Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

BACKGROUND AND PURPOSE: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. METHODS: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. RESULTS: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0-2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3-5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. CONCLUSIONS: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03245866.

Implementation of an infection prevention bundle is associated with reduced surgical site infections in cranial neurosurgery.

OBJECTIVE: The objective of this study was to quantify surgical site infection (SSI) rates after cranial neurosurgery in a tertiary care hospital, identify risk factors for SSI, and evaluate the impact of standardized surveillance and an infection prevention bundle (IPB). METHODS: The authors compared SSI rates during 7 months before and after the intervention. The IPB included standardized patient preparation, perioperative antibiotic/antiseptic use, barrier precautions, coaching of surgeons, and the implementation of a specialized technical operation assistant team. RESULTS: Three hundred twenty-two unselected consecutive patients were evaluated before the IPB, and 296 were evaluated after implementation. Infection rates after 1 year decreased from 7.8% (25/322) to 3.7% (11/296, p = 0.03) with similar mortality rates (14.7% vs 13.8%, p = 0.8). The isolated bacteria included Staphylococcus aureus (42%), Cutibacterium acnes (22%), and coagulase-negative staphylococci (14%). Organ/space infections dominated with 67%, and mostly consisted of subdural empyema and meningitis/ventriculitis. Among the 36 SSIs, 13 (36%) occurred during hospitalization, and 29 (81%) within the first 3 months of follow-up. In multivariable analysis including established risk factors described in the literature, non-CNS neoplasia (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.39-10.53), postoperative bleeding (OR 4.09, 1.44-11.62), operations performed by or under supervision of a senior faculty surgeon (OR 0.38, 0.17-0.84), and operations performed after the implementation of standardized surveillance and an IPB (OR 0.38, 0.17-0.85) significantly influenced the infection rate. CONCLUSIONS: The introduction of an IPB combined with routine surveillance and personal feedback was associated with a 53% reduced infection rate. The lower infection rates of senior faculty and the strong association between postoperative bleeding and infection underline the importance of both surgical experience as well as thorough supervision and coaching of younger surgeons.

Correction to: Ruptured posterior circulation aneurysms: epidemiology, patterns of care, and outcomes from the Swiss SOS national registry.

The name of Roy Thomas Daniel was incorrectly captured in the original manuscript.

Ruptured posterior circulation aneurysms: epidemiology, patterns of care, and outcomes from the Swiss SOS national registry.

BACKGROUND: The treatment of ruptured posterior circulation aneurysms remains challenging despite progresses in the endovascular and neurosurgical techniques. OBJECTIVE: To provide epidemiological characterization of subjects presenting with ruptured posterior circulation aneurysms in Switzerland and thereby assessing the treatment patterns and neurological outcomes. METHODS: This is a retrospective analysis of the Swiss SOS registry for patients with aneurysmal subarachnoid hemorrhage. Patients were divided in 3 groups (upper, lower, and middle third) according to aneurysm location. Clinical, radiological, and treatment-related variables were identified and their impact on the neurological outcome was determined. RESULTS: From 2009 to 2014, we included 264 patients with ruptured posterior circulation aneurysms. Endovascular occlusion was the most common treatment in all 3 groups (72% in the upper third, 68% in the middle third, and 58.8% in the lower third). Surgical treatment was performed in 11.3%. Favorable outcome (mRS ≤ 3) was found in 56% at discharge and 65.7% at 1 year. No significant difference in the neurological outcome were found among the three groups, in terms of mRS at discharge (p = 0.20) and at 1 year (p = 0.18). High WFNS grade, high Fisher grade at presentation, and rebleeding before aneurysm occlusion (p = 0.001) were all correlated with the risk of unfavorable neurological outcome (or death) at discharge and at 1 year. CONCLUSIONS: In this study, endovascular occlusion was the principal treatment, with a favorable outcome for two-thirds of patients at discharge and at long term. These results are similar to high volume neurovascular centers worldwide, reflecting the importance of centralized care at specialized neurovascular centers.

Ruptured PICA aneurysms: presentation and treatment outcomes compared to other posterior circulation aneurysms. A Swiss SOS study.

