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01 april 2023, Item does not contain fulltext, In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies.

Item does not contain fulltext, OBJECTIVE: Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS: Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS: The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In

Item does not contain fulltext, IMPORTANCE: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear. OBJECTIVE: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth. EXPOSURES: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging. MAIN OUTCOMES AND MEASURES: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. RESULTS: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio

Item does not contain fulltext, BACKGROUND: In patients with spontaneous cerebellar intracerebral hemorrhage (ICH) guidelines advocate evacuation when the hematoma diameter is > 3 cm. We studied outcome in patients with cerebellar ICH > 3 cm who did not undergo immediate hematoma evacuation. METHODS: We included consecutive patients with cerebellar ICH > 3 cm at two academic hospitals between 2008 and 2017. Patients who died < 24 h (h) were excluded because of probable confounding by indication. We determined patient characteristics, hematoma volumes, EVD placement, secondary hematoma evacuation, in-hospital and 3-month case-fatality, and functional outcome. RESULTS: Of 130 patients with cerebellar ICH, 98 (77%) had a hematoma > 3 cm of whom 22 (23%) died < 24 h and 28 (29%) underwent hematoma evacuation < 24 h. Thus, 48 patients were initially treated conservatively (mean age 70 ± 13, 24 (50%) female). Of these 48 patients, 7 (15%) underwent secondary hematoma evacuation > 24 h, of whom 1 (14%) had received an EVD < 24 h. Five others also received an EVD < 24 h without subsequent hematoma evacuation. Of the 41 patients without secondary hematoma evacuation, 11 (28%) died and 20 (51%) had a favorable outcome (mRS of 0-3) at 3 months. The 7 patients who underwent secondary hematoma evacuation had a decrease in GCS score of at least two points prior to surgery; two (29%) had deceased at 3 months; and 5 (71%) had a good functional outcome (mRS 0-3). CONCLUSIONS: While cerebellar ICH > 3 cm is often considered an indication for immediate hematoma evacuation, there may be a subgroup of patients in whom surgery can be safely deferred. Further data are needed to assess the optimal timing and indications of surgical treatment in these patients.

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Item does not contain fulltext, OBJECTIVE: To conduct a systematic review and meta-analysis of studies reporting on risk factors according to location of the intracerebral hemorrhage. METHODS: We searched PubMed and Embase for cohort and case-control studies reporting ≥100 patients with spontaneous intracerebral hemorrhage that specified the location of the hematoma and reported associations with risk factors published until June 27, 2019. Two authors independently extracted data on risk factors. Estimates were pooled with the generic variance-based random-effects method. RESULTS: After screening 10,013 articles, we included 42 studies totaling 26,174 patients with intracerebral hemorrhage (9,141 lobar and 17,033 nonlobar). Risk factors for nonlobar intracerebral hemorrhage were hypertension (risk ratio [RR] 4.25, 95% confidence interval [CI] 3.05-5.91, I (2) = 92%), diabetes mellitus (RR 1.35, 95% CI 1.11-1.64, I (2) = 37%), male sex (RR 1.63, 95% CI 1.25-2.14, I (2) = 61%), alcohol overuse (RR 1.48, 95% CI 1.21-1.81, I (2) = 19%), underweight (RR 2.12, 95% CI 1.12-4.01, I (2) = 31%), and being a Black (RR 2.83, 95% CI 1.02-7.84, I (2) = 96%) or Hispanic (RR 2.95, 95% CI 1.69-5.14, I (2) = 71%) participant compared with being a White participant. Hypertension, but not any of the other risk factors, was also a risk factor for lobar intracerebral hemorrhage (RR 1.83, 95% CI 1.39-2.42, I (2) = 76%). Smoking, hypercholesterolemia, and obesity were associated with neither nonlobar nor lobar intracerebral hemorrhage. CONCLUSIONS: Hypertension is a risk factor for both nonlobar and lobar intracerebral hemorrhage, although with double the effect for nonlobar intracerebral hemorrhage. Diabetes mellitus, male sex, alcohol overuse, underweight, and being a Black or Hispanic person are risk factors for nonlobar intracerebral hemorrhage only. Hence, the term hypertensive intracerebral hemorrhage for nonlobar intracerebral hemorrhage is not appropriate.

