Feasibility of CT attenuation values in distinguishing acute ischemic stroke, old cerebral infarction and leukoaraiosis.

PURPOSE: This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). MATERIALS AND METHODS: This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. RESULTS: A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P < 0.001). The AUC of CT values, ΔHU, and RatioHU for distinguishing AIS from OCI were 0.802, 0.896 and 0.878, respectively (all P < 0.001). Meanwhile, the AUC for distinguishing OCI from LA was 0.789, 0.883, and 0.857, respectively (all P < 0.001). Nevertheless, none of the parameters could distinguish AIS from LA. CONCLUSION: CT attenuation parameters can be utilized to differentiate between AIS and OCI or OCI and LA in indeterminate hypodense lesions on CT images. However, distinguishing AIS from LA remains challenging.

Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.

Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

Assessing brain involvement in Fabry disease with deep learning and the brain-age paradigm.

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

BACKGROUND: The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. METHODS: We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. RESULTS: Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. CONCLUSION: Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

Correlation analysis between cerebral microangiopathy and autonomic nervous dysfunction.

OBJECTIVE: Our study was conducted aimed at investigating the potential correlation between cerebral microangiopathy and autonomic nervous dysfunction. METHODS: We initially included 164 hospitalized patients with cerebral microangiopathy at our hospital from November 2019 to January 2021. Based on the inclusion and exclusion criteria, a final total of 162 patients with cerebral microangiopathy were selected. According to the patient's Autonomic Symptom Profile (ASP) score, patients with a score greater than 22 were categorized into a group with concomitant autonomic dysfunction (71 cases, combined group), while those with a score below 22 were categorized into a group of isolated cerebral microangiopathy (83 cases, cerebral microangiopathy group). The general data and laboratory examination results of the two groups were analyzed, and Pearson correlation analysis was performed to evaluate the correlation between cerebral microangiopathy and autonomic dysfunction, as well as the influencing factors of cerebral microangiopathy patients combined with autonomic dysfunction. RESULTS: There were no significant differences between the two groups in terms of sex, BMI, smoking, drinking, family dementia history, diabetes, hypothyroidism, carotid atherosclerosis, obstructive sleep apnea hypopnea syndrome, hyperuricemia, hyperlipidemia, chronic obstructive pulmonary disease, Hamilton Anxiety Scale score, Hamilton Depression Scale score, 24-h mean systolic blood pressure (SBP), 24-h mean diastolic blood pressure DBP, daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure, nighttime mean systolic blood pressure (nSBP), nighttime mean diastolic blood pressure, 24-h systolic blood pressure standard deviation (SBPSD), 24-h diastolic blood pressure standard deviation, daytime diastolic blood pressure standard deviation, nighttime diastolic blood pressure standard deviation (nDBPSD), nDBPSD (p > .05). However, significant differences were observed between the two groups regarding age, history of coronary heart disease, hypertension, leukoaraiosis, cognitive function, ASP score, SSR, 24-h SBPSD, daytime systolic blood pressure standard deviation (dSBPSD), nighttime systolic blood pressure standard deviation (nSBPSD), standard deviation of RR interval (SDNN), root mean square value of successive RR interval difference (RMSSD), high-frequency component (HF), and low-frequency component (LF) (p < .05). Moreover, the levels of TG, TC, HDL-C, and LDL-C did not show significant differences between the two groups (p > .05), but there were significant differences in blood uric acid and homocysteine (Hcy) levels (p < .05). Age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy levels, 24-h SBPSD, dSBPSD, and nSBPSD showed positive correlations with ASP scores and SSR in patients with cerebral microangiopathy (p < .001). In contrast, hypertension, SDNN, RMSSD, HF, and LF showed negative correlations with ASP scores and SSR (p < .001). Moreover, coronary heart disease was negatively correlated with ASP scores but positively correlated with SSR (p < .001). The independent variables included age, history of leukoaraiosis, cognitive function assessment, ASP score, SSR, blood uric acid, Hcy, bradykinin, coronary heart disease, hypertension, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF, which were indicators with differences in general data and laboratory indicators. The dependent variable was patients with cerebral microangiopathy combined with autonomic nervous dysfunction. The analysis results showed that age, history of leukoaraiosis, ASP score, SSR, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF were the influencing factors of patients with cerebral microangiopathy complicated with autonomic nervous dysfunction. CONCLUSION: We demonstrates that age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy level, 24-h SBPSD, dSBPSD, nSBPSD, blood pressure, SDNN, RMSSD, HF, LF, and coronary heart disease were highly associated with cerebral microangiopathy with autonomic dysfunction. Furthermore, the influencing factors of cerebral microangiopathy with autonomic dysfunction are age, history of leukoaraiosis, ASP score, SSR, blood pressure variability, and HRV.

