Regional Cerebral Blood Flow Research Articles

The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance

Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both critical process in the supply of energy for the brain. Thirty-four younger (20–42 years) and 41 older (66–86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive correlation. In insulin resistant younger adults, the association showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5T or 3T. Healthy controls were investigated with both 1.5T and 3T ASL-MRI. We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56years, range 18-82years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50years, range 21-77years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2mL/100g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

A rare case of invasive mucormycosis with thrombosis of cerebral vasculature in diabetic ketoacidosis

Mucormycosis is a rare fungal infection. It is an aggressive angio invasive infection hence if left untreated is always fatal. This necrotising infection commonly involves the nose, paranasal sinuses, orbits and brain. Uncontrolled diabetes, immunosuppression, transplant recipients, COVID-19 infection are the commonest risk factors. Most common form is rhino orbital cerebral involvement. Antifungal agents along with surgical debridement is the mainstay of treatment. We are reporting such a case of invasive mucormycosis in a young diabetic male to stress the importance of clinical examination and early recognition of clinical signs of this rare invasive infection and aggressive management.

Effects of Progressive Muscle Relaxation Training on Anxiety, Depression, and Quality of Life in Patients with Cerebral Small Vessel Disease

Objective: To explore the effects of progressive muscle relaxation training on anxiety, depression, and quality of life in patients with cerebral small vessel disease (CSVD). Methods: Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group (28 patients) and a control group (33 patients) by lottery method. The control group received conventional nursing care, while the observation group received progressive muscle relaxation training interventions in addition to the conventional care. The Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), and the Stroke-Specific Quality of Life Scale (SS-QOL) were used to compare the effects before the intervention, 7 days after the intervention, and 30 days after the intervention. Results: Over time, at different time points after the intervention, the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group (P < 0.05). The quality of life scores were significantly higher in the observation group compared to the control group (P < 0.05), and these differences were statistically significant. Conclusion: Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.

Evidence of microbiota–host dysbiosis between periodontitis and cerebral small vessel disease

AbstractObjectivesTo investigate the correlation between periodontitis and cerebral small vessel disease (CSVD) from the clinical and microbiological aspects.Subjects and methodsPeriodontitis patients (CP group, n = 31) and CSVD patients (CSVD group, n = 30) were examined for neurological and periodontal condition. Subgingival plaque was collected and performed using 16S rRNA sequencing. Logistic regression and LASSO regression were used to analyze the periodontal parameters and subgingival microbiota related to CSVD, respectively. Inflammatory factors in gingival crevicular fluid (GCF) were also detected and compared between the two groups.ResultsClinical attachment level (CAL), teeth number and plaque index demonstrated a significant difference between CP and CSVD group, meanwhile, CAL was independently associated with CSVD. Besides, the microbial richness and composition were distinct between two groups. Five genera related to periodontal pathogens (Treponema, Prevotella, Streptococcus, Fusobacterium, Porphyromonas) were screened out by LASSO regression, suggesting a potential association with CSVD. Finally, the levels of inflammatory factors in GCF were statistically higher in CSVD group than those in CP group.ConclusionsCerebral small vessel disease patients demonstrated worse periodontal condition, meanwhile the interaction between microbiota dysbiosis and host factors (inflammation) leading to a better understanding of the association between periodontitis and CSVD.

