New Insight into Cerebrovascular Diseases

“Brain circulation is a true road map that consists of large extended navigation territories and a number of unimagined and undiscovered routes.” Dr. Patricia Bozzetto Ambrosi This book combines an update on the review of cerebrovascular diseases in the form of textbook chapters, which has been carefully reviewed by Dr. Patricia Bozzetto Ambrosi, Drs. Rufai Ahmad and Auwal Abdullahi and Dr. Amit Agrawal, high-performance academic editors with extensive experience in neurodisciplines, including neurology, neurosurgery, neuroscience, and neuroradiology, covering the best standards of neurological practice involving basic and clinical aspects of cerebrovascular diseases. Each topic was carefully revised and prepared using smooth, structured vocabulary, plus superb graphics and scientific illustrations. In emphasizing the most common aspects of cerebrovascular diseases: stroke burden, pathophysiology, hemodynamics, diagnosis, management, repair, and healing, the book is comprehensive but concise and should become the standard reference guide for this neurological approach

Modelling the UK burden of cardiovascular disease to 2020

This new research report demonstrates the scale of the burden of cardiovascular disease (CVD) - shown to be large, costly, and increasing. Whilst mortality from CVD has fallen, an increasing population over the next decade will create further demands on services as the actual numbers of people living with CVD climb higher.<br /

Animal Models of Ischemic Stroke. Part One: Modeling Risk Factors

Ischemic stroke is one of the leading causes of long-term disability and death in developed and developing countries. As emerging disease, stroke related mortality and morbidity is going to step up in the next decades. This is both due to the poor identification of risk factors and persistence of unhealthy habits, as well as to the aging of the population. To counteract the estimated increase in stroke incidence, it is of primary importance to identify risk factors, study their effects, to promote primary and secondary prevention, and to extend the therapeutic repertoire that is currently limited to the very first hours after stroke. While epidemiologic studies in the human population are essential to identify emerging risk factors, adequate animal models represent a fundamental tool to dissect stroke risk factors to their molecular mechanism and to find efficacious therapeutic strategies for this complex multi- factorial disorder. The present review is organized into two parts: the first part deals with the animal models that have been developed to study stroke and its related risk factors and the second part analyzes the specific stroke models. These models represent an indispensable tool to investigate the mechanisms of cerebral injury and to develop novel therapies

Smoking, Respiratory Diseases and Endothelial Dysfunction

Vascular endothelium actively participates in inflammatory reactions in the majority of chronic respiratory diseases. Smoking is a major risk factor for bronchopulmonary diseases, and it plays an important role in endothelial dysfunction development. Some experiments prove that aggressive pollutants of tobacco smoke (benzopyrene, peroxynitrite, acrolein, cyanides, peroxides, etc.) can cause direct damage to endothelial cells due to expression of adhesion molecules on their surface and intensification of lipid peroxidation. In turn, oxidized lipoproteins in the tunica intima of the vessel work as attractants for chemotaxis of leukocytes and monocytes that start to produce pro-inflammatory cytokines in big amounts. These processes trigger systemic inflammatory response that leads to irreversible thickening of the vessel walls and deterioration of their mechanical properties. Chronic exposure to tobacco smoke and the products of combustion of tobacco leads to chronic system inflammatory reaction, oxidative stress, endothelial dysfunction and morpho-functional damage of target organs. Nowadays, the connection between chronic obstructive pulmonary disease (COPD) and some cardiovascular and cerebrovascular diseases has been well established. Studying the mechanisms of endothelial dysfunction in brain blood vessels of patients with smoking habits and COPD can be very important for preventing acute vascular events

