Cerebrovascular Diseases最新文献

Background: Stroke remains a leading cause of disability and death worldwide. While reperfusion therapies such as tissue plasminogen activator and mechanical thrombectomy have significantly improved stroke management, their effectiveness is limited by ischemia/reperfusion injury, which disrupts the blood-brain barrier (BBB), increases neuroinflammation, and exacerbates secondary neuronal damage. Consequently, there is an urgent need for adjunctive therapies that specifically target these secondary injury mechanisms.

Summary: This review explores novel therapeutic strategies aimed at mitigating neuroinflammation, poststroke edema, and BBB permeability. Key approaches discussed include anti-inflammatory therapies targeting tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinases (MMPs); neuromodulation by vagus nerve stimulation (VNS); and the inhibition of edema-related molecules such as sulfonylurea receptor 1 (SUR1), aquaporin-4 (AQP4), and both systemic and peripheral hypothermic cooling. While these therapies show promise in preclinical models, their clinical translation is hindered by challenges such as systemic immunosuppression, susceptibility to infection, and limited therapeutic windows. Among these therapies assessed, SUR1 inhibition and remote administration of hypothermia (RAH) are promising candidates for improving stroke outcomes.

Key messages: Secondary injury from BBB disruption, inflammation, and edema remains a major barrier to optimal stroke recovery. Pharmacologic, neuromodulatory, and molecular-targeting strategies, including TNF-α, IL-6, MMP inhibition, VNS, and hypothermia, each offer distinct therapeutic mechanisms, but face critical clinical translation barriers. Among emerging therapies, RAH and SUR1 inhibition represent novel interventions that address many of the translational challenges of other therapies by addressing key mechanisms of neuroinflammation and edema with favorable safety profiles.

Introduction: Evolution patterns and contributing factors of leptomeningeal collaterals (LMCs) in symptomatic intracranial atherosclerotic stenosis (sICAS) remain elusive.

Methods: Patients with atherosclerotic M1 middle cerebral artery (MCA-M1) stenosis (50%-99%), who were treated medically and had CT angiography (CTA) at baseline and 1 year, were recruited. LMC status was determined by the laterality of distal vessels in anterior and posterior cerebral artery territories in baseline and 1-year CTA. Computational fluid dynamics models were constructed based on baseline and 1-year CTA, to quantify post-stenotic to pre-stenotic pressure ratio (PR) in MCA-M1 lesions. Decreased PR over 1 year indicated enlarged translesional pressure gradient.

Results: Among 33 patients (median age 62 years), 18 (54.5%) and 15 (45.5%) had good and poor baseline LMCs; 11 (33.3%) and 22 (66.7%) had good and poor 1-year LMCs. Twelve (36.4%), 16 (48.5%), and 5 (15.2%) patients had worse, similar and better LMCs at 1 year versus baseline. Sixteen (48.5%) patients had decreased PR over 1 year, associated with good LMCs at 1 year (adjusted odds ratio 6.40; p = 0.038), independent of baseline LMC status.

Conclusion: LMCs may evolve over time in medically treated sICAS patients, when an enlarged translesional pressure gradient may be a driving force.

Introduction: Brain edema is a common finding after intracranial aneurysm rupture and the severity of brain edema has been associated with the risk for delayed cerebral infarction (DCI). In this retrospective comparative study, we investigate (a) the role of brain edema for DCI development and (b) the impact of active blood clearance on the association between brain edema and DCI.

Methods: This study included 799 aSAH patients treated between October 2005 and October 2019, excluding those with early mortality (<96 h). The Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) was recorded in all patients. DCIs were determined by an independent rating board and neurological outcome was independently assessed by modified Rankin Scale at 6 months. Active blood clearance by cisternal lavage therapy was introduced in October 2015. Overall, 609 patients were treated before and 190 after implementation of cisternal lavage, with 61 high-risk patients (32.1%) receiving lavage. Multivariable regression models were applied to analyze the role of brain edema for DCI and a matched pairs analysis assessed the impact of cisternal lavage.

Results: DCI increased the risk of poor neurological outcome (mRS 4-6) by over 10 times (OR: 10.3, 95% CI: 6.8-15.8, p < 0.001). Poor WFNS scores on admission and high blood volume in the basal cisterns and ventricles were key DCI predictors. Brain edema raised the DCI risk by 2-3 times across all SEBES grades ≥1 (OR: 1.90-2.80). Cisternal lavage was negatively associated with DCI development (OR: 0.23, 95% CI: 0.13-0.42, p < 0.001). In patients selected for cisternal lavage, there was no association between brain edema severity and DCI risk.

