Predictors of hemorrhagic transformation differences between patients treated or not with reperfusion therapy.

BACKGROUND: Hemorrhagic transformation (HT) is a dreaded complication in stroke patients who were treated or not with recombinant tissue plasminogen activator (tPA). There are many predictive scores of HT, but all of them included patients treated with tPA. Molecular effects of tPA and clinical aspects of eligible patients for tPA therapy may imply specific HT's risk factors. We aimed to describe HT's characteristics and risk factors in patients treated or not with tPA. METHODS: We included 1565 consecutive stroke patients admitted to a Comprehensive Stroke Center, from 2015 to 2017. All included patients underwent a follow-up neuroimaging within seven days after admission. From a logistic regression model, we derived a score based on the beta-coefficients. The accuracy of the models was attested by Receiver Operating Characteristic analysis. RESULTS: Low ASPECTS, blood glucose ≥ 180 mg/dL, tPA treatment, and cardio-aortic embolism were predictors of HT. Male sex, leukoaraiosis, and hyperdense MCA sign were associated with HT in non-treated patients. Diastolic blood pressure ≥ 105 mmHg was a risk factor only in non-treated patients. The cutoff of our predictive score of HT was higher in patients not treated with tPA (5 vs 2 points). CONCLUSIONS: High arterial blood pressure was associated with HT only in patients treated with tPA. Different cutoffs and accuracy measurements suggest that scoring systems derived from patients treated with tPA may not be efficient to predict HT in non-treated patients. Further directions indicate considering the use of reperfusion therapies to select the most accurate predictive variables of HT.

Impact of White Matter Hyperintensity Burden on Outcome in Large-Vessel Occlusion Stroke.

Background White matter hyperintensity (WMH) has been linked to poor clinical outcomes after acute ischemic stroke. Purpose To assess whether the WMH burden on pretreatment MRI scans is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) or poor functional outcome in patients with acute ischemic stroke treated with endovascular thrombectomy (EVT). Materials and Methods In this retrospective study, consecutive patients treated with EVT for anterior circulation acute ischemic stroke at a comprehensive stroke center (where MRI was the first-line pretreatment imaging strategy; January 2015 to December 2017) were included and analyzed. WMH volumes were assessed with semiautomated volumetric analysis at fluid-attenuated inversion recovery MRI by readers who were blinded to clinical data. The associations of WMH burden with sICH and 3-month functional outcome (modified Rankin Scale [mRS] score) were assessed. Results A total of 366 patients were included (mean age, 69 years ± 19 [SD]; 188 women [51%]). Median total WMH volume was 3.61 cm3 (IQR, 1.10-10.83 cm3). Patients demonstrated higher mRS scores with increasing WMH volumes (odds ratio [OR], 1.020 [95% CI: 1.003, 1.037] per 1.0-cm3 increase for each mRS point increase; P = .018) after adjustment for patient and clinical variables. There were no significant associations between WMH severity and 90-day mortality (OR, 1.007 [95% CI: 0.990, 1.024]; P = .40) or the occurrence of sICH (OR, 1.001 [95% CI: 0.978, 1.024]; P = .94). Conclusion Higher white matter hyperintensity burden was associated with increased risk for poor 3-month functional outcome after endovascular thrombectomy for large-vessel occlusive stroke. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mossa-Basha and Zhu in this issue.

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.

The relationship between diabetes-related cognitive dysfunction and leukoaraiosis.

Cognitive dysfunction is a degenerative disease of the central nervous system, which often associates with ageing brain as well as neurodegenerative diseases. A growing body of evidence suggests that patients with diabetes mellitus (DM) have a significantly higher risk of cognitive impairment. In recent years, studies have found that patients with diabetes-related cognitive dysfunction have an increased burden of leukoaraiosis (LA), and larger white matter hyperintensity (WMH) volume. With the recent advancement of technologies, multimodal imaging is widely exploited for the precise evaluation of central nervous system diseases. Emerging studies suggest that LA pathology can be used as a predictive signal of white matter lesions in patients with diabetes-related cognitive dysfunction, providing support for early identification and diagnosis of disease. This article reviews the findings, epidemiological characteristics, pathogenesis, imaging features, prevention and treatment of LA pathophysiology in patients with diabetes-related cognitive dysfunction.

Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke.

