Diss. (sammanfattning) Göteborg : Univ., 2008. / Härtill 5 uppsatser.

Background: Primary subarachnoid hemorrhage (1°SAH) is an important disease that causes significant morbidity and mortality. The sparse Canadian epidemiologic literature on 1° SAH is outdated and relies on diagnostic coding for case ascertainment which misses true cases and incorrectly labels non-cases. Objectives: Primary objective was to identify all patients with 1° SAH presenting to the Ottawa Hospital (TOH) between July 1, 2002 and June 30, 2011 by deriving and validating a search algorithm using an enriched administrative database. Secondary objectives included: 1) determine incidence and case-fatality rates (CFR) of 1° SAH at TOH; and 3) derive and validate a method to identify 1° SAH using routinely collected administrative data. Methods: A cohort of 1° SAH patients were identified with a case-defining algorithm that was derived and validated using a combination of cerebrospinal fluid analysis results and text-search algorithms of both cranial imaging and post-mortem reports. The incidence of 1° SAH was calculated using the total number of hospital encounters over the same time period. CFR was calculated by linking to vital statistic data of hospitalized patients at discharge. An optimal1° SAH prediction model was derived and validated using binomial recursive partitioning built with independent variables obtained from routinely collected administrative data. Results: Using the case-defining algorithm, 831 patients were identified with a 1° SAH over the study period. Hospital incidence of 1° SAH was 17.2 events per 10,000 inpatient encounters (or 0.17% of encounters) with a case-fatality rate of 18.1%. A validated SAH prediction model based on administrative data using a recursive partitioning model had a sensitivity of 96.5% (95% CI 93.9-98.0), a specificity of 99.8% (95%CI 99.6-99.9), and a +LR of 483 (95% CI 254-879). This results in a post-test probability of disease of 45%. Conclusion: We identified almost all cases of 1° SAH at our hospital using an enriched administrative data. Accurately identifying such patients with routinely collected health administrative data is possible, providing important opportunities to examine and study this patient population. Further studies, involving multiple centres are needed to reproduce these results.

No description available.

BACKGROUND: Subarachnoid Hemorrhage (SAH) accounts for 3-5% of total stroke patients annually. Despite its rare incidence, SAH carries a 50% mortality rate. Survivors are often left with varying degrees of disability, many will never return to their previous jobs and require long-term care. One of the leading causes for this high mortality and morbidity rate in SAH is Delay Cerebral Ischemia (DCI). Researchers are now beginning to investigate neuroinflammation as the underlying cause for DCI. Studies have shown the activation of the innate immune system in the central nervous system is initiated by excess hemoglobin in the subarachnoid space. This process is mediated by the Toll-Like Receptor 4 expressed on the tissue-resident macrophages. Activated macrophages release pro-inflammatory cytokines and cause neuronal apoptosis in the surrounding tissue. However, macrophages may also mediate neuroprotection in SAH. A macrophage surface receptor called CD163 is responsible for the recognition and endocytosis of excess hemoglobin. The thesis provides a closer assessment of the neuroprotective role of macrophages in SAH patients. METHODS: Cerebrospinal fluid (CSF) was obtained from twenty three patients diagnosed with SAH (on day 1 and day 7 post-admission) or unruptured aneurysms. Immune cells were separated from CSF and analyzed by flow cytometry. The following antibody panel was used in this study: PE-anti-CD163, PeCy7-anti-CD15, and APC-anti-CD14. Macrophage expression of CD14 and CD163 was quantified using FlowJo. SAH patients were graded by the Hunt and Hess scale for the clinical states upon admission; modified Fisher scale for the size of the hemorrhage; and modified Rankin scale for clinical outcome at the time of discharge. RESULTS: Significant increase in macrophage CD14 and CD163 expression is observed in day 1 SAH patients (p<0.05) as compared to the control group. Male SAH patients have equivocal macrophages CD163 expression on day 1 as compared to the control group (p>0.05), and significantly higher expression on day 7 as compared to day 1(p<0.05). Female SAH patients have significantly higher macrophages CD163 expression on day 1 as compared to control patients (p<0.05), but slightly decreased expression on day 7 as compared to day 1(p>0.05). Lower macrophages CD163 expression is observed in SAH patients with more severe hemorrhage (marked by higher modified Fisher score), but not in patients with more severe clinical states at admission (marked by higher Hunt and Hess score). Furthermore, SAH patients with low day 1 macrophage CD163 expression and low expression on day 7 may be correlated with better clinical outcome (marked by lower modified Rankin score). However, more patients are required before correlation can be established. CONCLUSION: The data further support our previous findings in mouse SAH model that macrophages in the central nervous system may mediate inflammation via the increased expression TLR4, measured by increased expression of its co-receptor CD14. Macrophages also may be neuroprotective, mediated by increased expression of CD163 in SAH patients. The macrophage CD163 expression may be the key in determining clinical outcome in SAH patients, but additional patients are required to establish statistical significance. / 2017-06-16T00:00:00Z

