Cerebrovascular Research Articles

Association of Cerebrovascular Reactivity With 1-Year Imaging and Clinical Outcomes in Small Vessel Disease: An Observational Cohort Study.

In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes. Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543). We acquired 3T brain MRI at baseline and 1 year. At baseline, we measured cerebrovascular reactivity to 6% inhaled CO2 in subcortical gray matter, normal-appearing white matter, and white matter hyperintensities (WMH). At baseline and 1 year, we quantified SVD MRI features, incident infarcts, assessed stroke severity (NIH Stroke Scale), recurrent stroke, functional outcome (modified Rankin Scale), and cognition (Montreal Cognitive Assessment). We performed linear and logistic regressions adjusted for age, sex, and vascular risk factors, reporting the regression coefficients and odds ratios with 95% CIs. We recruited 208 patients of whom 163 (mean age and SD: 65.8 ± 11.2 years, 32% female) had adequate baseline CVR and completed the follow-up structural MRI. The median increase in WMH volume was 0.32 mL with (Q1, Q3) = (-0.48, 1.78) mL; 29% had a recurrent stroke or incident infarct on MRI. At 1 year, patients with lower baseline cerebrovascular reactivity in normal-appearing tissues had increased WMH (regression coefficient: B = -1.14 [-2.13, -0.14] log10 (%ICV) per %/mm Hg) and perivascular space volumes (B = -1.90 [-3.21, -0.60] log10 (%ROIV) per %/mm Hg), with a similar trend in WMH. CVR was not associated with clinical outcomes at 1 year. Lower baseline cerebrovascular reactivity predicted an increase in WMH and perivascular space volumes after 1 year. CVR should be considered in SVD future research and intervention studies.

Current Landscape of Clinical Diagnosis in Multiple System Atrophy: A 15-Year Analysis From 2008 to 2022.

Clinical diagnosis of multiple system atrophy (MSA) is challenging. In 2022, new diagnostic criteria for MSA were proposed. We hypothesized that the positive predictive value (PPV) of clinical diagnosis of MSA improved because of advanced diagnostic tools, including brain MRI. This study aimed to understand temporal changes in PPV of MSA. We conducted a retrospective analysis of patients clinically diagnosed with MSA whose brains were examined in the Mayo Clinic brain bank from 2008 to 2022. PPV was compared between 2 periods (2008-2017 and 2018-2022) and successively with a 4-year moving average. PPV for each clinical subtype (parkinsonism type [MSA-P] and cerebellar type [MSA-C]) was assessed. This study included 321 patients (136 women, age at death 68 ± 9 years) with a clinical diagnosis of MSA. Among them, 225 were pathologically confirmed as MSA, resulting in an overall PPV of 70%. The remaining 30% had alternative pathologic diagnoses including Lewy body disease (18%), progressive supranuclear palsy (4%), cerebrovascular disease (1%), corticobasal degeneration (1%), and others (6%). PPV improved from 63% in 2008-2017 to 78% in 2018-2022 (odds ratio [OR] 2.0 [1.2-3.5], p = 0.005). Linear analysis also demonstrated increased PPV over time (r = 0.66 [0.14-0.89], p = 0.02). Brain MRI scans were more frequently performed in 2018-2022 compared with 2008-2017 (91% vs 80%; OR 2.4 [1.2-5.0], p = 0.012). PPV was higher in patients with brain MRI compared with those without (73% vs 52%; OR 2.5 [1.3-4.9], p = 0.0057). PPV for MSA-C was similar in both groups (87% in 2008-2017 and 93% in 2018-2022), while that for MSA-P improved from 59% in 2008-2017 to 72% in 2018-2022 (OR 1.8 [1.0-3.2], p = 0.04). This study demonstrates an improvement in the PPV of MSA in recent years, potentially attributed to the increased use of brain MRI. Nevertheless, it also highlights that it remains difficult to make a correct diagnosis for some patients based on their clinical presentation. These findings provide a baseline for future clinicopathologic research on MSA.

Longitudinal changes in white matter free water in cerebral small vessel disease: Relationship to cerebral blood flow and white matter fiber alterations.

