Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Data on health-related costs after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim was to evaluate outcome, return to work and costs after aSAH with focus on differences between high- and low-grade aSAH (defined as World Federation of Neurological Surgeons [WFNS] grades 4-5 and WFNS 1-3, respectively). METHODS: A cross-sectional study was performed, including all consecutive survivors of aSAH over a 4-year period. A telephone interview was conducted to assess the Glasgow Outcome Scale Extended and employment status before and after aSAH. Direct costs were calculated by multiplying the length of hospitalization by the average daily costs. Indirect costs were calculated for productivity losses until retirement age according to the human capital approach. RESULTS: Follow-up was performed 2.7 years after aSAH (range 1.3-4.6). Favorable outcome was achieved in 114 of 150 patients (76%) and work recovery in 61 of 98 patients (62%) employed prior to aSAH. High-grade compared to low-grade aSAH resulted less frequently in favorable outcome (52% vs. 85%; p < 0.001) and work recovery (39% vs. 69%; p = 0.013). The total costs were € 344.277 (95% CI 268.383-420.171) per patient, mainly accounted to indirect costs (84%). The total costs increased with increasing degree of disability and were greater for high-grade compared to low-grade aSAH (€ 422.496 vs. € 329.193; p = 0.039). The effective costs per patient with favorable outcome were 2.1-fold greater for high-grade compared to low-grade aSAH (€ 308.625 vs. € 134.700). CONCLUSION: Favorable outcome can be achieved in a considerable proportion of high-grade aSAH patients, but costs are greater compared to low-grade aSAH. Further cost-effectiveness studies in the current era of aSAH management are needed.

Comparison of statistical learning approaches for cerebral aneurysm rupture assessment.

PURPOSE: Incidental aneurysms pose a challenge to physicians who need to decide whether or not to treat them. A statistical model could potentially support such treatment decisions. The aim of this study was to compare a previously developed aneurysm rupture logistic regression probability model (LRM) to other machine learning (ML) classifiers for discrimination of aneurysm rupture status. METHODS: Hemodynamic, morphological, and patient-related information of 1631 cerebral aneurysms characterized by computational fluid dynamics simulations were used to train support vector machines (SVMs) with linear and RBF kernel (RBF-SVM), k-nearest neighbors (kNN), decision tree, random forest, and multilayer perceptron (MLP) neural network classifiers for predicting the aneurysm rupture status. The classifiers' accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were evaluated and compared to the LRM using 249 test cases obtained from two external cohorts. Additionally, important variables were determined based on the random forest and weights of the linear SVM. RESULTS: The AUCs of the MLP, LRM, linear SVM, RBF-SVM, kNN, decision tree, and random forest were 0.83, 0.82, 0.80, 0.81, 0.76, 0.70, and 0.79, respectively. The accuracy ranged between 0.76 (decision tree,) and 0.79 (linear SVM, RBF-SVM, and MLP). Important variables for predicting the aneurysm rupture status included aneurysm location, the mean surface curvature, and maximum flow velocity. CONCLUSION: The performance of the LRM was overall comparable to that of the other ML classifiers, confirming its potential for aneurysm rupture assessment. To further improve the predictions, additional information, e.g., related to the aneurysm wall, might be needed.

Computational fluid dynamics as a risk assessment tool for aneurysm rupture.

OBJECTIVE: The authors reviewed the clinical role of computational fluid dynamics (CFD) in assessing the risk of intracranial aneurysm rupture. METHODS: A literature review was performed to identify reports on CFD assessment of aneurysms using PubMed. The usefulness of various hemodynamic parameters, such as wall shear stress (WSS) and the Oscillatory Shear Index (OSI), and their role in aneurysm rupture risk analysis, were analyzed. RESULTS: The authors identified a total of 258 published articles evaluating rupture risk, growth, and endovascular device assessment. Of these 258 articles, 113 matching for CFD and hemodynamic parameters that contribute to the risk of rupture (such as WSS and OSI) were identified. However, due to a lack of standardized methodology, controversy remains on each parameter's role. CONCLUSIONS: Although controversy continues to exist on which risk factors contribute to predict aneurysm rupture, CFD can provide additional parameters to assess this rupture risk. This technology can contribute to clinical decision-making or evaluation of efficacy for endovascular methods and devices.

Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics.

OBJECTIVE: Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors' goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS: Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm's shape and hemodynamics. Next, the previously developed model's discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS: The US model's AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10. CONCLUSIONS: Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH)-phase II: rupture risk assessment.

PURPOSE: Assessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited. METHODS: To provide an overview of state-of-the-art blood flow simulation capabilities, the Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was conducted. Seventeen research groups from all over the world performed segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient harboring five IAs. Although simulation setups revealed good similarity, clear differences exist with respect to the analysis of aneurysm shape and blood flow results. Most groups (12/71%) included morphological and hemodynamic parameters in their analysis, with aspect ratio and wall shear stress as the most popular candidates, respectively. RESULTS: The majority of groups (7/41%) selected the largest aneurysm as being the ruptured one. Four (24%) of the participating groups were able to correctly select the ruptured aneurysm, while three groups (18%) ranked the ruptured aneurysm as the second most probable. Successful selections were based on the integration of clinically relevant information such as the aneurysm site, as well as advanced rupture probability models considering multiple parameters. Additionally, flow characteristics such as the quantification of inflow jets and the identification of multiple vortices led to correct predictions. CONCLUSIONS: MATCH compares state-of-the-art image-based blood flow simulation approaches to assess the rupture risk of IAs. Furthermore, this challenge highlights the importance of multivariate analyses by combining clinically relevant metadata with advanced morphological and hemodynamic quantification.

Towards the Clinical utility of CFD for assessment of intracranial aneurysm rupture - a systematic review and novel parameter-ranking tool.

BACKGROUND: Intracranial aneurysms (IAs) are vascular dilations on cerebral vessels that affect between 1%-5% of the general population, and can cause life-threatening intracranial hemorrhage when ruptured. Computational fluid dynamics (CFD) has emerged as a promising tool to study IAs in recent years, particularly for rupture risk assessment. However, despite dozens of studies, CFD is still far from clinical use due to large variations and frequent contradictions in hemodynamic results between studies. PURPOSE: To identify key gaps in the field of CFD for the study of IA rupture, and to devise a novel tool to rank parameters based on potential clinical utility. METHODS: A Pubmed search identified 231 CFD studies for IAs. Forty-six studies fit our inclusion criteria, with a total of 2791 aneurysms. For included studies, study type, boundary conditions, solver resolutions, parameter definitions, geometric and hemodynamic parameters used, and results found were recorded. DATA SYNTHESIS: Aspect ratio, aneurysm size, low wall shear stress area, average wall shear stress, and size ratio were the parameters that correlate most strongly with IA rupture. LIMITATIONS: Significant differences in parameter definitions, solver spatial and temporal resolutions, number of cycles between studies as well as frequently missing information such as inlet flow rates were identified. A greater emphasis on prospective studies is also needed. CONCLUSIONS: Our recommendations will help increase standardization and bridge the gaps in the CFD community, and expedite the process of making CFD clinically useful in guiding the treatment of IAs.

Assessment of Risk of Aneurysmal Rupture in Patients with Normotensives, Controlled Hypertension, and Uncontrolled Hypertension.

BACKGROUND: The prevalence of hypertension in patients with intracranial aneurysms has been an increased concern, but it is not well understood if uncontrolled hypertension has impact on aneurysmal rupture. The aim of this study was to determine whether the risk of aneurysmal rupture is higher in uncontrolled hypertensive cohorts than in controlled hypertensive cohorts and normotensive cohorts. METHODS: We retrospectively analyzed the records and angiographies of 456 patients with aneurysms who were treated at our center between June 2013 and June 2014. Three groups of patients were included in the study following the ESH-ESC (European Society of Hypertension-European Society of Cardiology) 2013 guidelines: normotensive group (n = 229), controlled hypertension group (n = 127), and uncontrolled hypertension group (n = 100). Paired comparisons of these 3 groups were analyzed with the Nemenyi test. Multivariate logistic regression analysis was used to exclude the impact of possible confounding factors. RESULTS: The results of the univariate analysis showed that hypertension, smoking, and size of the aneurysms were significantly associated with intracranial aneurysmal rupture (P < .05). The multivariate logistic regression analysis containing clinical and aneurysmal characteristics showed that uncontrolled hypertension, smoking, and aneurysm size were statistically significant predictors of intracranial aneurysmal rupture (P < .05). The paired comparisons of 3 groups showed that the risk of rupture of intracranial aneurysms in the uncontrolled hypertension group was significantly greater than that in the normotensive group (P < .05) and in the controlled hypertension group (P < .05). CONCLUSIONS: Uncontrolled hypertension is associated with increased risk of rupture of intracranial aneurysms. Given that aneurysmal rupture is a potentially fatal-but preventable-complication, these findings are of clinical relevance.