BACKGROUND: It is important to predict poststroke cognitive outcome to guide individualized treatment and prevention strategy. We aimed to evaluate the predictive value of the combination of a serum biomarker for axonal damage (neurofilament light chain [NfL]) and neuroimaging markers (volume of infarction and white matter hyperintensities [WMH]) for neuronal abnormality in poststroke cognitive outcome. METHODS: A total of 1028 patients were screened; among them, 144 patients with acute ischemic stroke (stroke group) and 30 patients without stroke (control group) were enrolled. Serum NfL levels of samples obtained from both groups were measured through single molecule array assay. Neuroimaging markers of neuroaxonal injury, including infarct volume and WMH in the stroke group were quantified on magnetic resonance images using an in-house MATLAB code (MATLAB 2017; MathWorks). The primary outcome was the functional independence measure (FIM) cognitive subscores on discharge. We assessed the association of serum NfL levels and neuroimaging markers with cognitive outcome. The prognosis value of the combination of serum NfL levels and imaging markers for predicting FIM cognitive subscores on discharge was calculated using the area under curve (AUC) of the receiver operating characteristic. RESULTS: Serum NfL levels of the stroke group were 9-fold higher than those of the control group (1449.7 vs 157.2 pg/mL, n = 144/30, P < .001). There was a correlation of serum NfL levels with infarct volume (r = 0.530, P < .001) and functional outcome, including FIM cognitive subscores (r = -0.387, P < .001) and FIM motor subscores on admission (r = -0.306, P < .001), but not with WMH volume after adjusting for infarct volume (r = -0.196, P = .245). Serum NfL levels on admission independently predicted poststroke FIM cognitive subscores on discharge (AUC = 0.672, P < .001). The predictive value for poststroke cognitive outcome was improved by combining serum NfL levels with infarct and WMH volume (AUC = 0.760, P < .001). CONCLUSION: The combination of serum NfL levels with volume of infarct and WMH shows an improved predictive value for cognitive function during acute rehabilitation phase after stroke, providing a promising panel of biomarkers for prognosis and guidance of treatment.

Systemic oxidative stress and cognitive function in Parkinson's disease with different PWMH or DWMH lesions.

BACKGROUND: Parkinson's disease (PD), frequently accompanied by cognitive impairments, is associated with systemic oxidative stress and abnormal structural changes on brain images. We aimed to identify the correlation between systemic oxidative stress and cognitive function in PD patients with different periventricular white matter hyperintensities (PWMH) and deep white matter hyperintensities (DWMH). METHODS: A total of 146 participants with idiopathic PD underwent brain MRI, which revealed PWMH and DWMH. The number of lesions were evaluated using the Fazekas criteria. Systemic oxidative stress was determined as early or late phase changes in leukocyte apoptosis and its subsets by flow cytometry. Cognitive functions, including attention, executive function, memory, language, and visual space, were assessed. RESULTS: For different DWMH, the leukocyte apoptosis and its subsets were significantly different.. However, there were no significant differences in oxidative stress biomarkers in PD patients with different PWMH. Attention and memory were significantly decreased in patients with more advanced DWMH injuries. Attention, memory, and language were significantly impaired in patients with worse PWMH lesions. CONCLUSION: Significant oxidative stress biomarker alternations in PD patients with DWMH, but not PWMH, might be associated with white matter injury. Systemic inflammatory responses may contribute to deep white matter damage in PD. Further, more cognitive deficits were seen in PD patients with worse deep white matter lesions, especially in moderate to severe periventricular white matter injury. TRIAL REGISTRATION: Retrospective study.

Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review.

OBJECTIVE: This systematic review aimed to synthesize early data on typology and topography of brain abnormalities in adults with COVID-19 in acute/subacute phase. METHODS: We performed systematic literature search via PubMed, Google Scholar and ScienceDirect on articles published between January 1 and July 05, 2020, using the following strategy and key words: ((covid[Title/Abstract]) OR (sars-cov-2[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND (brain[Title/Abstract]). A total of 286 non-duplicate matches were screened for original contributions reporting brain imaging data related to SARS-Cov-2 presentation in adults. RESULTS: The selection criteria were met by 26 articles (including 21 case reports, and 5 cohort studies). The data analysis in a total of 361 patients revealed that brain abnormalities were noted in 124/361 (34%) reviewed cases. Neurologic symptoms were the primary reason for referral for neuroimaging across the studies. Modalities included CT (-angiogram, -perfusion, -venogram), EEG, MRI (-angiogram, functional), and PET. The most frequently reported brain abnormalities were brain white matter (WM) hyperintensities on MRI 66/124 (53% affected cases) and hypodensities on CT (additional 23% affected cases), followed by microhemorrhages, hemorrhages and infarcts, while other types were found in <5% affected cases. WM abnormalities were most frequently noted in bilateral anterior and posterior cerebral WM (50% affected cases). CONCLUSION: About a third of acute/subacute COVID-19 patients referred for neuroimaging show brain abnormalities suggestive of COVID-19-related etiology. The predominant neuroimaging features were diffuse cerebral WM hypodensities / hyperintensities attributable to leukoencephalopathy, leukoaraiosis or rarefield WM.

