Small ruptured cerebral aneurysms-do they rupture on formation or not?

PURPOSE: Of patients presenting with subarachnoid haemorrhage, most are due to rupture of a small aneurysm. It has been postulated that in most cases, these aneurysms form and rupture rapidly over a short period of time of days to weeks. We evaluated the hypothesis that such aneurysms therefore should never be discoverable as a pre-existing condition on medical imaging studies. METHODS: All patients presenting with subarachnoid haemorrhage due to a small cerebral aneurysm over an 11-year period were reviewed for prior imaging studies capable of detecting small aneurysms. In the subgroup that had such imaging studies, these were reviewed for the presence or absence of the index aneurysm. RESULTS: Of 851 patients presenting with subarachnoid haemorrhage over an 11-year period, 35 had prior imaging studies capable of detecting small aneurysms. In 18 out of these 35 (51%) patients, the index aneurysm was identified as a small unruptured aneurysm on these prior studies. The median time between prior imaging and aneurysm rupture was 31 months. CONCLUSION: The theory that nearly all cases of subarachnoid haemorrhage due to small aneurysms occur as a result of aneurysm formation, and rupture over a short time period is incorrect. Our findings indicate that at least half of all subarachnoid haemorrhage cases arise from the population harbouring small aneurysms as a pre-existing condition.

Impact of Treatment Delay on Outcome in the International Subarachnoid Aneurysm Trial.

Background and Purpose- ISAT (International Subarachnoid Aneurysm Trial) demonstrated that 1 year after aneurysmal subarachnoid hemorrhage, coiling resulted in a significantly better clinical outcome than clipping. After 5 years, this difference did not reach statistical significance, but mortality was still higher in the clipping group. Here, we present additional analyses, reporting outcome after excluding pretreatment deaths. Methods- Outcome measures were death with or without dependency at 1 and 5 years after treatment, after exclusion of all pretreatment deaths. Treatment differences were assessed using relative risks (RRs). With sensitivity and exploratory analyses, the relation between treatment delay and outcome was analyzed. Results- After exclusion of pretreatment deaths, at 1-year follow-up coiling was favorable over clipping for death or dependency (RR, 0.77 [95% CI, 0.67-0.89]) but not for death alone (RR, 0.88 [95% CI, 0.66-1.19]). After 5 years, no significant differences were observed, neither for death or dependency (RR, 0.88 [95% CI, 0.77-1.02]) nor for death alone (RR, 0.82 [95% CI, 0.64-1.05]). Sensitivity analyses showed a similar picture. In good-grade patients, coiling remained favorable over clipping in the long-term. Time between randomization and treatment was significantly longer in the clipping arm (mean 1.7 versus 1.1 days; P<0.0001), during which 17 patients died because of rebleeding versus 6 pretreatment deaths in the endovascular arm (RR, 2.81 [95% CI, 1.11-7.11]). Conclusions- These additional analyses support the conclusion of ISAT that at 1-year follow-up after aneurysmal subarachnoid hemorrhage coiling has a better outcome than clipping. After 5 years, with pretreatment mortality excluded, the difference between coiling and clipping is not significant. The high number of pretreatment deaths in the clipping group highlights the importance of urgent aneurysm treatment to prevent early rebleeding.

Prediction of Outcome After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Early prediction of clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) is still lacking accuracy. In this observational cohort study, we aimed to develop and validate an accurate bedside prediction model for clinical outcome after aSAH, to aid decision-making at an early stage. Methods- For the development of the prediction model, a prospectively kept single-center cohort of 1215 aSAH patients, admitted between 1998 and 2014, was used. For temporal validation, a prospective cohort of 224 consecutive aSAH patients from the same center, admitted between 2015 and 2017, was used. External validation was performed using the ISAT (International Subarachnoid Aneurysm Trial) database (2143 patients). Primary outcome measure was poor functional outcome 2 months after aSAH, defined as modified Rankin Scale score 4-6. The model was constructed using multivariate regression analyses. Performance of the model was examined in terms of discrimination and calibration. Results- The final model included 4 predictors independently associated with poor outcome after 2 months: age, World Federation of Neurosurgical Societies grade after resuscitation, aneurysm size, and Fisher grade. Temporal validation showed high discrimination (area under the receiver operating characteristic curve, 0.90; 95% CI, 0.85-0.94), external validation showed fair to good discrimination (area under the receiver operating characteristic curve, 0.73; 95% CI, 0.70-0.76). The model showed satisfactory calibration in both validation cohorts. The SAFIRE grading scale was derived from the final model: size of the aneurysm, age, Fisher grade, world federation of neurosurgical societies after resuscitation. Conclusions- The SAFIRE grading scale is an accurate, generalizable, and easily applicable model for early prediction of clinical outcome after aSAH.