White matter (WM) free water (FW) is a potential imaging marker for cerebral small vessel disease (CSVD). This study aimed to characterize longitudinal changes in WM FW and investigate factors contributing to its elevation in CSVD. We included 80 CSVD patients and 40 normal controls (NCs) with multi-modality MRI data. Cerebral blood flow (CBF) was measured, and fiber alterations were assessed using total apparent fiber density (AFDt). FW were extracted from whole WM, white matter hyperintensities (WMH) and normal-appearing WM (NAWM). Baseline and longitudinal FW elevation were compared between patients and NCs, and between WMH and NAWM. We investigated whether baseline vascular risk factor score, CBF, and AFDt could predict longitudinal FW elevation. Association between cognition and WM FW in CSVD was also assessed. Results shown that FW was higher and increased faster in CSVD compared to NCs and in WMH compared to NAWM. Baseline AFDt predicted longitudinal FW elevation in CSVD patients, while CBF predicted FW changes only in controls. WM FW was associated with cognitive impairment. These findings suggest that CSVD is associated with a faster increase in WM FW. Hypoperfusion and WM fiber alterations might accelerate FW elevation, which is associated with cognitive decline.

Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI.

White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease. Structural T2-weighted imaging, multishell diffusion imaging, and dynamic contrast-enhanced magnetic resonance imaging were performed at 3T in 44 participants with sporadic cerebral small vessel disease and 32 participants with monogenic cerebral small vessel disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; 59±12 years, 41 males) between June 2017 and May 2020 as part of the prospective, multicenter (Edinburgh, the United Kingdom; Maastricht, the Netherlands; and Munich, Germany), observational INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases). The mean diffusivity, free water content, and perfusion (all derived from multishell diffusion imaging), as well as the blood-brain barrier leakage and plasma volume fraction (derived from dynamic contrast-enhanced magnetic resonance imaging), were compared between deep and periventricular WMH types using paired t tests. Additional spatial analyses were performed inside and outside the WMH types to determine the internal heterogeneity and the extent of the penumbras, that is, adjacent white matter at risk for conversion to WMH. Periventricular WMH had higher mean diffusivity, higher free water content, and more plasma volume compared with deep WMH (P<0.001, P=0.01, and P<0.001, respectively). No differences were observed in perfusion (P=0.94) and blood-brain barrier leakage (P=0.65) between periventricular and deep WMHs. The spatial analyses inside WMH and the adjacent white matter revealed a gradual gradient in white matter microstructure, free water content, perfusion, and plasma volume but not in blood-brain barrier leakage. We showed different pathophysiological heterogeneity of the 2 WMH types. Periventricular WMHs display more severe damage and fluid accumulation compared with deep WMH, whereas deep WMHs reflect stronger hypoperfusion in the lesion's core. URL: https://www.isrctn.com; Unique identifier: ISRCTN10514229.

Moyamoya Angiopathy and Antiphospholipid Antibodies: A Coincidental Association?

The presence of antiphospholipid antibodies (aPL) has been suggested as a potential cause of moyamoya angiopathy (MMA), but this remains uncertain. In this case-control study, we aimed to compare the prevalence of circulating aPL in patients with MMA and in non-MMA cerebrovascular controls. For comparison, we included 95 patients with MMA from the French National Referral Centre for this condition and 182 age- and sex-matched non-MMA controls with a different cerebrovascular disease, all younger than 55 years. Anticardiolipin antibodies, anti-β2-glycoprotein I antibodies, and lupus anticoagulant were assessed using the guidelines of the International Society on Thrombosis and Haemostasis. aPL prevalence was 22% in patients with MMA and 25% in controls (P=0.74) with no differences in aPL subtypes between the 2 groups. The prevalence of transient ischemic attacks, ischemic stroke, and hemorrhagic stroke did not differ between patients with aPL-positive and aPL-negative MMA. The prevalence of aPL in patients with MMA is comparable to that in non-MMA controls. The present results do not support any causal relationship between aPL and MMA.

Ceftriaxone encephalopathy in a very elderly dialysis patient.

