Current and Future Applications of Arterial Spin Labeling MRI in Cerebral Arteriovenous Malformations.

Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

Variations in Autoregulation-Based Optimal Cerebral Perfusion Pressure Determination Using Two Integrated Neuromonitoring Platforms in a Trauma Patient.

BACKGROUND: Neuromonitoring devices are often used in traumatic brain injury. The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO). METHODS: We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute. RESULTS: Using the Bland and Altman method, we found a mean variation of - 3.8 (95% confidence internal from - 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from - 26.6 to 19.1 mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10 mm Hg. CONCLUSIONS: These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use.

Benchmarking the CoW with the TopCoW Challenge: Topology-Aware Anatomical Segmentation of the Circle of Willis for CTA and MRA.

The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.

Mixed reality compared to the traditional ex cathedra format for neuroanatomy learning: the value of a three-dimensional virtual environment to better understand the real world.

OBJECTIVE: Neuroanatomy comprehension is a keystone of understanding intracranial surgeries. Traditionally taught to students during ex cathedra courses, neuroanatomy is described as complex. Mixed reality (MxR) opens new perspectives in the learning process. This study aims to compare MxR-based courses with traditional ex cathedra lectures for neuroanatomy education. METHODS: Two lectures describing the neuroanatomy of the anterior circulation arteries ("Vascular Lecture" [VS]) and important white matter fiber tracts ("White Fibers Lecture" [WF]) were designed and delivered in ex cathedra and MxR-based formats with the same audio content. Ninety-one medical students were randomly assigned to group A (ex cathedra WF/MxR VS) or group B (MxR WF/ex cathedra VS). The MxR content was delivered via MxR goggles. Prior to each lecture, students took a 10-item multiple choice question (MCQ) pretest. After the lectures, students took a 20-item MCQ posttest (75% neuroanatomy, 25% clinical correlation). RESULTS: The pretest scores showed no statistical difference between groups. Median posttest scores increased by 14.3% after using the MxR-based format compared to the ex cathedra format (16.00 [13.0, 18.0] vs 14.0 [11.0, 17.0], respectively, p < 0.01). Regarding the VS, students scored 21.7% better using the MxR format compared to the ex cathedra format (14.0 [12.0, 16.0] vs 11.5 [10.0, 14.0], p < 0.001). Concerning the WF, the median score using MxR was 18.0 (17.0, 19.0), and the median score using the ex cathedra format was 17.0 (16.0, 18.0; p < 0.01). Students showed high motivation to learn neuroanatomy in the future using MxR (74%) rather than ex cathedra format (25%; p < 0.001). Mild discomfort using the MxR goggles was reported by 48.3% of participants. Most participants (95.5%) preferred the MxR-based teaching. CONCLUSIONS: Students acquired a better knowledge of the anatomy of the anterior circulation arteries and white fiber tracts using MxR-based teaching as compared to the standard ex cathedra format. The perception of lecture quality and learning motivation was better using MxR-based teaching despite some mild discomfort. The development of MxR-based solutions is promising to improve neuroanatomy education.

Time-of-flight and black-blood MRI to study intracranial arteries in rats.

Intracranial aneurysms (IAs) are usually incidentally discovered by magnetic resonance imaging (MRI). Once discovered, the risk associated with their treatment must be balanced with the risk of an unexpected rupture. Although clinical observations suggest that the detection of contrast agent in the aneurysm wall using a double-inversion recovery black-blood (BB) sequence may point to IA wall instability, the exact meaning of this observation is not understood. Validation of reliable diagnostic markers of IA (in)stability is of utmost importance to deciding whether to treat or not an IA. To longitudinally investigate IA progression and enhance our understanding of this devastating disease, animal models are of great help. The aim of our study was to improve a three-dimensional (3D)-time-of-flight (TOF) sequence and to develop a BB sequence on a standard preclinical 3-T MRI unit to investigate intracranial arterial diseases in rats. We showed that our 3D-TOF sequence allows reliable measurements of intracranial artery diameters, inter-artery distances, and angles between arteries and that our BB sequence enables us to visualize intracranial arteries. We report the first BB-MRI sequence to visualize intracranial arteries in rats using a preclinical 3-T MRI unit. This sequence could be useful for a large community of researchers working on intracranial arterial diseases.Relevance statement We developed a black-blood MRI sequence to study vessel wall enhancement in rats with possible application to understanding IAs instability and finding reliable markers for clinical decision-making.Key points• Reliable markers of aneurysm stability are needed for clinical decision.• Detection of contrast enhancement in the aneurysm wall may be associated with instability.• We developed a black-blood MRI sequence in rats to be used to study vessel wall enhancement of IAs.

ChatGPT in glioma adjuvant therapy decision making: ready to assume the role of a doctor in the tumour board?