Contains fulltext : 229738.pdf (Publisher’s version ) (Closed access), Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Contains fulltext : 218871.pdf (Publisher’s version ) (Closed access), BACKGROUND: Guidelines regarding recommendations for surgical treatment of spontaneous cerebellar intracerebral haemorrhage (ICH) differ. We aimed to systematically review the literature to assess treatment strategies and outcomes. METHODS: We searched PubMed and Embase between 1970 and 2019 for randomised or otherwise controlled studies and observational cohort studies. We included studies according to predefined selection criteria and assessed their quality according to the Newcastle-Ottawa Scale (NOS) and risk of bias according to a predefined scale. We assessed case fatality and functional outcome in patients treated conservatively or with haematoma evacuation. Favourable functional outcome was defined as a modified Rankin Scale score of 0-2 or a Glasgow Outcome Scale score of 4-5. RESULTS: We included 41 observational cohort studies describing 2062 patients (40% female) with spontaneous cerebellar ICH. A total of 1171 patients (57%) underwent haematoma evacuation. Ten studies described a cohort of surgically treated patients (n=533) and 31 cohorts with both surgically and conservatively treated patients (n=638 and n=891, respectively). There were no randomised clinical trials nor studies comparing outcome between the groups after adjustment for differences in baseline characteristics. The median NOS score (IQR) was 5 (4-6) out of 8 points and the bias score was 2 (1-3) out of 8, indicative of high risk of bias. Case fatality at discharge was 21% (95% CI 17% to 25%) after conservative treatment and 24% (95% CI 19% to 29%) after haematoma evacuation. At >/=6 months after conservative treatment, case fatality was 30% (95% CI 25% to 30%) and favourable functional outcome was 45% (95% CI 40% to 50%) and after haematoma evacuation, case fatality was 34% (95% CI 30% to 38%) and 42% (95% CI 37% to 47%). CONCLUSIONS: Controlled studies on the effect of neurosurgical treatment in patients with spontaneous cerebellar ICH are lacking, and the risk of bias in published seri

Contains fulltext : 235713.pdf (Publisher’s version ) (Open Access), INTRODUCTION: The aim of this study was to determine the risk of recurrent intracerebral haemorrhage (ICH), ischaemic stroke, all stroke, any vascular event and all-cause mortality in 30-day survivors of ICH, according to age and sex. PATIENTS AND METHODS: We linked national hospital discharge, population and cause of death registers to obtain a cohort of Dutch 30-day survivors of ICH from 1998 to 2010. We calculated cumulative incidences of recurrent ICH, ischaemic stroke, all stroke and composite vascular outcome, adjusted for competing risk of death and all-cause mortality. Additionally, we compared survival with the general population. RESULTS: We included 19,444 ICH-survivors (52% male; median age 72 years, interquartile range 61-79; 78,654 patient-years of follow-up). First-year cumulative incidence of recurrent ICH ranged from 1.5% (95% confidence interval 0.9-2.3; men 35-54 years) to 2.4% (2.0-2.9; women 75-94 years). Depending on age and sex, 10-year risk of recurrent ICH ranged from 3.7% (2.6-5.1; men 35-54 years) to 8.1% (6.9-9.4; women 55-74 years); ischaemic stroke 2.6% to 7.0%, of all stroke 9.9% to 26.2% and of any vascular event 15.0% to 40.4%. Ten-year mortality ranged from 16.7% (35-54 years) to 90.0% (75-94 years). Relative survival was lower in all age-groups of both sexes, ranging from 0.83 (0.80-0.87) in 35- to 54-year-old men to 0.28 (0.24-0.32) in 75- to 94-year-old women. DISCUSSION: ICH-survivors are at high risk of recurrent ICH, of ischaemic stroke and other vascular events, and have a sustained reduced survival rate compared to the general population. CONCLUSION: The high risk of recurrent ICH, other vascular events and prolonged reduced survival-rates warrant clinical trials to determine optimal secondary prevention treatment after ICH.

Contains fulltext : 215616.pdf (publisher's version ) (Open Access), Background and PURPOSE: Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth. METHODS: From 11 international cohorts of patients >/=18 years with >/=1 unruptured intracranial aneurysm and >/=6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic). RESULTS: We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the development cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort. CONCLUSION: s The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.

Item does not contain fulltext, Epidemiological studies show that type 2 diabetes (T2D) is inversely associated with intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Although adiposity has not been considered a risk factor for IA, there have been inconsistent reports relating adiposity to AAA risk. We assessed whether these observations have a genetic, causal basis. To this end, we extracted genotypes of validated single-nucleotide polymorphisms associated with T2D (n=65), body mass index (BMI) (n=97) and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=47) from genotype data collected in 717 IA cases and 1988 controls, and in 818 AAA cases and 3004 controls, all of Dutch descent. For each of these three traits, we computed genetic risk scores (GRS) for each individual in these case-control data sets by summing the number of risk alleles weighted by their published effect size, and tested whether these GRS were associated with risk of aneurysm. We divided the cohorts into GRS quartiles, and compared IA and AAA risk in the highest with the lowest GRS quartile using logistic regression. We found no evidence for association in IA or AAA risk between top and bottom quartiles for the genetic risk scores for T2D, BMI and WHRadjBMI. However, additional Mendelian randomization analyses suggested a trend to potentially causal associations between BMI and WHRadjBMI and risk of AAA. Overall, our results do not support epidemiological observations relating T2D to aneurysm risk, but may indicate a potential role of adiposity in AAA that requires further investigation.

