Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial

BACKGROUND AND PURPOSE: Magnesium reverses cerebral vasospasm and reduces infarct volume after experimental subarachnoid hemorrhage (SAH) in rats. We aimed to assess whether magnesium reduces the frequency of delayed cerebral ischemia (DCI) in patients with aneurysmal SAH. METHODS: Patients were randomized within 4 days after SAH. Magnesium sulfate therapy consisted of a continuous intravenous dose of 64 mmol/L per day, to be started within 4 days after SAH and continued until 14 days after occlusion of the aneurysm. The primary outcome DCI (defined as the occurrence of a new hypodense lesion on computed tomography compatible with clinical features of DCI) was analyzed according to the "on-treatment" principle. For the secondary outcome measures "poor outcome" (Rankin >3) and "excellent outcome" (Rankin 0), we used the "intention-to-treat" principle. RESULTS: A total of 283 patients were randomized. Magnesium treatment reduced the risk of DCI by 34% (hazard ratio, 0.66; 95% CI, 0.38 to 1.14). After 3 months, the risk reduction for poor outcome was 23% (risk ratio, 0.77; 95% CI, 0.54 to 1.09). At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9). CONCLUSIONS: This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. A next step should be a phase III trial to confirm the beneficial effect of magnesium therapy, with poor outcome as primary outcom

Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5-14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (χ = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2-264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (χ = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p

Prevention and treatment of medical and neurological complications in patients with aneurysmal subarachnoid haemorrhage

Item does not contain fulltextTreatment of patients with aneurysmal subarachnoid haemorrhage not only involves securing the aneurysm by endovascular coiling or surgical clipping but also prevention and treatment of the medical and neurological complications of the bleed. These acutely ill patients should be looked after in specialised centres by a multidisciplinary team that is available 24 h a day, 7 days a week. No medical intervention is known to improve outcome by reducing the risk of rebleeding but oral nimodipine should be standard care to prevent delayed cerebral ischaemia. For patients who develop delayed ischaemia, there is no evidence that hypervolaemia, haemodilution, hypertension, balloon angioplasty or intra-arterial vasodilating agents improve outcome. Lumbar puncture is a safe and reasonably effective way of treating those forms of acute hydrocephalus that are not caused by intraventricular obstruction

Aneurysm occlusion in elderly patients with aneurysmal subarachnoid hemorrhage: a cost-utility analysis

BACKGROUND: Aneurysm occlusion after subarachnoid hemorrhage (SAH) aims to improve outcome by reducing the rebleeding risk. With increasing age overall prognosis decreases and the complications of aneurysm occlusion increase. The balance of risks for aneurysm occlusion in elderly SAH patients in different age categories and clinical conditions is unknown. METHODS: A Markov model was used to evaluate quality-adjusted life years (QALY), additional costs, and incremental cost-effectiveness ratios (ICER) of aneurysm occlusion in 192 patient subgroups, based on age, gender, neurological condition at admission, time since SAH, and aneurysm size and location. Probabilistic sensitivity analyses were performed. RESULTS: For patients admitted in poor condition >/=10 days after SAH, and patients older than 80 year, admitted in poor condition admitted >/=4 days after SAH, occlusion implied QALY loss and increased costs. Only for women younger than 79 and men younger than 74 years admitted in good condition within 4 days the ICER of occlusion fell below euro 50,000 per QALY. Occlusion was beneficial and cost-saving in women aged 74 years or younger admitted in good condition within 4 days and a small posterior circulation aneurysm. CONCLUSIONS: Aneurysm occlusion is harmful in some subgroups of elderly patients and beneficial in others. It is cost-effective only in specific subgroups that comprise a large part of the patients encountered in clinical practice. Beyond the age of 80 years the balance between risks and benefits is often no longer positive for occlusion, and it should only be considered if the predicted life expectancy leaves margin for benefit

Cost-effectiveness of preventive treatment of intracranial aneurysms. New data and uncertainties

BACKGROUND: Previous modeling studies on treatment of unruptured intracranial aneurysms largely disregarded detailed data on treatment risks and omitted several factors that could influence cost-effectiveness. We performed a cost-effectiveness analysis of surgical and endovascular treatment of unruptured aneurysms for different rupture rates and life expectancies, and assessed the influence of excess mortality risks in these persons, de novo development of aneurysms, and utility of awareness of having an untreated aneurysm, and also identified important factors for which data are lacking. METHODS: We used a Markov model to compare surgical, endovascular, and no treatment of unruptured intracranial aneurysms. Inputs for the model were taken mainly from meta-analyses. Direct medical costs were derived from Dutch cost studies and expressed in 2005 Euros. We performed sensitivity analyses to evaluate model robustness. RESULTS: For 50-year-old patients, treatment of unruptured aneurysms is cost-effective for all rupture rate scenarios between 0.3% and 3.5%/year. In 70-year-old patients, treatment is not cost-effective in men with rupture rates </=1%/year and women with rupture rates </=0.5%/year. With lower utility of awareness of an untreated aneurysm, the cost-effectiveness of treatment strongly increased. The effect of excess mortality risks on the incremental cost-effectiveness ratios was modest. The risk of formation of new aneurysms had no relevant impact. CONCLUSIONS: Patients' life expectancy, risk of rupture, and utility of awareness of an untreated aneurysm mainly define cost-effectiveness. However, important uncertainties remain on the rupture risk according to size and location of the aneurysm and on the utility of awareness of untreated aneurysm. More data on these factors are needed to define and individualize cost-effectiveness analyses

Risk of aneurysm rupture at intracranial arterial bifurcations.