An approach to quantitative assessment of hemodynamic differences between unruptured and ruptured ophthalmic artery aneurysms.

BACKGROUND AND PURPOSE: Hemodynamic parameters are important in the pathogenesis, evolution and rupture of intracranial aneurysm. Energy loss (EL) has been applied for the rupture risk prediction of artery aneurysms recently. We proposed a new EL and further investigate its effects on the rupture of aneurysms. MATERIALS AND METHODS: Sixty-four patient-specific ophthalmic aneurysm datasets were divided into ruptured and unruptured groups based on their clinical history. Based on patient-specific 3D-DSA data, realistic models were retrospectively reconstructed and then analyzed by using computational fluid dynamic method. RESULTS: The flow field feature EL in ruptured cases was significantly higher than that in unruptured cases. The average wall shear stress (WSS) and the maximum WSS in ruptured cases were higher than those in unruptured cases. Modified pressure loss coefficient (PLCM) in ruptured cases was slight higher than that in unruptured cases but the difference has no statistical significance. Multivariate logistic regression analysis demonstrated flow field feature EL (p < 0.05) and the maximum WSS (p < 0.05) were the only independently significant variables to predict rupture of ophthalmic aneurysm. There were no differences in PLCM, the maximum oscillatory shear index (OSI), the average OSI and AR between the two groups. CONCLUSION: Flow field feature EL may be a reliable factor to predict the rupture risk of aneurysms.

CFD: computational fluid dynamics or confounding factor dissemination? The role of hemodynamics in intracranial aneurysm rupture risk assessment.

Image-based computational fluid dynamics holds a prominent position in the evaluation of intracranial aneurysms, especially as a promising tool to stratify rupture risk. Current computational fluid dynamics findings correlating both high and low wall shear stress with intracranial aneurysm growth and rupture puzzle researchers and clinicians alike. These conflicting findings may stem from inconsistent parameter definitions, small datasets, and intrinsic complexities in intracranial aneurysm growth and rupture. In Part 1 of this 2-part review, we proposed a unifying hypothesis: both high and low wall shear stress drive intracranial aneurysm growth and rupture through mural cell-mediated and inflammatory cell-mediated destructive remodeling pathways, respectively. In the present report, Part 2, we delineate different wall shear stress parameter definitions and survey recent computational fluid dynamics studies, in light of this mechanistic heterogeneity. In the future, we expect that larger datasets, better analyses, and increased understanding of hemodynamic-biologic mechanisms will lead to more accurate predictive models for intracranial aneurysm risk assessment from computational fluid dynamics.

Biomechanical assessment of the individual risk of rupture of cerebral aneurysms: a proof of concept.

This study is a step towards a new biomechanical-based measurement of the patient specific risk of rupture of cerebral aneurysms. Following a previous experimental investigation suggesting a correlation between the risk of rupture and the material properties of cerebral aneurysms, fluid-structure interaction simulations are performed to compare the deformations of a patient-specific aneurysm when using degraded or undegraded materials. Results show that material properties have a major impact on the magnitude of systolic/diastolic aneurysmal volume variations along the cardiac cycle. Changes in terms of aneurysmal volume variations depending on the tissue characteristics are shown to be measurable by medical imaging. A one-at-a-time data uncertainty analysis is also presented and shows the robustness of this result to input data uncertainties. The study thus suggests that aneurysmal volume variations may be used as the basis of a biomechanical index of rupture risk.

Biomechanical rupture risk assessment of abdominal aortic aneurysms: model complexity versus predictability of finite element simulations.