Ceftriaxone is widely used clinically but it can potentially cause ceftriaxone encephalopathy in individuals who are on dialysis. We describe ceftriaxone encephalopathy in a dialysis patient. The 87-year-old Japanese woman had a 9-year dialysis history. She was admitted to our department with right subcostal pain and lower back pain and was diagnosed with renal cyst hemorrhage and infection. Post-admission, we treated her with ceftriaxone (CTRX) 2g/day and bed rest, which improved her symptoms. On the 7th hospitalization day, she began to exhibit incoherent speech and unresponsiveness; by day 10, her consciousness level had decreased to grade III and myoclonus appeared. Brain MRI and a cerebrospinal fluid examination ruled out cerebrovascular disease and encephalitis. EEG showed triphasic waves predominantly in the frontal lobe. Suspecting ceftriaxone encephalopathy, we switched the antibiotic to cefazolin 1g/day. By day 12, the myoclonus decreased and the patient was able to communicate. By day 14, her consciousness level had improved to her admission level. We treated ceftriaxone encephalopathy in a dialysis patient. Although CTRX is generally thought to not require dose reduction in patients with renal failure (due to its hepatic excretion), caution is necessary as overdosage in dialysis patients can lead to myoclonus and encephalopathy.

Summary of clinical features of 1800 cases of pyogenic liver abscess.

This study aimed to summarize the clinical and microbiological characteristics of patients with pyogenic liver abscess (PLA) and to explore the clinical features of PLA with extrahepatic migratory infection (EMI). A retrospective analysis was conducted on clinical data from 1800 PLA patients at Jilin University First Hospital from January 2019 to December 2023. Patients were divided into two groups based on the presence of EMI: with EMI and without EMI. Clinical features and prognoses of the two groups were compared using rank-sum tests and chi-square tests for continuous and categorical data, respectively. PLA patients were predominantly male (65.56%) with an average age of 60. Abscesses were mainly located in the right lobe (64.83%) and were often single (68.17%). Klebsiella pneumoniae was the primary pathogen (68.46%), with 9.50% of strains being multidrug-resistant. The majority of patients improved with effective treatment (96.17%). Compared with the non-EMI group, patients with EMI were younger, had longer hospital stays, smaller abscesses, and a higher incidence of diabetes and cerebrovascular disease, with poorer prognoses. PLA is most commonly observed in middle-aged and elderly males, often presenting as single abscesses in the right lobe, with diabetes as a frequent underlying condition. Most patients recover with appropriate antibiotic treatment and ultrasound-guided drainage. PLA patients with EMI generally have poorer outcomes and require special attention.

Regional dynamic cerebral autoregulation across anterior and posterior circulatory territories: A detailed exploration and its clinical implications.

Cerebral autoregulation (CA) is the mechanism that maintains stable cerebral blood flow (CBF) despite fluctuations in systemic blood pressure, crucial for brain homeostasis. Recent evidence highlights distinct regional variations in CA between the anterior (carotid) and posterior (vertebrobasilar) circulations. Non-invasive neuromonitoring techniques, such as transcranial Doppler, transfer function analysis, and near-infrared spectroscopy, facilitate the dynamic assessment of CBF and autoregulation. Studies indicate a robust autoregulatory capacity in the anterior circulation, characterized by rapid adjustments in vascular resistance. On the contrary, the posterior circulation, mainly supplied by the vertebral arteries, may have a lower autoregulatory capacity. in acute brain injuries such as intracerebral and subarachnoid hemorrhage, and traumatic brain injuries, dynamic CA can be significantly altered in the posterior circulation. Proposed physiological mechanisms of impaired CA in the posterior circulation include: (1) Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity; (2) Endothelial dysfunction; (3) Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBF-metabolism (i.e., neurovascular) uncoupling; and (4) Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances (e.g. nitric oxide, potassium, and calcium ions). Furthermore, more research is needed on the effects of collateral circulation, as well as the circle of Willis variants, such as the fetal-type posterior cerebral artery, on dynamic CA. Improving our understanding of these mechanisms is crucial to improving the diagnosis, prognosis, and management of various cerebrovascular disorders.

NOTCH3 variants of unknown significance underpin vascular dysfunction in neurodegenerative disease: a case series of three nfvPPA-FTD patients.

