiosis severity was graded according to the van Swieten scale. NIHSS was assessed at baseline, discharge, and 90-days. Multivariable linear and ordinal logistic regression analyses were constructed to identify independent predictors of the degree of NIHSS-improvement (ΔNIHSS) and 90-day outcome as assessed by the modified Rankin Scale (mRS)., Results: Patients with severe leukoaraiosis had attenuated ΔNIHSS at 90 days as compared to patients with none-to-mild leukoaraiosis (p=0.028). After adjustment, leukoaraiosis severity (p<0.001) but not chronological age (p=0.771) was independently associated with the ΔNIHSS by day 90. Severe leukoaraiosis (p=0.003, OR 3.1, 95%-CI 1.5-6.4), older age (p=0.001, OR 1.0 95%-CI 1.0-1.1), and admission NIHSS (p<0.001, OR 1.5, 95%-CI 1.2-1.8) were independent predictors of the 90-day mRS., Conclusion: Leukoaraiosis is a more sensitive predictor for neurological deficit recovery after ischemic stroke than chronological age. Further study is required to establish the specific contribution of leukoaraiosis to functional outcome after minor ischemic stroke beyond its impact on recovery mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: Early neurological worsening is common in minor subcortical strokes (SS) and may lead to a poor outcome. We aimed to describe clinical and imaging features associated with progression., Material and Methods: Consecutive patients with SS were divided into progressive and non-progressive. Progression was defined as an increase of NIHSS motor score ≥ 1 point within 72 h from onset. Vascular risk factors and imaging features (vascular territory, size and number of slices in which the lesion was visible, the presence of leukoaraiosis) were compared in the two groups. We investigated potential independent determinants of progression using stepwise logistic regression., Results: Thirty of 94 patients (31.9%) underwent progression. The distribution of vascular risk factors did not differ significantly between the two groups. Increasing number of risk factors was associated with a higher risk of progression (OR 2.2; 95% CI 1.1-4.5). Patients who progressed were more likely to have a lesion ≥ 15 mm in diameter (P = 0.004) or a lesion visible ≥ 3 slices (P = 0.007). After logistic regression stepwise adjustment for all the considered potential determinants, diameter ≥ 15 mm and severe leukoaraiosis proved to be independently associated with neurological worsening (OR = 6.3, 95% CI 2.0-19.6 and OR = 5.9, 95% CI 1.3-25.7, respectively)., Conclusion: In a series of consecutive SS, early neurological worsening was associated with a high vascular risk profile, a larger infarct size and the presence of severe leukoaraiosis. Based on the knowledge that extensive microvascular changes are a feature of severe leukoaraiosis, we hypothesize that stroke progression could be promoted through an impaired compensatory flow in the penumbral area., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The blood-brain barrier (BBB) plays a major role in the development of leukoaraiosis (LA). The junctional complex of BBB consists of tight junction (TJ) and adherens junction (AJ). Claudin-1 is the integral component of TJ. The aim of this study was to evaluate whether genetic variations in claudin-1 gene are associated with the development of LA., Methods: LA has to be diagnosed based on images. A total of 228 LA cases and 203 controls were enrolled from the individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of claudin-1 single-nucleotide polymorphisms (SNPs) (rs17501010, rs893051, and rs9290927) was performed by real-time polymerase chain reaction with LightSNiP reagents (coupled primer and probe) and FastStart DNAMaster HybProbe (Roche Diagnostic, GmBH, Mannheim, Germany) in LightCycler 2.0., Results: Among the 3 SNPs of claudin-1, a significant genetic difference was found only between control and LA (both LA-periventricular white matter [PVWM] and LA-subcortical deep white matter) with SNP rs9290927. However, their haplotypes G-G-T and G-C-A were significantly different between LA-PVWM and control, which increase the development of LA-PVWM with odds ratios of 1.45 and .57, respectively., Conclusions: This study demonstrated first evidence of genetic polymorphism of TJ component claudin-1 and their haplotypes associated with LA., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) provides a reliable, quantitative measure of ischemic stroke severity and is predicted by the infarct size. We sought to determine whether leukoaraiosis severity affects the association between infarct size and NIHSS., Methods: NIHSS and diffusion-weighted imaging-defined infarct volumes from 312 prospectively enrolled patients with supratentorial, ischemic strokes were analyzed. Leukoaraiosis severity was graded according to the Fazekas scale and conceptually defined as absent (0; n=44), mild (1-2; n=106), moderate (3-4; n=105), and severe (5-6; n=57). ANCOVA was used to describe the effect of leukoaraiosis on the association between infarct volume and NIHSS. Multivariable linear regression models were constructed to assess whether the association of leukoaraiosis and infarct volume on NIHSS was independent of other clinically relevant covariates., Results: Overall, there was a significant correlation between the infarct volume and NIHSS (r=0.591; P<0.001). This correlation significantly attenuated with increasing leukoaraiosis severity from r=0.786 (P<0.001; absent leukoaraiosis) to r=0.498 (P<0.001; severe leukoaraiosis) and as shown by ANCOVA (P<0.001). Leukoaraiosis (coefficient, 0.107; 95% confidence interval, 0.036-0.179; P=0.016) and infarct volume (coefficient, 0.360; 95% confidence interval, 0.305-0.416; P<0.001) were independently associated with a greater NIHSS deficit in the fully adjusted multivariable model., Conclusions: Leukoaraiosis significantly modulates the association between infarct volume and NIHSS. The clinical implications of these findings need further exploration in prospective studies but may be relevant to mitigate outcome differences in patients with stroke by aiding treatment decisions that rely on the NIHSS., (© 2015 American Heart Association, Inc.)

