Cerebrovascular Diseases最新文献

Introduction: Intracerebral hemorrhage (ICH) seriously threatens human health with a high mortality and disability rate. Promoting the microglia-mediated endogenous removal of hematoma can effectively reduce brain tissue damage. Adenosine 3 receptor (ADORA3) has been shown to participate in microglial phagocytosis; however, its role in ICH remains unclear. This study was performed to explore the potential role of ADORA3 and related mechanism in endogenous hematoma resolution after ICH.

Methods: Autologous blood injection was used to construct ICH model. Mice were administered with the microglial depletion agent (PLX3397) and the specific antagonist of ADORA3, MRS1523. The neurobehavioral function was evaluated through a serious of tests. The residual hematoma volume and hemoglobin content were measured. Erythrophagocytosis was assessed using flow cytometry. Immunofluorescence, Western blot, Nissl and TUNEL staining were also performed.

Results: The expression of ADORA3 increased dynamically, and ADORA3 was mainly located in the microglia after ICH. The ADORA3 inhibitor MRS1523 could improve neurological recovery, reduce the residual hematoma volume and hemoglobin content, and promote erythrophagocytosis of microglia. In addition, the inhibition of ADORA3 reduced the expression of phagocytotic receptors AXL and MerTK, decreased the number of damaged and apoptotic neurons around hematoma on day 3 after ICH, and alleviated the neuroinflammation. In addition, PLX3397, a microglial depletion agent, impaired the protective effect of MRS1523.

Conclusion: The inhibition of ADORA3 by MRS1523 promoted phagocytosis of microglia on erythrocytes, accelerating hematoma clearance after ICH, reducing the damage of neurons and neuroinflammation around the hematoma, and ultimately promoting neurological recovery.

Introduction: There is a need for measures of early stages of cerebral small vessel diseases (cSVDs). Recently, using 7T MRI, abnormalities of small vessel function were reported in patients with clinically manifest cSVD. The question is if such abnormalities are also present in early, covert stages of cSVD. We, therefore, studied the relation between cerebral small vessel function measures on 7T MRI and the burden of covert cSVD in the general aging population.

Methods: Two hundred participants (mean age [years] ± SD: 71 ± 5, 43% women) without a history of stroke or dementia from the Rotterdam Study were included. Small vessel measures at 7T MRI, including perforating artery blood flow velocity and pulsatility and cerebrovascular reactivity (CVR) to carbon dioxide, were related to markers of cSVD burden at 1.5T MRI, including white matter hyperintensity (WMH) volume and microbleed, enlarged perivascular spaces, and lacune presence, using linear and logistic regression analyses. We also included cognitive performance as a clinical indicator of covert cSVD.

Results: Across the population, neither perforating artery flow measures nor CVR were significantly associated with cSVD lesion burden or cognition, with small point estimates and no consistent direction of effects. Yet, within individuals, CVR was lower inside WMHs compared to normal-appearing white matter (CVR_NAWM = 0.54 ± 0.48%; CVR_WMH = 0.24 ± 0.94%; p = 0.006).

Conclusion: Although these data confirm that vascular function is affected within WMH, we did not observe relations between small vessel function measures at 7T MRI and the burden of covert cSVD in this population-based sample. Apparently, these measures have limited sensitivity to early stages of cSVD.

Background: Moyamoya disease (MMD), a chronic and occlusive cerebrovascular disorder, is characterized by progressive bilateral terminal stenosis or occlusion of the internal carotid arteries, accompanied by the formation of abnormal collateral vascular networks at the base of the brain. It is more prevalent in East Asia, with regional variation in China.

Summary: The clinical features of MMD differ significantly between children and adults. Most children with MMD experience cerebral ischemia, while most adult patients develop intracranial hemorrhage. Our understanding of MMD has advanced considerably. Recent advances indicate that MMD arises from a complex interplay of genetic predisposition, immune dysregulation, and abnormal angiogenesis. RNF213 has been identified as the major genetic determinant contributing to MMD susceptibility. However, issues still existed in diagnosis and treatment, including atypical early symptoms, a lack of specific diagnostic tools, and unclear indications for surgical treatment.

Key messages: MMD is a heterogeneous disease with distinct age-related clinical patterns and a strong genetic component. Advances in imaging and genetics are expanding our understanding. Future studies integrating genomics, immune biology, and angiogenesis research may enable biomarker discovery, precision risk stratification, and the development of disease-modifying treatments to improve long-term outcomes.

Introduction: Females have a higher incidence of aneurysmal subarachnoid hemorrhage and a higher prevalence and rupture risk of unruptured intracranial aneurysms than men. Underrepresentation of females in clinical trials would, therefore, limit their generalizability. The study aimed to evaluate sex disparities in aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysm trial enrollment and identify factors influencing female representation.

Methods: The authors searched Ovid Medline, Embase, Cochrane Central, Clinicaltrials.gov, and International Clinical Trials Registry for clinical trials on aneurysmal subarachnoid hemorrhage or unruptured intracranial aneurysms, published before June 2023, with ≥100 adult patients, requiring informed consent for participation. The primary outcome was the proportion of female patients enrolled. Random effects meta-analysis was performed, and multivariate beta-regression was used to assess the impact of trial characteristics and predefined subgroups on female participation.