Conclusion: Brain edema following aSAH is strongly linked to an increased risk of DCI. However, this association disappears once the underlying cause of DCI - intracranial blood - is cleared. Thus, brain edema serves as a marker of bleeding severity rather than a direct causal factor in the development of DCI.

Introduction: The aim of this study was to explore the potential of magnetic resonance spectroscopy (MRS) for the early diagnosis of the ischemic brain tissue with negative diffusion-weighted imaging (DWI) results in the model of acute internal carotid artery occlusion (AICAO) in rats.

Methods: Fifteen rats were randomly assigned to three groups: the sham group (SHAM, n = 5), the 2-h ischemia model group (CI2H, n = 5), and the 12-h ischemia model group (CI12H, n = 5). In the experimental group, the method of AICAO was adopted to establish a right cerebral ischemia model. After the successful establishment of the model, DWI and MRS scans were first performed, and then the MRS results were recorded. Immunohistochemical analysis of zonula occludens-1 (ZO-1), neuron-specific enolase, S-100β protein, and cytochrome C (CytC) was conducted on paraffin-embedded brain sections, followed by Spearman correlation analysis between relevant parameters and these proteins.

Results: Lipid (Lip) levels were lower in the SHAM group compared to the CI2H group (p < 0.05), but no significant difference was observed between the SHAM and CI12H groups. Lip was negatively correlated with ZO-1 across all groups (ρ = -0.768, p < 0.001). Lactate (Lac) levels were lower in the SHAM group than in the CI2H and CI12H groups (p < 0.05), and Lac was positively correlated with CytC across all groups (ρ = 0.801, p < 0.001). Apparent diffusion coefficient (ADC) values on the right side of the brain were lower in the CI12H group than in the SHAM group (p < 0.05), with no significant difference compared to the CI2H group. The level of N-acetyl aspartate (NAA) in the CI12H group was lower than that in the SHAM group and the CI2H group (p < 0.05), and there was no statistically significant difference in the level of NAA between the CI2H group and the SHAM group. The Choline (Cho) level in the CI12H group exhibited a statistically significant increase compared to both the SHAM and CI2H groups (p < 0.05), and there was no statistically significant difference in the level of Cho between the CI2H group and the SHAM group.

Conclusion: Brain damage in AICAO rats became evident at 2 h after successful modeling. MRS detected brain damage earlier than DWI, with Lac and Lip as the most sensitive markers, preceding changes in NAA, Cho, and ADC values.

Introduction: Acute large vessel occlusion patients can be categorized into fast and slow progressors based on infarction growth rate (IGR) before endovascular treatment (EVT). However, the characteristics of fast progressors remain uncertain, and a comprehensive review investigating the adverse effects of fast IGR is needed.

Methods: A systematic search of studies published before March 24, 2025, was conducted using PubMed, Web of Science, Embase, and Cochrane Library following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies comparing fast and slow progressors before EVT were screened. Baseline characteristics and clinical outcomes were collected. Meta-analysis was performed to pool the results. Weighted odds ratio (OR), mean difference (MD), and confidence intervals (CIs) were calculated. This study was registered on the International Prospective Register of Systematic Reviews platform (CRD420251016945).

Results: A total of 8 studies involving 2,718 patients were pooled. Age and gender were similar between fast and slow progressors. Fast progressors had significantly higher baseline National Institute of Health Stroke Scale scores (MD, 2.7; 95% CI, 2.0-3.4; I2 = 0), higher intravenous thrombolysis rates (OR, 1.41; 95% CI, 1.07-1.86; I2 = 62%), larger proportions of internal carotid artery occlusion (OR, 1.74; 95% CI, 1.39-2.19; I2 = 0), and lower percentages of good collateral status (OR, 0.33; 95% CI, 0.22-0.50; I2 = 53%). Cardioembolism etiology was also prevalent in fast progressors (OR, 1.42; 95% CI, 1.10-1.83; I2 = 0). Regarding outcomes, fast IGR was associated with significantly lower rates of successful reperfusion (OR, 0.70; 95% CI, 0.57-0.86; I2 = 0) and a modified Rankin Scale (mRS) score 0-2 at 90-day (OR, 0.34; 95% CI, 0.28-0.42; I2 = 0). Meanwhile, the proportions of symptomatic intracranial hemorrhage (OR, 3.54; 95% CI, 1.78-7.01; I2 = 33%) and 90-day mRS scores (MD, 0.94; 95% CI, 0.61-1.26; I2 = 51%) were higher in fast progressors.

Conclusion: Increased stroke severity, proximal vessel occlusion, worse collateral status, and cardioembolism etiology were key features of fast progressors before EVT. Fast progressors exhibit significantly elevated risks of poor outcomes. Taking IGR into consideration during clinical practice and research is essential.

