Summary More and more patients survive aneurysmal subarachnoid haemorrhage (aSAH), with case fatality decreasing by 17% in absolute terms over the past three decades and incidence remaining ...relatively stable at nine per 100 000 patient-years. The mean age at which aSAH occurs is reasonably young at 55 years, and people of this age in the general population have a good life expectancy. However, there are few data for life expectancy after aSAH, and the risks of late recurrent aSAH and other vascular diseases are unclear. The course of associated long-term physical and cognitive deficits after aSAH is not well established, leading to questions about potential outcomes to quality of life and working capacity, as well as best clinical practices.
Subarachnoid haemorrhage van Gijn, Jan, Prof; Kerr, Richard S, Mr; Rinkel, Gabriel JE, Prof
The Lancet (British edition),
01/2007, Letnik:
369, Številka:
9558
Journal Article
Recenzirano
Summary Subarachnoid haemorrhage accounts for only 5% of strokes, but occurs at a fairly young age. Sudden headache is the cardinal feature, but patients might not report the mode of onset. CT brain ...scanning is normal in most patients with sudden headache, but to exclude subarachnoid haemorrhage or other serious disorders, a carefully planned lumbar puncture is also needed. Aneurysms are the cause of subarachnoid haemorrhage in 85% of cases. The case fatality after aneurysmal haemorrhage is 50%; one in eight patients with subarachnoid haemorrhage dies outside hospital. Rebleeding is the most imminent danger; a first aim is therefore occlusion of the aneurysm. Endovascular obliteration by means of platinum spirals (coiling) is the preferred mode of treatment, but some patients require a direct neurosurgical approach (clipping). Another complication is delayed cerebral ischaemia; the risk is reduced with oral nimodipine and probably by maintaining circulatory volume. Hydrocephalus might cause gradual obtundation in the first few hours or days; it can be treated by lumbar puncture or ventricular drainage, dependent on the site of obstruction.
Summary Background Since the early 1980s, imaging techniques have enabled population-based studies of intracerebral haemorrhage. We aimed to assess the incidence, case fatality, and functional ...outcome of intracerebral haemorrhage in relation to age, sex, ethnic origin, and time period in studies published since 1980. Methods From PubMed and Embase searches with predefined inclusion criteria, we identified population-based studies published between January, 1980, and November, 2008. We calculated incidence and case fatality. Incidences for multiple studies were pooled in a random-effects binomial meta-analysis. Time trends of case fatality were assessed with weighted linear-regression analysis. Findings 36 eligible studies described 44 time periods (mid-year range 1983–2006). These studies included 8145 patients with intracerebral haemorrhage. Incidence did not decrease between 1980 and 2008. Overall incidence was 24·6 per 100 000 person-years (95% CI 19·7–30·7). Incidence was not significantly lower in women than in men (overall incidence ratio 0·85, 95% CI 0·61–1·18). Using the age group 45–54 years as reference, incidence ratios increased from 0·10 (95% CI 0·06–0·14) for people aged less than 45 years to 9·6 (6·6–13·9) for people older than 85 years. Median case fatality at 1 month was 40·4% (range 13·1–61·0) and did not decrease over time, and was lower in Japan (16·7%, 95% CI 15·0–18·5) than elsewhere (42·3%, 40·9–43·6). Six studies reported functional outcome, with independency rates of between 12% and 39%. Incidence of intracerebral haemorrhage per 100 000 person-years was 24·2 (95% CI 20·9–28·0) in white people, 22·9 (14·8–35·6) in black people, 19·6 (15·7–24·5) in Hispanic people, and 51·8 (38·8–69·3) in Asian people. Interpretation Incidence of intracerebral haemorrhage increases with age and has not decreased between 1980 and 2006. Case fatality is lower in Japan than elsewhere, increases with age, and has not decreased over time. More data on functional outcome are needed. Funding Netherlands Heart Foundation.
Summary Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed ...cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage. Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio RR 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·84–1·10). Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. Funding Netherlands Heart Foundation, UK Medical Research Council.