The NOTCH3 gene encodes for an evolutionarily conserved protein, whose functions encompass both embryonic cell proliferation and adult tissue-specific differentiation. Among others, a pivotal role in maintaining functional integrity of neurovascular unit (NVU) is supported by the association of several NOTCH3 gene mutations with neuroimaging markers of cerebral small vessel disease (SVD). Indeed, a pathogenic role of NOTCH3 is recognised in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, an increasing number of NOTCH3 variants with unclear pathogenic role have been identified in patients suspected of having CADASIL. The following case series describes three patients under the age of 65 with clinical diagnosis of nonfluent-variant of primary progressive aphasia (nfvPPA), whose genetic analysis revealed the presence of three distinct novel variants of unknown significance (VUS) in NOTCH3 gene. The diagnostic work-up revealed common features among the patients: clinical presentation -nfvPPA at neuropsychological evaluation with consistent extrapyramidal symptoms; neuroimaging -low brain MR burden of SVD and FDG-PET impairment of cortical areas involved in speech production network; and biomarkers -Cerebrospinal fluid (CSF) analysis negative for Alzheimer's Disease (AD), corroborating suspicion of underlying Frontotemporal Lobe Degeneration (FTLD). The retrieved VUS in NOTCH3 suggest that the involvement of Notch signalling in pathophysiology of neurodegenerative disease is more complex and needs to be fully explored. Rare variants in SVD-associated genes may influence progression of neurodegeneration via the dysfunction of several vascular pathways.

Severe Maternal Morbidity and Postpartum Care: An Investigation Among a Privately Insured Population in the United States, 2008-2019.

Objective: This study examines postpartum health care utilization among women with severe maternal morbidity (SMM) subtypes (e.g., blood transfusion, renal), focusing on both early (within 7 days) and late (8-42 days) postpartum periods. By including outpatient visits alongside inpatient and emergency department (ED) visits, the study offers a comprehensive view of postpartum health care needs among women with SMM. Methods: This retrospective cohort study used data from Optum's de-identified Clinformatics® Data Mart Database from 2008 to 2019. The primary outcomes were early and late postpartum inpatient readmissions, early and late ED visits, and outpatient care within 42 days after delivery. Multilevel logistic regression models were used to estimate the association between SMM subtypes and postpartum readmission, ED, and outpatient care. Results: Except for hemorrhage, most SMM subtypes increased the postpartum odds of health care utilization. Women with other medical SMM (e.g., puerperal cerebrovascular disorders or sickle cell disease with crisis) had 2.9 times the odds (odds ratio [OR]: 2.87, 95% confidence interval [CI]: 1.30-6.34) of experiencing early readmissions compared with those without other medical SMM. Women with sepsis had 4.5-fold elevated odds (OR: 4.53, 95% CI: 2.48-8.28) of late readmission, a 1.9-fold increased odds (OR: 1.85, 95% CI: 1.12-3.04) of early ED visits, and over a 2-fold increased odds (OR: 2.27, 95% CI: 1.67-3.08) of postpartum outpatient visits compared with those without sepsis. Conclusion: This study reveals that certain SMM subtypes significantly increase postpartum health care utilization, emphasizing the need for further research and interventions to improve outcomes for affected women.

The Comparative Effects of Anakinra and Tocilizumab on Inflammation and Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model

Objective: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. Methods: Forty male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (p &lt; 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (p &lt; 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (p &lt; 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (p &lt; 0.05). Conclusions: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications.

Ultrastructural features of the brain of patients with cognitive impairment in Alzheimer’s disease and vascular dementia

BACKGROUND: Nowadays, due to the increase in life expectancy, the problem of cognitive disorders, quite often found in elderly people and being a formidable syndrome of a number of neurodegenerative diseases, is extremely relevant. According to epidemiological data, the most common causes of cognitive dysfunction are Alzheimer’s disease and cerebrovascular diseases, accounting for about 90% of all cases. AIM: to investigate the morphological features underlying the development of cognitive disorders in Alzheimer’s disease and cerebrovascular pathology. MATERIALS AND METHODS: According to our developed and patented method of preparation of sectional material for electron microscopy а detailed study of the brain of elderly patients with Alzheimer’s disease and cerebrovascular pathology was carried out using electron microscopy on autopsy material. RESULTS: Electron microscopy of the brains of patients with Alzheimer’s disease often reveals large extracellular reticulate-fiber structures closely adjacent to myelin fibers, which are part of a fibrous plaque. In vascular dementia, irregularly shaped hyperchromic masses with heterogeneous contents are found in the neuropil, which may represent future so-called “diffuse” plaques. In Alzheimer’s disease, fragments of future “diffuse” plaques are also observed in the cytoplasm of some cortical oligodendrocytes. In all deceased with Alzheimer’s disease, synaptic changes were found in the form of roughly granular disintegration of the entire synaptocomplex, i.e., synaptic vesicles, mitochondria, and the synaptic cleft proper. CONCLUSION: This study provides an opportunity to take a new look at some questions of etiology and pathogenesis of such a disease as cognitive disorders, which is not easy to diagnose and treat.