Item does not contain fulltextBACKGROUND: Aneurysms on the posterior circulation, most commonly located at the basilar top, have a higher risk of rupture than aneurysms on the anterior circulation. If hemodynamic shear stress, which has its maximum impact at the distal carina of bifurcations, explains the higher rupture rate of basilar top aneurysms, aneurysms at the top of the carotid artery should have similar rupture rates given their geometrical similarities. AIM: Our purpose was to compare rupture risks of carotid and basilar artery bifurcation aneurysms. METHODS: We included studies from Medline and Embase searches and compared proportions of ruptured and unruptured aneurysms at the basilar and carotid bifurcation with the assumption that carotid aneurysms are twice as prevalent based on the presence of 2 carotid and 1 basilar artery bifurcation on the circle of Willis. Results: Of all unruptured aneurysms, 8.3% were located on the basilar and 6.0% on the carotid bifurcation; 8.0% of all ruptured aneurysms were located on the basilar and 4.3% on the carotid bifurcation. Subsequently the ratios of carotid versus basilar aneurysms were 0.72 for unruptured and 0.55 for ruptured aneurysms, instead of the expected 2.0. CONCLUSIONS: Aneurysms are less frequently located on the carotid than on the basilar artery bifurcation. The proportion of ruptured carotid aneurysms is smaller than that of unruptured carotid aneurysms, suggesting a lower rupture risk for aneurysms at the carotid artery bifurcation. The anatomical geometry of the bifurcations and concomitant hemodynamic stress are considered an unlikely explanation for the higher risk of posterior circulation aneurysms

Growth rates of intracranial aneurysms: exploring constancy

Object The annual rate of rupture of intracranial aneurysms is often assumed to be constant, but it is unknown whether this assumption is true. Recent case reports have suggested that aneurysms grow fast in a short period of time. The authors of the present report investigated the plausibility of a constant growth rate for intracranial aneurysms. Methods Assuming a constant aneurysm growth rate within an individual and varying rates between individuals, a hypothetical cohort was simulated. Individuals with high growth rates will display aneurysm formation and rupture at a young age; such persons disappear early from the hypothetical cohort. As a result the mean lesion growth rate varies over time. In hypothetical cohorts with different initial mean growth rates, the authors calculated age-specific incidence rates (per 100,000 person-years) of subarachnoid hemorrhage and compared these rates with population-based data on the incidence of subarachnoid hemorrhage (per 100,000 person-years). Results A hypothetical cohort with a mean initial growth rate of 0.18 mm/year reproduced most closely the incidence rates observed in the population. However, even for this most plausible hypothetical cohort, age-specific incidence rates in the model differed substantially and statistically significantly from those observed in the population. Conclusions Based on the results of this study, it is unlikely that intracranial aneurysms in general grow at a constant time-independent rate. The authors hypothesized that the actual growth process is irregular and discontinuous, which results in periods with and without aneurysm growth and with high and low risks of rupture

Outcome after intracranial haemorrhage from dural arteriovenous fistulae; a systematic review and case-series

Contains fulltext : 152558.pdf (publisher's version ) (Open Access)Dural arteriovenous fistulae (DAVFs) are a rare cause of intracranial haemorrhage. We aimed to investigate outcome of patients with intracranial haemorrhage from a DAVF. We performed a systematic literature search for studies reporting outcome after intracranial haemorrhage caused by a DAVF. We used predefined selection criteria and assessed the quality of the studies. In addition, we studied outcome in all patients with DAVF who had presented with intracranial haemorrhage at two university centers in the Netherlands, between January 2007 and April 2012. We calculated case fatality and proportions of patients with poor outcome (defined as modified Rankin Scale >/= 3 or Glasgow Outcome Scale </= 3) during follow-up. We investigated mean age, sex, mid-year of study and percentage of patients with parenchymal haemorrhage as determinants of case fatality and poor outcome. The literature search yielded 16 studies, all but two retrospective and all hospital-based. Combined with our cohort of 29 patients the total number of patients with DAVF-related intracranial haemorrhage was 326 (58 % intracerebral haemorrhage). At a median follow-up of 12 months case fatality was 4.7 % (95 % CI 2.5-7.5; 17 cohorts) and the proportion of patients with poor outcome 8.3 % (95 % CI 3.1-15.7; nine cohorts). We found no effect of mean age, sex, mid-year of the cohorts and percentage of patients with parenchymal haemorrhage on either outcome. Hospital based case-series suggest a relatively low risk of death and poor outcome in patients with intracranial haemorrhage due to rupture of a DAVF. These risks may be underestimated because of bias