Purpose: Diffusional kurtosis imaging is an advanced diffusion magnetic resonance imaging method that yields, in addition to conventional diffusion information, non-Gaussian diffusion effects, which may allow a more comprehensive characterization of tissue microstructure. The purpose of this study is to use diffusional kurtosis to assess white matter integrity in patients with hydrocephalus and to determine whether changes in kurtosis correlate with the severity of hydrocephalus and leukoaraiosis (LA), a commonly seen comorbidity in hydrocephalus., Methods: 26 patients with imaging evidence of hydrocephalus and 26 age- and sex- matched subjects with normal ventricular size were retrospectively analyzed. Standard diffusion tensor imaging and diffusional kurtosis metrics were compared between the two groups. Correlation between kurtosis and severity of hydrocephalus and presence and severity of LA was determined., Results: Hydrocephalus patients relative to controls demonstrated statistically significant decrease in all kurtosis metrics in most brain regions studied. The severity of hydrocephalus was associated with greater decrease in kurtosis in the corpus callosum. There was more LA in the hydrocephalus group, and severity of LA was associated with decrease in kurtosis. After controlling for the degree of LA, kurtosis was still decreased in hydrocephalus relative to the controls., Conclusion: Diffusional kurtosis imaging detects microstructural changes in the white matter of patients with hydrocephalus. Our results suggest that hydrocephalus plays a role in altering white matter integrity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background/aim: Cerebral white matter changes (WMC) are commonly observed in magnetic resonance imaging (MRI) scans of elderly people. Information about the prevalence of WMC is limited, and little is known about site-specific risk factors for the subcortical and periventricular regions in patients with ischaemic stroke. The study aims to analyse the prevalence and severity of WMC and investigate the risk factors of periventricular WMC (PVWMC) and deep WMC (DWMC) separately in patients with ischaemic stroke., Methods: The data were collected between January and December 2013 from a medical centre in southern Taiwan. Every patient underwent a cerebral MRI scan, and WMC was separately rated as PVWMC and DWMC by using the modified Fazekas scale., Results: In total, 527 patients who had experienced ischaemic stroke were included. The mean age of the patients was 67.0 ± 12.5 years (range: 31-94) and 62% of them were men. The mean age was significantly different among the four grades of severity in both the PVWMC (P < 0.001) and DWMC (P < 0.001) groups after adjustments for sex and vascular risk factors. Hypertension was independently correlated with severity of DWMC (P = 0.032) but not with PVWMC (P = 0.222). In multiple logistic regressions model, hypertension was a significant independent indicator of DWMC (odds ratio = 4.30; 95% confidence interval = 1.70-10.89)., Conclusion: Our results suggest a region-specific pathogenesis of cerebral white matter in Asian patients with ischaemic stroke that may differ from those in the general population., (© 2015 Royal Australasian College of Physicians.)