OBJECTIVE: Investigation of the predictability of finite element (FE) models regarding rupture risk assessment of abdominal aortic aneurysms (AAAs). MATERIALS AND MATERIALS: Peak wall stress (PWS) and peak wall rupture risk (PWRR) of ruptured (n = 20) and non-ruptured (n = 30) AAAs were predicted by four FE models of different complexities derived from computed tomography (CT) data. Two matching sub-groups of ruptured and non-ruptured aneurysms were used to investigate the usability of different FE models to discriminate amongst them. RESULTS: All FE models exhibited a strong positive correlation between PWS and PWRR with the maximum diameter. FE models, which excluded the intra-luminal thrombus (ILT) failed to discriminate between ruptured and non-ruptured aneurysms. The predictability of all applied FE models was strengthened by including wall strength data, that is, computing the PWRR. The most sophisticated FE model applied in this study predicted PWS and PWRR 1.17 (p = 0.021) and 1.43 (p = 0.016) times higher in ruptured than diameter-matched non-ruptured aneurysms, respectively. CONCLUSIONS: PWRR reinforces PWS as a biomechanical rupture risk index. The ILT has a major impact on AAA biomechanics and rupture risk, and hence, needs to be considered in meaningful FE simulations. The applied FE models, however, could not explain rupture in all analysed aneurysms.

Growth rates of intracranial aneurysms: exploring constancy.

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

Risk of aneurysmal rupture: the importance of neck orifice positioning-assessment using computational flow simulation.

OBJECTIVE: The aim of the present study was to clarify the risk of rupture in terminal-type intracranial aneurysms using computational flow simulation analysis. METHODS: First, idealized three-dimensional aneurysmal models were built from a solid voxel on the computer. We focused on round terminal-type aneurysms with the positioning of the neck orifice set according to the following three patterns in relationship to the axis of the parent artery: the Type-A neck orifice was positioned directly in line with the flow of the parent artery; the Type-B neck orifice was shifted 1.5 mm offline toward the unilateral branch; and the Type-C neck orifice was shifted 3 mm offline. Computational flow simulations were applied with Fujitsu alpha-Flow software (Fujitusu, Tokyo, Japan). We analyzed flow patterns using modified patient-specific models. We also investigated actual clinical situations to evaluate the differences in neck-orifice positioning between 20 ruptured aneurysms and 26 unruptured ones using three-dimensional angiograms. RESULTS: The Type-A neck orifice showed completely symmetrical stream lines in the aneurysm, whereas the Type-C orifice showed a clear round circulation. The Type-B neck orifice, on the other hand, exhibited intra-aneurysmal flow separation. The clinical research demonstrated that Type-B aneurysms were more likely to be found in the ruptured group (P < 0.05). CONCLUSION: Flow separation, recognized as one of the causes of intimal injury, could be observed only in Type-B aneurysms, a result that corresponded well with our clinical experience. From the flow-dynamics point of view, this positioning of the neck orifice may be one of the risk factors most likely to induce the rupture of unruptured aneurysms.

[Angio-MR assessment of vasomotor reactivity impairment as a long-term outcome of SAH following intracerebral aneurysm rupture]. / Reaktywnosc naczyn mózgowych w póznym okresie po SAH z peknietego tetniaka sródczaszkowego w badaniu angio-MR.

Studies on long-term outcome of subarachnoid hemorrhage (SAH) have been carried out for many years using various neuroimaging techniques, such as e.g.: SPECT, PET, TCD and XeCT. In our study angio-MRI supplemented with the acetazolamide test was used to assess cerebrovascular reserve impairment in 30 patients within 6 months since clipping an intracranial aneurysm. Severity of the SAH course was evaluated using the WFNS (World Federation of Neurosurgical Societies) scale [3]. The patients' clinical status was assessed at follow-up by means of the Glasgow Outcome Scale (GOS) [8]. Cereberovascular reserve evaluated at the follow-up in hypercapneal conditions was found to be insufficient. The degree of vessel reactivity dysfunction as a long-term outcome of SAH turned out to depend on massiveness of hemorrhage from the ruptured aneurysm.

[Preanesthetic assessment of a patient with giant negative T waves on ECG following subarachnoid hemorrhage].