Altered brain expression and cerebrospinal fluid levels of TIMP4 in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a highly prevalent and progressive pathology, involving amyloid-β (Aβ) deposition in the cerebral blood vessel walls. CAA is associated with an increased risk for intracerebral hemorrhages (ICH). Insight into the molecular mechanisms associated with CAA pathology is urgently needed, to develop additional diagnostic tools to allow for reliable and early diagnosis of CAA and to obtain novel leads for the development of targeted therapies. Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) is associated with cardiovascular functioning and disease and has been linked to vascular dementia. Using immunohistochemistry, we studied occipital brain tissue samples of 57 patients with CAA (39 without ICH and 18 with ICH) and 42 controls, and semi-quantitatively assessed expression levels of TIMP4. Patients with CAA had increased vascular expression of TIMP4 compared to controls (p < 0.001), and in these patients, TIMP4 expression correlated with CAA severity (τb = 0.38; p = 0.001). Moreover, TIMP4 expression was higher in CAA-ICH compared to CAA-non-ICH cases (p = 0.024). In a prospective cross-sectional study of 38 patients with CAA and 37 age- and sex-matched controls, we measured TIMP4 levels in cerebrospinal fluid (CSF) and serum using ELISA. Mean CSF levels of TIMP4 were decreased in patients with CAA compared to controls (3.36 ± 0.20 vs. 3.96 ± 0.22 ng/ml, p = 0.033), whereas median serum levels were increased in patients with CAA (4.51 ng/ml [IQR 3.75–5.29] vs 3.60 ng/ml [IQR 3.11–4.85], p-9.013). Moreover, mean CSF TIMP4 levels were lower in CAA patients who had experienced a symptomatic hemorrhage compared to CAA patients who did not (2.13 ± 0.24 vs. 3.57 ± 0.24 ng/ml, p = 0.007). CSF TIMP4 levels were associated with CSF levels of Aβ40 (spearman r (rs) = 0.321, p = 0.009). In summary, we show that TIMP4 is highly associated with CAA and CAA-related ICH, which is reflected by higher levels in the cerebral vasculature and lower levels in CSF. With these findings we provide novel insights into the pathophysiology of CAA, and more specifically in CAA-associated ICH.

Unusual Predominant Memory Decline in an Early-Stage CADASIL Patient: A Four-Year Longitudinal Follow-Up of Hereditary Vascular Dementia

Introduction: Deficits in executive function and processing speed have traditionally been viewed as the chief cognitive manifestation of vascular contributions to cognitive impairment and dementia. This case study describes the longitudinal progression of cognitive symptoms in a 42-year-old Colombian woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary condition leading to the early onset of cerebral small vessel disease. Because of the young age of onset of vascular cognitive impairment, CADASIL allows examining the early cognitive consequences of cerebrovascular changes in the absence of age-related comorbidities. Methods: We followed the neuropsychological progression of a non-demented and stroke-free patient carrying a CADASIL mutation, in parallel to that of 13 non-carrier control subjects. At baseline, all subjects completed detailed clinical, neurological, and neuropsychological evaluations as well as an MRI scan. After a period of four years, subjects completed a follow-up neuropsychological evaluation. Results: Examination of the patient’s baseline MRI revealed the presence of significant areas of white matter hyperintensity. The patient did not present cerebral microbleeds, lacunes, notable brain atrophy, or evidence of previous strokes. In contrast to non-carrier subjects, the patient experienced predominant memory decline, with relatively preserved executive function and processing speed. Conclusions: This case highlights the heterogeneity of cognitive deficits associated with cerebrovascular disease.

Progression of white matter hyperintensities is related to blood pressure increases and global cognitive decline – A registered report

Abstract White matter hyperintensities (WMH) reflect cerebral small vessel disease (cSVD), a major brain pathology contributing to cognitive decline and dementia. Vascular risk factors, including higher diastolic blood pressure (DBP), have been associated with the progression of WMH yet longitudinal studies have not comprehensively assessed these effects for abdominal obesity or reported sex/gender-specific effects. In this pre-registered analysis of a longitudinal population-based neuroimaging cohort, we investigated the association of baseline DBP and waist-to-hip ratio with WMH progression in linear mixed models. We also examined the relationship of WMH progression and executive and global cognitive function. We conducted gender interaction and stratified analyses. We included data from 596 individuals (44.1 % females, mean age = 63.2 years) with two MRI scans over approximately 6 years. We did not find a significant association of baseline DBP with WMH progression. WMH progression significantly predicted global cognitive decline but not decline in executive function. In exploratory analyses, increases in DBP as well as baseline and increase in systolic blood pressure were associated with WMH progression, confined to frontal periventricular regions. There was no association of WHR nor any gender-specific associations with WMH progression. Adequate BP control might contribute to limit WMH progression and negative effects on global cognitive function in the middle-aged to older population for men and women.