Item does not contain fulltext, Background It is unclear whether the risk of bleeding from brain arteriovenous malformations is higher during pregnancy, delivery, or puerperium. We compared occurrence of brain arteriovenous malformation hemorrhage in women during this period with occurrence of hemorrhage outside this period during their fertile years. Methods We included all women with ruptured brain arteriovenous malformations (16-41 years) from a retrospective database of patients with brain arteriovenous malformations in four Dutch university hospitals (n = 95) and from the population-based Scottish Audit of Intracranial Vascular Malformations (n = 44). We estimated the relative rate of brain arteriovenous malformation rupture (before any treatment) during exposed time (pregnancy, delivery, puerperium) versus non-exposed time during fertile years, using the case-crossover design as primary analysis, and the self-controlled case-series design as secondary analysis. Results In 17 of 95 Dutch women and in 3 of 44 Scottish women, hemorrhages occurred while pregnant; none occurred during delivery or puerperium. In Dutch women, the relative rate of brain arteriovenous malformation rupture during pregnancy, delivery, or puerperium was 6.8 (95% confidence interval 3.6-13) according to the case-crossover method and 7.1 (95% confidence interval 3.4-13) using the self-controlled case-series method. In Scottish women, the relative rate was 1.3 (95% confidence interval 0.39-4.1) using the case-crossover method and 1.7 (95% confidence interval 0.0-4.4) according to the self-controlled case-series method. Because of limited overlap of confidence intervals, we refrained from pooling the cohorts. Conclusions Case-crossover and self-controlled case series analyses reveal an increase in relative rate of brain arteriovenous malformation rupture during pregnancy in the Dutch cohort but not in the Scottish cohort. Since point estimates varied between both cohorts and numbers are relatively small, the clinical implic

Item does not contain fulltext, BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations and perform a meta-analysis including all previously published results. METHODS: We included 167 Dutch patients and 1038 Dutch controls. Case genotyping was performed by KASPar assays. Controls had been previously genotyped with a genome wide single nucleotide polymorphisms (SNP) array. Differences in genotype frequencies between cases and controls were estimated by chi(2) testing in Plink V.1.07. Meta-analysis was performed in RevMan V.5.3. RESULTS: In our case-control study we found no significant association with brain AVM (BAVM) for previously discovered SNPs near ANGPTL4, IL-1beta, GPR124, VEGFA and MMP-3. The meta-analysis revealed a statistically significant association with BAVMs for the polymorphism rs11672433 near ANGPTL4 (OR 1.39; 95% CI 1.10 to 1.75, p value 0.005). CONCLUSIONS: The results of this study support a role for the previously identified SNP near ANGPTL4 in the pathogenesis of AVMs. Previously found associations with SNPs near IL-1beta, GPR124, VEGFA and MMP-3 genes could not be substantiated in our replication cohort or in the meta-analysis.

Contains fulltext : 171496.pdf (publisher's version ) (Open Access), BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND RESULTS: We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1x10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1x10(-3)). CONCLUSIONS: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.

Contains fulltext : 154499.pdf (publisher's version ) (Open Access), BACKGROUND: There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation. These patients are currently treated with oral anticoagulants, antiplatelet drugs, or no antithrombotic treatment, depending on personal and institutional preferences. Compared with warfarin, the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism, intracranial haemorrhage, and case fatality in patients with atrial fibrillation. Compared with aspirin, apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation, and has a similar risk of intracerebral haemorrhage. Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage. To inform a phase III trial, the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided. METHODS/DESIGN: APACHE-AF is a phase II, multicentre, open-label, parallel-group, randomised clinical trial with masked outcome assessment. One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherlands. These patients will be randomly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation. Patients in the control group may be treated with antiplatelet drugs at the discretion of the