Dietary Inflammatory Index and Leukoaraiosis in Patients with Ischemic Stroke.

OBJECTIVES: Diet may change the chronic levels of systemic inflammation, which in turn influence the development of leukoaraiosis (LA). This study aimed to examine the association between dietary inflammatory index (DII) and LA in patients with ischemic stroke. METHODS: Patients with first-ever ischemic stroke were enrolled from two centers. A semi-quantitative food frequency questionnaire (FFQ) was used to evaluate diet contents. The DII score of each patient was calculated based on the reported diet contents. Presence and degree of LA were evaluated with a magnetic resonance imaging (MRI) scan. LA was graded according to Fazekas scale. RESULTS: Of the 497 enrolled patients, 337 (67.8%) were detected with LA. Patients with LA had a higher DII score (0.23 vs -0.88, P < 0.001). Logistic regression analysis detected that patients with highest quartile of DII score had an OR of 3.61 (95% CI: 2.05-6.36, P < 0.001) for LA compared with those with lowest quartile of DII. After adjusting for major confounders, the highest DII quartile remained as an independent predictor for LA (OR = 2.66, 95% CI: 1.41-5.00, P = 0.008). CONCLUSIONS: A pro-inflammatory diet pattern, as indicated by higher DII values, appears to be associated with a higher risk of LA. This result suggested that dietary-mediated inflammation may involved in the pathogenesis of LA, which warrant further study.

Generalized chorea associated with subcortical leukoaraiosis of Binswanger type: a case report.

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.

Abnormal blood pressure circadian rhythms are relevant to cerebral infarction and Leukoaraiosis in hypertensive patients.

BACKGROUND: To investigate the relationships between blood pressure (BP) circadian rhythms and acute cerebral infarction (ACI), silent cerebral infarction (SCI) and the severity of leukoaraiosis in hypertensive patients. METHODS: A retrospective case-control study was performed among hypertensive patients with 24-h ambulatory blood pressure monitoring (ABPM) and cranial magnetic resonance imaging (MRI). RESULTS: A total of 1267 patients were enrolled. Lower nocturnal blood pressure (BP) decreases were observed in ACI patients than in controls (3.3% vs 8.2%, P<0.001). Reverse-dipper pattern (RD) and non-dipper pattern (ND) were found to be independent risk factors for ACI. In ACI patients, both RD and ND BP circadian rhythms were revealed to be independent risk factors for moderate-severe leukoaraiosis. In addition, in SCI patients, RD (OR = 1.7, 95% CI, 0.9-3.0; P = 0.047) or extreme-dipper pattern (ED) (OR = 2.9, 95% CI, 1.2-7.0; P = 0.015) were found to be independent risk factors for moderate-severe leukoaraiosis. Moreover, the greater the severity of leukoaraiosis was, the higher the ratio of abnormal BP circadian rhythms. CONCLUSION: RD and ND BP circadian rhythms might not only be relevant to the onset of ACI but also correlate with the severity of leukoaraiosis. Thus, when modulating BP with antihypertensive drugs, the BP circadian rhythms, and not merely the BP level, should warrant more attention.

White matter hyperintensity load on stroke recurrence and mortality at 1 year after ischemic stroke.