Objective: We aimed to investigate the association between leukoaraiosis and long-term risk of stroke recurrence adjusting for clinical scores developed and validated for the prediction of stroke risk, such as CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or TIA) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category)., Methods: Study population was derived from the Athens Stroke Registry and was categorized in 2 subgroups according to the presence of atrial fibrillation (AF). Cox proportional hazards analysis was performed to assess the independent predictors of stroke recurrence. To investigate whether leukoaraiosis adds to the prognostic accuracy of CHADS2 and CHA2DS2-VASc scores, we used the likelihood ratio test. Overall model assessment was performed with Nagelkerke R(2) and Harrell C statistic. Kaplan-Meier analyses were also performed., Results: Among 1,892 patients, there were 320 (16.9%) with leukoaraiosis and 670 (35.4%) with AF. In the Kaplan-Meier analysis, there was significant difference in cumulative probability of stroke recurrence between patients with and without leukoaraiosis in the non-AF group (p < 0.01), but not in the AF group (p = 0.46). On Cox multivariate analysis, leukoaraiosis was found to be a significant independent predictor of stroke recurrence only in the non-AF group, in the models adjusting for CHADS2 (hazard ratio: 1.86, 95% confidence interval: 1.35-2.56) and CHA2DS2-VASc (hazard ratio: 1.82, 95% confidence interval: 1.32-2.51) scores. Leukoaraiosis was not a predictor of stroke recurrence in the AF group. Leukoaraiosis did not improve the predictive accuracy of the 2 scores, whether in the non-AF group (Harrell C statistic: 0.56 vs 0.59 [p = 0.31] for the model including CHADS2; 0.56 vs 0.59 [p = 0.44] for the model including CHA2DS2-VASc) or the AF group (Harrell C statistic: 0.63 vs 0.62 for the model including CHADS2; 0.64 vs 0.64 for the model including CHA2DS2-VASc)., Conclusions: Leukoaraiosis is an independent predictor of stroke recurrence in non-AF stroke patients. However, leukoaraiosis did not increase the accuracy of the CHADS2 and CHA2DS2-VASc scores to predict stroke recurrence in AF or non-AF stroke patients., (© 2015 American Academy of Neurology.)

Background: Leukoaraiosis (LA) is closely associated with stroke. Despite the fact that LA has consistently been shown to predict development of recurrent stroke, prior studies on the association of LA and stroke subtypes have been unsatisfactory. In this study, we sought to identify whether LA contributes to the recurrence of certain subtypes of stroke at long term., Methods: Data from the Ege Stroke Registry were examined, and 5 years follow-up data for LA and stroke recurrence were analyzed. We performed survival curves using the Kaplan-Meier method (unadjusted) and log-rank tests in patients with stroke to determine the relationship between LA and recurrent stroke by stroke subtypes within a time period of 5 years. Multivariate survival analyses were undertaken using Cox proportional hazards models to determine the prognostic value of LA, stroke subtypes, and other vascular risk factors before recurrent stroke., Results: Of 9522 patients with stroke, 1280 (26%) with LA and 901 (19%) without LA experienced a stroke recurrence within 5 years of follow-up (odds ratio, 1.53; 95% confidence interval, 1.39-1.69). After stratification by stroke subtypes, multivariable analysis revealed a significant association between LA and large artery disease (LAD; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.18-1.64), small artery disease (SAD; OR, 1.57; 95% CI, 1.27-1.94), and intracerebral hemorrhage (ICH; OR, 1.88; 95% CI, 1.32-2.66), except cardioembolic stroke and "other" stroke subtypes at 5 years after stroke onset. The survival analysis showed that stroke recurrence was significantly higher in patients with severe LA compared with those with mild/moderate LA (log-rank test [Mantel-Cox], P < .001)., Conclusions: Our results showed that LA is related to the recurrent strokes in patients with stroke within 5 years after stroke, specifically to the LAD, SAD and ICH., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM., Methods: In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression., Results: We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05)., Conclusions: We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.

Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness.

Background: Leukoaraiosis (LA) patients may suffer from sensorimotor dysfunctions. The relationship between behavioral disturbances and changes in the sensorimotor network (SMN) has not been thoroughly elucidated., Objective: This study investigated the hypothesized breakdown of communication of SMN and its behavioral consequences in LA., Methods: Fluid-attenuated inversion recovery (FLAIR) images, resting-state functional magnetic resonance images (fMRI) and behavioral data were collected from 30 LA patients and 26 healthy individuals (normal controls, NC). The subjects were grouped according to LA severity, as indicated by their FLAIR images. Group independent component analysis was applied to the fMRI data to map the functional connectivity of SMN for NC and LA patients. A whole-brain, voxel-wise analysis was employed to investigate the functional connectivity alteration of SMN in LA. The relationships between LA severity, functional connectivity alteration of the SMN and behavioral clinical symptoms were examined by correlation analysis., Results: The right cingulate motor area (rCMA), left posterior insula and left ventral premotor area showed attenuated functional connectivity in the LA patients. The extent of the attenuation was related to the severity of the disease. Furthermore, the attenuation in the rCMA was associated with worse sensorimotor integration performance., Conclusions: These results suggest that LA impairs sensorimotor integration by interfering with the communication or coordination of these aforementioned regions related to the SMN., (© 2015 S. Karger AG, Basel.)