Association of Glycemic Variability With Imaging Markers of Vascular Burden, ß-Amyloid, Brain Atrophy, and Cognitive Impairment.

BACKGROUND AND OBJECTIVE: We aimed to investigate the association between glycemic variability (GV) and neuroimaging markers of white matter hyperintensities (WMH), beta-amyloid (Aß), brain atrophy, and cognitive impairment. METHODS: This was a retrospective cohort study that included participants without dementia from a memory clinic. They all had Aß PET, brain MRI, and standardized neuropsychological tests and had fasting glucose (FG) levels tested more than twice during the study period. We defined GV as the intraindividual visit-to-visit variability in FG levels. Multivariable linear regression and logistic regression were used to identify whether GV was associated with the presence of severe WMH and Aß uptake with DM, mean FG levels, age, sex, hypertension, and presence of APOE4 allele as covariates. Mediation analyses were used to investigate the mediating effect of WMH and Aß uptake on the relationship between GV and brain atrophy and cognition. RESULTS: Among the 688 participants, the mean age was 72.2 years, and the proportion of female participants was 51.9%. Increase in GV was predictive of the presence of severe WMH (coefficient [95% CI] 1.032 [1.012-1.054]; p = 0.002) and increased Aß uptake (1.005 [1.001-1.008]; p = 0.007). Both WMH and increased Aß uptake partially mediated the relationship between GV and frontal-executive dysfunction (GV → WMH → frontal-executive; direct effect, -0.319 [-0.557 to -0.080]; indirect effect, -0.050 [-0.091 to -0.008]) and memory dysfunction (GV → Aß â†’ memory; direct effect, -0.182 [-0.338 to -0.026]; indirect effect, -0.067 [-0.119 to -0.015]), respectively. In addition, increased Aß uptake completely mediated the relationship between GV and hippocampal volume (indirect effect, -1.091 [-2.078 to -0.103]) and partially mediated the relationship between GV and parietal thickness (direct effect, -0.00101 [-0.00185 to -0.00016]; indirect effect, -0.00016 [-0.00032 to -0.000002]). DISCUSSION: Our findings suggest that increased GV is related to vascular and Alzheimer risk factors and neurodegenerative markers, which in turn leads to subsequent cognitive impairment. Furthermore, GV can be considered a potentially modifiable risk factor for dementia prevention.

White matter hyperintensity burden and collateral circulation in acute ischemic stroke with large artery occlusion.