OBJECTIVE: To evaluate ChatGPT's performance in brain glioma adjuvant therapy decision-making. METHODS: We randomly selected 10 patients with brain gliomas discussed at our institution's central nervous system tumour board (CNS TB). Patients' clinical status, surgical outcome, textual imaging information and immuno-pathology results were provided to ChatGPT V.3.5 and seven CNS tumour experts. The chatbot was asked to give the adjuvant treatment choice, and the regimen while considering the patient's functional status. The experts rated the artificial intelligence-based recommendations from 0 (complete disagreement) to 10 (complete agreement). An intraclass correlation coefficient agreement (ICC) was used to measure the inter-rater agreement. RESULTS: Eight patients (80%) met the criteria for glioblastoma and two (20%) were low-grade gliomas. The experts rated the quality of ChatGPT recommendations as poor for diagnosis (median 3, IQR 1-7.8, ICC 0.9, 95% CI 0.7 to 1.0), good for treatment recommendation (7, IQR 6-8, ICC 0.8, 95% CI 0.4 to 0.9), good for therapy regimen (7, IQR 4-8, ICC 0.8, 95% CI 0.5 to 0.9), moderate for functional status consideration (6, IQR 1-7, ICC 0.7, 95% CI 0.3 to 0.9) and moderate for overall agreement with the recommendations (5, IQR 3-7, ICC 0.7, 95% CI 0.3 to 0.9). No differences were observed between the glioblastomas and low-grade glioma ratings. CONCLUSIONS: ChatGPT performed poorly in classifying glioma types but was good for adjuvant treatment recommendations as evaluated by CNS TB experts. Even though the ChatGPT lacks the precision to replace expert opinion, it may serve as a promising supplemental tool within a human-in-the-loop approach.

Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

Imaging of intracranial aneurysms in animals: a systematic review of modalities.

Intracranial aneurysm (IA) animal models are paramount to study IA pathophysiology and to test new endovascular treatments. A number of in vivo imaging modalities are available to characterize IAs at different stages of development in these animal models. This review describes existing in vivo imaging techniques used so far to visualize IAs in animal models. We systematically searched for studies containing in vivo imaging of induced IAs in animal models in PubMed and SPIE Digital library databases between 1 January 1945 and 13 July 2022. A total of 170 studies were retrieved and reviewed in detail, and information on the IA animal model, the objective of the study, and the imaging modality used was collected. A variety of methods to surgically construct or endogenously induce IAs in animals were identified, and 88% of the reviewed studies used surgical methods. The large majority of IA imaging in animals was performed for 4 reasons: basic research for IA models, testing of new IA treatment modalities, research on IA in vivo imaging of IAs, and research on IA pathophysiology. Six different imaging techniques were identified: conventional catheter angiography, computed tomography angiography, magnetic resonance angiography, hemodynamic imaging, optical coherence tomography, and fluorescence imaging. This review presents and discusses the advantages and disadvantages of all in vivo IA imaging techniques used in animal models to help future IA studies finding the most appropriate IA imaging modality and animal model to answer their research question.

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.

BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (ß=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

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.

A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis.

Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10-4), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10-8) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment.

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.

External Validation of the HATCH (Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus) Score for Prediction of Functional Outcome After Subarachnoid Hemorrhage.

BACKGROUND: The Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus (HATCH) Score has previously shown to predict functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To validate the HATCH score. METHODS: This is a pooled cohort study including prospective collected data on 761 patients with aSAH from 4 different hospitals. The HATCH score for prediction of functional outcome was validated using calibration and discrimination analysis (area under the curve). HATCH score model performance was compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score. RESULTS: At the follow-up of at least 6 months, favorable (Glasgow Outcome Score 4-5) and unfavorable functional outcomes (Glasgow Outcome Score 1-3) were observed in 512 (73%) and 189 (27%) patients, respectively. A higher HATCH score was associated with an increased risk of unfavorable outcome with a score of 1 showing a risk of 1.3% and a score of 12 yielding a risk of 67%. External validation showed a calibration intercept of -0.07 and slope of 0.60 with a Brier score of 0.157 indicating good model calibration and accuracy. With an area under the curve of 0.81 (95% CI 0.77-0.84), the HATCH score demonstrated superior discriminative ability to detect favorable outcome at follow-up compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score with 0.72 (95% CI 0.67-0.75) and 0.63 (95% CI 0.59-0.68), respectively. CONCLUSION: This multicenter external validation analysis confirms the HATCH score to be a strong independent predictor for functional outcome. Its incorporation into daily practice may be of benefit for goal-directed patient care in aSAH.

Bayesian network analysis reveals the interplay of intracranial aneurysm rupture risk factors.