Neuroimaging of older adults commonly reveals abnormality (leukoaraiosis) in the cerebral white matter. Studies have established that extensive leukoaraiosis predicts dementia and disability, but the pathogenesis of leukoaraiosis remains unclear. We recruited 5 patients with leukoaraiosis and performed magnetic resonance mapping of the brain for 16 consecutive weeks. We observed tiny lesions arising de novo in the cerebral white matter. These lesions were clinically silent. They had the signature features of acute ischemic stroke. With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis. Together, these findings suggest that tiny silent acute infarcts are a cause of leukoaraiosis., (© 2014 American Neurological Association.)

Background and Purpose: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI., Methods: We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively., Results: After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) ≤12; p = 0.001], or had mild TBI (GCS 13-15; p = 0.002), respectively., Conclusion: We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization.

Background: Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke., Methods: A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA., Results: A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA., Conclusions: LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Identifying MRI biomarkers that can differentiate multiple sclerosis patients from other neurological disorders is a subject of intense research. Our aim was to investigate phase WM signal abnormalities for their presence, prevalence, location, and diagnostic value among patients with clinically isolated syndrome and other neurologic disorders and age-, sex-, and group-matched healthy controls., Materials and Methods: Forty-eight patients with clinically isolated syndrome and 30 patients with other neurologic diseases and a healthy control group (n = 47) were included in the study. Subjects were scanned at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities ≥3 mm being classified., Results: Patients with clinically isolated syndrome had significantly more phase and T2 WM signal abnormalities than healthy controls (P < .001). Phase WM signal abnormalities were more prevalent among patients with clinically isolated syndrome compared with patients with other neurologic disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity for differentiating patients with clinically isolated syndrome and healthy controls, patients with other neurologic disorders, and patients with other neurologic disorders of other autoimmune origin (specificity, 70%-76.7%). Combining the presence of ≥2 phase lesions with the McDonald 2005 and 2010 criteria for dissemination in space improved the specificity (90%), but not the accuracy, in differentiating patients with clinically isolated syndrome from those with other neurologic disorders. In subanalyses among patients with clinically isolated syndrome who converted to clinically definite multiple sclerosis versus those who did not within a 3-year follow-up period, converters had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities., Conclusions: Phase WM signal abnormalities are prevalent among patients with clinically isolated syndrome. The presence of (multiple) phase WM signal abnormalities tended to be more predictive of conversion to clinically definite multiple sclerosis and was specific in differentiating patients with clinically isolated syndrome and other neurologic disorders, compared with T2 WM signal abnormalities; however, the accuracy remains similar to that of the current McDonald criteria., (© 2014 by American Journal of Neuroradiology.)

Background and Purpose: There are some controversial results on the relationship between cerebral atherosclerosis and leukoaraiosis in the published papers, where cerebral atherosclerosis was often evaluated by ultrasonography, CTA or MRA. We analyzed data in which patients underwent both MRI and DSA to explore the above relationship in the aged people., Methods: Three hundred and thirty-three patients were enrolled in the study from the Nanjing Stroke Registry. They underwent both cerebral DSA and MRI. Age, sex, and vascular risk factors were collected. Atherosclerosis was scored from grade 0 to 4. Leukoaraiosis was scored from grade 0 to 3., Results: Cerebral artery stenosis was not correlated with the presence of leukoaraiosis. There were no correlations between the number of cerebral moderately or more severely stenotic arteries and the severity of leukoaraiosis in periventricular, deep, or whole white matter (P = .747, .268, and .608, respectively). Old age (odds ratio = 1.103, P = .027) and hypertension (odds ratio = 2.748, P = .003) were correlated with leukoaraiosis in the periventricular white matter. Old age (odds ratio = 1.073, P = .031) and prior stroke (odds ratio = 2.678, P = .002) were correlated with leukoaraiosis in the deep white matter., Conclusions: No apparent correlation exists between cerebral artery stenosis and the presence and severity of leukoaraiosis., (Copyright © 2013 by the American Society of Neuroimaging.)