OBJECTIVE: To define the role and risks associated with white matter hyperintensity (WMH) load in a stroke population with respect to recurrent stroke and mortality after ischemic stroke. METHODS: A total of 7,101 patients at a network of university hospitals presenting with ischemic strokes were followed up for 1 year. Multivariable Cox proportional hazards model and competing risk analysis were used to examine the independent association between quartiles of WMH load and stroke recurrence and mortality at 1 year. RESULTS: Overall recurrent stroke risk at 1 year was 6.7%/y, divided between 5.6%/y for recurrent ischemic and 0.5%/y for recurrent hemorrhagic strokes. There was a stronger association between WMH volume and recurrent hemorrhagic stroke by quartile (hazard ratio [HR] 7.32, 14.12, and 33.52, respectively) than for ischemic recurrence (HR 1.03, 1.37, and 1.61, respectively), but the absolute incidence of ischemic recurrence by quartile was higher (3.8%/y, 4.5%/y, 6.3%/y, and 8.2%/y by quartiles) vs hemorrhagic recurrence (0.1%/y, 0.4%/y, 0.6%/y, and 1.3%/y). All-cause mortality (10.5%) showed a marked association with WMH volume (HR 1.06, 1.46, and 1.60), but this was attributable to nonvascular rather than vascular causes. CONCLUSIONS: There is an association between WMH volume load and stroke recurrence, and this association is stronger for hemorrhagic than for ischemic stroke, although the absolute risk of ischemic recurrence remains higher. These data should be helpful to practitioners seeking to find the optimal preventive/treatment regimen for poststroke patients and to individualize risk-benefit ratios.

Carotid Artery Stiffness Accurately Predicts White Matter Hyperintensity Volume 20 Years Later: A Secondary Analysis of the Atherosclerosis Risk in the Community Study.

BACKGROUND AND PURPOSE: Arterial stiffness is a biomarker of cerebrovascular disease and dementia risk. Studies have shown an association between carotid artery stiffness and increased white matter hyperintensity volume and, as a result, reduced total brain volume on MR imaging, but none have had prolonged follow-up to fully evaluate the slow change seen in white matter hyperintensity volume and total brain volume with time. Our objective was to determine whether common carotid artery stiffness on sonography accurately predicts white matter hyperintensity volume and total brain volume on MR imaging more than 20 years later. MATERIALS AND METHODS: We performed a secondary analysis of the Atherosclerosis Risk in the Community study to compare 5 measurements of carotid artery stiffness, including strain, distensibility, compliance, Stiffness index, and pressure-strain elastic modulus, with the white matter hyperintensity volume and total brain volume on a follow-up MR imaging using linear regression. RESULTS: We included 1402 patients enrolled in the Atherosclerosis Risk in the Community study. There was a significant relationship between increasing carotid artery stiffness and both higher white matter hyperintensity volume and lower total brain volume on MR imaging, measured at a mean of 21.5 years later. In multivariable linear regression models, the carotid strain, distensibility, Stiffness index, and pressure-strain elastic modulus were associated with white matter hyperintensity volume. Only compliance was associated with total brain volume in the multivariate models. CONCLUSIONS: Sonography measurements of carotid artery stiffness are predictive of white matter hyperintensity volume and total brain volume on MR imaging more than 20 years later. The association is more robust for white matter hyperintensity volume than total brain volume. These findings support the role of arterial stiffness as a method for identifying patients at risk of developing white matter hyperintensity volume and as a potential mechanism leading to small-artery disease of the brain.

Factors Associated with Leukoaraiosis Severity in Acute Stroke Patients.

OBJECTIVE: Age-related cerebral white matter abnormalities, commonly termed leukoaraiosis (LA), are frequent manifestation of cerebral microvascular disease. Aging and hypertension are well linked to LA. We compared additional vascular risk factors and socioeconomic factors with LA severity in acute stroke patients. METHODS: We analyzed 271 patients with acute ischemic or hemorrhagic stroke from a hospital registry. We collected clinical and socioeconomic data prospectively with a standardized questionnaire during acute stroke hospitalization. We scored LA severity on all available head computed tomography and magnetic resonance imaging (MRI) scans with the Wahlund LA scale. Mean response modeling analyzed for associations between LA severity and multiple potential predictors. RESULTS: Among 238 patients with CT LA scores, ageing and history of hypertension emerged as independent predictors of LA severity in multivariable analysis. Among 186 patients with MRI LA scores, ageing and severe left ventricular hypertrophy emerged as independent predictors of LA severity in multivariable analysis. We did not find an independent significant association between LA severity and the other factors we tested. CONCLUSIONS: Our study confirms the association of LA severity with ageing, and with hypertension. However, other vascular and socioeconomic factors we tested were not independently associated with LA severity.

Leukoaraiosis is an independent predictor of intracranial hemorrhage in patients with atrial fibrillation.