OBJECTIVE: This study aimed to investigate the association between white matter hyperintensity (WMH) burden and pial collaterals in acute strokes caused by intracranial large artery occlusion treated with mechanical thrombectomy in the anterior circulation, focusing on stroke subtypes. METHODS: Consecutive patients undergoing mechanical thrombectomy between December 2019 and June 2022 were retrospectively screened. The Fazekas scale assessed WMH burden. Pial collaterals were categorized as either poor (0-2) or good (3-4) based on the Higashida score. A multivariable analysis was used to determine the relationship between WMH burden and pial collaterals. Subgroup analyses delved into associations stratified by stroke subtypes, namely cardioembolism (CE), tandem lesions (TLs), and intracranial atherosclerosis (ICAS). RESULTS: Of the 573 patients included, 274 (47.8%) demonstrated poor pial collaterals. Multivariable regression indicated a strong association between extensive WMH burden (Fazekas score of 3-6) and poor collaterals [adjusted OR 3.04, 95% CI 1.70-5.46, P < 0.001]. Additional independent predictors of poor collaterals encompassed ICAS-related occlusion (aOR 0.26, 95% CI 0.09-0.76, P = 0.014), female sex (aOR 0.63, 95% CI 0.41-0.96, P = 0.031), and baseline Alberta Stroke Program Early Computed Tomography scores (aOR 0.80, 95% CI 0.74-0.88, P < 0.001). Notably, an interaction between extensive WMH burden and stroke subtypes was observed in predicting poor collaterals (P = 0.001), being pronounced for CE (adjusted OR 2.30, 95% CI 1.21-4.37) and TLs (adjusted OR 5.09, 95% CI 2.32-11.16), but was absent in ICAS (adjusted OR 1.24, 95% CI 0.65-2.36). CONCLUSIONS: Among patients treated with mechanical thrombectomy for anterior circulation large artery occlusion, extensive WMH burden correlates with poor pial collaterals in embolic occlusion cases (CE and TLs), but not in ICAS-related occlusion.

Impact of leukoaraiosis on the infarct growth rate and clinical outcome in acute large vessel occlusion stroke after endovascular thrombectomy.

INTRODUCTION: As a marker of chronic cerebral small vessel disease, leukoaraiosis (LA) was reported to impact the recruitment of collaterals in acute ischemic stroke (AIS). We intended to explore the impact of LA on the infarct growth rate (IGR) and clinical outcome by impaired collateral development in AIS patients with large vessel occlusion (LVO) who underwent endovascular thrombectomy (EVT). PATIENTS AND METHODS: Two hundred thirty-six AIS patients who underwent EVT were retrospectively reviewed. The severity of LA was graded using the Fazekas scale with non-contrast CT. IGR was calculated by the acute core volume on CT perfusion divided by the time from stroke onset to imaging. The collateral status after LVO was assessed using the ASITN/SIR collateral scale. The clinical outcomes after EVT were evaluated using a modified Rankin Scale (mRS). The Alberta stroke program early CT score (ASPECTS), the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the modified treatment in cerebral infarction (mTICI) score after EVT were also included. Correlations between those factors were analyzed. RESULTS: Patients with severe LA had significantly larger core volume on CTP (p = 0.022) and lower collateral grade (p < 0.001). Faster IGR was significantly associated with higher LA severity (adjusted odds ratio [aOR]: 1.53; 95% CI: 1.02-2.33; p = 0.046), higher NIHSS (aOR: 1.04; 95% CI: 1.00-1.09; p = 0.032) and impaired collaterals (aOR: 2.26; 95% CI: 1.27-4.03; p = 0.005). In mediation analysis, collaterals explained 33% of the effect of LA on fast IGR. There was correlation between the severity of LA and mRS (p = 0.007). DISCUSSION AND CONCLUSION: The increasing severity of LA is associated with impaired collateral status and fast infarct growth. These findings suggest that LA may become a predictive imaging biomarker for the likelihood of progression of tissue injury and clinical outcome after EVT in acute large vessel occlusion stroke.

Accuracy of TrUE-Net in comparison to established white matter hyperintensity segmentation methods: An independent validation study.

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the established relationship between WMH burden and age. We found that TrUE-Net was highly reliable at identifying WMH regions with low false positive rates, when compared to semi-manual segmentation as the reference standard. TrUE-Net performed similarly or favorably when compared to the other automated techniques. Moreover, TrUE-Net was able to detect relationships between WMH and age to a similar degree as the reference standard semi-manual segmentation at both the global and regional level. These results support the use of TrUE-Net for identifying WMH at the global or regional level, including in large, combined datasets.

White matter hyperintensity burden and functional outcomes in acute ischemic stroke patients after mechanical thrombectomy: A systematic review and meta-analysis.