Aim: Leukoaraiosis and high intraocular pressure are strongly associated with cardiovascular disease, vascular angiopathy, and geriatric syndrome. Until now, little is known about the relationship between intraocular pressure and leukoaraiosis in its preclinical stage. The aim of this study was to evaluate the association between intraocular pressure and leukoaraiosis among middle-aged and elderly Koreans without glaucoma or dementia., Methods: We examined the relationship of intraocular pressure with leukoaraiosis at a preclinical stage in 753 Korean adults (474 men, 279 women; mean age 57.8 ± 6.6 years). A multiple logistic regression analysis was performed in order to determine whether intraocular pressure is an independent determinant for leukoaraiosis., Results: The overall prevalence of leukoaraiosis was 7.3%. Mean ocular pressure (±SD) was significantly higher in the leukoaraiosis group than the control group (14.3 ± 2.9 and 13.5 ± 2.9, respectively; P=0.028). In multiple logistic regression analysis, the odds ratio for leukoaraiosis was 1.18 (95% confidence interval: 1.06-1.31) for each 1 mm Hg increase in intraocular pressure., Conclusion: Intraocular pressure was found to be independently and positively associated with leukoaraiosis. This finding indicates that higher intraocular pressure may be a useful additional measure in assessing the risk of leukoaraiosis in the clinical setting.

Background: Leukoaraiosis (LA) is associated with structural and functional vascular changes that correlate with motor and gait disturbances, depressive symptoms, urinary disturbances, and dementia. The blood-brain barrier (BBB) plays a key role in development of lacunar stroke, leukoaraiosis, and other feature of cerebral small-vessel disease, and there are numerous studies examining changes in the BBB with normal aging and in dementia and LA. Aquaporin-4 (AQP-4), the primary water channel protein in the central nervous system, is involved in BBB development, function, and integrity, and its dysfunction induces several neurologic diseases. The aim of our study was to evaluate whether genetic variations in AQP-4 gene are associated with the development of LA., Methods: DNA was amplified and the single-nucleotide polymorphisms in AQP-4 gene were investigated by melting curve analysis using real-time polymerase chain reaction., Results: The frequency of both T allele and CT/TT genotypes of rs2075575 was significantly higher in LA group than in control group (C versus T, P = .0145; CC versus CT/TT, P = .038). However, no significant difference was observed between LA group and control group in rs9951307. Interestingly, the rs9951307 AG + GG genotype may confer a synergistic effect in odds ratio (OR) values when combined with the rs2075575 CT + TT genotypes (OR = 1.65 → 2.51). The C-A haplotype was significantly different between LA group and the control group (P = .005). By stratified analysis, rs2075575 and rs9951307 polymorphisms were statistically significant in the subjects with hypertension and hemoglobin A1c (P < .05), whereas the rs2075575 polymorphism was associated with high serum cholesterol (P < .05) and the rs9951307 polymorphism was associated with low serum homocysteine (P < .05)., Conclusions: Our results indicate that AQP-4 genetic variations and haplotypes might contribute to the risk factors for LA., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Aim: Cerebral white matter lesions (WML) are known to increase with age, as is left ventricular (LV) diastolic dysfunction with normal contraction. Although aging is a common risk factor, the link between these diseases is not fully understood. The aim was to clarify this relationship, using the ratio between early diastolic mitral inflow and early diastolic mitral annular tissue velocity (E/E'). E/E' measured by tissue Doppler echocardiography offers an indicator of the severity of LV diastolic dysfunction, reflecting both diastolic LV stiffness and diastolic LV filling pressure., Methods: Participants comprised 75 patients aged between 65 and 75 years with normal LV contraction and no signs or history of symptomatic heart failure, ischemic heart diseases, atrial fibrillation, stroke, or cognitive dysfunction. The volume of WML was quantified on brain magnetic resonance imaging., Results: The participants were classified into three groups: Low E/E', E/E' ≤ 8; Middle E/E', 8 < E/E' < 15; and High E/E', E/E' ≥ 15. WML volume was 3.6 ± 3.0 mL in Low E/E', 5.4 ± 6.5 mL in Middle E/E' and 12.0 ± 11.0 mL in High E/E', increasing significantly with increased diastolic LV stiffness (Low vs High, P = 0.034; Middle vs High, P = 0.016). Linear regression analysis showed the positive association between the volume of WML and E/E' ratio (r = 0.377, P = 0.0009)., Conclusions: This investigation identified an association between LV diastolic dysfunction and WML. Further investigations are required to clarify whether there is a direct association between the two diseases., (© 2014 Japan Geriatrics Society.)