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

Item does not contain fulltext, BACKGROUND: In genome-wide association studies (GWAS) five putative risk loci are associated with intracranial aneurysm. As brain arteriovenous malformations (AVM) and intracranial aneurysms are both intracranial vascular diseases and AVMs often have associated aneurysms, we investigated whether these loci are also associated with sporadic brain AVM. METHODS: We included 506 patients (168 Dutch, 338 American) and 1548 controls, all Caucasians. Controls had been recruited as part of previous GWAS. Dutch patients were genotyped by KASPar assay and US patients by Affymetrix SNP 6.0 array. Associations in each cohort were tested by univariable logistic regression modelling, with subgroup analysis in 205 American cases with aneurysm data. Meta-analysis was performed by a Mantel-Haenszel fixed-effect method. RESULTS: In the Dutch cohort none of the single nucleotide polymorphisms (SNPs) were associated with AVMs. In the American cohort, genotyped SNPs near SOX-17 (OR 0.74; 95% CI 0.56-0.98), RBBP8 (OR 0.76; 95% CI 0.62-0.94) and an imputed SNP near CDKN2B-AS1 (OR 0.79; 95% CI 0.64-0.98) were significantly associated with AVM. The association with SNPs near SOX-17 and CDKN2B-AS1 but not RBBP8 were strongest in patients with AVM with associated aneurysms. In the meta-analysis we found no significant associations between allele frequencies and AVM occurrence, but rs9298506, near SOX-17 approached statistical significance (OR 0.77; 95% CI 0.57-1.03, p=0.08). CONCLUSIONS: Our meta-analysis of two Caucasian cohorts did not show an association between five aneurysm-associated loci and sporadic brain AVM. Possible involvement of SOX-17 and RBBP8, genes involved in cell cycle progression, deserves further investigation.

Item does not contain fulltext, OBJECTIVE: We studied the yield of MRI of the spinal neuraxis in patients with nonperimesencephalic subarachnoid hemorrhage (NPSAH). METHODS: In a prospective, multicenter study, we performed T1-weighted and T2-weighted MRI of the spinal axis in a consecutive series of patients with a spontaneous NPSAH without intracranial vascular pathology on intracranial vascular imaging. RESULTS: A spinal origin of the hemorrhage was found in 3 of 75 patients (4%; 95% confidence interval 0-8.4). The lesions were 1 lumbar ependymoma and 2 cervical cavernous malformations. All 3 patients presented without focal neurologic deficits and 2 had a CT-negative subarachnoid hemorrhage but positive lumbar puncture. Patients with a spinal origin were younger than patients without a spinal origin (38 vs 56 years; p < 0.05), which was the only significant difference between groups. CONCLUSIONS: The yield and clinical relevance of MRI of the spinal axis in patients who present with NPSAH is low. We do not recommend routine MRI of the spinal axis in this patient population, but it might be justified in a subgroup of patients.

Contains fulltext : 152122.pdf (Publisher’s version ) (Open Access), 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 permanent sequelae. Not all patients with negative CT angiography and MR

Contains fulltext : 138172.pdf (publisher's version ) (Open Access), 3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2x increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42x10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17x10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87x10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08x-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87x10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases.

Item does not contain fulltext, BACKGROUND AND PURPOSE: It is uncertain whether familial occurrence of brain arteriovenous malformations (BAVMs) represents coincidental aggregation or a shared familial risk factor. We aimed to compare the prevalence of BAVMs in first-degree relatives (FDRs) of patients with BAVM and the prevalence in the general population. METHODS: We sent a postal questionnaire to 682 patients diagnosed with a BAVM in 1 of 4 university hospitals to retrieve information about the occurrence of BAVMs among their FDRs. We calculated a prevalence ratio using the BAVM prevalence among FDRs and the prevalence from a Scottish population-based study (93 per 628 788 adults). A prevalence ratio of >/=9 with a lower limit of the 95% confidence interval of 3 was considered indicative of a shared familial risk factor. RESULTS: Informed consent was given by 460 (67%) patients, who had 2992 FDRs. We identified 3 patients with a FDR with a BAVM, yielding a prevalence ratio of 6.8 (95% CI, 2.2-21). CONCLUSIONS: The prevalence of BAVMs in FDRs of patients with a BAVM was increased but did not meet our prespecified criterion for a shared familial risk factor. In combination with the low absolute risk of a BAVM in FDRs, our results do not support screening of FDRs for BAVMs.