Role of the vessel morphology on the lenticulostriate arteries hemodynamics during atrial fibrillation: A CFD-based multivariate regression analysis

Background and objectiveAtrial fibrillation (AF) is the most common cardiac arrhythmia, inducing accelerated and irregular beating. Beside well-known disabling symptoms - such as palpitations, reduced exercise tolerance, and chest discomfort - there is growing evidence that an alteration of deep cerebral hemodynamics due to AF increases the risk of vascular dementia and cognitive impairment, even in the absence of clinical strokes. The alteration of deep cerebral circulation in AF represents one of the least investigated among the possible mechanisms. Lenticulostriate arteries (LSAs) are small perforating arteries mainly departing from the middle cerebral artery (MCA) and susceptible to small vessel disease, which is one of the mechanisms of subcortical vascular dementia development. The purpose of this study is to investigate the impact of different LSAs morphologies on the cerebral hemodynamics during AF. MethodsBy combining a computational fluid dynamics (CFD) analysis of LSAs with 7T high-resolution magnetic resonance imaging (MRI), we performed different CFD-based multivariate regression analyses to detect which geometrical and morphological vessel features mostly affect AF hemodynamics in terms of wall shear stress. We exploited 17 cerebral 7T-MRI derived LSA vascular geometries extracted from 10 subjects and internal carotid artery data from validated 0D cardiovascular-cerebral modeling as inflow conditions. ResultsOur results revealed that few geometrical variables - namely the size of the MCA and the bifurcation angles between MCA and LSA - are able to satisfactorily predict the AF impact. In particular, the present study indicates that LSA morphologies exhibiting markedly obtuse LSA-MCA inlet angles and small MCA size downstream of the LSA-MCA bifurcation may be more prone to vascular damage induced by AF. ConclusionsThe present MRI-based computational study has been able for the first time to: (i) investigate the net impact of LSAs vascular morphologies on cerebral hemodynamics during AF events; (ii) detect which combination of morphological features worsens the hemodynamic response in the presence of AF. Awaiting necessary clinical confirmation, our analysis suggests that the local hemodynamics of LSAs is affected by their geometrical features and some LSA morphologies undergo greater hemodynamic alterations in the presence of AF.

Contributing factors of spontaneous intracerebral hemorrhage development in young adults.

The incidence of spontaneous intracerebral hemorrhage (ICH) in young people is relatively low; however, it leads to devastating lifelong neurologic deficits. We focused on spontaneous ICH occurring in young adults between 30 and 50 years of age. We retrospectively reviewed the records of 139 patients, aged 30-50 years, diagnosed with spontaneous ICH between 2011 and 2021. Cases of ICH attributable to discernible causative lesions were excluded. Demographic data, laboratory results, image findings, and clinical outcome were analyzed. After exclusions, 73 patients were included in this study. Common characteristics among the study patients included male sex (83.6%), high body mass index (>25 kg/m2, 45.8%), smoking history (47.2%), heavy alcohol consumption (30.6%), previously diagnosed hypertension (41.1%), high serum triglyceride level (>150 mg/dL, 33.3%), and microbleeds or white matter changes observed on magnetic resonance images (51.3%). In the multivariate analysis, previously diagnosed hypertension was the sole significant risk factor for cerebral small vessel (OR 7.769, P=0.031). Age, brain stem location, Glasgow Coma Scale score at admission, and hematoma volume were associated with poor outcomes. Hypertension, obesity, smoking, and cerebral small vessel disease were important factors associated with non-lesional spontaneous intracerebral hemorrhage in young patients. Radiologic changes corresponding to cerebral small vessel disease appeared in young patients (in their 30s) and they were associated with hypertension.

Imbalance of the von Willebrand Factor — ADAMTS-13 axis in patients with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)

BackgroundRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S.MethodsvWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls.ResultsWhile vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p < 0.05) in the deceased RVCL-S patient compared to the eight controls without brain pathology. One of the hypomethylated genes coded for ADAMTS-13 (p = 0.00056).ConclusionsThese findings point to an imbalance of the vWF – ADAMTS-13 axis in patients with RVCL-S, that may finally lead to an accumulation of vWF-Ag in renal and cerebral small vessels. Elevated vWF-Ag levels may serve as an early serum marker reflecting disease activity. If confirmed, therapeutic approaches might aim at an inhibition of vWF-Ag or increase of ADAMTS-13 activity in the future.