Introduction: For patients with acute ischaemic stroke caused by large vessel occlusion (LVO), there is limited evidence regarding the long-term outcomes of endovascular treatment (EVT) compared with best medical treatment (BMT). The objective of this study was to evaluate the long-term efficacy and safety of EVT in LVO stroke patients.

Methods: This study systematically searched electronic databases from January 2015 to August 2024 and included seven eligible trials. These studies reported 1-2 year of follow-up data on functional independence (modified Rankin Scale [mRS] score 0-2), distribution of mRS on shift analysis, quality of life (European Quality of Life 5-Dimensions Questionnaire score), and mortality.

Results: A total of 1,236 patients who received EVT and 1,122 who received BMT were included in the analysis. Compared with BMT, EVT was associated with a significantly greater likelihood of functional independence (odds ratio [OR] 2.55, 95% confidence interval [CI], 1.76-3.70), improved distribution of mRS scores on shift analysis (common OR 1.67, 95% CI, 1.37-2.02), and a better quality of life (beta coefficient 0.13, 95% CI, 0.07-0.19) at 1-2 years of follow-up. Compared with BMT, EVT was also associated with lower rates of all-cause mortality (OR 0.67, 95% CI, 0.56-0.81). Compared with 90-day follow-up, long-term follow-up demonstrated an improvement in functional independence among LVO stroke patients (1.7% vs. 0.2%), whereas the increase in mortality was slower (9.3% vs. 11.3%).

Conclusions: This meta-analysis indicated that LVO stroke patients can achieve long-term benefits following EVT. The findings provide valuable evidence to inform clinical decision-making.

Introduction: Antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by arterial and venous thrombosis. Acute ischemic stroke (AIS) and transient ischemic attack (TIA) are common neurological manifestations in APS patients. Cerebral microbleeds (CMB) are indicators for cerebral small vessel disease and associated with intracerebral hemorrhage (ICH) and AIS. In the present study, we aimed to look at the association and clinical significance of CMB in patients with APS.

Methods: This is a retrospective cohort study that utilized data obtained from health service data of more than 5 million patients. We included patients aged 18 and older diagnosed with APS who underwent brain MRI between January 2014 and April 2020 and an age-matched control group with negative APS laboratory results. APS diagnosis was confirmed by positive laboratory findings from two separate tests conducted at least 12 weeks apart. The first available brain MRI was assessed for the presence of CMB. We compared the prevalence of CMB between patients with APS and controls. Among APS patients, we assessed the association between CMB and future AIS/TIA or ICH during 48-month follow-up using Cox proportional hazards models.

Results: The study included 276 patients, of which 195 were in the APS group and 81 in the control group. Patients with APS exhibited a higher prevalence of CMB (16% vs. 4%, p < 0.01). Among the APS group, those with CMB had a significantly higher risk of subsequent AIS/TIA (hazard ratio = 8.5, 95% confidence interval [CI]: 3.1-23), cumulative incidence 30% (95% CI: 13%-50%). None of the patients with APS had ICH during follow-up.

Conclusion: Patients with APS have a higher prevalence of CMB compared with non-APS individuals, and the presence of CMB in APS patients is associated with an increased risk of AIS/TIA.

Introduction: The aim of the study was to investigate the rural-urban differences in acute stroke care in a large cohort of patients hospitalized for acute ischemic stroke (AIS), using a nationwide inpatient sample.

Methods: In this retrospective cohort study, the National Inpatient Sample database was investigated for patients admitted with AIS from 2016 to 2022. Sociodemographics and comorbidities were reviewed. Interventions (rtPA and thrombectomy) were investigated. Outcome measures were prolonged length of stay (PLOS) and mortality. PLOS was defined as length of stay exceeding the 75th percentile of the entire cohort. The cohort was divided in rural and urban location. Propensity score matching (PSM) was applied to balance demographics and comorbidities between the two groups, and outcomes were analyzed between the two matched groups. Multivariable logistic models were used to determine the association between each intervention and rural location. Risk ratio was calculated for PLOS and mortality. Subgroup analyses were performed by age, race, and income. p value was set at 0.05 for all analyses.

Results: Of 897,206 AIS patients, 64,640 (7.2%) were cared for in rural location. Rural group was older (74 [64-83] vs. 71 [60-81], p < 0.01 years). Rural group had higher rate of females (51.8% vs. 49%), white racial group (79.8% vs. 64.5%), lower median household income (54.3% vs. 29.1%), and lower private insurance (14.3% vs. 19.2%), p < 0.01 for all. After PSM 1:1, rural group independently retained lower odds of rtPA (OR: 0.532, 95% CI: 0.505-0.561), lower odds of thrombectomy (OR: 0.074, 95% CI: 0.061-0.089), lower risk of PLOS (RR: 0.887, 95% CI: 0.882-0.892), and higher risk of mortality (RR: 1.149, 95% CI: 1.122-1.177), p < 0.01 for all. Older patients in rural setting had lowest odds of interventions, whereas younger, Black, and Hispanic rural patients had highest risk of mortality after AIS.