Item does not contain fulltext, OBJECTIVE: The reported effects of treating cerebral cavernous malformations (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and vary between studies. METHODS: We searched Ovid Medline, EMBASE and The Cochrane Library for peer-reviewed publications of cohort studies describing outcomes of treating 20 or more patients with CCM with at least 80% completeness of follow-up. Two reviewers extracted data to quantify the incidence of a composite outcome (death, non-fatal intracranial haemorrhage, or new/worse persistent focal neurological deficit) after CCM treatment. We explored associations between summary measures of study characteristics and outcome using Poisson meta-regression analyses. RESULTS: We included 63 cohorts, involving 3424 patients. The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person-years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI 4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After neurosurgical excision the incidence of the composite outcome increased with every per cent point increase in patients with brainstem CCM (rate ratio (RR) 1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR 0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find significant associations in studies of stereotactic radiosurgery. CONCLUSIONS: The reported risks of CCM treatment (and the lower risks of neurosurgical excision over time, from recently bled CCMs, and for CCMs outside the brainstem) compare favourably with the risks of recurrent haemorrhage from CCM. Long-term effects, especially important for stereotactic radiosurgery, are unknown.

Item does not contain fulltext, OBJECTIVE: To determine whether the CT angiography (CTA) spot sign marks bleeding complications during and after surgery for spontaneous intracerebral hemorrhage (ICH). METHODS: In a 2-center study of consecutive spontaneous ICH patients who underwent CTA followed by surgical hematoma evacuation, 2 experienced readers (blinded to clinical and surgical data) reviewed CTAs for spot sign presence. Blinded raters assessed active intraoperative and postoperative bleeding. The association between spot sign and active intraoperative bleeding, postoperative rebleeding, and residual ICH volumes was evaluated using univariable and multivariable logistic regression. RESULTS: A total of 95 patients met inclusion criteria: 44 lobar, 17 deep, 33 cerebellar, and 1 brainstem ICH; >/=1 spot sign was identified in 32 patients (34%). The spot sign was the only independent marker of active bleeding during surgery (odds ratio [OR] 3.4; 95% confidence interval [CI] 1.3-9.0). Spot sign (OR 4.1; 95% CI 1.1-17), female sex (OR 6.9; 95% CI 1.7-37), and antiplatelet use (OR 4.6; 95% CI 1.2-21) were predictive of postoperative rebleeding. Larger residual hematomas and postoperative rebleeding were associated with higher discharge case fatality (OR 3.4; 95% CI 1.1-11) and a trend toward increased case fatality at 3 months (OR 2.9; 95% CI 0.9-8.8). CONCLUSIONS: The CTA spot sign is associated with more intraoperative bleeding, more postoperative rebleeding, and larger residual ICH volumes in patients undergoing hematoma evacuation for spontaneous ICH. The spot sign may therefore be useful to select patients for future surgical trials.

Item does not contain fulltext, BACKGROUND: Epidemiological studies show that an unfavorable lipid profile and coronary artery disease (CAD) are risk traits for abdominal aortic aneurysms (AAAs) but not for intracranial aneurysms (IAs), and that hypertension is a main risk trait for IAs but not for AAAs. To evaluate these observations, we investigated single-nucleotide polymorphisms associated with serum lipid levels, hypertension, and CAD and tested their contribution to AAA and IA risk. METHODS AND RESULTS: We defined sets of single-nucleotide polymorphisms previously reported to be associated with serum lipid levels, CAD, and blood pressure. From previously collected genome-wide data, we extracted genotypes for these single-nucleotide polymorphism sets in 709 IA cases and 2692 controls and 807 AAA cases and 1905 controls (all of Dutch origin). We computed genetic scores for each individual by summing the observed number of risk alleles weighted by their previously published effect size. Using logistic regression, we tested the genetic scores for association with IAs and AAAs and found significant associations for genetic scores of total cholesterol (P=3.6x10(-)(6)), low-density lipoprotein-cholesterol (P=5.7x10(-)(7)), and CAD (P=0.0014) with AAAs and for the blood pressure score with IAs (P=0.0030). CONCLUSIONS: We demonstrate that genetic risk profiles of lipid factors and CAD are associated with AAAs but not with IAs, and the genetic risk profile of blood pressure is associated with IAs but not with AAAs. These findings are consistent with epidemiological observations.

Item does not contain fulltext, BACKGROUND AND PURPOSE: Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. METHODS: We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. RESULTS: In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. CONCLUSIONS: The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.