Results: A total of 134 trials were included, with a total of 38,042 patients. Meta-analysis of the proportions of female participants resulted in a pooled proportion of 0.64 (95% CI: 0.63-0.66). Female participation was higher in trials on endovascular treatment (beta-estimate 1.32; 95% CI: 1.01-1.71) and in multicenter studies (beta-estimate 1.16; 95% CI: 1.01-1.33) but lower in Asian (beta-estimate 0.80; 95% CI: 0.67-0.95) and South American trials (beta-estimate 0.67; 95% CI: 0.47-0.97). Recruitment and consent procedures, sex of primary investigator, or burden of trial participation had no significant impact on female representation. Time trend analysis showed no statistically significant change in female participation over time.

Conclusion: Females are not underrepresented in clinical trials for aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms. Female participation is higher in trials on endovascular treatment and in multicenter studies and has regional differences, but other factors did not influence female representation. Our findings imply a good generalizability regarding sex distribution of the study results, strengthening the evidence guiding current clinical practice.

Introduction: Drug screening with a zebrafish model of acute intracerebral hemorrhage (ICH) identified a neuroprotective effect of angiotensin converting enzyme inhibitor (ACE-I) drugs. We identified an association of early ACE-I treatment and favorable 90-day functional outcome in participants of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial. We aimed to confirm a relation between angiotensin inhibitors and good outcome in the larger, third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) dataset.

Methods: This is a post hoc analysis of INTERACT3 in patients with ICH surviving to day 7. Associations of early ACE-I or angiotensin-II receptor blocker (ARB) treatment and neurological impairment (National Institutes of Health Stroke Scale [NIHSS] scores) at day 7 and functional recovery (modified Rankin Scale [mRS] scores) at 6 months were tested in multiple regression and ordinal regression models, respectively, with adjustment for confounding variables.

Results: Of 6,692 participants included in analyses, 2,525 (36.2%) received ACE-I/ARB treatment by day 7. Treatment with an ACE-I/ARB (vs. no ACE-I/ARB) was significantly and independently associated with lower NIHSS scores at day 7 (β-coefficient -1.17, 95% confidence interval [CI] -1.59 to -0.74; p < 0.001) and better mRS scores at 6 months (odds ratio 0.83, 95% CI 0.75-0.93; p = 0.0007).

Conclusion: Early treatment with an angiotensin inhibitor is associated with improved outcome after ICH. Further research is needed to test for heterogeneity by ACE-I/ARB drug and treatment window to plan a clinical trial in ICH.

Introduction: While mid-life hypertension is a recognised risk factor for dementia, data also suggest elevated blood pressure is detrimental to brain health. We aimed to determine the frequency of various stages of hypertensions and use of antihypertensive treatment, among participants attending an Australian brain health and memory clinic, and their association with neuropsychological functioning.

Methods: Older adults (age ≥50 years) with cognitive concerns underwent neuropsychological, mental health and geriatric medical assessments. Participants were classified based on systolic blood pressure (SBP) and diastolic blood pressure (DBP) into normal (SBP <120 mm Hg and DBP <80 mm Hg), elevated (SBP 120-129 mm Hg and DBP <80 mm Hg), stage 1 (SBP 130-139 mm Hg or DBP 80-89 mm Hg), and stage 2 (SBP ≥140 mm Hg or DBP ≥90 mm Hg) hypertension. Global cognition and age-corrected z-scores were computed for the neuropsychological domains of processing speed, verbal learning, verbal memory, executive function, and an overall composite.

Results: Of 1,236 participants (mean age 67.7 years, 62% female), 84.7% were considered either stage 1 (31.7%) or stage 2 (53%) hypertension, but only 32.4% were taking antihypertensive treatment. The stage 2 hypertensive group was significantly older, had a higher mean body mass index, and higher comorbidities than the other groups (normal, elevated, and stage 1). No significant between-group differences were found in neuropsychological domains.

Conclusion: Hypertension (stages 1 and 2) is common, and use of antihypertensive medication is low, among attendees of a brain health and memory clinic. Efforts to screen and treat hypertension in a brain health and memory clinic setting appear justified, although further research is needed to better understand associated positive and negative effects of treatment in this patient group.

Introduction: Some studies suggest an increased risk of intracerebral haemorrhage (ICH) with HMG-CoA reductase inhibitors (statins). However, other studies focusing on continuation of statins after ICH have shown consistent association with better outcomes. No clear mechanism has been identified, but reduced inflammation and/or infection have been hypothesised. We tested whether statin use, both before and after acute ICH, is associated with risk of death in our cohort. We then investigated potential mediators and tested for indication bias.

Methods: We conducted a secondary analysis of a prospective spontaneous ICH registry including patients between December 22, 2009 to March 23, 2019. Multifactorial logistic regression was used to test for an association between 30-day case fatality (collected by linkage to national databases) and statin exposure before the index ICH and in the 72 h after onset. A mediation analysis was conducted including available markers of inflammation and infection, including C-reactive protein, white cell count, lymphocyte count, and red cell distribution width on admission and urinary tract infections and pneumonia in the 7 days after arrival. A sensitivity analysis, including only those able to take a statin in the 72 h after onset (not palliated, enteral access), was also performed.