Shortened Cerebral Circulation Time Predicts Resistance to Obliteration in High-Flow Brain Arteriovenous Malformations After Stereotactic Radiosurgery.

Treatment selection for brain arteriovenous malformations (BAVMs) is complicated by BAVM size, location, and hemodynamics. Quantitative digital subtraction angiography is used to quantify the hemodynamic impact of BAVMs on cerebral circulation. This study investigated the association between cerebral circulation time and the complete obliteration (CO) rate of BAVMs after stereotactic radiosurgery (SRS). We analyzed the data of 143 patients who underwent SRS for BAVMs between January 2011 and December 2019 in our institute. Their pre-SRS magnetic resonance imaging and angiography images were analyzed to acquire BAVM characteristics and quantitative digital subtraction angiography parameters. Modified cerebral circulation time (mCCT) was defined as the time difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and that of the parietal vein, as determined from the lateral view of images obtained using digital subtraction angiography. Cox regression with hazard ratios and Kaplan-Meier analyses were conducted to determine the associations between the parameters and BAVM CO after SRS. Of the 143 patients, 101 (70.6%) achieved BAVM CO. According to the multivariate analyses, an increased mCCT (hazard ratio: 1.24, P = .041) was the independent factor associated with BAVM CO after adjustment for age, sex, hemorrhagic presentation, a BAVM volume of >5 cm3, and a margin dose of >18 Gy. Individuals with an mCCT of ≤2.32 s had a lower 36-month probability of BAVM CO than did those with an mCCT of >2.32 s (44.1% ± 6.8% vs 63.3% ± 5.6%, P = .034). The hemodynamic impact of high-flow BAVM demonstrated by a shortened mCCT is associated with a lower BAVM CO rate after SRS.

Associations of serum uric acid variability with neuroimaging metrics and cognitive decline: a population-based cohort study

BackgroundThe relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function.MethodsThis study recruited 1111 participants aged 25–83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function.ResultsCompared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta = − 0.25, 95% confidence interval [CI] − 0.39 to − 0.11 and beta = − 0.15, 95% CI − 0.29 to − 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta = − 0.24, 95% CI − 0.38 to − 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta = − 0.18, 95% CI − 0.32 to − 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline.ConclusionsIt is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.

Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.

Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

Performance of antisaccades in patients with cerebral small vessel disease accompanied by white matter hyperintensities

ABSTRACT Objectives The antisaccades (AS) task is considered a reliable indicator of inhibitory control of eye movements in humans. Achieving good AS performance requires efficient cognitive processes that are sensitive to changes in brain structure. White matter hyperintensities (WMH) can cause subcortical-cortical dysconnectivity, affecting diverse cognitive domains. Thus, the AS task was investigated in patients with WMH in cerebral small vessel disease (CSVD). Methods In this retrospective study, 75 participants with WMH, determined by neuroimaging standards for CSVD research, were admitted to the Department of Neurology of Beijing Luhe Hospital, Capital Medical University from January 2021 to December 2022. All subjects underwent the AS task, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and 3.0T brain MRI. Additionally, 61 healthy subjects were recruited to characterize WMH profiles. Results Compared to the control group, patients with WMH had a significantly increased AS error rate (49.81%, p = 0.001) and lower gain (76.00%, p = 0.042). The AS error rate was significantly higher in patients with WMH in the frontal lobe than in those without WMH (p = 0.004). After adjusting for confounders (age), a positive correlation was found between the AS error rate and MoCA scores for patients with WMH (coefficient = 0.262, p = 0.024). Conclusions Patients with WMH due to CSVD exhibited abnormal AS performances, particularly in the frontal lobe. The eye movement paradigms, the new diagnostic forms in neurology, can be utilized to investigate the distributed cortical and subcortical systems involved in cognitive control processes, offering simple, well-tolerated and highly sensitive advantages over traditional measures.