Emerging Biomarkers in Atherosclerosis: Advancing Early Detection and Risk Stratification

Introduction: Atherosclerosis is a complex, multifactorial disease influenced by both genetic and environmental factors, including obesity, cigarette smoking, excessive alcohol consumption, and certain chronic conditions such as hypertension and diabetes mellitus type 2. The disease progresses gradually, and often remains unnoticed for years until serious health complications such as coronary artery disease (CAD), peripheral artery disease (PAD) or cerebrovascular disease arise. Nowadays, the diagnosis of atherosclerosis relies on the identification of specific biological markers, enabling early detection and assessment of disease progression. The most common markers used in clinical practice include low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and lipoprotein(a) (Lpa). However, considering that atherosclerosis is one of the leading causes of mortality worldwide and its etiology still remains insufficiently elucidated, there is a pressing need for new, more specific biomarkers for its earlier detection. Aim of the study: The aim of this study is to summarize the knowledge concerning new potential biomarkers for the early detection of atherosclerosis through analyzing the biological processes associated with the initiation and progression of the disease, such as inflammation, oxidative stress, and endothelial dysfunction, to better understand its pathophysiology. Materials and methods: A systematic review of scientific and medical literature from the PubMed and Google Scholar databases was conducted. Results: The analysis of available studies indicates that there are numerous potential biomarkers that might be used for the early diagnosis of atherosclerosis, such as molecules associated with inflammation, lipid oxidation, or endothelial damage. However, further research is needed to establish their full clinical utility.

The impact of meteorological conditions on cardiovascular and cerebrovascular diseases in different microclimatic zones of low-latitude mountainous areas

IntroductionEpidemiological evidence suggests cerebrovascular disease (CVD) incidence is correlated to meteorological conditions. However, research on the primary meteorological factors influencing the incidence of CVD and their influence thresholds in low-latitude mountainous regions remains insufficient. We aimed to investigate the association between meteorological conditions and CVD occurrence in Guizhou province.MethodsUtilizing daily incidence cases for CVD alongside concurrent meteorological data from four microclimate representative stations in Guizhou Province during 2021-2022, we firstly performed random forest and decision tree analysis to identify the significant meteorological factors influencing the incidence of CVD, and then we applied distributed lag non-linear model (DLNM) to assess the effect of meteorological factors on CVD incidence.ResultsCritical meteorological factors associated with CVD incidence include diurnal temperature range (DTR), temperature change between neighboring days (TCN), diurnal pressure range (DPR), pressure change between neighboring days (PCN), and minimum temperature. The risk of CVD incidence markedly increased with narrow DTR, positive TCN, and colder conditions. The thresholds of minimum temperature and TCN droped with the decrease of annual average temperature in microclimate zone. In the middle subtropical region of Jiangkou, the northern subtropical region of Xishui, and the warm temperate region of Shuicheng, there was a risk of CVD when the minimum temperature falled below 12.2°C, 10.7°C, and 6.7°C, respectively. When TCN exceeded the critical threshold (0.2°C in Shuicheng, 0.3°C in Xishui, and 0.4°C in Jiangkou and Ceheng), the risk of CVD incidence increased linearly. DPR and PCN displayed varied thresholds across different microclimate without consistent patterns. DPR in middle subtropical region of Jiangkou and warm temperate region of Shuicheng played a protective role, while the risk of the disease increased linearly when DPR was lower than 3.2 hPa and 2.7 hPa in south subtropical region of Ceheng and north subtropical region of Xishui, respectively. The short-term effects within 5 days with small DTR and narrow positive TCN were more obvious. The thresholds and lag times of other meteorological environmental factors remained indistinct in the four microclimate zones.DiscussionOur findings delineated the common characteristics of the effect on the incidence of CVD of meteorological environments in various microclimate zones, and clarified the influence of minimum temperature and TCN exhibited spatial heterogeneity, Which may be assistance for meteorological risk forecasting in CVD prevention and control.