BACKGROUND: The influence of white matter hyperintensity (WMH) on clinical outcomes in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) remains controversial. We performed a systematic review and meta-analysis to examine whether WMH burden is associated with clinical outcomes in AIS patients after MT. METHODS: PubMed, Embase, and Web of Science were searched from inception to Sep 03, 2023. The registration number for PROSPERO is CRD42022340568. Studies reporting an association between the burden of WMH in AIS patients and clinical outcomes after MT were included in the meta-analysis. A random-effects model was used for meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Additionally, the presence of imprecise-study effects was evaluated using Egger's test and funnel plot. RESULTS: Fifteen studies with 3,456 patients were enrolled in this meta-analysis. Among AIS patients who underwent MT, moderate/severe WMH had higher odds of 90-day unfavorable functional outcomes (odds ratio [OR] 2.72, 95% confidence interval [CI] 2.14-3.44; I2 = 0.0%; 95% CI 0.0%-42.7%), 90-day mortality (OR 1.94, 95% CI 1.45-2.60; I2 = 19.5%; 95% CI 0.0%-65.2%) and futile recanalization (OR 2.99, 95% CI 1.42-6.28; I2 = 69.7%; 95% CI 0.0%-91.0%) compared with none/mild WMH. However, the two groups had no significant difference in successful recanalization, symptomatic hemorrhagic transformation, and hemorrhagic transformation. A subset analysis of patients from 3 articles showed that WMH volume was not significantly associated with these outcomes. A notable limitation is that this meta-analysis lacks direct adjustment for imbalances in important baseline covariates. CONCLUSIONS: Patients with moderate/severe WMH on baseline imaging are associated with substantially increased odds of 90-day unfavorable outcomes, futile recanalization, and 90-day mortality after MT. This association suggests that moderate/severe WMH may contribute to the prediction of clinical outcomes in AIS patients after MT.

Correlation between body composition and white matter hyperintensity in patients with acute ischemic stroke.

White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. The relationship between WMH and obesity is somewhat controversial which might be interfered by different body composition such as skeletal muscle, fat and bone density. However, few researchers have evaluated the relationship between WMH burden and disaggregated body constituents in acute ischemic stroke (AIS) patients systematically. A total of 352 AIS patients were enrolled in this study. The subcutaneous adipose tissue, erector spinae muscle area and bone density were evaluated on the computed tomography scanning. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none-mild WMH (total Fazekas score 0-2) or moderate-severe WMH (total Fazekas score 3-6). Based on the severity of periventricular WMH (P-WMH) and deep WMH, patients were categorized into either a none-mild (Fazekas score 0-1) group or a moderate-severe (Fazekas score 2-3) group. We found that patients with moderate-severe WMH showed lower bone density and smaller erector spinae muscle area and subcutaneous adipose tissue than none-mild. The logistic regression analysis showed that the bone density was independently associated with moderate-severe overall WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001) and similar results were found in the analyses according to P-WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001). These findings suggest that among the AIS body composition, the bone density is independently associated with the severity of overall WMH and P-WMH.

Urinary microalbumin/creatinine ratio is a predictor of the occurrence and severity of leukoaraiosis.

OBJECTIVE: To investigate the correlation between the urinary microalbumin/creatinine ratio (UACR) and the occurrence and severity of leukoaraiosis. METHODS: A total of 323 patients were retrospectively recruited. Demographic, clinical, and laboratory data were collected at the time of admission, and the UACR was calculated based on the levels of urinary microalbumin and creatinine. All patients showed improvement in cranial magnetic resonance imaging (MRI) examination. The subjects were divided into leukoaraiosis and non-leukoaraiosis groups according to the results of the cranial MRI examination. According to the Fazekas standard score, the patients in the leukoaraiosis group were divided into the mild leukoaraiosis group: Fazekas (1-2 points), moderate leukoaraiosis group: Fazekas (3-4points); and severe leukoaraiosis group: Fazekas (5-6 points). RESULTS: A regression analysis was performed to adjust for confounding factors. (1) Compared with the non-leukoaraiosis group, UACR level was higher in the leukoaraiosis group at admission, and the difference between the groups was statistically significant (p < 0.05). (2) In the multivariate logistic regression analysis, UACR was correlated with the occurrence of leukoaraiosis, which may be an independent risk factor. (3) The UACR levels increased gradually in the mild, moderate and severe leukoaraiosis groups, and the difference was statistically significant (p< 0.05). (4) In the ordered multi-category logistic regression analysis, UACR was correlated with the severity of leukoaraiosis, which may be an independent risk factor. CONCLUSION: UACR is associated with the occurrence and severity of leukoaraiosis, and may be an independent risk factor.