Aneurysmal subarachnoid haemorrhage (SAH) accounts for only 3-5% of all strokes but has the highest morbidity and mortality rates among all types of stroke. Experimental studies have confirmed that magnesium inhibits excitatory amino acid (EAA) release, blocks N-methyl-D-aspartate (NMDA) receptors and prevents calcium from entering cells. These changes may minimise neuronal injury during episodes of cerebral vasospasm. / Based on the aforementioned biological evidence, a pilot study of magnesium sulphate (MgSO4) infusion for aneurysmal SAH was conducted. This pilot study indicated that MgSO4 infusion for aneurysmal SAH is safe and has the potential to improve clinical outcomes. The pilot study results are supported by the findings of other research groups. / In summary, our results do not support a clinical benefit of intravenous magnesium sulphate infusion in patients with acute aneurysmal SAN. / Studies were carried out to investigate the distribution of magnesium in the cerebrospinal fluid (CSF) and the brain after intravenous magnesium sulphate infusion. We found that magnesium sulphate infusion resulted in an 11% to 21% increase in CSF magnesium, which was sustained for at least nine days. We further investigated intracellular free magnesium using 31 P-MRS, in aneurysmal SAH patients receiving and not receiving intravenous magnesium sulphate infusion. Intravenous magnesium sulphate infusion was found to produce a significant increase (15.6%) in the level of intracellular free magnesium during the first week, which covered the time frame required for neuroprotection, to improve outcomes in patients with aneurysmal SAH. / Three hundred and twenty-seven patients with aneurysmal SAH were recruited and randomly assigned to receive magnesium sulphate infusion or a saline placebo for 10 to 14 days. In the primary outcome analysis, the proportions of patients with a favourable outcome at six months (Extended Glasgow Outcome Scale [GOSE] score of 5-8) were similar, 64% in the MgSO4 group and 63% in the saline group (OR 1.0, 0.7-1.6). In the secondary outcome analyses, there were also no significant differences between the two groups. Analysis of the plasma magnesium concentration levels did not suggest that higher levels of plasma magnesium concentration result in better clinical outcomes. / Wong Kwok Chu. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 132-152). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