Association between moderate-to-vigorous physical activity and chronic disease risk in adults and elderly: insights from the UK Biobank study

BackgroundThis study aimed to determine the associations between different intensities of moderate to vigorous physical activity (MVPA) and the incidence of chronic diseases, and to assess the risk levels associated with these activities over time.MethodsA prospective cohort study (UK Biobank Activity Project) with data collected between June 2013 and December 2015 included 59,896 adults (mean age = 59.68; male = 38.03%) free from chronic diseases. Participants were categorized into tertiles based on their weekly MVPA: lowest (&amp;lt;224 min for males, &amp;lt;143 min for females), medium (224–444 min for males, 143–308 min for females), and highest (≥444 min for males, ≥308 min for females), stratified by gender. The mean onset of chronic disease symptoms occurred at 3.57 years, with participants followed up during this period. Wearable accelerometry data were used to quantify MVPA levels.FindingsLowest tertile of MVPA were significantly correlated with increased risks of chronic disease (24%–110% increased risk) based on odds ratios (ORs), with dose-response relationship observed. In males with the lowest tertile of MVPA, significant associations were identified with type 2 diabetes mellitus (T2DM) (OR = 1.90; CI: 1.44–2.51), neurodegenerative disease (OR = 1.80; CI: 1.19–2.71), metabolic syndrome (OR = 1.34; CI: 1.18–1.53), hypertension (OR = 1.27; CI: 1.12–1.44), and atherosclerotic cardiovascular disease (ASCVD) (OR = 1.24; CI: 1.03–1.49). In females, the lowest tertile of MVPA levels were associated with increased risks of neurodegenerative disease (OR = 2.10; CI: 1.36–3.24), T2DM (OR = 1.88; CI: 1.37–2.58), cerebrovascular disease (OR = 1.61; CI: 1.12–2.29), ASCVD (OR = 1.58; CI: 1.23–2.03), metabolic syndrome (OR = 1.49; CI: 1.32–1.69), and hypertension (OR = 1.44; CI: 1.29–1.61). Longitudinally, the lowest tertile of MVPA in males showed elevated risks for neurodegenerative disease (HR = 2.13; CI: 1.24–3.66), T2DM (HR = 1.83; CI: 1.30–2.57), hypertension (HR = 1.33; CI: 1.15–1.53), metabolic syndrome (HR = 1.32; CI: 1.14–1.54), and ASCVD (HR = 1.29; CI: 1.03–1.61). In females, the lowest tertile of MVPA was associated with similar risks for ASCVD (HR = 1.59; CI: 1.16–2.20), T2DM (HR = 1.57; CI: 1.08–2.29), hypertension (HR = 1.53; CI: 1.34–1.74), and metabolic syndrome (HR = 1.50; CI: 1.29–1.73).ConclusionUsing wearable accelerometry data, this study demonstrated the quantifiable risks of chronic diseases and their development, highlighting the importance of MVPA.

Dexmedetomidine Is Associated with Reduced In-Hospital Mortality Risk of Subarachnoid Hemorrhage Patients undergoing surgery