Association between National Institutes of Health Stroke Scale and Functional Independence Measure scores in patients with ischemic stroke from convalescent rehabilitation outcomes.

We investigated the associations among neurological severity, activities of daily living (ADLs), and clinical factors in patients with ischemic stroke in convalescent rehabilitation outcome. The study sample included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years) for inpatient convalescent rehabilitation. National Institutes of Health Stroke Scale (NIHSS) was used to measure the neurological severity, and Functional Independence Measure (FIM) was used to assess ADLs at discharge. Leukoaraiosis was graded based on periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on magnetic resonance imaging. The correlations between NIHSS scores and total FIM scores were significant but relatively mild (r = -0.684, P < 0.001). Multiple regression analysis revealed that age and PVH grade significantly decreased their total FIM scores and affected the discrepancies between NIHSS scores at discharge (P < 0.001), but DWMH scores did not affect these results. Factors such as positive history of heart disease (P = 0.008) and bilateral infarction (P = 0.038) additionally decreased their total FIM scores and affected the discrepancies between NIHSS scores. These findings suggest that age, PVH, history of heart disease positive, and bilateral infarction in patients with ischemic stroke affected their performance of ADLs and the discrepancies between their neurological severities in convalescent rehabilitation outcomes, probably because the pathophysiological background of leukoaraiosis and these factors strongly decrease their ADL performance in post-phase ischemic stroke.

Graph network measures reveal distinct white matter abnormalities in motor and extra-motor brain regions of two UMN-predominant ALS subtypes.

BACKGROUND: Routine clinical magnetic resonance imaging (MRI) shows bilateral corticospinal tract (CST) hyperintensity in some patients with upper motor neuron (UMN)-predominant ALS (ALS-CST+) but not in others (ALS-CST-). Although, similar in their UMN features, the ALS-CST+ patient group is significantly younger in age, has faster disease progression and shorter survival than the ALS-CST- patient group. Reasons for the differences are unclear. METHOD: In order to evaluate more objective MRI measures of these ALS subgroups, we used diffusion tensor images (DTI) obtained using single shot echo planar imaging sequence from 1.5 T Siemens MRI Scanner. We performed an exploratory whole brain white matter (WM) network analysis using graph theory approach on 45 ALS patients (ALS-CST+) (n = 21), and (ALS-CST-) (n = 24) and neurological controls (n = 14). RESULTS: Significant (p < 0.05) differences in nodal degree measure between ALS patients and controls were observed in motor and extra motor regions, supplementary motor area, subcortical WM regions, cerebellum and vermis. Importantly, WM network abnormalities were significantly (p < 0.05) different between ALS-CST+ and ALS-CST- subgroups. Compared to neurologic controls, both ALS subgroups showed hubs in the right superior occipital gyrus and cuneus as well as significantly (p < 0.05) reduced small worldness supportive of WM network damage. CONCLUSIONS: Significant differences between ALS-CST+ and ALS-CST- subgroups of WM network abnormalities, age of onset, symptom duration prior to MRI, and progression rate suggest these patients represent distinct clinical phenotypes and possibly pathophysiologic mechanisms of ALS.

Correlation study and clinical value analysis between cerebral microbleeds and white matter hyperintensity with high-field susceptibility-weighted imaging.