BACKGROUND AND PURPOSE: Aneurysms of the posterior inferior cerebellar artery (PICA) are relatively uncommon and evidence is sparse about patients presenting with ruptured PICA aneurysms. We performed an analysis of the Swiss SOS national registry to describe clinical presentation, treatment pattern, and neurological outcome of patients with ruptured PICA aneurysms compared with other ruptured posterior circulation (PC) aneurysms. METHODS: This was a retrospective analysis of anonymized data from the Swiss SOS registry (Swiss Study on Aneurysmal Subarachnoid Hemorrhage; 2009-2014). Patients with ruptured PC aneurysms were subdivided into a PICA and non-PICA group. Clinical, radiological, and treatment-related variables were identified, and their impact on the neurological outcome was determined in terms of modified Rankin score at discharge and at 1 year of follow-up for the two groups. RESULTS: Data from 1864 aneurysmal subarachnoid hemorrhage patients were reviewed. There were 264 patients with a ruptured PC aneurysm. Seventy-four PICA aneurysms represented 28% of the series; clinical and radiological characteristics at admission were comparable between the PICA and non-PICA group. Surgical treatment was accomplished in 28% of patients in the PICA group and in the 4.8% of patients in the non-PICA group. No statistically significant difference was found between the two groups in terms of complications after treatment. Hydrocephalus requiring definitive shunt was needed in 21.6% of PICA patients (p = 0.6); cranial nerve deficit was present in average a quarter of the patients in both PICA and non-PICA group with no statistical difference (p = 0.3). A more favorable outcome (66.2%) was reported in the PICA group at discharge (p < 0.05) but this difference faded over time with a similar neurological outcome at 1-year follow-up (p = 0.09) between both PICA and non-PICA group. The Kaplan-Meyer estimation showed no significant difference in the mortality rate between both groups (p = 0.08). CONCLUSIONS: In the present study, patients with ruptured PICA aneurysms had a favorable neurological outcome in more than two thirds of cases, similar to patients with other ruptured PC aneurysms. Surgical treatment remains a valid option in a third of cases with ruptured PICA aneurysms.

Correction to: Ruptured PICA aneurysms: presentation and treatment outcomes compared to other posterior circulation aneurysms. A Swiss SOS study.

Incorrect authorgroup and authorname.

Factors associated with clinical and radiological status on admission in patients with aneurysmal subarachnoid hemorrhage.

Grading scales yield objective measure of the severity of aneurysmal subarachnoid hemorrhage and serve as to guide treatment decisions and for prognostication. The purpose of this cohort study was to determine what factors govern a patient's disease-specific admission scores in a representative Central European cohort. The Swiss Study of Subarachnoid Hemorrhage includes anonymized data from all tertiary referral centers serving subarachnoid hemorrhage patients in Switzerland. The 2009-2014 dataset was used to evaluate the impact of patient and aneurysm characteristics on the patients' status at admission using descriptive and multivariate regression analysis. The primary/co-primary endpoints were the GCS and the WFNS grade. The secondary endpoints were the Fisher grade, the presence of a thick cisternal or ventricular clot, the presence of a new focal neurological deficit or cranial nerve palsy, and the patient's intubation status. In our cohort of 1787 consecutive patients, increasing patient age by 10 years and low pre-ictal functional status (mRS 3-5) were inversely correlated with "high" GCS score (GCS ≥ 13) (OR 0.91, 95% CI 0.84-0.97 and OR 0.67, 95% CI 0.31-1.46), "low" WFNS grade (grade VI-V) (OR 1.21, 95% CI 1.04-1.20 and OR 1.47, 95% CI 0.66-3.27), and high Fisher grade (grade III-IV) (OR 1.08, 95% CI 1.00-1.17 and OR 1.54, 95% CI 0.55-4.32). Other independent predictors for the patients' clinical and radiological condition at admission were the ruptured aneurysms' location and its size. In sum, chronological age and pre-ictal functional status, as well as the ruptured aneurysm's location and size, determine the patients' clinical and radiological condition at admission to the tertiary referral hospital.

Decision-making and neurosurgeons' agreement in the management of aneurysmal subarachnoid haemorrhage based on computed tomography angiography.