BackgroundSubarachnoid hemorrhage (SAH) is a severe neurological event with high mortality. The choice of sedatives in SAH management may influence patient outcomes. This study aimed to investigate the association between sedatives and in-hospital mortality among SAH patients. MethodsThis study analyzed data from the MIMIC-IV database, and in-hospital mortality was the primary outcome. Key variables collected included sedatives, demographics, comorbidities, vital signs, laboratory tests, and severity scores. Univariate and multivariate logistic regression analyses were used to assess associations between sedative use and in-hospital mortality, with adjustments for confounding factors. Further stratified analyses explored the effects of dexmedetomidine across different patient subgroups, and mediation analysis evaluated creatinine's role in the relationship between dexmedetomidine and mortality. ResultsA total of 527 patients were included in this study, with 301 males. Compared to propofol and midazolam, the use of dexmedetomidine was significantly related to the reduction of in-hospital mortality in SAH patients (OR = 0.369, 95% CI: 0.237-0.574, p < 0.001). After adjusting for variables such as demographics, comorbidities, and laboratory tests, dexmedetomidine remained associated with lower in-hospital mortality. Additionally, our findings indicated that dexmedetomidine use was associated with a reduced risk of in-hospital mortality regardless of the presence of cerebrovascular disease. Importantly, we discovered that creatinine acted as a mediator in the protective effect of dexmedetomidine on in-hospital mortality. ConclusionDexmedetomidine is associated with significantly lower in-hospital mortality in SAH patients. These findings underscore the importance of sedative choice for SAH patients, suggesting that dexmedetomidine could enhance patient outcomes.

A Rare Arterial Congenital Variant: The Internal Carotid Artery Agenesis.

The cerebral arterial circle has been extensively investigated in recent literature. A scarce congenital arterial variant is considered the internal carotid artery (ICA) agenesis. The computed tomography angiogram of a 65-year-old female patient is reported. The left ICA was absent in the head and neck region. Intracranially, the left middle cerebral artery derived from a hyperplastic posterior communicating artery, and the first segment of the left anterior cerebral artery was absent. This variant corresponds to Lie's type A agenesis of the ICA that coexisted with an aneurysm on the anterior communicating artery. Overall, the absence of ICA has a prevalence of <0.01%. It was associated with clinical symptoms of cerebrovascular insufficiency or intracranial aneurysm. Although extremely rare, the congenital variant is important for radiologists and neurosurgeons planning a surgical procedure in the area.

Surface-based morphometry of the cerebral cortex in cognitive impairments of varying severity in patients with age-related cerebral small vessel disease

BACKGROUND: Analysis of structural magnetic resonance images is essential to assessing the main substrate of cognitive impairment in sporadic age-related cerebral small vessel disease, accounting for up to 45% of all dementia cases. Variations in the results of magnetic resonance morphometry applied in cerebral small vessel disease require extensive studies and clinical correlation. AIM: To assess cerebral atrophy features in cognitive impairment in patients with cerebral small vessel disease by surface-based morphometry. MATERIALS AND METHODS: A prospective study was conducted to assess patients with cerebral small vessel disease and cognitive impairments of varying severity levels (subjective, moderate, and dementia) and sex- and age-matched groups of volunteers. The assessment included the analysis of signs of cerebral small vessel disease based on the results of magnetic resonance imaging with the computation of general cerebral small vessel disease index and processing T1 multiplanar reconstruction images by surface-based morphometry to quantify general and regional brain parameters, including the thickness of the cerebral cortex. RESULTS: The main group consisted of 173 patients with cerebral small vessel disease, whereas the control group included 47 healthy volunteers. As the severity of brain structural changes and cognitive impairments increased, a significant (p 0.05) decrease in the cortical thickness of certain regions following a similar pattern was reported, particularly in the cingulate gyri, mainly their posterior sections; medial and middle sections of the frontal lobes, various areas of the insular cortex, and temporoparietal areas, particularly the supramarginal gyri. The brain volumes (overall, gray matter, and white matter volumes) in cerebral small vessel disease were significantly different only in controls but not between patients with cognitive impairment of different severity levels. The hyperintense white matter volume was significantly different between patients with dementia and moderate cognitive impairment, dementia, and subjective cognitive impairment (p 0.0001). CONCLUSIONS: The results confirm secondary/mixed atrophy in cerebral small vessel disease. The clarification of the severity level of cognitive impairment in cerebral small vessel disease based on atrophy data is limited by the wide variety of regions with significant cortical thinning. Thus, the quantification of the cortex can only be a supplementary method in predicting cerebral small vessel disease progression.