The ability of the brain to keep a stable and adequate cerebral blood flow (CBF) independently of fluctuations in systemic blood pressure is referred to as cerebral pressure autoregulation (CPA). When the brain is injured by trauma or hemorrhage, this ability may be impaired, leaving the brain vulnerable to events of high or low blood pressure. The aims of this thesis were to study CPA in patients with severe traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH), the relation between CPA and other physiological parameters, and the influence of CPA on outcome. Four retrospective studies are included in the thesis. All patients were treated at the neurointensive care unit, Uppsala University hospital. In paper I, 58 TBI patients were studied. In patients with impaired CPA, cerebral perfusion pressure between 50-60 mm Hg was associated with favorable outcome while CPP &gt; 70 and &gt;80 mm Hg was associated with unfavorable outcome. In patients with intact CPA there was no association between CPP and outcome. In paper II, 107 TBI patients were studied. High CPP was associated with unfavorable outcome in patients with focal injuries. In patients with diffuse injury and impaired CPA, CPP &gt; 70 mm Hg was associated with favorable outcome. In paper III, 47 SAH patients were studied. CBF was measured bedside with Xenon-enhance CT (Xe-CT). Patients with impaired CPA had lower CBF, both in the early (day 0-3) and late (day 4-14) acute phase of the disease. In paper IV, 64 SAH patients were studied. Optimal CPP (CPPopt) was calculated automatically as the level of CPP where CPA works best for the patient, i.e., where PRx is lowest. Patients with actual CPP below their calculated optimum had higher amounts of low-flow regions (CBF &lt; 10 ml/100g/min). The findings in this thesis emphasize the importance of taking CPA into account in the management of TBI and SAH patients, and suggest that treatment should be individualized depending on status of autoregulation. PRx and CPPopt may be used bedside to guide management according to status of autoregulation. In the future CPA-guided management should be tested in prospective studies

No description available.

Subarachnoid hemorrhage (SAH) comprises 7% of all stroke cases, and is associated with a disproportionately high morbidity and mortality with few therapeutic options available. The goal of this project was to understand the mechanism of neurological deterioration after experimental SAH, with a focus on cerebral vasospasm and brain injury after SAH. We tested the hypothesis that endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled after SA, resulting in exacerbated neurological injury in a mouse model of SAH. The project entailed the investigation of eNOS-dimer uncoupling, its association with oxidative and nitrosative stress in the brain parenchyma and finally its association with secondary complications after SAH. In our studies we demonstrated the crucial role eNOS plays in anti-microthromboembolism, anti-apoptosis and maintenance of physiological superoxide (O2-)/NO balance. This study suggests that SAH up-regulates and disrupts eNOS, producing peroxynitrite (OONO-) and other radicals that further exacerbate the oxidative insult and neurological injury.

Subarachnoid hemorrhage (SAH) comprises 7% of all stroke cases, and is associated with a disproportionately high morbidity and mortality with few therapeutic options available. The goal of this project was to understand the mechanism of neurological deterioration after experimental SAH, with a focus on cerebral vasospasm and brain injury after SAH. We tested the hypothesis that endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled after SA, resulting in exacerbated neurological injury in a mouse model of SAH. The project entailed the investigation of eNOS-dimer uncoupling, its association with oxidative and nitrosative stress in the brain parenchyma and finally its association with secondary complications after SAH. In our studies we demonstrated the crucial role eNOS plays in anti-microthromboembolism, anti-apoptosis and maintenance of physiological superoxide (O2-)/NO balance. This study suggests that SAH up-regulates and disrupts eNOS, producing peroxynitrite (OONO-) and other radicals that further exacerbate the oxidative insult and neurological injury.

Cerebral vasospasm following subarachnoid hemorrhage has high morbidity and mortality. Mathematical modeling of the progression of the condition provides insight to improve clinical treatment of patients post subarachnoid hemorrhage. An existing model of the clotting cascade is expanded to include the theoretical conditions of cerebral vasospasm. We consider clotting factor XIIIa, which has been implicated as a primary cause of the entrenchment of the smaller diameter. Solutions for clotting are used as boundary conditions to solve the concentration of diffusible clotting factors in the vessel wall and cerebrospinal fluid (CSF). Each domain (clot, vessel wall, CSF) is described by a separate initial-boundary value problem, requiring unique conditions, reaction-diffusion equations, and diffusion coefficients. Additionally, the results from the first domain (the clot) provide a subset of the boundary conditions for the second and third domains (arterial wall and CSF, respectively). Although this approach captures many detailed components of the clotting process, a simpler method for investigating the formation and dissolution of a clot post subarachnoid hemorrhage is to neglect the bulk of the clot cascade to focus on the most salient features, namely, the formation of cross-linked fibrin and the degradation of fibrin by plasmin. By assuming first order kinetics in the initial hours following hemorrhage, we find a simplified expression with kinetic rates that may be adjusted depending on experimental conditions.