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"cerebrovascular disorders"
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Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress
Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson’s disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.
Journal Article
Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges
The term cerebral small vessel disease refers to a group of pathological processes with various aetiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. Age-related and hypertension-related small vessel diseases and cerebral amyloid angiopathy are the most common forms. The consequences of small vessel disease on the brain parenchyma are mainly lesions located in the subcortical structures such as lacunar infarcts, white matter lesions, large haemorrhages, and microbleeds. Because lacunar infarcts and white matter lesions are easily detected by neuroimaging, whereas small vessels are not, the term small vessel disease is frequently used to describe the parenchyma lesions rather than the underlying small vessel alterations. This classification, however, restricts the definition of small vessel disease to ischaemic lesions and might be misleading. Small vessel disease has an important role in cerebrovascular disease and is a leading cause of cognitive decline and functional loss in the elderly. Small vessel disease should be a main target for preventive and treatment strategies, but all types of presentation and complications should be taken into account.
Journal Article
Mechanical thrombectomy for basilar artery occlusion: efficacy, outcomes, and futile recanalization in comparison with the anterior circulation
BackgroundPerforming mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based.ObjectiveTo compare patients’ outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT.MethodsIn the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms.ResultsMT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 – 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 – 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO.ConclusionsIn selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR.Trial registration number NCT03496064
Journal Article
Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study
Background and purposeCOVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.Materials and methodsDemographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.ResultsOf 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3–127.9) vs 12.1 (0.1–212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3–20.0) vs 0.5 (0.1–20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%).ConclusionAcute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.
Journal Article
Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761
Background The Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer’s disease (AD). Methods To guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence‐based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease. Results Key randomized trials and robust meta‐analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761®versus placebo in patients with mild‐to‐moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk‐benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta‐analyses have not supported this association. Conclusions The Expert Group foresee an important role for EGb 761®, used alone or as an add‐on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.
Journal Article
Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial
Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease.
ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years.
ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.
Journal Article
Cytokines as therapeutic targets for cardio- and cerebrovascular diseases
Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.
Journal Article
Integrated care in atrial fibrillation: a systematic review and meta-analysis
ObjectiveAtrial fibrillation (AF) is an emerging global epidemic associated with significant morbidity and mortality. Whilst other chronic cardiovascular conditions have demonstrated enhanced patient outcomes from coordinated systems of care, the use of this approach in AF is a comparatively new concept. Recent evidence has suggested that the integrated care approach may be of benefit in the AF population, yet has not been widely implemented in routine clinical practice. We sought to undertake a systematic review and meta-analysis to evaluate the impact of integrated care approaches to care delivery in the AF population on outcomes including mortality, hospitalisations, emergency department visits, cerebrovascular events and patient-reported outcomes.MethodsPubMed, Embase and CINAHL databases were searched until February 2016 to identify papers addressing the impact of integrated care in the AF population. Three studies, with a total study population of 1383, were identified that compared integrated care approaches with usual care in AF populations.ResultsUse of this approach was associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80, p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77, p=0.0002) but did not significantly impact on AF-related hospitalisations (OR 0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI 0.48 to 2.09, p=1.00).ConclusionsThe use of the integrated care approach in AF is associated with reduced cardiovascular hospitalisations and all-cause mortality. Further research is needed to identify optimal settings, methods and components of delivering integrated care to the burgeoning AF population.
Journal Article
Impact of multiple pathologies on the threshold for clinically overt dementia
Longitudinal clinical–pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer’s disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis). These additional pathologies lower the threshold for clinical diagnosis of AD. Many of these findings from pathologic studies, especially for CVD, have been confirmed using sophisticated neuroimaging technologies. In vivo biomarker studies are necessary to provide an understanding of specific pathologic contributions and time course relationships along the spectrum of accumulating pathologies. In this review, we provide a clinical–pathological perspective on the role of multiple brain pathologies in dementia followed by a review of the available clinical and biomarker data on some of the mixed pathologies.
Journal Article