Cerebrovascular Diseases Extra最新文献

Introduction: Our research aimed to investigate the potential role and mechanism of lysyl oxidase (LOX)-like 2 (LOXL2) in atherosclerosis (AS) by using the human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL).

Methods: HUVECs were treated with ox-LDL at different concentrations (0, 10, 25, 50, and 100 μg/mL) and incubated for 24 h. The transfection efficacy of siLOXL2 was investigated by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Cell migration, intracellular ROS measurement, oxidative stress, enzyme-linked immunosorbent assay, and adhesion assays were carried out to examine the ox-LDL-induced HUVECs injury. RT-qPCR and Western blot were used to determine gene and protein expression levels.

Results: LOXL2 protein expression increased in ox-LDL-induced endothelial cells (ECs). ox-LDL + siLOXL2 significantly inhibited the migration ability of HUVECs and reduced the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 9 gene expressions (all, p < 0.05). The ox-LDL + siLOXL2 significantly reduced intracellular ROS production and inhibited the expression of Malondialdehyde, whereas it markedly enhanced superoxide dismutase and catalase (all, p < 0.05). Supernatant levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were significantly attenuated by the ox-LDL + siLOXL2 treatment (all, p < 0.05). ox-LDL + siLOXL2 markedly suppressed the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (all, p < 0.05). ox-LDL + siLOXL2 treatment remarkably reduced the expression of α-smooth muscle actin and vimentin, while increased CD31 and von Willebrand factor gene expression (all, p < 0.05).

Conclusion: LOXL2 silencing is protected against ox-LDL-induced EC dysfunction, and the mechanism may be related to the inhibition of the EndMT pathway.

Introduction: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities.

Methods: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments. Data will be extracted from included papers, including patient demographics, study methods, keystroke inclusion criteria, details of intervention and control, and the reported outcomes.

Result: "The best available studies" based on study design, study size, and/or date of publication for different therapies and stroke subtypes will be selected and graded for level of evidence by consensus.

Conclusion: There are conflicting study results of pharmacological interventions after an acute stroke to enhance recovery. This systematic search and review will identify the best evidence and knowledge gaps in the pharmacological treatment of post-stroke patients as well as guide clinical decision-making and planning of future studies.

Introduction: Moyamoya disease (MMD) is an uncommon cause of stroke. Antiplatelet treatment is commonly prescribed for patients with MMD despite the lack of strong evidence supporting its efficacy. We conducted a systematic review to evaluate evidence of antiplatelet treatment and clinical outcomes among patients with MMD.

Methods: A systematic literature search was performed to identify studies that evaluated the association between antiplatelet treatment and clinical outcomes, including ischemic stroke, hemorrhagic stroke, functional outcome, survival, and bypass patency, in patients with MMD. The following databases were searched: PubMed, Embase, Scopus, and the Cochrane Library, from the inception date to February 2022.

Results: Eight studies were included in this systematic review. Six studies evaluated antiplatelet treatment and ischemic stroke. Most studies did not demonstrate a protective effect of antiplatelet treatment against ischemic stroke. Five studies evaluated antiplatelet treatment and hemorrhagic stroke. All of them did not demonstrate an increased risk of hemorrhagic stroke. One study found the benefit of antiplatelet treatment in terms of survival. Regarding the effect of antiplatelet treatment on functional outcome and patency of surgical bypass, the results were inconclusive.

Conclusion: Current evidence suggests that antiplatelet treatment in patients with MMD did not demonstrate a protective effect against ischemic stroke. However, antiplatelet treatment did not increase the risk of hemorrhagic stroke in patients with MMD. The well-designed randomized controlled trial should be highlighted.

Introduction: The Hub-and-Spoke stroke system seeks to enhance the efficiency of stroke care by establishing a cohesive network between healthcare facilities providing quality stroke care to patients. This study endeavors to evaluate the effectiveness and characterize the outcomes of acute ischemic stroke patients treated within the Hub-and-Spoke hospital system over 2 years. The assessment focused on thrombolysis rates, mortality, and disability at 3-month follow-up.

Methods: We conducted a retrospective single-center review to assess the service delivery and outcomes of acute ischemic stroke patients within the Hub-and-Spoke framework which was implemented in Q3 2021. The Hub-and-Spoke model aimed to provide appropriate neurological care for stroke patients, growing from four to eight spoke hospitals in 2 years.