Item does not contain fulltext, BACKGROUND AND PURPOSE: We aimed to validate externally in a setting outside the United States the secondary intracerebral hemorrhage (ICH) score that was developed to predict the probability of macrovascular causes in patients with nontraumatic ICH. METHODS: Patients with nontraumatic ICH admitted to the University Medical Center Utrecht, the Netherlands, between 2003 and 2011 were included if an angiographic examination, neurosurgical inspection, or pathological examination had been performed. Secondary ICH score performance was assessed by calibration (agreement between predicted and observed outcomes) and discrimination (separation of those with and without macrovascular cause). RESULTS: Forty-eight of 204 patients (23.5%) had a macrovascular cause. The secondary ICH score showed modest calibration (P=0.06) and modest discriminative ability (c-statistic 0.73; 95% confidence interval, 0.65-0.80). Discrimination improved slightly using only noncontrast computed tomography categorization (c-statistic 0.79; 95% confidence interval, 0.72-0.86). CONCLUSIONS: The discriminative ability and calibration of the secondary ICH score are moderate in a university hospital setting outside the United States. Clues on noncontrast computed tomography are the strongest predictor of a macrovascular cause in patients with ICH.

Item does not contain fulltext, We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.

Item does not contain fulltext, OBJECTIVE: To systematically review the literature on female risk factors and risk of SAH. METHODS: We searched Medline and EMBASE for articles published between January 1985 and July 2011. For all studies fulfilling the predefined criteria, we obtained risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for female risk factors. We pooled crude and adjusted ORs (aORs) with a general variance-based random-effects method. We evaluated methodologic quality with the Newcastle-Ottawa Scale. RESULTS: We included 16 studies; 8 had good quality. Twelve studies had a case-control design, 3 studies had a longitudinal design, and 1 study had a case-crossover design. Overall aORs were 1.31 (95% CI 1.05-1.64; 5 studies, 2 with good quality [GQ]) for current use of combined oral contraceptives (COC), 0.90 (95% CI 0.74-1.09; 7 studies, 4 GQ) for ever COC use, 0.86 (95% CI 0.69-1.08; 6 studies, 3 GQ) for current use of hormone replacement therapy (HRT), 0.74 (95% CI 0.54-1.00; 3 studies, 1 GQ) for ever use of HRT, and 1.29 (95% CI 1.03-1.61; 5 studies, 2 GQ) for postmenopausal women. Data on parity and age at menarche were heterogeneous. Risk of subarachnoid hemorrhage (SAH) was not increased during pregnancy, labor, or puerperium (RR 0.40, 95% CI 0.20-0.90; 1 GQ study). CONCLUSIONS: Female hormone levels might influence risk of SAH, but the pathophysiology of this effect and its influence on the difference in incidence of SAH between the sexes remains unclear. Further studies are needed to identify modifiable risk factors of SAH in women older than age 50.

Item does not contain fulltext, BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare cause of stroke, initially described in Japan. In other countries, incidences and presenting symptoms may differ from those in Japan. The literature on regional differences in incidence and patient characteristics of MMD was systematically reviewed. METHODS: Medline, EMBASE and CINAHL were searched for population based studies on MMD published between January 1969 and January 2011. From studies that met predefined inclusion criteria, information was extracted on incidence and patient characteristics. Incidences with corresponding 95% CIs if possible were calculated and descriptive statistics for patient characteristics were used. RESULTS: 8 studies were included: three from Japan, one each from Taiwan and China and three from the USA. Incidences per 100 000 patient years ranged in Japan from 0.35 to 0.94 (95% CI 0.69 to 1.19), in the USA from 0.05 (-0.04 to 0.12) in Iowa to 0.17 (-0.06 to 0.40) in Hawaii and were 0.41 (0.28 to 0.54) in Nanjing, China and 0.02 (0.003 to 0.04) in Taiwan. Female to male ratio ranged from 1.1 (0.9 to 1.5) in Nanjing to 2.8 (1.2 to 6.1) in Iowa. Proportions with intracerebral haemorrhage as the initial presentation were 56% in China, 52% in Taiwan, 29% in Hawaii, 21% in Japan and 10% in Iowa. Patients with childhood onset presented most often with ischaemia (>75%) in all regions. CONCLUSIONS: MMD incidence was higher in Japan and China than in Taiwan and North America and presenting symptoms showed regional differences, which are thus far unexplained. Population based data on MMD in Europe are lacking.

Item does not contain fulltext, CONTEXT: Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES: To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES: We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION: We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS: We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95%

Item does not contain fulltext, BACKGROUND: 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.