Genetic Characterization and Pathology of Porcine Teschovirus (PTV) in India

Background: The porcine teschovirus (PTV) is common swine pathogen which causes a wide range of illnesses ranging from asymptomatic infection to acute fatal encephalomyelitis, diarrhoea and pneumonia. Despite of its economical importance very limited studies are available on the pathology of PTV. The present study was conducted with the objective to investigate the PTV infection and associated pathology in piglets. Methods: A total of 78 piglets below 3 months of age were necropsied and representative tissue samples along with intestinal content were collected for histopathological examination and molecular investigation during April 2019 to November 2020. The 5' UTR region of PTV was amplified via RT-PCR and further confirmed by sequencing. Thereafter, genetic characterization of the Indian PTV isolate was done on the basis of 5' UTR gene. Result: A total of seven out of 78 cases were found positive for the PTV. On necropsy the intestinal wall was thinned and distended with yellowish coloured diarrhoeic content. Congestion of serosal and mucosal vessels along with severe meningeal congestion was observed. Microscopic lesions included congestion of mucosal vessels and destruction of villous structure of jejunum along with perivascular cuffing, focal gliosis, neuronophagia, congestion of meningeal and cerebral vessels and interstitial pneumonia. The phylogenetic analysis revealed that the isolate PTV/India/IVRI-381/2020 (MW022462) and PTV/India/IVRI-1093/2020 (MW022463) were clustered with PTV-13 strain wild boar/WB2C-TV/2011/HUN (JQ429405) and PTV-2 strain Vir 6711-12/83 (AF296107) of Hungary and Germany respectively. This study reported the genotypic and pathological investigation of PTV from Indian piglets. Further explorative surveillance along with studies in suitable cell lines and animal model will pave the way for better understanding of PTV among Indian pigs.

The time-course augmentation of perivascular space enlargement in the basal ganglia among a community-dwelling elder population

PurposeWe examined whether time-course augmentation of perivascular space enlargement in the basal ganglia (BG-PVS) reflected cerebral small vessel disease (CSVD) severity by considering white matter hyperintensity lesion (WMHL) as an indicator for CSVD.Materials and methodsThis study population included 416 older participants from a community-based cohort. They participated in magnetic resonance imaging (MRI) studies more than once during the study period. The grades for BG-PVS and WMHL were evaluated by visual rating scales; BG-PVS time-course augmentation in 4–9 years was also evaluated. At baseline, the participants were asked about their smoking and drinking history, and medical history. They also underwent a blood examination and their office blood pressure (BP) examination. In addition, 24-h ambulatory BP monitoring was also performed within the study period.ResultsOf the 416 participants, 48 participants (11.5%) had BG-PVS time-course augmentation. The participants with BG-PVS augmentation had significantly lower LDL levels, hyper-nighttime BP, and lower nighttime BP fall in univariate analysis (p = 0.03, p = 0.03, p = 0.003, respectively). In multivariate analysis, lower nighttime BP fall and male sex showed significance (p = 0.02, 0.03, respectively). Additionally, BG-PVS time-course augmentation was significantly associated with subsequent WMHL severity in univariate analysis (p < 0.001), which remained significant in multivariate analysis adjusted by imaging and demographic factors (p = 0.03). In multivariate analysis, additionally adjusted by the clinical factors, the significance disappeared (p = 0.07).ConclusionThis study revealed that the lower nighttime BP fall in ambulatory blood pressure monitoring was a factor significantly associated with BG-PVS augmentation. Moreover, the BG-PVS time-course augmentation would be a notable finding that was associated with the subsequent WMHL.