Objective: To explore the independent risk factors and predictive factors of cognitive deterioration in patients of vascular cognitive impairment no dementia with subcortical ischemic vascular disease (VCIND-SIVD)., Methods: The clinical and neuropsychological characteristics of 96 VCIND-SIVD patients were collected and their cognitive states re-assessed after one year. The distribution of continuous and categorical variables was examined with univariate analysis. And Logistic regression in multivariate modeling was employed to identify the risk and predictive factors of cognitive deterioration., Results: After 1-year follow-up, 8 patients dropped out, 2 died and the remainder remained. There were 48 males and 38 females with an average age of 64.3 ± 5.4 years. Among them, 17 (19.8%) deteriorated into dementia, 24 (27.9%) upgraded to normal cognition and 45 (52.3%) maintained their cognitive status. They were divided into dementia group (cognition deteriorating into dementia) and control group (elevated/sustained cognition). After univariate analysis of general information and vascular risk factors, Logistic regression demonstrated that education level (P < 0.05, OR = 0.7) was a preventive factor of dementia while age (P < 0.05, OR = 1.2), hypertension (P < 0.05, OR = 5.6) and high homocysteine (P < 0.05, OR = 4.2) were independent risk factors of dementia. After univariate analysis of neuropsychological scores, Logistic regression demonstrated that visual reproduction-immediate recall (P < 0.05, OR = 3.4), digit span forward (P < 0.05, OR = 1.2), clock drawing test (P < 0.05, OR = 6.8) and completion time of London tower (P < 0.05, OR = 5.4) were predictive factors of dementia., Conclusion: VCIND-SIVD patients with low score of visual reproduction-immediate recall, digit span forward, clock drawing test and completion time of London tower should receive vigorous controls of hypertension and high homocysteine.

The paper presents the case of a 61-year-old man with specific symptoms of non-arteritic anterior ischemic optic neuropathy. The head computed tomographyscans revealed multiple leukoaraiotic lesions. Leukoaraiosis is a disease affecting small cerebral vessels. Its pathogenesis is associated with a chronic inflammatory process and ischemic vascular endothelial dysfunction which reduce the cerebral blood flow. It cannot be ruled out that this process, alongside with Horton disease, hypertension, diabetes and atherosclerosis, may also be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. leukoaraiosis, non-arteritic anterior ischemic optic neuropathy.

Diagnosis of benign paroxysmal positional vertigo (BPPV) often causes difficulties, in particular, in elderly people with concomitant diseases. The article presents a case of a 77 year-old woman with BPPV. A patient's complaint on vertigo was mistakenly diagnosed as brain ischemia because the patient had long suffered from uncontrolled arterial hypertension. MRI-study revealed leucoaraiosis and one lacuna as well as a meningioma which was mistakenly linked to vertigo. The diagnosis of BPPV, use of Epley maneuver with the following vestibular exercises resulted in complete stopping of vertigo. Effective treatment of arterial hypertension with the normalization of arterial pressure, use of aspirin and statins reduced the risk of stroke. Exclusion of BPPV is needed in all cases of vertigo with unclear etiology.

Objective: The amount of cerebral white matter lesions (WMLs) and the severity of carotid artery disease are correlated in this study. The association between the severity of WMLs and the volume of the different components of carotid artery plaque is also evaluated., Materials and Methods: Fifty consecutive patients (39 men, 11 women; mean [SD] age, 71 ± 9 years) with carotid artery stenosis who underwent carotid endarterectomy were included in this study. On admission, patients underwent head and neck CT angiography (CTA) and brain MRI. The CTA-based plaque volume and the percentages of the three main plaque components (fatty, mixed, and calcified) were calculated according to the attenuation values. Leukoaraiosis lesion volume on FLAIR images was determined using a semiautomated segmentation technique. Pearson correlation was conducted between the leukoaraiosis lesion volume on FLAIR images and the volumes of the different plaque components., Results: Pearson correlation analysis was performed to determine WML volume versus total carotid plaque volume (ρ = 0.2531; p = 0.0262), fatty plaque volume (ρ = 0.387; p = 0.0005), mixed plaque volume (ρ = 0.1709; p = 0.15), and calcified plaque volume (ρ = 0.0146; p = 0.899). The WML volume was also compared against fatty plaque percentage (ρ = 0.343; p = 0.0018), mixed plaque percentage (ρ = 0.181; p = 0.124), and calcified plaque percentage (ρ = -0.209; p = 0.068)., Conclusion: The cerebral WML volume and the total volume of the plaque are correlated. The amount of fat within the plaque is an additional risk factor, whereas the calcified component seems to be protective.