Giant negative T waves on ECG are associated with intracranial hemorrhage such as subarachnoid hemorrhage, ischemic heart disease such as subendocardial infarction, myocardial disease and others. They embarrass us in anesthetic management of urgent neurosurgical patients because of the requirement of making differential diagnosis among these diseases accompanying the ECG abnormality. An 80 year old woman undergoing radical clipping for cerebral artery aneurysm showed giant negative T waves on ECG. Although the ECG taken on admission to the hospital had been normal, huge giant negative T waves of 2 mV and QTc prolongation were detected on arrival in the operating room. Therefore, her cardiac function was evaluated by echocardiography to rule out subendocardial infarction. The echocardiogram revealed that wall motion of the left ventricle was mildly depressed, but her cardiac function was well maintained since the cardiac output was 4.1 l.min-1 and the ejection fraction was 59%. We thought that giant negative T waves were caused by subarachnoid hemorrhage and decided to perform anesthesia and surgery. Circulation during anesthesia and surgery was stable except a transient decrease in blood pressure due to massive hemorrhage during rupture of the aneurysm. We conclude that preanesthetic assessment of cardiac function by echocardiography is useful for anesthetic management of patients with giant negative T waves on ECG undergoing urgent radical operation for cerebral aneurysm.

Hemodynamic assessment of the development and rupture of intracranial aneurysms using computational simulations.

Intracranial aneurysms manifest themselves as sacculations within a weakened region of the vessel wall and pose substantial neurological risks upon rupture. A primary factor in the development and rupture stages of an aneurysm is hemodynamics and its degrading effects on the aneurysm wall. Wall dynamics and hemodynamics within a fully developed aneurysm were investigated using computational simulation techniques. To study wall dynamics, the aneurysm was modeled as a thing spherical shell with linearly elastic and plastic (viscoelastic) wall behavior. The sensitivity of this model to the biophysical parameters which describe it will assist in the quantitative assessment of factors predisposing to aneurysm rupture and subarachnoid hemorrhage. Flow dynamics simulations were performed for spherical aneurysms with rigid walls. We observed the development and motion of an annular vortex within the lateral sacculation. We also simulated a ruptured aneurysm by placing a tear near the neck of the aneurysm. Flow patterns showed blood flowing out during the initial stages of the flow, but displayed an inflow of blood soon thereafter, as the internal pressure dropped. These results are substantiated by the clinical observations that turbulent flow is observed within the aneurysm as evidenced by reduced bruits.

Neuroangiographic assessment of aneurysm stability and impending rupture based on a non-linear biomathematical model.

The probability or risk of aneurysm rupture is assessed using conventional angiography by applying the aneurysm radius and systolic blood pressure obtained at examination to a non-linear biomathematical model of an aneurysm. A non-linear biomathematical model was developed based on Laplace's law to represent the viscoelastic relation between the wall tension and the radius. A differential expression of this relation was used to derive the critical radius: Rc = [2Et/P]2At/P where E is the elastic modulus of the aneurysm, t is the wall thickness, P is the pressure, and A is the elastic modulus of collagen. Using average values of E, A, and t, the risk of aneurysm rupture is defined as the area of integration under the curve defined by the minimum value of pressure (50 mmHg) and the patient pressure recorded at examination. This area was normalized by the area of integration defined by the pressure limits: 50 to 300 mmHg. This method of risk assessment was applied to four previously published case studies of patients with documented aneurysm rupture in which both the aneurysm size at rupture and the patient systolic blood pressure were reported. Two additional parameters were calculated to further evaluate aneurysm stability: (1) a ratio given as (Rexp/Rth) where Rexp is the radius of aneurysm rupture measured from angiography and Rth is the critical radius based on the model; and (2) chi 2 analysis defined by chi 2 = (O - E)2/E where O and E are the observed (Rexp) and expected (Rth) variables, respectively. The average systolic blood pressure and radius of aneurysm rupture was 147.2 mmHg and 3.95 mm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[The assessment of brain stem function in the acute period of aneurysm rupture]. / Otsenka funktsional'nogo sostoianiia stvola golovnogo mozga v ostrom periode razryva anevrizm.

The functional status of the brain stem was assessed by recording evoked stem auditory potentials (ESAP) in 76 patients in the acute period of arterial aneurysm rupture. Abnormalities of ESAP were detected in 39.4% of the patients. The determinant of ESAP disorder in aneurysm rupture is the occlusive-dislocation syndrome caused by intracranial hematoma, more than 50 ml in volume, ventricular tamponade or extensive vascular spasm.