Risk Analysis of Unruptured Intracranial Aneurysms: Prospective 10-Year Cohort Study.

BACKGROUND AND PURPOSE: The natural history of unruptured intracranial aneurysms remains unclear, and management strategy is not well defined. METHODS: From January 2003 to December 2012, we enrolled patients with aneurysm in our institution. In total, 2252 patients with 2897 aneurysms were eligible for analysis, and 1960 eligible aneurysms were conservatively managed. Precise 3-dimensional evaluation was conducted using computed tomography angiography, digital subtraction angiography, or magnetic resonance angiography. We then assessed the risk of aneurysm rupture, mortality, and morbidity associated with aneurysm characteristics, demographics, and known health/lifestyle risk factors. RESULTS: The mean follow-up duration was 7388 aneurysm-years. During observation, 56 aneurysms ruptured, resulting in an overall rupture rate per year of 0.76% (95% confidence interval, 0.58-0.98). The mean initial visit to rupture interval was 547 days. Aneurysm size, location, daughter sac, and history of subarachnoid hemorrhage were significant independent predictors for aneurysm rupture. Aneurysms that were ≥5 mm were associated with a significantly increased risk of rupture when compared with 2- to 4-mm aneurysms (unadjusted hazard ratio, 12.24; 95% confidence interval, 7.15-20.93). Of 56 patients who experienced hemorrhage, 29 (52 %) died or were rendered severely disabled. Of the patients who had large or giant aneurysms, none recovered without deficits, and the mortality rate after rupture was 69%. For aneurysms sized <5 mm, the mortality rate was 18%. CONCLUSIONS: Larger aneurysms are at greater risk for rupture and poor outcome. Ethnic factors may play a role in the risk of rupture.

The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms: 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. At 1 year there was a 7% absolute and a 24% relative risk reduction of death and dependency in the coiling group compared with the clipping group, but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling. We report the long-term follow-up of patients in this UK cohort. METHODS: In ISAT, patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage, assuming treatment equipoise, between Sept 12, 1994, and May 1, 2002. We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0-18·5 years. We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires. Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records. The Office for National Statistics supplied data on deaths. This study is registered, number ISRCTN49866681. FINDINGS: At 10 years, 674 (83%) of 809 patients allocated endovascular coiling and 657 (79%) of 835 patients allocated neurosurgical clipping were alive (odds ratio [OR] 1·35, 95% CI 1·06-1·73). Of 1003 individuals who returned a questionnaire at 10 years, 435 (82%) patients treated with endovascular coiling and 370 (78%) patients treated with neurosurgical clipping were independent (modified Rankin scale score 0-2; OR 1·25; 95% CI 0·92-1·71). Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group (OR 1·34, 95% CI 1·07-1·67). 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage (17 from the target aneurysm). INTERPRETATION: Although rates of increased dependency alone did not differ between groups, the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group. Rebleeding was more likely after endovascular coiling than after neurosurgical clipping, but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years. FUNDING: UK Medical Research Council.

Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. METHODS: Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. RESULTS: Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE: To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS: After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS: Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS: Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Aneurysm treatment <24 versus 24-72 h after subarachnoid hemorrhage.

INTRODUCTION: In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24-72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24-72 h after aSAH. METHODS: We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24-72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24-72 h after aSAH. RESULTS: We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95% CI: 1.25-2.70), in ISAT 1.14 (95% CI 0.84-1.55), in the pooled analysis 1.37 (95% CI 1.11-1.68), and in the worst-case scenario pooled analysis 1.24 (95% CI 1.01-1.52). CONCLUSION: Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.

The Subarachnoid Hemorrhage International Trialists (SAHIT) Repository: advancing clinical research in subarachnoid hemorrhage.