Clinical decision making regarding the treatment of unruptured intracranial aneurysms (IA) benefits from a better understanding of the interplay of IA rupture risk factors. Probabilistic graphical models can capture and graphically display potentially causal relationships in a mechanistic model. In this study, Bayesian networks (BN) were used to estimate IA rupture risk factors influences. From 1248 IA patient records, a retrospective, single-cohort, patient-level data set with 9 phenotypic rupture risk factors (n=790 complete entries) was extracted. Prior knowledge together with score-based structure learning algorithms estimated rupture risk factor interactions. Two approaches, discrete and mixed-data additive BN, were implemented and compared. The corresponding graphs were learned using non-parametric bootstrapping and Markov chain Monte Carlo, respectively. The BN models were compared to standard descriptive and regression analysis methods. Correlation and regression analyses showed significant associations between IA rupture status and patient's sex, familial history of IA, age at IA diagnosis, IA location, IA size and IA multiplicity. BN models confirmed the findings from standard analysis methods. More precisely, they directly associated IA rupture with familial history of IA, IA size and IA location in a discrete framework. Additive model formulation, enabling mixed-data, found that IA rupture was directly influenced by patient age at diagnosis besides additional mutual influences of the risk factors. This study establishes a data-driven methodology for mechanistic disease modelling of IA rupture and shows the potential to direct clinical decision-making in IA treatment, allowing personalised prediction.

Evaluation of the precision of navigation-assisted endoscopy according to the navigation tool setup and the type of endoscopes.

OBJECT: Preoperative image-based neuronavigation-assisted endoscopy during intracranial procedures is gaining great interest. This study aimed to analyze the precision of navigation-assisted endoscopy according to the navigation setup, the type of optic and its working angulation. METHODS: A custom-made box with four screws was referenced. The navigation-assisted endoscope was aligned on the screws (targets). The precision on the navigation screen was defined as the virtual distance-to-target between the tip of the endoscope and the center of the screws. Three modifiers were assessed: (1) the distance D between the box and the reference array (CLOSE 13 cm - MIDDLE 30 cm - FAR 53 cm), (2) the distance between the tip of the endoscope and the navigation array on the endoscope (close 5 cm - middle 10 cm - far 20 cm), (3) the working angulation of the endoscope (0°-endoscope and 30°-endoscope angled at 90° and 45° with the box). RESULTS: The median precision was 1.3 mm (Q1: 1.1; Q3: 1.7) with the best setting CLOSE/close. The best setting in surgical condition (CLOSE/far) showed a distance-to-target of 2.3 mm (Q1: 1.9; Q3: 2.5). The distance D was correlated to the precision (Spearman rho = 0.82), but not the distance d (Spearman rho = 0.04). The type of optic and its angulation with the box were also correlated to the precision (Spearman rho = - 0.37). The best setting was the use of a 30°-endoscope angled at 45° (1.4 mm (Q1: 1.0; Q3: 1.9)). CONCLUSION: Navigated-assisted endoscopy is feasible and offers a good precision. The navigation setup should be optimized, reducing the risk of inadvertent perifocal damage.

Shape Trumps Size: Image-Based Morphological Analysis Reveals That the 3D Shape Discriminates Intracranial Aneurysm Disease Status Better Than Aneurysm Size.

Background: To date, it remains difficult for clinicians to reliably assess the disease status of intracranial aneurysms. As an aneurysm's 3D shape is strongly dependent on the underlying formation processes, it is believed that the presence of certain shape features mirrors the disease status of the aneurysm wall. Currently, clinicians associate irregular shape with wall instability. However, no consensus exists about which shape features reliably predict instability. In this study, we present a benchmark to identify shape features providing the highest predictive power for aneurysm rupture status. Methods: 3D models of aneurysms were extracted from medical imaging data (3D rotational angiographies) using a standardized protocol. For these aneurysm models, we calculated a set of metrics characterizing the 3D shape: Geometry indices (such as undulation, ellipticity and non-sphericity); writhe- and curvature-based metrics; as well as indices based on Zernike moments. Using statistical learning methods, we investigated the association between shape features and aneurysm disease status. This processing was applied to a clinical dataset of 750 aneurysms (261 ruptured, 474 unruptured) registered in the AneuX morphology database. We report here statistical performance metrics [including the area under curve (AUC)] for morphometric models to discriminate between ruptured and unruptured aneurysms. Results: The non-sphericity index NSI (AUC = 0.80), normalized Zernike energies Z N s u r f (AUC = 0.80) and the modified writhe-index W ¯ m e a n L 1 (AUC = 0.78) exhibited the strongest association with rupture status. The combination of predictors further improved the predictive performance (without location: AUC = 0.82, with location AUC = 0.87). The anatomical location was a good predictor for rupture status on its own (AUC = 0.78). Different protocols to isolate the aneurysm dome did not affect the prediction performance. We identified problems regarding generalizability if trained models are applied to datasets with different selection biases. Conclusions: Morphology provided a clear indication of the aneurysm disease status, with parameters measuring shape (especially irregularity) being better predictors than size. Quantitative measurement of shape, alone or in conjunction with information about aneurysm location, has the potential to improve the clinical assessment of intracranial aneurysms.

Longitudinal neuropsychological assessment after aneurysmal subarachnoid hemorrhage and its relationship with delayed cerebral ischemia: a prospective Swiss multicenter study.

OBJECTIVE: While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias. METHODS: In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without. RESULTS: The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III-V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (-2.6 vs -1.4, p = 0.013) and 14 days (-3.4 vs -0.9, p < 0.001), and 3 months (-0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07-8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28-8.89; p = 0.606). CONCLUSIONS: Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear. Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov).

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.

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.