The neurovascular unit and its correlation with cognitive performance in patients with cerebral small vessel disease: a canonical correlation analysis approach

Growing evidence indicates an important role of neurovascular unit (NVU) dysfunction in the pathophysiology of cerebral small vessel disease (cSVD). Individually measurable functions of the NVU have been correlated with cognitive function, but a combined analysis is lacking. We aimed to perform a unified analysis of NVU function and its relation with cognitive performance. The relationship between NVU function in the white matter and cognitive performance (both latent variables composed of multiple measurable variables) was investigated in 73 patients with cSVD (mean age 70 ± 10 years, 41% women) using canonical correlation analysis. MRI-based NVU function measures included (1) the intravoxel incoherent motion derived perfusion volume fraction (f) and microvascular diffusivity (D*), reflecting cerebral microvascular flow; (2) the IVIM derived intermediate volume fraction (fint), indicative of the perivascular clearance system; and (3) the dynamic contrast-enhanced MRI derived blood–brain barrier (BBB) leakage rate (Ki) and leakage volume fraction (VL), reflecting BBB integrity. Cognitive performance was composed of 13 cognitive test scores. Canonical correlation analysis revealed a strong correlation between the latent variables NVU function and cognitive performance (r 0.73; p = 0.02). For the NVU, the dominating variables were D*, fint, and Ki. Cognitive performance was driven by multiple cognitive tests comprising different cognitive domains. The functionality of the NVU is correlated with cognitive performance in cSVD. Instead of focusing on individual pathophysiological mechanisms, future studies should target NVU dysfunction as a whole to acquire a coherent understanding of the complex disease mechanisms that occur in the NVU in cSVD.Trial registration: NTR3786 (Dutch Trial Register).

Using individualized structural covariance networks to analyze the heterogeneity of cerebral small vessel disease with cognitive impairment

BackgroundCerebral small vessel disease (CSVD) includes vascular disorders characterized by heterogeneous pathomechanisms and different neuropathological clinical manifestations. Cognitive dysfunction in CSVD is associated with reductions in structural covariance networks (SCNs). A majority of research conducted on SCNs focused on group-level analysis. However, it is crucial to investigate the individualized variations in order to gain a better understanding of heterogeneous disorders such as CSVD. Therefore, this study aimed to utilize individualized differential structural covariance network (IDSCN) analysis to detect individualized structural covariance aberration. MethodsA total of 35 healthy controls and 33 CSVD patients with cognitive impairment participated in this investigation. Using the regional gray matter volume in their T1 images, the IDSCN was constructed for each participant. Finally, the differential structural covariance edges between the two groups were determined by comparing their IDSCN using paired-sample t-tests. On the basis of these differential edges, the two subtypes of cognitively impaired CSVD patients were identified. ResultsThe findings revealed that the differential structural covariance edges in CSVD patients with cognitive impairment showed a highly heterogeneous distribution, with the edges primarily cross-distributed between the occipital lobe (specifically inferior occipital gyrus and cuneus), temporal lobe (specifically superior temporal gyrus), and the cerebellum. To varying degrees, the inferior frontal gyrus and the superior parietal gyrus were also distributed. Subsequently, a correlation analysis was performed between the resulting differential edges and the cognitive scale scores. A significant negative association was observed between the cognitive scores and the differential edges distributed in the inferior frontal gyrus and inferior occipital gyrus, the superior temporal gyrus and inferior occipital gyrus, and within the temporal lobe. Particularly in the cognitive domain of attention, the two subtypes separated by differential edges exhibited differences in cognitive scale scores [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)]. The differential edges of the subtype 1, characterized by lower cognitive level, were mainly cross-distributed in the limbic lobe (specifically the cingulate gyrus and hippocampus), the parietal lobe (including the superior parietal gyrus and precuneus), and the cerebellum. In contrast, the differential edges of the subtype 2 with a relatively high level of cognition were distributed between the cuneus and the cerebellum. ConclusionsThe differential structural covariance was investigated between the healthy controls and the CSVD patients with cognitive impairment, showing that differential structural covariance existed between the two groups. The edge distributions in certain parts of the brain, such as cerebellum and occipital and temporal lobes, verified this. Significant associations were seen between cognitive scale scores and some of those differential edges .The two subtypes that differed in both differential edges and cognitive levels were also identified. The differential edges of subtype 1 with relatively lower cognitive levels were more distributed in the cingulate gyrus, hippocampus, superior parietal gyrus, and precuneus. This could potentially offer significant benefits in terms of accurate diagnosis and targeted treatment of heterogeneous disorders such as CSVD.

Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.