Summary Background In a systematic review, published in 1997, we found that the case fatality of aneurysmal subarachnoid haemorrhage (SAH) decreased during the period 1960–95. Because diagnostic and ...treatment strategies have improved and new studies from previously non-studied regions have been published since 1995, we did an updated meta-analysis to assess changes in case fatality and morbidity and differences according to age, sex, and region. Methods A new search of PubMed with predefined inclusion criteria for case finding and diagnosis identified reports on prospective population-based studies published between January, 1995, and July, 2007. The studies included in the previous systematic review were reassessed with the new inclusion criteria. Changes in case fatality over time and the effect of age and sex were quantified with weighted linear regression. Regional differences were analysed with linear regression analysis, and the regions of interest were subsequently defined as reference regions and compared with the other regions. Findings 33 studies (23 of which were published in 1995 or later) were included that described 39 study periods. These studies reported on 8739 patients, of whom 7659 88% were reported on after 1995. 11 of the studies that were included in the previous review did not meet the current, more stringent, inclusion criteria. The mean age of patients had increased in the period 1973 to 2002 from 52 to 62 years. Case fatality varied from 8·3% to 66·7% between studies and decreased 0·8% per year (95% CI 0·2 to 1·3). The decrease was unchanged after adjustment for sex, but the decrease per year was 0·4% (−0·5 to 1·2) after adjustment for age. Case fatality was 11·8% (3·8 to 19·9) lower in Japan than it was in Europe, the USA, Australia, and New Zealand. The unadjusted decrease in case fatality excluding the data for Japan was 0·6% per year (0·0 to 1·1), a 17% decrease over the three decades. Six studies reported data on case morbidity, but these were insufficient to assess changes over time. Interpretation Despite an increase in the mean age of patients with SAH, case-fatality rates have decreased by 17% between 1973 and 2002 and show potentially important regional differences. This decrease coincides with the introduction of improved management strategies. Funding Netherlands Organisation for Scientific Research; ZonMw.
Summary Background Unruptured intracranial aneurysms (UIAs) are increasingly detected and are an important health-care burden. We aimed to assess the prevalence of UIAs according to family history, ...comorbidity, sex, age, country, and time period. Methods Through searches of PubMed, Embase, and Web of Science we updated our 1998 systematic review up to March, 2011. We calculated prevalences and prevalence ratios (PRs) with random-effects binomial meta-analysis. We assessed time trends with year of study as a continuous variable. Findings We included 68 studies, which reported on 83 study populations and 1450 UIAs in 94 912 patients from 21 countries. The overall prevalence was estimated as 3·2% (95% CI 1·9–5·2) in a population without comorbidity, with a mean age of 50 years, and consisting of 50% men. Compared with populations without the comorbidity, PRs were 6·9 (95% CI 3·5–14) for autosomal dominant polycystic kidney disease (ADPKD), 3·4 (1·9–5·9) for a positive family history of intracranial aneurysm of subarachnoid haemorrhage, 3·6 (0·4–30) for brain tumour, 2·0 (0·9–4·6) for pituitary adenoma, and 1·7 (0·9–3·0) for atherosclerosis. The PR for women compared with men was 1·61 (1·02–2·54), with a ratio of 2·2 (1·3–3·6) in study populations with a mean age of more than 50 years. Compared with patients older than 80 years, we found no differences by age, except for patients younger than 30 years (0·01, 0·00–0·12). Compared with the USA, PRs were similar for other countries, including Japan (0·8, 0·4–1·7) and Finland (1·0, 0·4–2·4). There was no statistically significant time trend. Interpretation The prevalence of UIAs is higher in patients with ADPKD or a positive family history of intracranial aneurysm of subarachnoid haemorrhage than in people without comorbidity. In Finland and Japan, the higher incidence of subarachnoid haemorrhage is not explained by a higher prevalence of UIAs, implicating higher risks of rupture. Funding Julius Centre for Health Sciences and Primary Care and Department of Neurology and Neurosurgery, University Medical Centre, Utrecht.
In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ...ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.
