Transcriptome Sequencing Identifies Potential Biomarker for White Matter Lesions Diagnosis in the Hypertension Population.

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.

Radiomics from magnetic resonance imaging may be used to predict the progression of white matter hyperintensities and identify associated risk factors.

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.

Pooled cohort risk equation and subclinical cerebrovascular diseases.

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 [ß = 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.

Degenerative dementia with proximal radial and lower vertical spatial neglect.

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.

COL4A1 Mutation as a Cause of Familial Recurrent Intracerebral Hemorrhage.

The COL4A1 mutation is a very rare monogenic cause of small vessel disease related to recurrent intracerebral hemorrhage. We report a family in which the index case presented with two intracerebral hemorrhages in the basal ganglia with severe periventricular leukoaraiosis and a cataract and vascular tortuosity in the ophthalmological study. His twin brother also had severe leukoaraiosis and multiple subcortical microhemorrhages as well as a congenital cataract and vascular tortuosity in the retina. The older sister had a porencephalic cyst and involvement of the periventricular white matter and intracerebral hemorrhage. In single-gene testing, all three were found to have the same COL4A1 mutation. Intracerebral subcortical hemorrhages or microhemorrhages and severe subcortical leukoaraiosis in familial cases may be related to COL4 mutations.

Structural and functional MRI correlates of T2 hyperintensities of brain white matter in young neurologically asymptomatic adults.

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) mm3. 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.

Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

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.

Association of Leukoaraiosis With Convalescent Rehabilitation Outcome in Patients With Ischemic Stroke.

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.

Impact of Leukoaraiosis Burden on Hemispheric Lateralization of the National Institutes of Health Stroke Scale Deficit in Acute Ischemic Stroke.

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.

Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease.

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.

White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study.

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 (ß = 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.

Severe White Matter Hyperintensity Is Associated with Early Neurological Deterioration in Patients with Isolated Pontine Infarction.

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.

The Influence of Age in the Relationship between Cerebral Small Vessel Disease and Edentulism. The Atahualpa Project.

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.

Leukoaraiosis Burden Significantly Modulates the Association Between Infarct Volume and National Institutes of Health Stroke Scale in Ischemic Stroke.

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.

Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology.

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.

Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks.

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.

Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF.

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.

Predictors of progression in patients presenting with minor subcortical stroke.

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.

Determinants of cerebral white matter changes in patients with stroke.

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.

Breakdown of Sensorimotor Network Communication in Leukoaraiosis.

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.