We evaluated the predictive value of several clinical, radiological and laboratory parameters on the risk of predict intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We conducted a case-control study on a consecutive hospital based series of patients with AF and ICH. A random sample of subjects with AF without ischemic or hemorrhagic stroke was selected from the same hospital in the same period to perform as the control group, with a ratio of two controls per case. All patients underwent the same evaluation protocol. Patients without neuroimaging exams were excluded. During the study period we identified 37 subjects with AF and ICH. 74 subjects without stroke events were randomly chosen among subjects with AF. Among cases 56.8% were female; mean age was 83.1 years. Patients with ICH were more often on anticoagulant therapy (75.7%), compared with controls (45.9%; p = 0.0002). On CT scans, cases had a greater severity of leukoaraiosis at the Blennow scale (p < 0.0001) and a higher frequency of lacunar infarcts (p = 0.006). No significant association was found between MRI parameters or the HAS-BLED score and the occurrence of ICH. CT scan is more useful than MRI and HAS-BLED score to predict ICH in patients with AF on antithrombotic therapy.

Leukoaraiosis is associated with poor outcomes after successful recanalization for large vessel occlusion stroke.

BACKGROUND: Leukoaraiosis (LA) is related to the dysfunction of the microcirculation and results in the impairment of the perfusion state. We investigated the association of LA and poor outcomes after successful recanalization by thrombectomy. METHODS: We retrospectively analyzed 97 patients with anterior large-artery occlusion who underwent thrombectomy and had successful recanalization (modified Treatment in Cerebral Ischemia Scale score 2b or 3). All patients underwent magnetic resonance imaging (MRI). LA was evaluated using fluid-attenuated inversion recovery MRI and graded using the Fazekas scale. Poor functional outcome at day 90 and symptomatic intracerebral hemorrhage (sICH) were compared between patients with absent to mild LA and moderate to severe LA. Logistic regression analyses were performed to determine the association of LA severity and outcomes. RESULTS: Moderate and severe LA occurred in 28.9% and 26.8% patients respectively. A higher proportion of poor outcomes were observed in patients with moderate to severe LA compared to patients with absent to mild LA (77.8% vs. 39.5%, p < 0.001). Logistic regression analyses showed patients with moderate to severe LA had 3.77 times (95%CI 1.21-11.76, p = 0.022) higher risk of having poor outcomes compared to patients with absent to mild LA. CONCLUSIONS: LA severity may be associated with poor outcomes after successful recanalization for ischemic stroke with anterior large vessel occlusion.

Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers.

OBJECTIVE: This study considers the use of a rapid molecular assay to evaluate apolipoprotein E (ApoE) status in military subjects who have been exposed to high altitude. We hypothesize that ApoE status may be protective against developing brain white matter hyperintensities (WMHs) after high altitude exposure. RESULTS: We tested 92 subjects who had been exposed to altitudes above 25,000 ft mean sea level, either as pilots or as altitude chamber technicians. We determined subject genetic status using rapid Taqman-style polymerase chain reaction genotyping and evaluated the association of ApoE subtype versus brain lesions using t-tests and two-way analyses of variance. Our results indicate that there is no significant association between ApoE genotype status and the presence of WMHs after high altitude exposure. We did observe a significantly higher number of hours spent at altitude for subjects with the ApoE E2 allele; however, the mechanism by which this may occur is not determined in this study. To more fully elucidate this effect, larger populations would be required to observe greater numbers of subjects with the E2 and E4 alleles.

Association between Cystatin C and SVD in Chinese population.

Leukoaraiosis is an important clinical feature of cerebral small vessel disease. To date, there is no reliable biomarker to reflect the degree of cerebral small vessel disease and white matter damage. This study aimed to explore the relationship between cystatin C levels and the degree of white matter damage in order to assess whether cystatin C could serve as a biomarker for white matter damage. We conducted a retrospective analysis of 408 non-critically ill hospitalized patients. The included patients underwent related biochemical and cerebral magnetic resonance imaging examinations. The magnetic resonance imaging results were assessed using the Fazekas scale in fluid attenuation inversion recovery imaging. We analyzed the association of each risk factor (sex, age, blood glucose, blood lipid, and cystatin C) with the degree of white matter damage using univariate logistic and multivariate cumulative odds logistic regression (stepwise). Serum cystatin C concentration was closely associated with the degree of white matter damage (odds ratio = 2.14), while age, sex, and hypertension were associated with selective damage of brain white matter. Triglycerides and apolipoprotein A may have a protective effect against white matter damage.

Hypertriglyceridemia Is Associated with Reduced Leukoaraiosis Severity in Patients with a Small Vessel Stroke.