The advent of non-invasive methods of imaging intracranial blood vessels has facilitated screening for intracranial aneurysms in people who are at risk. A strong risk factor for intracranial ...aneurysm, which causes subarachnoid haemorrhage, is a positive family history, defined as two or more first-degree relatives with subarachnoid haemorrhages (relative risk RR=6·6). The greatest familial risk is associated with an affected sibling. Another strong risk factor is polycystic kidney disease (RR=4·4). People who have these risk factors are potential candidates for screening. Even if screening does not find abnormality, there is a high risk of new aneurysms 5 years later. Repeated screening might be done, although the optimum interval between screening assessments and the duration of repeated screening is unclear. Patients who have survived a subarachnoid haemorrhage are at increased risk of another from a newly developed aneurysm, but whether screening is beneficial in such patients is not clear. Most occurrences of subarachnoid haemorrhage in the general population are related to the more common risk factors of hypertension (RR=2·8) and smoking (RR=1·9). Therefore, screening of individuals who have a family history of subarachnoid haemorrhage or polycystic kidney disease will have little effect on the incidence of subarachnoid haemorrhage in the general population. When patients present for screening, the construction of a family tree and discussion of the history of relatives with stroke can be revealing. Before referring a patient for non-invasive imaging of the circle of Willis, the physician should discuss the risks and benefits of screening, the implications for holding a licence to drive or fly and for life insurance, and whether or not the patient wants to be informed about other incidental findings.
Pulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular ...volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED.
Circulating blood volume (CBV) was determined daily during the first 10 days after SAH by means of pulse dye densitometry. CBV of 60-80 ml/kg was considered normal. PED was diagnosed from clinical signs and characteristic bilateral pulmonary infiltrates on the chest radiograph. We compared CBV, cardiac index, and fluid balance between patients with and without PED with weighted linear regression, taking into account only measurements from the first day after SAH through to the day on which PED was diagnosed. Differences were adjusted for age, bodyweight, and clinical condition.
In total, 102 patients were included, 17 of whom developed PED after a mean of 4 days after SAH. Patients developing PED had lower mean CBV (56.6 ml/kg) than did those without PED (66.8 ml/kg). The mean difference in CBV was -11.3 ml/kg (95% CI, -16.5 to -6.1); adjusted mean difference, -8.0 ml/kg (95% CI, -14.0 to -2.0). After adjusting, no differences were found in cardiac index or fluid balance between patients with and without PED.
SAH patients developing pulmonary edema have a lower blood volume than do those without PED and are hypovolemic. Measures taken to counteract pulmonary edema must be balanced against the risk of worsening hypovolemia.
NTR1255.
Introduction
Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is thought to cause ischemia. To evaluate the contribution of vasospasm to delayed cerebral ischemia (DCI), we investigated the ...effect of vasospasm on cerebral perfusion and the relationship of vasospasm with DCI.
Methods
We studied 37 consecutive SAH patients with CT angiography (CTA) and CT perfusion (CTP) on admission and within 14 days after admission or at time of clinical deterioration. CTP values (cerebral blood volume, cerebral blood flow (CBF) and mean transit time), degree of vasospasm on CTA, and occurrence of DCI were recorded. Vasospasm was categorized as follows: no spasm (0–25% decrease in vessel diameter), moderate spasm (25–50% decrease), and severe spasm (>50% decrease). The correspondence of the flow territory of the most spastic vessel with the least perfused region was evaluated, and differences in perfusion values and occurrence of DCI between degrees of vasospasm were calculated with 95% confidence intervals (95% CI).
Results
Fourteen patients had no vasospasm, 16 were moderate, and seven were severe. In 65% of patients with spasm, the flow territory of the most spastic vessel corresponded with the least perfused region. There was significant CBF (milliliters per 100 g per minute) difference (−21.3; 95% CI, −37 ↔ −5.3) between flow territories of severe and no vasospasm. Four of seven patients with severe, six of 16 with moderate, and three of 14 patients with no vasospasm had DCI.
Conclusion
Vasospasm decreases cerebral perfusion, but corresponds with the least perfused region in only two thirds of our patients. Furthermore, almost half of patients with severe vasospasm do not have DCI. Thus, although severe vasospasm can decrease perfusion, it may not result in DCI.
PDF