Prevention of stroke: risk stratification and targeted and novel therapies

Stroke is a common disorder with dire consequences for the patient and for society and will increase in prevalence over the coming years. Following stroke, many patients unfortunately suffer a further stroke, and recurrent strokes account for approximately 25% of the total. Considerable scope therefore exists to improve both primary and secondary stroke prevention. This thesis has addressed several areas at key stages in the prevention of stroke by developing strategies to better identify those at highest risk, attempting to better target pre-existing anti-platelet therapy and by beginning the evaluation of xanthine oxidase reduction and uric acid lowering therapy in the prevention of stroke. A clinical scoring system to aid diagnostic recognition in those with suspected transient ischaemic attack (TIA) was successfully developed and has the ability to reduce the referral of those without cerebrovascular disease to busy TIA clinics. The score was developed on data from 3216 patients and included 9 clinically useful predictive variables. After adjustment to reflect the greater seriousness of missing true TIA patients, 97% of TIA and 22% of non-TIA patients were accurately identified. The results were confirmed during prospective validation. Use of the score could have a substantial effect on waiting times for assessment; there is potential double the numbers seen within the timeframe recommended by guidelines with no other change to services. This would be an important advance given the recent evidence that rapid assessment and treatment of those with TIA greatly reduces stroke risk. Aspirin resistance was found to be higher in those with cerebrovascular microembolic signals (MES) and carotid disease compared to those with equivalent carotid disease and no MES. This study included sixty-two patients who mostly had symptomatic carotid disease. Approximately a quarter had MES. The rate of aspirin resistance on at least one test was 25.8% (16 patients), with 13 (21%) resistant on PFA-100 testing, 8 (12.9%) using the Verify-Now system and 5 (8.1%) resistant on both. Aspirin resistance was more common in patients with MES (50% compared to 17.4% without, p=0.018 on Fishers exact test). This provides a link to a well established and robust surrogate marker of outcome and thus a useful model to further study the benefits of guided anti-platelet strategies. An interventional clinical anti-platelet trial based upon individual aspirin responsiveness in high risk individuals such as those with MES is now warranted. Aspirin resistance was also confirmed to be a common phenomenon in a case-control study of 180 patients. It was present in 34% of those with recent stroke and in 18% of those with risk factors but no established disease. However, the role of poor compliance with therapy as a cause in a substantial number of cases was established; it accounted for approximately half of those labelled resistant in the stroke group. Further, when only those with objective evidence of recent aspirin ingestion were considered, the prevalence of aspirin resistance was similar in both groups (at 26%). This suggests that objective measures to confirm compliance with aspirin therapy should be mandatory in future studies of aspirin resistance. Increasing serum uric acid was found to be a predictor of poor functional outcome following acute stroke but not in an independent fashion. In total, 852 patients were included in this study and greater uric acid levels were associated with increased odds of poor outcome on univariate but not multivariate analysis (OR 1.3, 95% CI 0.73-2.31). However, there was no evidence of an association with favourable outcome as other groups have found. Increasing serum uric acid was also shown to be predictive of increased risk of stroke, total, vascular and coronary mortality in treated hypertensive patients but interestingly, the relationship between stroke mortality and serum uric acid appears J-shaped and most apparent in females. A study of the use of allopurinol in those with diabetes showed that xanthine oxidase inhibition improves cerebral nitric oxide bioavailability suggesting a beneficial effect of allopurinol on cerebrovascular health. This study included 14 participants who had impaired baseline cerebrovascular nitric oxide bioavailability. Allopurinol led to a significant improvement in responses to NG-monomethyl-L-arginine (L-NMMA) when compared to placebo (p=0.032, median improvement in ICA flow reduction following L-NMMA of 3144 (95% CI 375 to 7143)) mls). L-NMMA is an inhibitor of endothelial nitric oxide synthase which reduces cerebral blood flow in healthy volunteers; the bigger the reduction, the greater the endothelial health. However, a study of the effect of allopurinol treatment on cerebrovascular reactivity (as measured by response to acetazolamide infusion) in a group of patients with recent subcortical stroke revealed no positive effect. Cerebrovascular reactivity was unchanged by treatment with allopurinol. This raises interesting questions regarding the longevity of any positive effect of allopurinol as this, and other studies of 3 month duration, have revealed no benefit. Further, subjects in this study did not, on balance, have elevated serum uric acid and it has recently been suggested that only those with significantly elevated levels benefit in the setting of congestive cardiac failure. Whether this is also true in those with stroke also requires to be clarified. A large study of the effect of allopurinol on carotid intima-media thickness, a robust and modifiable marker of vascular risk, in those with recent stroke is planned to address these questions. The studies in this thesis therefore include a number of pragmatic findings which could improve care at all stages in the prevention of stroke. The TIA scoring system could improve recognition of the high risk condition TIA, a useful model has been developed in which to study a population of patients truly resistant to aspirin and important lessons have been learned to aid further evaluation of xanthine oxidase inhibition; a promising therapy for the prevention of stroke

Clinical recurrent events after incident stroke or transient ischemic attack

Ischemic stroke survivors are at high risk of experiencing new or re-expressed focal neurological symptoms. This may be due to a recurrent stroke or due to other medical conditions, known as stroke mimics. Long-term outcomes after ischemic stroke are scarcely studied. In addition, distinguishing recurrent stroke from stroke mimics is challenging. Admissions with stroke mimics are resource-consuming and may be troublesome for the patients. Knowledge on recurrence, its associated factors, mortality and stroke mimics after ischemic stroke is of value in clinical decision-making. The present study investigated incidence, predictors and impact of recurrent stroke in a hospital-based ischemic stroke population. In addition, we investigated the burden of stroke mimics after ischemic stroke. This thesis is based on a hospital-based cohort of patients registered in the Norwegian Stroke Research Registry (NORSTROKE) at the stroke unit at the Department of Neurology, Haukeland University Hospital. A total of 1874 surviving patients who were admitted with ischemic stroke or transient ischemic attack (TIA) between July 1, 2007, and December 31, 2013 were followed for new hospital admissions with recurrent ischemic stroke/TIA or stroke mimics. The 30-day recurrence rate was 1.8%. Patients with large artery atherosclerosis and stroke of other etiology had increased risk of 30-day recurrence. The long-term recurrence rates were modest, being 5.4% and 11.3% at 1 and 5 years respectively. Hypertension, prior symptomatic stroke, chronic infarcts on MRI and increasing age were independently associated with long-term recurrence. Recurrence more than doubled the all-cause mortality. Stroke mimics were more common than recurrence after ischemic stroke or TIA. Stroke mimics were multi-etiological and unspecific diagnoses were most frequent directly after index stroke

Hypertension as a factor associated with hearing loss

SummaryAimTo identify likely association between blood hypertension and hearing loss. Design: A non-paired case-control study. Setting: Institutional work carried out at Universidade Norte do Paraná, in South Brazil.Material and Method154 cases and 154 controls, both genders, aged 45 to 64, included in the research after sample estimation. Methodology: Hypertension was verified through blood pressure readings and by a systematized questionnaire about hypertension and the use of medication for blood pressure. Hearing was assessed through tonal threshold audiometrics and audiologic anamneses. Non-conditional logistic regression was used in order to control likely confusion or modification of effect of other variables on interest associations.ResultsThere is a significant association between blood hypertension and hearing loss. Hearing loss in the population under study suggests that hypertension is an accelerating factor of degeneration of the hearing apparatus due to aging.ConclusionsThe results in this research, through evidence of association between blood hypertension and hearing loss, can allow for an integrated work of cardiologists, nephrologists, otorhinolaryngologists, audiologists and other health professionals concerned with alterations caused by blood hypertension