Results: The study consisted of 132 stroke patients transferred to the hub hospital, and 42 (31.8%) of them had acute ischemic stroke. Among these 42 ischemic stroke patients, 76% of them were candidates for thrombolysis with a mean NIHSS of 12 (6-22). Among the subset of 32 patients eligible for intervention within the specified time window, a total of 23 individuals, constituting 72% received r-TPA. Regarding patients administered r-TPA, 91.2% demonstrated favorable functional outcomes with an mRS score of 0-1, while 8.7% exhibited a score of 2-3. Among those not given r-TPA, the mean NIHSS was 17 (ranging from 2 to 32). Their functional outcomes after 3 months revealed 52.5% with an mRS score of 0-1, 16% with a score of 2-3, 21.2% with a score of 4-5, and 10.5% with an mRS score of 6.

Conclusion: Hub-and-Spoke networks represent a crucial advancement in stroke treatment, particularly for facilities lacking the capacity to manage strokes effectively. By leveraging added expertise and reducing the time from onset to diagnosis to treatment, these networks have significantly enhanced patient care. This enhancement is particularly evident in the increased rate of thrombolysis, resulting in reduced morbidity and prevention of mortality.

Introduction: Moyamoya disease (MMD) and non-MMD intracranial cerebral artery stenosis (ICAS) have been linked to the RNF213 rs112735431 gene in Korean and Japanese populations. This cross-sectional study investigates the prevalence of the RNF213 rs112735431 gene in non-cardioembolic ischemic stroke (NCIS) among Thai patients.

Methods: A cross-sectional investigation was conducted on patients aged 18 years or older admitted to King Chulalongkorn Memorial Hospital between June 2015 and March 2016 with acute NCIS. ICAS and extracranial carotid artery stenosis (ECAS) were assessed through computer tomography angiography or magnetic resonance angiography. Blood samples were collected, and Sanger sequencing was performed.

Results: Among 234 acute NCIS cases, 113 exhibited ICAS, 12 had ECAS, 20 had both, and 89 had neither. The RNF213 rs112735431 gene variant was detected in 2 patients, both heterozygous A/G. The frequency of the RNF213 rs112735431 variant was 0.9% (2/234; 95% CI: 0-2.1%) in acute NCIS patients and 1.8% (2/113; 95% CI: 0-4.2%) in ICAS. All individuals with the RNF213 variant were males with hypertension, diabetes mellitus, dyslipidemia, and ICAS, without a family history of ischemic stroke.

Conclusion: This study reveals that the RNF213 rs112735431 gene variant is uncommon among Thai NCIS patients, suggesting a discrepancy in the prevalence of this genetic variation between Thai and other Eastern Asian populations.

Background: Cerebral venous sinus thrombosis (CVT) is a life-threatening cause of stroke in Asian countries. South Asia, comprising of India, Pakistan, and Bangladesh, contributed to 40% of strokes in women. Major CVT registries are from the Western nations, which differs from the Asian countries with respect to epidemiology, gender biases, and risk factors. This review focuses on the various aspects of relevance in evaluation and management of patients with CVT in the Asian context.

Summary: The incidence of CVT is higher in Asia than in Western nations. Young age, female gender, especially in pregnancy and puerperal period, and dehydration appear to be the critical risk factors. Tropical infections like malaria, scrub typhus, and flaviviral encephalitis predispose to CVT. There is a higher prevalence of inherited thrombophilia in the Asian cohorts, contributing to prothrombotic states. Anticoagulation and supportive management offer excellent outcomes. Newer anticoagulants are safe and efficacious. In medically refractory cases, endovascular treatment offers modest benefits. Decompressive hemicraniectomy, when done early, offers mortality benefits in patients with large hemorrhagic venous infarctions.

Key messages: CVT is an important cause of stroke with a high burden in South Asian countries. Establishment of robust registries is the need of the hour to study the natural history, course, and outcomes and to develop management algorithms tailored to the available resources.

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is a cause of early onset ischemic lacunar stroke. COVID-19 infection may lead, in addition to acute respiratory syndrome, to vascular complications including stroke. Herein, we report three CADASIL patients presenting with cerebral border-zone infarcts concomitant to COVID-19 infection and summarize similar cases previously published in literature.

Methods: Clinical and radiological features of the 3 patients were collected and described. A narrative review of literature was performed in PubMed and Google Scholar by the end of 2022 using the "CADASIL" AND "COVID-19" AND "stroke" terms.

Results: In our 3 patients, aged 40-58 years, stroke symptoms occurred one to 11 days after the first COVID-19 manifestations. Pulmonary symptoms were mild or absent. One patient presented with hemodynamic failure presumably related to acute cardiomyopathy. Brain magnetic resonance imaging revealed in all cases, ischemic lesions within border-zone areas in both cerebral hemispheres, lesions in the genu of the corpus callosum or in the medium cerebellar peduncles in two cases. The watershed pattern of ischemic lesions was detected in two cases despite any blood pressure drop or severe respiratory dysfunction. Seven CADASIL patients presenting with acute brain infarcts (multiple in 4/7) in context of SARS-CoV-2 infection were identified in literature, despite no fall in blood pressure except for one of them.