BACKGROUND: To determine the neurosurgeon's agreement in aneurysmal subarachnoid haemorrhage (aSAH) management with special emphasis on the rater's level of experience. A secondary aim was to analyse potential aneurysm variables associated with the therapeutic recommendation. METHOD: Basic clinical information and admission computed tomography angiography (CTA) images of 30 consecutive aSAH patients were provided. Twelve neurosurgeons independently evaluated aneurysm characteristics and gave recommendations regarding the emergency management and aneurysm occlusion therapy. Inter-rater variability and predictors of treatment recommendation were evaluated. RESULTS: There was an overall moderate agreement in treatment decision [κ = 0.43; 95% confidence interval ((CI), 0.387-0.474] with moderate agreement for surgical (κ = 0.43; 95% CI, 0.386-0.479) and endovascular treatment recommendation (κ = 0.45; 95% CI, 0.398-0.49). Agreement on detailed treatment recommendations including clip, coil, bypass, stent, flow diverter and ventriculostomy was low to moderate. Inter-rater agreement did not significantly differ between residents and consultants. Middle cerebral artery (MCA) aneurysm location was a positive predictor of surgical treatment [odds ratio (OR), 49.57; 95% CI, 10.416-235.865; p < 0.001], while patients aged >65 years (OR, 0.12; 95% CI, 0.03-0.0434; p = 0.001), fusiform aneurysm type (OR, 0.18; 95% CI, 0.044-0.747; p = 0.018) and intracerebral haematoma (ICA) aneurysm location (OR, 0.24; 95% CI, 0.088-0.643; p = 0.005) were associated with a recommendation for endovascular treatment. CONCLUSIONS: Agreement on aSAH management varies considerably across neurosurgeons, while therapeutic decision-making is challenging on an individual patient level. However, patients aged >65 years, fusiform aneurysm shape and ICA location were associated with endovascular treatment recommendation, while MCA aneurysm location remains a surgical domain in the opinion of neurosurgeons without formal endovascular training.

DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress.

During apoptosis mitochondria undergo cristae remodeling and fragmentation, but how the latter relates to outer membrane permeabilization and downstream caspase activation is unclear. Here we show that the mitochondrial fission protein Dynamin Related Protein (Drp) 1 participates in cytochrome c release by selected intrinsic death stimuli. While Bax, Bak double deficient (DKO) and Apaf1(-/-) mouse embryonic fibroblasts (MEFs) were less susceptible to apoptosis by Bcl-2 family member BID, H(2)O(2), staurosporine and thapsigargin, Drp1(-/-) MEFs were protected only from BID and H(2)O(2). Resistance to cell death of Drp1(-/-) and DKO MEFs correlated with blunted cytochrome c release, whereas mitochondrial fragmentation occurred in all cell lines in response to all tested stimuli, indicating that other mechanisms accounted for the reduced cytochrome c release. Indeed, cristae remodeling was reduced in Drp1(-/-) cells, potentially explaining their resistance to apoptosis. Our results indicate that caspase-independent mitochondrial fission and Drp1-dependent cristae remodeling amplify apoptosis. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

HECTD1 controls the protein level of IQGAP1 to regulate the dynamics of adhesive structures.

BACKGROUND: Cell migration including collective cell movement and individual cell migration are crucial factors in embryogenesis. During the spreading/migration of cells, several types of adhesive structures physically interacting with the extracellular matrix (ECM) or with another cell have been described and the formation and maturation of adhesion structures are coordinated, however the molecular pathways involved are still not fully understood. RESULTS: We generated a mouse embryonic fibroblast line (MEF) from homozygous mutant (Hectd1 R/R , Hectd1 Gt(RRC200) ) mouse of the E3 ubiquitin ligase for inhibin B receptor (Hectd1). Detailed examination of cell motion on MEF cells demonstrated that loss of Hectd1 resulted in accelerated cell spreading and migration but impaired directionality of migration. In Hectd1 R/R cells paxillin and zyxin were largely mis-localized, whereas their expression levels were unchanged. In addition the formation of focal adhesions (FAs) was impaired and the focal complexes (FXs) were increased. We further identified HECTD1 as a key regulator of IQGAP1. IQGAP1 co-localized together with HECTD1 in the leading edge of cells. HECTD1 interacted with IQGAP1 and regulated its degradation through ubiquitination. Over-expression of IQGAP1 in control MEF phenocopied the spreading and migration defects of Hectd1 R/R cells. In contrast, siRNA-mediated knockdown of IQGAP1 rescued the defects in cellular movement of Hectd1 R/R cells. CONCLUSIONS: The E3 ligase activity of Hectd1 regulates the protein level of IQGAP1 through ubiquitination and therefore mediates the dynamics of FXs including the recruitment of paxillin and actinin. IQGAP1 is one of the effectors of HECTD1.

Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated. OBJECTIVE: To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge. METHODS: Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm. RESULTS: This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke. CONCLUSION: Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.

Quality of Life After Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH. OBJECTIVE: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives. METHODS: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 & 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Rankin Scale. RESULTS: Two hundred-fifty patients were enrolled, of whom 237 were included in the analysis after 6 months and 223 after 12 months. After 6 months, 118 (49.8%) patients were alive, and after 12 months, 104 (46.6%) patients were alive. Of those, 95 (80.5%) and 89 (85.6%) reached a favorable outcome with mean EQ-5D-3L index values of 0.85 (±0.18) and 0.86 (±0.18). After 6 and 12 months, 23 (19.5%) and 15 (14.4%) of those alive had an unfavorable outcome with mean EQ-5D-3L index values of 0.27 (±0.25) and 0.19 (±0.14). CONCLUSION: Despite high initial mortality, the proportion of poor-grade aSAH survivors with good QoL is reasonably large. Only a minority of survivors reports poor QoL and requires permanent care.

Development of a Complication- and Treatment-Aware Prediction Model for Favorable Functional Outcome in Aneurysmal Subarachnoid Hemorrhage Based on Machine Learning.

BACKGROUND: Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission. OBJECTIVE: To develop and validate a complication- and treatment-aware outcome prediction tool in aSAH. METHODS: This cohort study included data from an ongoing prospective nationwide multicenter registry on all aSAH patients in Switzerland (Swiss SOS [Swiss Study on aSAH]; 2009-2015). We trained supervised machine learning algorithms to predict a binary outcome at discharge (modified Rankin scale [mRS] ≤ 3: favorable; mRS 4-6: unfavorable). Clinical and radiological variables on admission ("Early" Model) as well as additional variables regarding secondary complications and disease management ("Late" Model) were used. Performance of both models was assessed by classification performance metrics on an out-of-sample test dataset. RESULTS: Favorable functional outcome at discharge was observed in 1156 (62.0%) of 1866 patients. Both models scored a high accuracy of 75% to 76% on the test set. The "Late" outcome model outperformed the "Early" model with an area under the receiver operator characteristics curve (AUC) of 0.85 vs 0.79, corresponding to a specificity of 0.81 vs 0.70 and a sensitivity of 0.71 vs 0.79, respectively. CONCLUSION: Both machine learning models show good discrimination and calibration confirmed on application to an internal test dataset of patients with a wide range of disease severity treated in different institutions within a nationwide registry. Our study indicates that the inclusion of variables reflecting the clinical course of the patient may lead to outcome predictions with superior predictive power compared to a model based on admission data only.

Comparison of Intra- and Postoperative 3-Dimensional Digital Subtraction Angiography in Evaluation of the Surgical Result After Intracranial Aneurysm Treatment.

