Treatment factors to suppress delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on VASOGRADE: multicenter cohort study.

Delayed cerebral ischemia (DCI) is one of the most important outcome determinants for aneurysmal subarachnoid hemorrhage (aSAH). VASOGRADE, which combines World Federation of Neurological Surgeons grade and modified Fisher grade, is a useful scale for predicting DCI after aSAH. However, no studies have investigated whether VASOGRADE influences the treatment options. We retrospectively analyzed 781 aSAH patients who were prospectively enrolled in 9 primary stroke centers from 2013 to 2021. The total cohort consisted of 76 patients (9.7%) with VASOGRADE-Green, 390 patients (49.9%) with VASOGRADE-Yellow, and 315 patients (40.3%) with VASOGRADE-Red. Worse VASOGRADE had higher incidences of DCI, which occurred in 190 patients (24.3%). As only 5 patients (6.6%) with VASOGRADE-Green developed DCI, we searched for DCI-associated factors in patients with VASOGRADEs-Yellow and -Red. Multivariate analyses revealed independent treatment factors suppressing DCI as follows: no postoperative hemorrhagic complication, combined administration of fasudil hydrochloride and cilostazol, combination of clipping and cisternal drainage, and coiling for VASOGRADE-Yellow; and clipping, and administration of fasudil hydrochloride with or without cilostazol for VASOGRADE-Red. The findings suggest that treatment strategies should be determined based on VASOGRADE to prevent DCI after aSAH.

Comparison of LVIS and Enterprise stent-assisted coiling embolization for ruptured intracranial aneurysms: a propensity score-matched cohort study.

The role of a low-profile visualized intraluminal support stent (LVIS) and Enterprise in the treatment of unruptured intracranial aneurysms is well established. Although previous studies have investigated one single type of stent for the treatment of ruptured intracranial aneurysms (RIA), the safety and efficacy between the two types of stents has not been fully explored. Herein we conducted a study to compare the outcomes of the two stents for treatment of RIA. This is a prospective registry database of aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a single institution between 2018 and 2021. We collected patient baseline information, secondary complications, follow-up angiographic data, long-term prognostic outcomes, and conducted propensity score matching (PSM) analysis with 1:1 ratio and a multivariable logistic regression to compare the outcomes of the two types of stents. A total of 231 patients with RIAs were included in this study, with 108 treated using the LVIS device and 123 treated using the Enterprise device. Before PSM analysis, only the incidence of poor prognosis after 12 months was higher in the Enterprise group comparing to the LVIS group (20% vs. 10%, P = 0.049). After PSM analysis, there was a higher occurrence of delayed cerebral ischemia (DCI) in the Enterprise group compared to the LVIS group (odds ratio [OR] 3.95, 95% confidence interval [CI] [1.20-13.01], P = 0.024). However, no significant difference in prognosis was observed after PSM adjustment. Furthermore, subgroup analysis revealed that patients with female (P = 0.019), hypertension (P = 0.048), and anterior circulation aneurysms (P = 0.019) receiving the Enterprise device had a higher risk of DCI. The overall efficacy of LVIS and Enterprise in the treatment of RIA is comparable, while the incidence of DCI in the LVIS group is lower than that in the Enterprise group after PSM analysis. Registration number: NCT05738083 ( https://clinicaltrials.gov/ ).

Computational fluid dynamics; a new diagnostic tool in giant intracerebral aneurysm treatment.