Researchers and other stakeholders continue to express concern about the failure of randomized clinical trials (RCT) in subarachnoid hemorrhage (SAH) to show efficacy of new treatments. Pooled data may be particularly useful to generate hypotheses about causes of poor outcomes and reasons for failure of RCT in SAH, and strategies to improve them. Investigators conducting SAH research collaborated to share data with the intent to develop a large repository of pooled individual patient data for exploratory analysis and testing of new hypotheses relevant to improved trial design and analysis in SAH. This repository currently contains information on 11,443 SAH patients from 14 clinical databases, of which 9 are datasets of recent RCTs and 5 are datasets of prospective observational studies and hospital registries. Most patients were managed in the last 15 years. Data validation and quality checks have been conducted and are satisfactory. Data is available on demographic, clinical, neuroimaging, and laboratory results and various outcome measures. We have compiled the largest known dataset of patients with SAH. The SAHIT repository may be an important resource for advancing clinical research in SAH and will benefit from contributions of additional datasets.

Clinical prediction models for aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND: Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. METHODS: We searched the EMBASE, MEDLINE, and Web of Science databases from January 1995 to June 2012 to identify studies that reported clinical prediction models for mortality and functional outcome in aSAH. Validated methods were used to minimize bias. RESULTS: Eleven studies were identified; 3 developed models from datasets of phase 3 clinical trials, the others from single hospital records. The median patient sample size was 340 (interquartile range 149-733). The main predictors used were age (n = 8), Fisher grade (n = 6), World Federation of Neurological Surgeons grade (n = 5), aneurysm size (n = 5), and Hunt and Hess grade (n = 3). Age was consistently dichotomized. Potential predictors were prescreened by univariate analysis in 36 % of studies. Only one study was penalized for model optimism. Details about model development were often insufficiently described and no published studies provided external validation. CONCLUSIONS: While clinical prediction models for aSAH use a few simple predictors, there are substantial methodological problems with the models and none have had external validation. This precludes the use of existing models for clinical or research purposes. We recommend further studies to develop and validate reliable clinical prediction models for aSAH.

Timing of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome.

BACKGROUND AND PURPOSE: The ideal timing of coiling or clipping after aneurysmal subarachnoid hemorrhage is unknown. Within the International Subarachnoid Aneurysm Trial we assessed differences in incidence of delayed cerebral ischemia and clinical outcome between different timings of treatment. METHODS: The treated 2106 patients randomized to coiling or clipping were divided into 4 categories: treatment <2 days, on days 3 to 4, on days 5 to 10, and >10 days after the hemorrhage. ORs with 95% CI were calculated with logistic regression analysis for delayed cerebral ischemia, poor outcome at 2 months, and 1 year for the different timing categories, with treatment <2 days as reference. Analyses were performed for all patients, and for coiled and clipped patients separately, and were adjusted for baseline characteristics. RESULTS: Adjusted ORs of delayed cerebral ischemia for treatment on days 5 to 10 were 1.18 (95% CI, 0.91-1.53) for all patients, 1.68 (95% CI, 1.17-2.43) after coiling, and 0.79 (95% CI, 0.54-1.16) after clipping. ORs for poor outcome at 2 months were 1.16 (95% CI, 0.89-1.50) for treatment (clipping and coiling combined) at 3 to 4 days, 1.39 (95% CI, 1.08-1.80) for treatment at 5 to 10 days, and 1.84 (95% CI, 1.36-2.51) for treatment >10 days. ORs for coiled and clipped patients separately were in the same range. Results for outcome at 1 year were similar. CONCLUSIONS: Our results support the current practice for early aneurysm treatment in subarachnoid hemorrhage patients. The risk for poor outcome was highest when treatment was performed after day 10; postponing treatment in patients who are eligible for treatment between days 5 to 10 after subarachnoid hemorrhage is not recommended.

Cerecyte coil trial: angiographic outcomes of a prospective randomized trial comparing endovascular coiling of cerebral aneurysms with either cerecyte or bare platinum coils.