BACKGROUND: Postoperative three-dimensional digital subtraction angiography (3D-DSA) is the gold standard in evaluating intracranial aneurysm (IA) remnants after clipping. Should intraoperative 3D-DSA image quality be equally good as postoperative 3D-DSA, it could supplant the latter as standard of care for follow-up of clipped IA. OBJECTIVE: To directly compare the quality of assessment of clipped IA by intraoperative and postoperative 3D-DSA. METHODS: From a prospective cohort of 221 consecutive patients who underwent craniotomy for IA treatment in a hybrid operating room, we retrospectively studied 26 patients who had both intraoperative and postoperative 3D-DSA imaging of their clipped aneurysm. Comparison of intraoperative and postoperative 3D-DSA images (blinded for review) included parameters that affected image quality and differences between the 2 periods. RESULTS: In the 26 patients with 32 clipped IAs, the mean interval was 11 ± 7 mo between intraoperative and postoperative imaging 3D-DSA examinations. Reconstruction with multiple clips was used in 14 (44%) cases. Of 15 remnants, 9 (60%) were small (<2 mm). In comparing intraoperative and postoperative 3D-DSA, no discordance or discrepancy in assessment of the surgical result was noted for any clipped IA, and overall imaging quality was excellent for both modalities. Factors affecting minor differences in image quality were not identified. CONCLUSION: Compared with postoperative 3D-DSA, intraoperative 3D-DSA images achieved equally high quality and effective, immediate interpretation of the surgical clipping result. With comparable imaging quality and no discordant findings, intraoperative 3D-DSA could replace postoperative 3D-DSA to become the standard of care in IA surgery.

Hectd1 is essential for embryogenesis in mice.

Many aspects of the functional role of the E3 ubiquitin ligase Hectd1 in embryogenesis and in cell biology still remain to be elucidated. In order to contribute to this task we now report the generation of a new transgenic mouse model for Hectd1 using the gene trap strategy. The HECT domain deletion mutant mouse was created by inserting a ß-geo cassette into the Hectd1 locus. Mice homozygous for Hectd1-mutant showed early embryonic lethality with abnormal placental development and defective of neural tube closure resulting in exencephaly. The thickness of the placenta of both Hectd1-mutant homozygous and heterozygous mice was distinctly thinner than that of wildtype mice, the difference being most pronounced in the labyrinth layer of the placenta. We also addressed the temporal and spatial expression profiles of Hectd1 in adult tissues by X-gal staining. Hectd1 expression was detected in specific cell populations of most but not all tissues of the adult organism. Furthermore, the expression of Hectd1 was regulated by insulin and by both heat and hypoxia. Thus, our studies reveal that Hectd1 is indispensable for normal embryogenesis and fetal survival. The generation of this new Hectd1 mutant mouse model provides ample opportunities to study the function of Hectd1 in mammalian cells in detail.

Patterns of care for ruptured aneurysms of the middle cerebral artery: analysis of a Swiss national database (Swiss SOS).

OBJECTIVE: The objective of this study was to determine patterns of care and outcomes in ruptured intracranial aneurysms (IAs) of the middle cerebral artery (MCA) in a contemporary national cohort. METHODS: The authors conducted a retrospective analysis of prospective data from a nationwide multicenter registry of all aneurysmal subarachnoid hemorrhage (aSAH) cases admitted to a tertiary care neurosurgical department in Switzerland in the years 2009-2015 (Swiss Study on Aneurysmal Subarachnoid Hemorrhage [Swiss SOS]). Patterns of care and outcomes at discharge and the 1-year follow-up in MCA aneurysm (MCAA) patients were analyzed and compared with those in a control group of patients with IAs in locations other than the MCA (non-MCAA patients). Independent predictors of a favorable outcome (modified Rankin Scale score ≤ 3) were identified, and their effect size was determined. RESULTS: Among 1866 consecutive aSAH patients, 413 (22.1%) harbored an MCAA. These MCAA patients presented with higher World Federation of Neurosurgical Societies grades (p = 0.007), showed a higher rate of concomitant intracerebral hemorrhage (ICH; 41.9% vs 16.7%, p < 0.001), and experienced delayed cerebral ischemia (DCI) more frequently (38.9% vs 29.4%, p = 0.001) than non-MCAA patients. After adjustment for confounders, patients with MCAA were as likely as non-MCAA patients to experience DCI (aOR 1.04, 95% CI 0.74-1.45, p = 0.830). Surgical treatment was the dominant treatment modality in MCAA patients and at a significantly higher rate than in non-MCAA patients (81.7% vs 36.7%, p < 0.001). An MCAA location was a strong independent predictor of surgical treatment (aOR 8.49, 95% CI 5.89-12.25, p < 0.001), despite statistical adjustment for variables traditionally associated with surgical treatment, such as (space-occupying) ICH (aOR 1.73, 95% CI 1.23-2.45, p = 0.002). Even though MCAA patients were less likely to die during the acute hospitalization (aOR 0.52, 0.30-0.91, p = 0.022), their rate of a favorable outcome was lower at discharge than that in non-MCAA patients (55.7% vs 63.7%, p = 0.003). At the 1-year follow-up, 68.5% and 69.6% of MCAA and non-MCAA patients, respectively, had a favorable outcome (p = 0.676). CONCLUSIONS: Microsurgical occlusion remains the predominant treatment choice for about 80% of ruptured MCAAs in a European industrialized country. Although patients with MCAAs presented with worse admission grades and greater rates of concomitant ICH, in-hospital mortality was lower and long-term disability was comparable to those in patients with non-MCAA.