Conclusion: Our observations, in line with previous reports, further suggest that COVID-19 infection may alter blood flow autoregulation in the deepest cerebral white matter in CADASIL patients. The thrombocytopathy and endotheliopathy developing during COVID-19 infection may participate to the underlying vascular processes.

Introduction: Early prediction of functional outcome after rtPA helps clinicians in prognostic conversations with stroke patients and their families. Three prognostic tools have been developed in this regard: DRAGON, MRI-DRAGON, and S-TPI scales. These tools, all performing with comparable accuracy, have been internally and externally validated in tertiary care centers. However, their performance in rural areas remains uncertain. This study addresses this gap in the literature by evaluating the effectiveness of those prognostic tools in stroke patients treated in a rural area of the Midwest.

Methods: We conducted a retrospective study of stroke patients treated with thrombolytics at Southern Illinois Healthcare Stroke Network from July 2017 to June 2024. Data on demographics, clinical presentations, laboratory values, neuroimaging, and stroke metrics were collected. Modified Rankin Scale (mRS) at 1 month, classified into good (mRS ≤2) and poor (mRS ≥5) outcomes were noted. DRAGON and MRI-DRAGON scores were calculated. S-TPI model was built. Area under the receiver operating characteristic curve (AUC) with its 95% confidence interval was calculated for each prognostic model.

Results: A total of 279 patients were included in this study. Of those, 43% (n = 119) were male. Median age (interquartile range [IQR]) was 69 (57-80) years. NIHSS at presentation (IQR) was 7 (4-13). 12% of the cohort (n = 34) had posterior circulation stroke. At 1 month, 66% of patients (n = 185) had mRS ≤2, whereas 14% of patients (n = 39) had mRS ≥5. MRI-DRAGON showed the highest accuracy in predicting both good (AUC = 0.86, 95% CI: 0.81-0.90) and poor outcomes (AUC = 0.84, 95% CI: 0.76-0.91). DRAGON also demonstrated high accuracy for good (AUC = 0.85, 95% CI: 0.80-0.89) and poor (AUC = 0.82, 95% CI: 0.75-0.90) outcomes. Conversely, in our population, the S-TPI model had the lowest accuracy for good (AUC = 0.56, 95% CI: 0.49-0.63) and poor (AUC = 0.68, 95% CI: 0.61-0.76) outcomes.

Conclusion: Among the available grading scores, MRI-DRAGON score can be considered the more accurate short-term prognostic tool for stroke patients treated with rtPA in the rural setting.

Background: Recent advances are in the genetics, diagnosis, pathophysiology, and management of moyamoya disease (MMD), and moyamoya syndrome (MMS), a term used to describe moyamoya-like vasculopathy associated with various systemic diseases or conditions.

Summary: Ring finger protein (RNF213) has been reported to be a susceptibility gene not only for MMD but also for atherosclerotic intracranial arterial stenosis and ischemic stroke attributable to large artery atherosclerosis. The latest guidelines by the Research Committee on MMD of the Japanese Ministry of Health, Labor, and Welfare, removed limitations of the previous definition that required bilateral involvement of the intracranial carotid artery to make the diagnosis, given the increasing evidence of progression to bilateral involvement in unilateral MMD. 3-dimensional constructive interference in steady-state MRI is useful for the differential diagnosis of MMD from atherosclerosis. Recent advances in the pathophysiology of MMD suggest that genetic and environmental factors play important roles in vascular angiogenesis and remodeling via complex mechanisms. The latest Japanese Guidelines and American Scientific Statement described that antiplatelet therapy can be considered reasonable. Endovascular interventional stent placement fails to prevent ischemic events and does not halt MMD progression. In the Japan Adult Moyamoya trial, a randomized controlled trial for bilateral extracranial-intracranial direct bypass versus conservative therapy in patients with MMD, who had intracranial hemorrhage, recurrent bleeding, completed stroke, or crescendo transient ischemic attack was significantly fewer with direct bypass than with conservative care.

Key messages: This review presents updated information on genetics, diagnosis, pathophysiology, and treatment of adult MMD and MMS. Despite recent advances, many mysteries still exist in the etiologies of moyamoya vasculopathy. The diagnostic criteria and treatment guidelines have been updated but not yet been globally established. Ongoing and future studies investigating underlying pathophysiological mechanisms of MMD and MMS may clarify potentially effective medical, surgical, or endovascular treatments.