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Abstract BACKGROUND Stress is associated with increased risk of stroke and might predispose to presence and rupture of intracranial aneurysms. OBJECTIVE To study the association of recent and lifelong stress with unruptured intracranial aneurysm (UIA) and aneurysmal subarachnoid hemorrhage (ASAH). METHODS In 227 UIA patients (mean age 61 ± 11 yr), 490 ASAH patients (59 ± 11 yr), and 775 controls (51 ± 15 yr) who were randomly retrieved from the general population, we assessed occurrence of major life events and perceived stress during the preceding 12 mo and the entire life. With multivariable logistic regression analysis, we calculated odds ratios (ORs) with 95% confidence intervals (95% CIs) for 4 categories of life events (financial-related, work-related, children-related, and death of family members) and for periods of perceived stress at home and at work (never vs sometimes, often, or always). We adjusted for sex, age, alcohol consumption, smoking, and hypertension. RESULTS The 4 categories of life events and perceived stress at work had ORs ranging from 0.4 to 1.7, of which financial stress for UIA was statistically significant (95% CI: 1.1-2.5). ORs for chronic perceived stress at home in the previous year were 4.3 (95% CI: 1.8-10.3) for UIA and 2.5 (1.2-5.5) for ASAH, and for lifelong exposure 5.7 (2.2-14.5) for UIA and 3.0 (1.3-7.0) for ASAH. CONCLUSION For some components of stress, there may be a relation with UIA and ASAH. The mechanisms underlying this relation should be unraveled; strategies to improve coping with stress may reduce the risk of rupture in patients with unruptured aneurysms.

This prospective study is designed to detect changes in the treatment of ruptured intracranial aneurysms over a period of 17 years. We compared 361 treated cases of aneurysm occlusion after subarachnoid hemorrhage from 1997 to 2003 with 281 cases from 2006 to 2014. Specialists of neuroradiology and vascular neurosurgery decided over the modality assignment. We established a prospective data acquisition in both groups to detect significant differences within a follow-up time of one year. With this setting we evaluated the treatment methods over time and compared endovascular with microsurgical treatment. When compared to the earlier group, microsurgical treatment was less frequently chosen in the more recent collective because of neck-configuration. Endovascular treatment was chosen more frequently over time (31.9% versus 48.8%). Occurrence of initial symptomatic ischemic stroke was significantly lower in the clipping group compared to the endovascular group and remained stable over time. The number of reinterventions due to refilled treated aneurysms significantly decreased in the endovascular group at one-year follow-up, but the significantly better occlusion- and reintervention-rate of the microsurgical group persisted. The rebleeding rate in the endovascular group at one year follow-up decreased from 6.1% to 2.2% and showed no statistically significant difference to the microsurgical group, anymore (endovascular 2.2% versus microsurgical 0.0%, p = 0.11). Microsurgical clipping still has some advantages, however endovascular treatment is improving rapidly.

Cerebral infarction would be expected to be associated with poor outcome after aneurysmal subarachnoid hemorrhage (SAH), although there are few data on which to base this assumption. The goals of this study were to determine the impact of cerebral infarction on outcome and to examine predictors of infarction in these patients. Univariate and multivariable statistical methods were used to examine the impact of cerebral infarction on the Glasgow Outcome Scale score 3 months after SAH among 3567 patients entered into four prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997. Patient demographics, clinical variables, radiographic characteristics, and treatment variables associated with cerebral infarction were also determined by the same methods. Seven hundred and seven (26%) out of 2741 patients with complete data had cerebral infarction on computed tomographic scans 6 weeks after SAH. Multivariable logistic regression showed that cerebral infarction increased the odds of unfavorable outcome by a factor of 5.4 (adjusted odds ratio, 5.4; 95% confidence interval, 4.2-6.8; P < 0.0001), which was a higher odds ratio than all other factors associated with outcome. The proportion of explained variance in outcome was also highest for cerebral infarction and accounted for 39% of the explained variance. Multivariable analysis found that cerebral infarction was significantly associated with increasing patient age, worse neurological grade on admission, history of hypertension or diabetes mellitus, larger aneurysm, use of prophylactically or therapeutically induced hypertension, temperature more than 38 degrees C 8 days after SAH, and symptomatic vasospasm. Cerebral infarction was strongly associated with poor outcome after aneurysmal SAH. The most important potentially treatable factor associated with infarction was symptomatic vasospasm.