BACKGROUND AND PURPOSE: We report the primary outcome of the Cerecyte Coil Trial, a randomized trial to determine whether polymer-loaded Cerecyte coils compared with Micrus bare platinum coils improved the proportion of patients with angiographic occlusion of the aneurysm at 6 months when assessed by a core laboratory. The secondary objectives were to compare the clinical outcomes and retreatment rates in the 2 groups. METHODS: Five hundred patients between 18 and 70 years of age with a ruptured or unruptured target aneurysm were randomized to be treated with either Cerecyte or bare platinum coils in 23 centers worldwide. Two hundred forty-nine patients were assigned to Cerecyte coils and 251 to bare platinum coils. Analysis was by intention to treat. RESULTS: Four hundred ninety-four patients were eligible for analysis. Four hundred eighty-one patients underwent coil treatment of their aneurysm, 227 patients with recently ruptured aneurysms and 254 with unruptured aneurysms. Four hundred thirty-three follow-up angiograms were assessed by the core laboratory; 127 of 215 (59%) and 118 of 218 (54%) in the Cerecyte and bare platinum groups, respectively, fulfilled the trial prespecified definition of success, namely that the treated aneurysm showed complete angiographic occlusion, had stable neck remnant, or improved in angiographic appearance compared with the end-of-treatment angiogram (P=0.17). Late retreatment was performed in 25 of 452 (5.5%) patients, 17 (7.7%) Cerecyte versus 8 (3.5%) bare platinum (P=0.064; range, 4-34 months). The clinical outcomes did not differ between the groups. CONCLUSIONS: There was no significant difference at 6 months in the angiographic outcomes between Cerecyte coils and bare platinum coils when assessed by the core laboratory. Clinical Trial Registration Information- URL: www.controlled-trials.com. Unique Identifier: ISRCTN82461286.

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis with machine learning.

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 a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS: Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design.

Survival, Dependency, and Health-Related Quality of Life in Patients With Ruptured Intracranial Aneurysm: 10-Year Follow-up of the United Kingdom Cohort of the International Subarachnoid Aneurysm Trial.

BACKGROUND: Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on clinical outcomes after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. OBJECTIVE: To evaluate the long-term quality-adjusted life years (QALYs) gained of endovascular coiling compare to neurosurgical clipping in the UK cohort of ISAT. METHODS: Between September 12, 1994 and May 1, 2002, patients with ruptured intracranial aneurysms who were assumed treatment equipoise were randomly allocated to either neurosurgical clipping or endovascular coiling. We followed-up 1644 patients in 22 UK neurosurgical centers for a minimum of 10 yr. Health-related quality of life (HRQoL) was collected through yearly questionnaires, measured by utilities calculated from the EQ-5D-3L. We compared HRQoL between the 2 treatment groups over a period of 10 yr. In all, 1-yr, 5-yr, and 10-yr QALYs were estimated by combining utility and survival information. RESULTS: Higher average utility values were found in the endovascular group throughout the follow-up period, with mean differences between groups statistically significant in most years. The 10-yr QALYs were estimated to be 6.68 (95% CI: 6.45-6.90) in the coiling group and 6.32 (95% CI: 6.10-6.55) in the clipping group, respectively, a significant mean difference of 0.36 (95% CI: 0.04-0.66). A third of this mean QALYs gain was estimated to derive solely from HRQoL differences. CONCLUSION: HRQoL after treatment of a ruptured intracranial aneurysm was better after endovascular coiling compared to neurosurgical clipping, which contributed significantly to the QALYs gained over a 10-yr period.

Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) reported lower rates of death and disability with endovascular versus neurosurgical treatment of ruptured intracranial aneurysms. However, assessment of functional outcome was limited to the modified Rankin Scale, which is known to be insensitive to cognitive function. A neuropsychological substudy (N-ISAT) was therefore done in all recruits from 8 ISAT centers in the United Kingdom. METHODS: Detailed neuropsychological assessment was performed at a 12-month follow-up visit. Impairment was defined as performance below the 5th percentile of the study population on at least 2 tests in >or=2 major cognitive domains. Analysis was restricted to patients who were not known to be otherwise disabled according to the modified Rankin Scale (ie, modified Rankin Scale 0 to 2). RESULTS: Of 836 patients randomized in ISAT in the 8 UK centers (411 allocated endovascular treatment versus 425 neurosurgery), 224 were dead or disabled before 12-month follow-up (78 allocated endovascular treatment versus 135 neurosurgery). Of the remaining 612 patients eligible for neuropsychological assessment, 137 (65 allocated endovascular treatment versus 72 neurosurgery) did not attend. Of the 474 nondisabled patients who were assessed, 152 (32.1%) had cognitive impairment. Patients with cognitive impairment had reduced self-reported health-related quality of life (P<0.001) in both treatment groups, but cognitive impairment was less common in those allocated endovascular treatment (70 of 262 versus 82 of 212 allocated neurosurgery, OR=0.58, 95% CI 0.38 to 0.87, P=0.0055). The incidence of epilepsy was also lower in the N-ISAT endovascular group (7 versus 18, OR=0.30, 0.11 to 0.77, P=0.005) but was independent of the effect on cognitive function. CONCLUSIONS: Cognitive impairment occurred in approximately one third of patients who were not otherwise disabled according to the modified Rankin Scale in N-ISAT and was more frequent in the neurosurgery group. These results have implications for management of ruptured intracranial aneurysms and more generally for interpretation of the outcomes of clinical trials that use the modified Rankin Scale.