Conclusions: Sociodemographic differences are present between rural and urban acute stroke care. Profound inequalities exist in the use of reperfusion therapy and outcomes. Great effort is needed by the stroke community to fill this gap and provide equality in acute stroke care.

Introduction: The effect of body mass index (BMI) on the outcome of acute cerebral large vessel occlusion (LVO) was uncertain in the era of endovascular therapy (EVT). We investigated the association between BMI and functional outcomes in patients with acute cerebral LVO.

Methods: We performed a post hoc analysis of the RESCUE-Japan Registry 2 including 2,408 LVO patients among 46 stroke centers in Japan. The patients were categorized into 3 groups depending on their BMI (kg/m2): Low-BMI group: BMI <18.5, Normal-BMI group: 18.5≤ BMI <25, and High-BMI group: BMI ≥25. We estimated the effect of the Low-BMI and High-BMI groups relative to the Normal-BMI group. The primary outcome was a modified Rankin Scale (mRS) score of 5 or 6 at 90 days from the onset. The secondary outcomes consisted of an mRS score of 0-2 at 90 days, symptomatic intracranial hemorrhage (ICH), and any ICH within 72 h from the onset.

Results: Among a total of 2,234 analyzed patients, Low-BMI, Normal-BMI, and High-BMI groups accounted for 14.5%, 63.7%, and 21.9%, respectively. The patients in the Low-BMI group were older, more female, poorer premorbid status, severe symptom presentation, and more dominant of occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. The Low-BMI group used less recombinant tissue plasminogen activator and EVT. The primary outcome occurred 46.4%, 31.2%, and 23.7% in the Low-BMI, Normal-BMI, and High-BMI groups, respectively. The adjusted odds ratios (ORs) (95% confidence intervals [CIs]) of the primary outcome of the Low-BMI and High-BMI groups relative to the Normal-BMI group were 1.59 (1.18-2.13) and 0.80 (0.60-1.07), respectively. The mRS score of 0-2 in the Low-BMI, Normal-BMI, and High-BMI groups consisted of 26.3%, 38.8%, and 41.9%, respectively. The adjusted OR (95% CIs) of an mRS score of 0-2 for the Low-BMI and High-BMI groups relative to the Normal-BMI group were 0.72 (0.53-0.99) and 0.83 (0.64-1.06), respectively. The adjusted OR (95% CIs) of symptomatic ICH of the Low-BMI and High-BMI groups relative to the Normal-BMI group were 1.57 (0.84-2.95) and 1.31 (0.75-2.29), respectively.

Conclusion: The low BMI was associated with a severity and poorer functional outcomes in patients with acute cerebral LVO.

Introduction: The focal cerebral hyperperfusion (CHP) is a potential complication after superficial temporal artery-middle cerebral artery (STA-MCA) bypass for moyamoya disease (MMD) that can result in delayed intracerebral hemorrhage and/or neurological deterioration. The focal CHP could accompany hemodynamic ischemia due to the "watershed shift (WS) phenomenon." Preoperative prediction of the focal CHP and WS phenomenon remains challenging. Here, we aimed to assess the diagnostic value of the "to and fro" conflict sign, conflicting blood flow around the vascular territory of the recipient arteries on an indocyanine green video angiography (ICG-VA) for predicting the focal CHP and WS phenomenon.

Methods: Ninety-seven consecutive adult patients with MMD, undergoing 106 surgeries, were enrolled. Serial quantitative analysis of cerebral blood flow was routinely conducted using n-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography preoperatively and postoperative day 1 and 7 after STA-MCA bypass. The association between the "to and fro" conflict sign on ICG-VA and the focal CHP/WS phenomenon incidence was then analyzed.

Results: The incidence of the focal CHP and WS phenomenon was 29.2% (31/106) and 10.4% (11/106), respectively. The "to and fro" conflict sign was evident in 35.5% (11/31) and 54.5% (6/11) of MMD patients with the focal CHP and WS phenomenon, respectively. The "to and fro" conflict sign was significantly associated with both the focal CHP and WS phenomena.

Conclusion: The "to and fro" conflict sign on ICG-VA may serve as an intraoperative warning sign of the focal CHP and WS phenomenon after STA-MCA bypass in adult patients with MMD, providing neurosurgeons with a valuable tool for early detection.