This study aimed to investigate the relationship between white matter hyperintensity (WMH) and cerebral microbleeds (CMBs) using susceptibility-weighted imaging (SWI) with high resolution. Additionally, it sought to analyze the clinical significance of SWI with high resolution and its potential to guide intravenous thrombolysis in stroke patients. In this retrospective analysis, we examined 96 patients with hypertension after acute stroke in our hospital using SWI. Demographic and medical data of these 96 patients were collected. Spearman correlation analysis was performed to investigate the relationship between CMBs and the grading of WMH. A significant positive correlation was observed between CMBs and the grade of WMH (R = 0.593, P < .05). The data also revealed a superior ROC area under the curve for the modified Fazekas grading of WMH, which was 0.814 (P < .05). There is a positive correlation between CMBs and the grading of leukoaraiosis in patients with acute stroke and hypertension. The higher the degree of WMH, the more severe the microvascular lesions, increasing the likelihood of intracranial hemorrhage. SWI can provide valuable guidance for administering intravenous thrombolysis in patients with acute stroke.

Identifying and reverting the adverse effects of white matter hyperintensities on cortical surface analyses.

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.

Persistence of post-traumatic stress disorder in Chinese Shidu parents is associated with combined gray and white matter abnormalities.

Post-traumatic stress disorder (PTSD) is one of the most common mental health disorders among Shidu parents. Identification of gray and white matter differences between persistence of PTSD (P-PTSD) and remission of PTSD (R-PTSD) is crucial to determine their prognosis. A total of 37 Shidu parents with PTSD were followed for five years. Surface-based morphometry and diffusion tensor imaging were carried out to analyze the differences in gray and white matter between P-PTSD and R-PTSD. Finally, 30 patients with PTSD were enrolled, including 12 with P-PTSD and 18 with R-PTSD. Compared with patients with R-PTSD, patients with P-PTSD exhibited lower fractional anisotropy (FA) in Cluster 1 (including body of the corpus callosum, superior longitudinal fasciculus, corticospinal tract) and Cluster 2 (including inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, splenium of the corpus callosum) in the left cerebral hemisphere and higher cortical thickness in the right lateral occipital cortex (LOC). In patients with P-PTSD, FA values of Cluster 2 were negatively correlated with cortical thickness of the right LOC. These results suggest that among Shidu parents, differences were observed in gray and white matter between P-PTSD and R-PTSD. Moreover, some certain gray and white matter abnormalities were often present simultaneously in P-PTSD.

Lower 25-hydroxyvitamin D is associated with severer white matter hyperintensity and cognitive function in patients with non-disabling ischemic cerebrovascular events.

OBJECTIVES: This study aimed to investigate the potential correlations among serum 25-hydroxyvitamin D [25(OH)D] levels, white matter hyperintensity (WMH) and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE). METHODS: This was a prospective investigation of 160 NICE patients with age of 40 years or older. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). White matter lesions were evaluated by WMH using Fazekas scores. Spearman correlation analysis and linear regression models were used to identify the associations between serum 25(OH)D levels and cognitive function. Binary logistic regression analysis models were used to evaluate the predictable value of serum 25(OH)D levels and WMH for cognitive impairment. RESULTS: Patients with inadequate 25(OH)D levels had lower MoCA score (P=0.008), and a higher proportion of severe WMH (P=0.043). Spearman correlation analysis demonstrated that serum 25(OH)D concentrations were positively associated with MoCA score (rs=0.185, P=0.019) while negatively related to the proportion of severe WMH (sWMH) (rs=-0.166, P=0.036).The association between 25(OH)D concentrations and MoCA score remained significant in linear regression (adjusted ß=0.012, 95%CI:0.001-0.203).Adjusted binary logistic regression analysis showed that the odds ratio of cognitive impairment with insufficient 25(OH)D concentration was 5.038 (95%CI:1.154-21.988) compared with the sufficient group and the sWMH (OR=2.728, 95%CI:1.230-6.051) was identified as an independent risk factor for cognitive decline in NICE patients. CONCLUSION: Serum 25(OH)D levels and white matter lesions were independently and significantly associated with cognitive impairment in NICE patients.