Objective The objective of this study was to compare the relative number of complications from peripherally inserted central venous catheters (PICC) and centrally inserted central venous catheters (CVC) in the neuroscience intensive care unit (NSICU). Methods This study was carried out in a 32-bed NSICU in a large academic hospital in the USA from July 2015 until January 2017. Patients admitted requiring central venous access were randomly assigned to have a PICC or CVC inserted. Complications were recorded and compared. The primary outcome was all complications as well as combined numbers of large vein thrombosis, central-line-associated blood stream infections, and insertional trauma. Outcomes were compared using the Fisher’s exact test, logistic regression, or unpaired T tests, as appropriate. Results One hundred and fifty-two patients were enrolled; 72 were randomized to the PICC arm and 80 to the CVC arm. There were no crossovers, withdrawals, nor losses to follow-up. The study was stopped at the second pre-planned interim analysis for futility. The combined number of large vein thrombosis, central-line-associated blood stream infection, and insertional trauma was 4/72 in the PICC arm and 1/80 in the CVC group (OR 4.6 (95% CI 0.5–42.6) p  = 0.14). The number of all complications in the PICC arm was 14/72 compared to 10/80 in the CVC arm (OR 1.7 (95% CI 0.7–4.1) p  = 0.24). Conclusions PICCs and CVCs have similar numbers of complications when placed in patients admitted to the NSICU.

Background and Purpose In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH. Methods Forty-four patients with SAH and high risk for vasospasm were randomized to goal HGB concentration of at least 10 or 11.5 g/dl. We obtained blinded clinical outcomes at 14 days (NIH Stroke Scale and modified Rankin Scale, mRS), 28 days (mRS), and 3 months (mRS), and blinded interpretation of brain MRI for cerebral infarction at 14 days. This trial is registered at www.stroketrials.org . Results Forty-four patients were randomized. Patients with goal HGB 11.5 g/dl received more PRBC units per transfusion [1 (1–2) vs. 1 (1–1), P  < 0.001] and more total PRBC units [3 (2–4) vs. 2 (1–3), P  = 0.045]. Prospectively defined safety endpoints were not different between groups. HGB concentration was different between study groups from day 4 onwards. The number of cerebral infarctions on MRI (6 of 20 vs. 9 of 22), NIH Stroke Scale scores at 14 days [1 (0–9.75) vs. 2 (0–16)], and rates of independence on the mRS at 14 days (65% vs. 44%) and 28 days (80% vs. 67%) were similar, but favored higher goal HGB ( P  > 0.1 for all). Conclusions Higher goal hemoglobin in patients with SAH seems to be safe and feasible. A phase III trial of goal HGB after SAH is warranted.

Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Bill & Melinda Gates Foundation.

Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage. However, no clinical data are available to answer whether a high-dose regimen is more effective than a normal-dose regimen, even though the biochemical actions and related neuroprotective mechanisms are thought to be dose related. To determine whether 80 mg simvastatin daily (high dose) over 3 weeks initiated within 96 hours of the ictus will reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with 40 mg simvastatin daily (normal dose), leading to improvements in clinical outcomes and thus cost-effectiveness. The study design is a randomized, controlled, double-blind clinical trial (www.ClinicalTrials.gov; identifier: NCT01077206). Two hundred forty patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers are being recruited over 3 years. The primary outcome measure is the presence of delayed ischemic deficits. Secondary outcome measures include modified Rankin Disability Score at 3 months and cost-effectiveness analysis. This will be the first study to clarify whether high-dose simvastatin is better than normal-dose simvastatin for patients with acute aneurysmal subarachnoid hemorrhage in terms of neurological outcomes and cost-effectiveness. In the present trial, we compare high-dose and normal-dose simvastatin; we know that another ongoing phase III multicenter trial (Simvastatin in Aneurysmal Subarachnoid Haemorrhage; http://www.stashtrial.com/home.html) is comparing normal-dose and no simvastatin. When the results are interpreted together, the research question of a possible beneficial effect of high-dose simvastatin in acute aneurysmal subarachnoid hemorrhage could be answered.