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. METHODS: We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients.Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. RESULTS: The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). CONCLUSION: We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision. Although generalizability of the model is limited due to the selected population in which it was developed, this model could eventually be used to support clinical decision making after external validation. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, Number ISRCTN49866681.

Aneurysm Treatment With Woven EndoBridge in the Cumulative Population of 3 Prospective, Multicenter Series: 2-Year Follow-Up.

BACKGROUND: Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown high safety with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy [WEBCAST], French Observatory, and WEBCAST-2). OBJECTIVE: To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials. METHODS: In a French Observatory, 2-yr clinical and anatomical data were collected. In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed. Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant. RESULTS: The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr. The population for efficacy was 121/169 aneurysms (71.6%). Aneurysm locations were middle cerebral artery in 65/121 aneurysms (53.7%), anterior-communicating artery in 25/121 (20.7%), basilar artery in 17/121 (14.0%), and internal carotid artery terminus in 14/121 (11.6%). No clinically relevant adverse events occurred between years 1 and 2. At 2 yr, complete occlusion was observed in 62/121 (51.2%) aneurysms, neck remnant in 36/121 (29.8%) aneurysms, and aneurysm remnant in 23/121 (19.0%) aneurysms. The global retreatment rate at 2 yr was 9.3%. CONCLUSION: This analysis confirms the high safety profile of WEB treatment at 2 yr. Aneurysm occlusion is generally stable at 2 yr, and the retreatment rate between 1 yr and 2 yr is low (2.0%).

Effect of antiplatelet therapy for endovascular coiling in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Antiplatelets are frequently used during or after endovascular coiling of aneurysm in patients with subarachnoid hemorrhage (SAH). This strategy is based on uncontrolled case series including also patients with unruptured aneurysms or other lesions. We collected data on effectiveness of antiplatelets in patients with SAH. METHODS: All 43 participating centers in the International Subarachnoid Aneurysm Trial (ISAT) were sent a questionnaire whether they never, sometimes, or always prescribed antiplatelets during or after coiling. Based on individual patient data, the relative risks (RRs) of coiling versus clipping were calculated separately for patients treated in hospitals with standard prescription during or after coiling versus patients treated in hospitals with no standard prescription of antiplatelets. We calculated ratios of RRs for standard versus not standard prescription of antiplatelets during coiling and for standard versus not standard prescription after coiling. RESULTS: Nineteen centers responded, representing 1422 (66%) of the 2143 ISAT patients. Antiplatelets were standard prescribed during coiling in 2 responding centers (8% of coiled patients) and after coiling in 6 centers (24%). For poor outcome at 2 months of coiling versus clipping the RR was 0.82 (95% CI: 0.45 to 1.49) in hospitals with a policy of antiplatelet prescription during coiling versus 0.66 (95% CI: 0.55 to 0.78) in those without such policy (ratio of RR's 1.24, P=0.56). The ratio of RRs for 1-year outcome was 1.01 (P=0.89) for antiplatelet use during coiling and 1.00 (P=0.77) for use after coiling. CONCLUSIONS: The results of this study do not support the assumption that antiplatelets during or after endovascular coiling improve outcome in patients with SAH.

Substantial observer variability in the differentiation between primary intracerebral hemorrhage and hemorrhagic transformation of infarction on CT brain imaging.

BACKGROUND AND PURPOSE: CT remains the most commonly used imaging technique in acute stroke but is often delayed after minor stroke. Interobserver reliability in distinguishing hemorrhagic transformation of infarction from intracerebral hemorrhage may depend on delays to CT but has not been reported previously despite the clinical importance of this distinction. METHODS: Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the kappa statistic. RESULTS: Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from kappa=0.15 to 0.48 with poor overall agreement (kappa=0.35; 95% CI, 0.15 to 0.54) even after unblinding (kappa=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from kappa=0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned >or=24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale or=24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management. CONCLUSIONS: Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.