Intracranial hemorrhage or microbleeds and leukoaraiosis have an overlap in biology. Hyperlipidemia may reduce the risk of ICH or cerebral microbleeds; studies focusing on the relationship between different lipid profiles and severity of periventricular hyperintensities (PVH) and subcortical white matter lesions (SWMLs) in the cerebral small vessel disease are limited. Methods. Patients with recent first lacunar infarct were recruited. PVH and SWMLs were accessed on MRI with the Fazekas scale, and lipid levels were measured. Univariate and multivariable regression analyses were used to assess the relation between different lipid profiles and severity of PVH and SWMLs. Results. In univariate analyses, advancing age was correlated with increasing severity of leukoaraiosis (P < 0.001). There was an inverse relationship between hypertriglyceridemia (hyper-TG) (≥1.7 mmol/l) and severity of leukoaraiosis (P < 0.05). In the multivariable analysis, after controlling for age, sex, and significant risk factors in the univariate and age-adjusted analyses, hyper-TG demonstrated a protective effect on the severity of PVH and SWMLs (P < 0.05). Higher total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were not associated with leukoaraiosis. Conclusions. Hyper-TG is associated with the severity of leukoaraiosis independent of other risk factors, and it might be a protective role in cerebral small vessel disease.

Relationship of cardiac biomarkers with white matter hyperintensities in cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease.

White matter hyperintensities (WMHs), which are common in elderly people and contribute to age-related disability, can coexist with cardiac injury. It remains unclear whether cardiac biomarkers are associated with WMHs.To investigate this question, we prospectively recruited patients with cardioembolic stroke due to atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Four cardiac biomarkers were measured: myoglobin, high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB, and terminal pro-brain natriuretic peptide. WMHs in periventricular and deep white matter were assessed separately.In the entire sample of 171 patients, 120 (70.2%) presented with WMHs, of whom 18 (10.5%) presented with moderate to severe deep white matter hyperintensities (DWMH) and 55 (32.2%) presented with moderate to severe periventricular hyperintensities (PVH). Risk of moderate to severe PVH, after adjusting for confounders, was 2.460-fold higher in patients with high myoglobin levels than in those with low levels, and the risk was 2.608-fold higher in patients with high hs-cTnT levels than in those with low levels. There were no significant associations between any of the 4 cardiac biomarkers and moderate to severe DWMH.This prospective observational study provides new evidence of the potential relationship of cardiac biomarkers with WMHs in patients with cardioembolic stroke due to AF and/or RHD. We found that elevated myoglobin levels and high hs-TnT levels were independently associated with the presence of moderate to severe PVH. Further studies are required to test our findings and explore whether cardiac biomarkers contribute directly to WMHs pathogenesis.

Rapid Automated Quantification of Cerebral Leukoaraiosis on CT Images: A Multicenter Validation Study.

Purpose To validate a random forest method for segmenting cerebral white matter lesions (WMLs) on computed tomographic (CT) images in a multicenter cohort of patients with acute ischemic stroke, by comparison with fluid-attenuated recovery (FLAIR) magnetic resonance (MR) images and expert consensus. Materials and Methods A retrospective sample of 1082 acute ischemic stroke cases was obtained that was composed of unselected patients who were treated with thrombolysis or who were undergoing contemporaneous MR imaging and CT, and a subset of International Stroke Thrombolysis-3 trial participants. Automated delineations of WML on images were validated relative to experts' manual tracings on CT images, and co-registered FLAIR MR imaging, and ratings were performed by using two conventional ordinal scales. Analyses included correlations between CT and MR imaging volumes, and agreements between automated and expert ratings. Results Automated WML volumes correlated strongly with expert-delineated WML volumes at MR imaging and CT (r2 = 0.85 and 0.71 respectively; P < .001). Spatial-similarity of automated maps, relative to WML MR imaging, was not significantly different to that of expert WML tracings on CT images. Individual expert WML volumes at CT correlated well with each other (r2 = 0.85), but varied widely (range, 91% of mean estimate; median estimate, 11 mL; range of estimated ranges, 0.2-68 mL). Agreements (κ) between automated ratings and consensus ratings were 0.60 (Wahlund system) and 0.64 (van Swieten system) compared with agreements between individual pairs of experts of 0.51 and 0.67, respectively, for the two rating systems (P < .01 for Wahlund system comparison of agreements). Accuracy was unaffected by established infarction, acute ischemic changes, or atrophy (P > .05). Automated preprocessing failure rate was 4%; rating errors occurred in a further 4%. Total automated processing time averaged 109 seconds (range, 79-140 seconds). Conclusion An automated method for quantifying CT cerebral white matter lesions achieves a similar accuracy to experts in unselected and multicenter cohorts.