Subarachnoid haemorrhage is an uncommon and severe subtype of stroke affecting patients at a mean age of 55 years, leading to loss of many years of productive life. The rupture of an intracranial aneurysm is the underlining cause in 85% of cases. Survival from aneurysmal subarachnoid haemorrhage has increased by 17% in the past few decades, probably because of better diagnosis, early aneurysm repair, prescription of nimodipine, and advanced intensive care support. Nevertheless, survivors commonly have cognitive impairments, which in turn affect patients' daily functionality, working capacity, and quality of life. Additionally, those deficits are frequently accompanied by mood disorders, fatigue, and sleep disturbances. Management requires specialised neurological intensive care units and multidisciplinary clinical expertise, which is better provided in high-volume centres. Many clinical trials have been done, but only two interventions are shown to improve outcome. Challenges that remain relate to prevention of subarachnoid haemorrhage by improved screening and development of lower-risk methods to repair or stabilise aneurysms that have not yet ruptured. Multicentre cooperative efforts might increase the knowledge that can be gained from clinical trials, which is often limited by small studies with differing criteria and endpoints that are done in single centres. Outcome assessments that incorporate finer assessment of neurocognitive function and validated surrogate imaging or biomarkers for outcome could also help to advance the specialty.

Introduction Endovascular treatment of cerebral aneurysms includes follow-up imaging to identify aneurysms that may need retreatment. The aim of this study was to determine predictors of incomplete aneurysm occlusion at 1 year after endovascular coiling for ruptured cerebral aneurysms. Methods In 129 patients of the Prospective Registry of Subarachnoid Aneurysms Treatment cohort, ruptured aneurysms were coiled within 14 days of onset and both initial post-coiling and 1-year follow-up digital subtraction angiography or magnetic resonance angiography were obtained. Factors predicting 1-year incomplete aneurysm occlusion (retreatment within 1-year or residual aneurysms at 1 year) were determined using multivariate logistic regression analyses. Results One-year incomplete aneurysm occlusion was identified in 59 patients, including ten patients who were retreated within 1-year post-coiling. Dome size ≥7.5 mm ( P  = 0.007, odds ratio (OR) = 5.00, 95% confidence interval (CI) = 1.55–16.15), pre-treatment aneurysm re-rupture ( P  = 0.023, OR = 3.50, 95% CI = 1.19–10.31), non-small size/small neck aneurysm (dome size, ≥10 mm or neck size, ≥4 mm; P  = 0.022, OR = 3.26, 95% CI = 1.19–8.96), and residual aneurysms on immediate post-coiling angiograms ( P  = 0.017, OR = 1.43, 95% CI = 1.07–1.93) significantly predicted incomplete aneurysm occlusion at 1-year post-coiling. Conclusions In addition to the characteristics of aneurysm and initially incomplete aneurysm occlusion, this study showed pre-treatment aneurysm re-rupture to be a predictor that favors closer imaging follow-ups for coiled aneurysms.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a neurologic emergency that typically warrants initial monitoring in a critical care setting. The aim of this study is to identify clinical and radiologic features on admission that predict a protracted critical care admission following aSAH. Methods Exploratory posthoc analysis was performed on the 413 patients enrolled in Clazosentan to Overcome Neurological iSChemia and Infarction OccUrring after Subarachnoid hemorrhage (CONSCIOUS-1), a prospective randomized control trial of clazosentan for the prevention of vasospasm after aSAH. The association between potential clinical and radiographic covariates, and the length of stay (LOS) in a critical care unit after aSAH was determined using a Cox proportional hazards model. Covariates with a significance level of p  < 0.20, on univariate analysis, were entered into a multivariate forward conditional analysis to identify independent predictors of prolonged LOS. Results The mean LOS was 12.6 ± 10.6 days. On multivariate analysis, age (hazard ratio [HR] 1.01, 95 % confidence interval [CI] 1.00–1.02; p  = 0.032), a history of hypertension (HR 1.30, CI 1.01–1.67; p  = 0.045), and a World Federation of Neurosurgical Societies Score of IV–V on admission (HR 1.38, CI 1.05–1.81; p  = 0.02) were the clinical features associated with a greater critical care LOS following aSAH. Intracerebral hemorrhage (HR 1.50, CI 1.03–2.21; p  = 0.004) and increasing intraventricular clot burden (HR 1.08, CI 1.03–1.14; p  = 0.037) on admission computed tomography were the radiologic features associated with prolonged LOS. Conclusions We have identified several early risk factors associated with a prolonged critical care stay following aSAH.