Impact of Aneurysm Multiplicity on Treatment and Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: One-third of patients with aneurysmal subarachnoid hemorrhage (aSAH) have multiple intracranial aneurysms (MIA). OBJECTIVE: To determine the predictors of outcome in aSAH patients with MIA compared to aSAH patients with a single intracranial aneurysm (SIA). METHODS: The Swiss Study of Subarachnoid Hemorrhage dataset 2009-2014 was used to evaluate outcome in aSAH patients with MIA compared to patients with SIA with the aid of descriptive and multivariate regression analysis. The primary endpoints of this cohort study were presence of new stroke on computed tomography (CT) after aneurysm treatment, and presence of stroke on CT prior to discharge. The secondary endpoints were the clinical and the functional status, and the overall mortality at discharge and at 1 yr. RESULTS: Among 1689 consecutive patients, 467 had MIA (prevalence: 26.4%). The incidence of stroke was higher in the MIA than in the SIA group, both after aneurysm treatment (19.3% vs 15.1%) and at discharge (24% vs 21.4%). However, the 95% confidence interval (CI) for the corresponding odds ratio (OR) in our multivariate model included 1, indicating that the detected trends did not reach statistical significance. As for the secondary endpoints, aneurysm multiplicity was found to be an independent, statistically significant predictor for occurrence of a new focal neurological deficit between admission and discharge (OR 1.40, 95% CI 1.08-1.81). Yet, the MIA and SIA groups did not differ in terms of either functional outcome or overall survival. CONCLUSION: aSAH patients with MIA have a higher short-term morbidity than patients with SIA. This excess morbidity does not worsen the functional outcome or lower overall survival.

Systematic Review of In Vivo Animal Models of Subarachnoid Hemorrhage: Species, Standard Parameters, and Outcomes.

In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.

Predictors of Occurrence and Anatomic Distribution of Multiple Aneurysms in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The literature on multiple intracranial aneurysms (MIA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) focuses largely on risk factor analysis and consists essentially of retrospective cohort studies of limited sample size, or studies in populations outside Europe and North America. The purpose of this cohort study was to identify predictors for aneurysm multiplicity and to investigate the anatomic distribution of MIA in a representative Western cohort of patients with aSAH. METHODS: The Swiss Study of Subarachnoid Hemorrhage (SOS) database includes anonymized data from all tertiary neurovascular facilities in Switzerland. The dataset for 2009-2014 was used to compare characteristics of patients with aSAH and MIA and those with a single intracranial aneurysm (SIA) by means of descriptive and multivariate regression analysis. RESULTS: Among 1689 unselected patients with aSAH, 467 had MIA (prevalence, 27.6%). The location of the ruptured index aneurysm was correlated with the probability of finding bystander aneurysms and predicted their likely anatomic distribution. Patients with a ruptured basilar artery aneurysm (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.30-3.44) or a ruptured middle cerebral artery aneurysm (OR, 1.86; 95% CI, 1.35-2.55) were at the greatest risk for having MIA. Larger size of the index aneurysm (OR per 1 mm, 1.03; 95% CI, 1.01-1.06) was also positively correlated with aneurysm multiplicity. Males were less likely than females to have MIA (OR, 0.79; 95% CI, 0.61-1.01). CONCLUSIONS: In patients with aSAH, the location of the ruptured index aneurysm is correlated with the probability of finding bystander aneurysms, and is predictive of the sites at which bystander aneurysms are most likely to be found.