Item does not contain fulltext, 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 outco

Item does not contain fulltext, BACKGROUND: A structured interview improves the reliability of the modified Rankin Scale (mRS), a commonly used functional outcome scale in stroke trials. Telephone interview is a fast and convenient way to assess the mRS grade, but its validity is unknown. We assessed the validity of a telephone interview in patients who had had an aneurysmal subarachnoid haemorrhage (SAH) by comparing it with a face-to-face assessment. METHODS: Eighty-three SAH patients were interviewed twice, once face-to-face and once by telephone, by 2 of 5 observers who used a structured interview to assess the mRS grade. Intermodality agreement was measured using weighted kappa statistics. To check for systematic differences between face-to-face and telephone assessment the Wilcoxon test for matched pairs was used. RESULTS: Agreement between telephone and face-to-face assessment was perfect in 47 (57%) patients. A difference of 1 level occurred in 31 (37%) patients and this was almost equally distributed over the grades of the mRS. Weighted kappa was 0.71 (95% CI 0.59-0.82). Telephone assessment did not result in a consistently more or less favourable grade than face-to-face assessment (Wilcoxon test for matched pairs, p = 0.33). CONCLUSIONS: Telephone assessment of the mRS with a structured interview has a good agreement with face-to-face assessment and can thus be used reliably in the setting of a clinical trial.

Contains fulltext : 169601.pdf (Publisher’s version ) (Closed access), BACKGROUND AND PURPOSE: Intracerebral hematomas (ICHs) often increase in size in the initial hours. It is unknown whether expansion of ICHs after aneurysmal rupture in the acute phase is always a sign of rerupture of the original aneurysm. METHODS: We included patients with an ICH from a ruptured aneurysm who underwent computed tomography imaging within 24 hours of symptom onset and a repeat computed tomography within 48 hours. Hematoma growth was considered present when there was a 33% increase in hematoma volume, as assessed by the ABC/2 method. Clinical and radiologic characteristics were compared between patients with ICH growth, with and without clinical signs of rerupture. Rerupture was defined as a sudden deterioration in the level of consciousness in the absence of ventricular enlargement or a systemic cause. RESULTS: Hematoma expansion within 48 hours after onset occurred in 12 of the 49 included patients and was preceded by clinical evidence of rerupture in 6 of these 12 patients. Of the 6 patients without an evident rerupture, 3 had no clinical deterioration, 1 had respiratory failure due to pneumonia, another had temporal brain herniation, and the last had acute hydrocephalus. CONCLUSIONS: Only half of the patients with early ICH expansion after aneurysmal rupture had clinical signs of rerupture of the aneurysm. Early ICH expansion after aneurysmal rupture can be caused by other mechanisms, which are possibly comparable to those responsible for hematoma expansion in spontaneous ICH.

Item does not contain fulltext, BACKGROUND AND PURPOSE: It is unclear whether the risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased during pregnancy, labor, and the puerperium. We compared the risk of aSAH during this period with the risk outside this period. METHODS: We included women with aSAH between 18 and 42 years of age (n=244) from our prospectively collected database of patients with subarachnoid hemorrhage treated in the University Medical Center Utrecht, the provincial referral center, between January 1987 and April 2006. We estimated the relative risk of aSAH during pregnancy, delivery, or the puerperium by a case-crossover design and calculated a standardized incidence ratio, dividing the observed number of patients with aSAH during pregnancy, delivery, or puerperium by the expected number based on the incidence in the general population of women of the same age during the study period. RESULTS: Of the 244 women, 4 were pregnant, 3 in the puerperium and none in labor. The relative risk of aSAH during pregnancy, delivery, or the puerperium was 0.4 (95% CI, 0.2 to 0.9). Based on the number of women aged 18 to 42 years within the catchment area of our hospital and the number of pregnancies within the study period, the expected number of patients with aSAH during pregnancy, delivery, or the puerperium was 12, resulting in a standardized incidence ratio of 0.6 (95% CI, 0.2 to 1.1). CONCLUSIONS: The risk of aSAH is not increased during pregnancy, labor, and the puerperium. There is no need to advise against pregnancy in women with an increased risk of subarachnoid hemorrhage and no evidence to advise against vaginal delivery in such women.

Item does not contain fulltext, Treatment 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.

Contains fulltext : 70663.pdf (publisher's version ) (Closed access), Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Item does not contain fulltext, BACKGROUND: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. METHODS: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. RESULTS: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. CONCLUSIONS: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Item does not contain fulltext, BACKGROUND: In approximately 5% of patients with intracranial subarachnoid haemorrhage (SAH), the cause is another than a ruptured aneurysm or perimesencephalic haemorrhage. One of these causes is a spinal arteriovenous shunt (SAVS). The aim of this study was to investigate the characteristics of patients with SAVS who present with intracranial SAH without symptoms and signs suggesting a spinal cause. METHODS: We systematically reviewed the literature and searched the SAH database of the University Medical Center Utrecht, The Netherlands, for patients with SAVS presenting with intracranial SAH and studied the characteristics of patients with SAVS whose clinical presentation mimicked intracranial SAH caused by rupture of a saccular aneurysm. RESULTS: Thirty-five patients were identified after a review of the literature. In our SAH database, comprising 2142 patients included in the period 1985-2004, we found one patient (0.05%, 95 % CI 0.006- 0.3%). SAH due to SAVS occurred at any age (4-72 years). The SAVS was located at the craniocervical junction in 14 patients, at the cervical level in 11, and at the thoracolumbar level in the remaining 11 patients. The majority of patients (n = 26, 72%) had no disabling deficits at discharge or follow-up. CONCLUSION: Rupture of a SAVS presenting as intracranial SAH is rare and can occur at any age. The SAVS can be located not only at the craniocervical junction or cervical level but also in the thoracolumbar region. Most patients with SAVS presenting as intracranial SAH have a good recovery.