Blood-brain barrier disruption mediates the association between cerebral small vessel disease and clinical outcome after stroke: a secondary analysis of the Lesion Evolution in Stroke and Ischemia on Neuroimaging study

IntroductionWhite matter hyperintensities (WMH) in patients presenting with acute ischemic stroke are associated with worse clinical outcomes, but the mechanisms underlying this association are unclear. The purpose of this study was to determine whether blood-brain barrier (BBB) disruption, detected as the hyperintense acute reperfusion marker (HARM) on post-gadolinium follow-up FLAIR MRI, is associated with WMH and mediates the association between WMH and stroke outcomes.MethodsThis is a secondary analysis of the LESION study, where patients with suspected acute ischemic stroke who were candidates for acute stroke intervention or had a baseline NIHSS ≥4 underwent serial multimodal MRI within 24 h of last-known-well time, and again at 2 or 24 h. WMH were visually graded on baseline FLAIR for presence and severity (minor or moderate-severe). HARM was evaluated on post-gadolinium FLAIR for presence and severity (minor, severe focal or severe diffuse). Using binomial and multinomial logistic regression, we tested whether WMH grade was associated with presence or severity of HARM, covarying for demographics, vascular risk factors, and stroke characteristics in sequential models. Finally, we used structural equation models to test the mediation effects of severe HARM on the association between WMH and stroke outcomes, including discharge NIHSS, hemorrhagic transformation, and 90-day modified Rankin scale.ResultsFor 213 stroke patients (mean age 70 years, 54% female), higher WMH grade was associated with increased risk for severe diffuse HARM (OR: 3.37, 95% CI: 1.45–7.81), although not after adjusting for vascular risk factors or stroke characteristics. In our univariate model, severe HARM had a partial mediating effect between WMH and discharge NIHSS, explaining 23% of the association.DiscussionThese findings suggest a possible association between severe diffuse HARM and WMH severity. The relationship between WMH severity and early stroke outcome may be mediated by blood-brain barrier disruption.

Association between plasma trimethylamine N-oxide and cerebral white matter hyperintensity: a cross-sectional study

BackgroundCerebral white matter hyperintensity (WMH) is a pivotal imaging feature of cerebral small vessel disease (CSVD), closely correlated with an elevated risk of ischemic stroke (IS). Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is increasingly associated with IS and atherosclerosis. However, the intricate relationship between TMAO and WMH remains ambiguous. This study aimed to study the connection between plasma TMAO and WMH. Furthermore, it assessed the potential of TMAO as a risk evaluation instrument for WMH.MethodsIn this cross-sectional study, we categorized WMH into periventricular WMH (P-WMH) and deep WMH (D-WMH), based on its locations. The severity of WMH was assessed and grouped according to the Fazekas scale. Plasma TMAO levels were quantitatively determined. We established the correlation between plasma TMAO levels and WMH severity using a Logistic regression model. Additionally, we employed ROC curves to evaluate the diagnostic efficacy of plasma TMAO concentration in distinguishing the severity of WMH.ResultsA higher plasma TMAO tertile was significantly linked to a higher Fazekas score, encompassing the overall score, P-WMH score, and D-WMH score (p &amp;lt; 0.001). A logical regression analysis revealed that plasma TMAO levels were independently associated with overall moderate and severe WMH, compared to overall non-mild WMH, in the unadjusted model (OR = 1.373, 95%CI 1.183–1.594 for moderate; OR = 1.384, 95%CI 1.192–1.607 for severe), the adjusted model a (OR = 1.436, 95%CI 1.214–1.669 for moderate; OR = 1.446, 95%CI 1.222–1.711 for severe) and the adjusted model b (OR = 1.490, 95%CI 1.234–1.800 for moderate; OR = 1.494, 95%CI 1.237–1.805 for severe). The analysis also showed an independent correlation between plasma TMAO levels and WMH severity, irrespective of the unadjusted model, adjusted model a, or adjusted model b, when considering P-WMH and D-WMH severity. The ROC indicated that, in overall WMH and P-WMH, the area under curve (AUC) for non-mild and severe WMH were both&amp;gt;0.5, while the AUC for moderate WMH was&amp;lt;0.5. In contrast, in D-WMH, the AUC for non-mild, moderate, and severe WMH were all&amp;gt;0.5.ConclusionPlasma TMAO levels exhibited a significant correlation with both overall and region-specific WMH severity. Furthermore, the plasma TMAO levels displayed robust predictive capability for D-WMH.