Results: A total of 1,423 patients were included. Statin continuation after admission (vs. none) was independently associated with lower case fatality (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.16-0.49; p < 0.001), but statins taken prior to the ICH and not after (vs. none) were not (OR: 0.77; 95% CI: 0.51-1.15; p = 0.2). Receiving a statin after the ICH, regardless of whether it was received before, was similarly associated with 30-day case fatality (OR: 0.30; 95% CI: 0.18-0.49; p < 0.001). None of the potential mediators tested were significant. The association between statins and mortality was no longer significant in our sensitivity analysis, excluding those unable to take a statin within 72 h of their ICH (n = 1,048; OR: 0.62; 95% CI: 0.37-1.05; p = 0.073).

Conclusion: Exposure to statins (vs. none) after ICH was associated with lower odds of death at 30 days after adjustment for confounders. Available inflammatory markers, urinary tract infections, and pneumonia did not mediate this association. Indication bias is likely to have contributed to the association observed between statins and mortality in prior studies.

Introduction: The middle meningeal artery (MMArt) is considered to be an important collateral in moyamoya angiopathy; however, an in-depth analysis of the underlying mechanisms directing this collateral formation is missing. The aim of this study was to analyze patterns of activation of MMArt in pediatric patients along with identifying factors influencing these collateral pathways.

Methods: Retrospective clinical and angiographic data of a pediatric moyamoya cohort managed at a single center were analyzed. Angiographic staging, MMArt activation, and collateral supply via posterior cerebral artery (PCA) were evaluated on cerebral angiograms. Stroke burden was evaluated using cerebral MRI. Associations with angiographic staging, stroke burden, and PCA collateral supply were determined.

Results: MMArt activation was observed in 49% of patients (n = 101). MMArt anterior division was activated more frequently (31% of all hemispheres). MMArt formed collaterals mostly to the frontal brain. Higher odds of activation of MMArt were observed in advanced anterior angiographic stages (stages 4-5) (OR 4.22, p < 0.001), higher posterior angiographic stages (stages 1-2) (OR 5.75, p < 0.001), longer duration of disease (OR 1.33, p = 0.014), and in cases showing collateral supply from the PCA (OR 3.39, p < 0.003). Age at symptom onset, stroke burden, and type of angiopathy (moyamoya disease/syndrome) were not associated with MMArt activation.

Conclusion: The MMArt serves as a crucial collateral in pediatric moyamoya, particularly to the frontal lobes. Increased MMArt activation is seen in advanced angiopathy with prolonged disease duration and PCA-derived collaterals. Stroke burden and angiopathy subtype do not appear to influence MMArt activation.

Introduction: The optimal intensity of statin therapy after nontraumatic intracerebral hemorrhage (ICH) remains controversial. This study aimed to compare safety and efficacy outcomes between moderate- and high-intensity statin therapy in post-ICH patients using real-world data to inform secondary prevention strategies.

Methods: In this retrospective analysis of the TriNetX Global Collaborative Network database (a federated electronic health records platform), patients with nontraumatic ICH who initiated statin therapy ≥7 days post-ICH were identified. Moderate-intensity statin therapy was defined as atorvastatin 10-20 mg, simvastatin 20-40 mg, rosuvastatin 5-10 mg, pravastatin 40-80 mg, lovastatin 40 mg, fluvastatin 40-80 mg, or pitavastatin 2-4 mg. High-intensity therapy included atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Primary outcomes included recurrent ICH, ischemic stroke, composite vascular events, and all-cause mortality. Safety outcomes included rhabdomyolysis and hepatic injury.

Results: After matching, 8,925 patient pairs were well balanced on baseline demographics and comorbidities. Mean follow-up was 283 days (median 365 days) in both groups. Compared with high-intensity statins, moderate-intensity therapy was associated with lower risks of recurrent ICH (23.4% vs. 24.9%; hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.86-0.97; p = 0.002), ischemic stroke (7.1% vs. 10.2%; HR, 0.68; 95% CI, 0.59-0.78; p < 0.001), composite vascular events (15.1% vs. 19.5%; HR, 0.74; 95% CI, 0.66-0.82; p < 0.001), and all-cause mortality (9.0% vs. 10.2%; HR, 0.87; 95% CI, 0.79-0.96; p = 0.004). Rates of rhabdomyolysis (0.3% vs. 0.4%) and hepatic injury (0.5% vs. 0.4%) were low and not significantly different between groups.

Conclusion: In this large, real-world analysis, moderate-intensity statins demonstrated statistically significant but modest reductions in recurrent ICH, ischemic stroke, composite vascular events, and all-cause mortality compared with high-intensity statins, without increased adverse events. These findings may support preferential use of moderate-intensity statin therapy in selected post-ICH patients pending confirmation from randomized trials. While these observational findings suggest potential benefits of moderate-intensity statin therapy in selected post-ICH patients, confirmation from randomized controlled trials is needed before definitive clinical recommendations can be made.