Item does not contain fulltext, BACKGROUND: In patients with SAH the amount of extravasated blood on the initial CT scan is related with delayed cerebral ischemia and clinical outcome. We investigated the interobserver variation of the Hijdra and Fisher scales for the amount of extravasated blood and the predictive values of these scales for delayed cerebral ischemia and outcome. METHODS: For 132 patients admitted within 48 hours after SAH three observers assessed the amount of blood on the initial CT scan by means of the Hijdra and Fisher scale. We analyzed interobserver agreement with kappa statistics and used multivariate logistic regression for the association with delayed cerebral ischemia and clinical outcome. RESULTS: The interobserver agreement of all three pairs of observers was good for the Hijdra scale (kappas for total sum scores ranging from 0.67 to 0.75) and mild to moderate for the Fisher scale (kappas ranging from 0.37 to 0.55). For the Hijdra scale the risk of DCI was higher for intermediate (OR 4.2; 95% CI 1.1-16.3) and large (OR 3.6; 95% CI 0.8-16.4) amounts of blood with small amount as reference. Fisher grade III (OR 1.0; 95% CI 0.2-5.2) and IV (OR 0.3; 95% CI 0.02-4.0) were not related with DCI. For the Hijdra scale and clinical outcome we found an increasing risk for poor outcome with intermediate (OR 3.9; 95% CI 1.0-15.9) and large (OR 10.7; 95% CI 2.3-50.1) amounts of blood. Such a relation was not found for Fisher grade III (OR 1.2; 95% CI 0.2-7.0) and IV (OR 0.2; 95% CI 0.01-3.4). CONCLUSIONS: For the Hijdra scale we found a distinct better interobserver agreement than for the Fisher score. Moreover, the Hijdra scale was an independent prognosticator for DCI and clinical outcome, which was not the case for the Fisher score.

Item does not contain fulltext, Background. There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period.Method. In eight hospitals we identified 1500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage.Findings. We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III).Management results. Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor

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Item does not contain fulltext, OBJECT: If clip application or coil placement for treatment of intracranial aneurysms is not feasible, the parent vessel can be occluded to induce thrombosis of the aneurysm. The Excimer laser-assisted anastomosis technique allows the construction of a high-flow bypass in patients who cannot tolerate such an occlusion. The authors assessed the complications of this procedure and clinical outcomes after the construction of high-flow bypasses in patients with intracranial aneurysms. METHODS: Data were retrospectively collected on patient and aneurysm characteristics, procedural complications, and functional outcomes in 77 patients in whom a high-flow bypass was constructed. Logistic regression analysis was used to quantify the relationships between patient and aneurysm characteristics on the one hand and outcome measures on the other. Fifty-one patients harbored a giant aneurysm, 24 patients suffered from a ruptured aneurysm, and 35 patients from an unruptured symptomatic aneurysm. In 22 patients (29%; 95% confidence interval [CI] 19-40%) a permanent deficit developed from an operative complication. At a median follow-up period of 2.5 months, 25 patients (32%; 95% CI 22-44%) were dependent or had died; in 10 of these patients (13% of all patients; 95% CI 6-23%) operative complications were the single cause of this poor outcome. Univariate analysis demonstrated that a poor clinical condition before treatment (odds ratio [OR] 4.7; 95% CI 1.7-13.3) and a history of cardiovascular disease (OR 4.1; 95% CI 1-16.2) increased the risk of poor outcome. Multivariate analysis demonstrated that only the clinical condition before treatment was significantly related to outcome (OR 4; 95% CI 1.3-11.9). CONCLUSIONS: In patients with an intracranial aneurysm that cannot be treated by clip application or coil placement, and in whom occlusion of the parent artery cannot be tolerated, the construction of a high-flow bypass should be considered. This procedure carries a considerable risk