Giant intracerebral aneurysms (GIA) comprise up to 5 % of all intracranial aneurysms. The indirect surgical strategy, which leaves the GIA untouched but reverses the blood flow by performing a bypass in combination with proximal parent artery occlusion is a useful method to achieve spontaneous aneurysm occlusion. The goal of this study was to assess the utility of computational fluid dynamics (CFD) in preoperative GIA treatment planning. We hypothesise that CFD simulations will predict treatment results. A fluid-structure interaction (FSI) CFD investigation was performed for the entire arterial brain circulation. The analyses were performed in three patient-specific CT angiogram models. The first served as the reference geometry with a C6 internal carotid artery (ICA) GIA, the second a proximal parent artery occlusion (PAO) and virtual bypass to the frontal M2 branch of the middle cerebral artery (MCA), and the third a proximal PAO in combination with a temporal M2 branch bypass. The volume of "old blood", flow residence time (FRT), dynamic viscosity and haemodynamic changes were also analysed. The "old blood" within the aneurysm in the bypass models reached 41 % after 20 cardiac cycles while in the reference model it was fully washed out. In Bypass 2 "old blood" was also observed in the main trunk of the MCA after 20 cardiac cycles. Extrapolation of the results yielded a duration of 4 years required to replace the "old blood" inside the aneurysm after bypass revascularization. In both bypass models a 7-fold increase in mean blood viscosity in the aneurysm region was noted. Bypass revascularization combined with proximal PAO favours thrombosis. Areas prone to thrombus formation, and subsequently the treatment outcomes, were accurately identified in the preoperative model. Virtual surgical operations can give a remarkable insight into haemodynamics that could support operative decision-making.

Does it stable? Intracranial aneurysm wall enhancement might be the warning signals: a meta-analysis of observational studies.

Magnetic resonance vessel wall imaging (MR-VWI) is an emerging imaging technology used to assess the progressive risk of unruptured intracranial aneurysms (UIAs). Unlike the standard evaluation model, MR-VWI is still debatable. This study aims to further define the potential relationship between aneurysm wall enhancement (AWE) and aneurysm stability. Using "intracranial aneurysm", "magnetic resonance", and "enhancement" as keywords, relevant studies were systematically searched in PubMed, Embase, and Cochrane, and the qualified studies were enrolled for further analysis. There were 13 case-control studies, 4 cohort studies, and 2,678 cases of intracranial aneurysms included in the meta-analysis. It was shown that AWE was correlated with intracranial aneurysm rupture (OR = 35.90, 95% CI: 15.58 to 82.75, p < 0.001), growth (OR = 6.69, 95% CI: 2.69 to 16.63, p < 0.001), and presence of symptoms (OR = 14.46, 95% CI: 9.07 to 23.05, p < 0.001). This finding had a high diagnostic value, but the correlation was probably not independent of aneurysm size. The pooled relative risks of the follow-up studies revealed that the risk of UIA progression was approximately 3.33 times higher with AWE than without AWE (RR = 3.33, 95% CI: 2.33 to 4.78, p < 0.001). In addition, the pooled results demonstrated that quantitative indices of VWI enhancement were equally linked with aneurysm stability (OR = 19.61, 95% CI: 10.63 to 36.17, p < 0.001). AWE is an effective imaging method to assess the stability of UIAs, and it can be a marker for the prophylactic treatment of small unruptured intracranial aneurysms in the future, which remains to be validated by prospective studies with large samples.

Outcomes and predictors of intraprocedural rupture in patients with cerebral aneurysm.

BACKGROUND: Intraprocedural rupture (IPR) is a devastating complication of cerebral aneurysm treatment. While several studies have investigated its risk factors and clinical impact, further research with larger populations is warranted. METHODS: We retrospectively reviewed data from 4,039 patients with 4,233 cerebral aneurysms treated at our institution between January 2009 and December 2018. Multivariate logistic regression with stepwise elimination was performed to identify the independent risk factors of IPR. Unfavorable clinical outcome was defined as a Modified Rankin Scale (mRS) ≥ 3 points at 3 months post-treatment. RESULTS: IPR occurred in 61 (1.44%) of the 4,233 aneurysms. Multivariate analysis showed that previously ruptured aneurysms (odds ratio [OR] 3.182; 95% confidence interval [CI] 1.851-5.470; p < 0.001), surgical clipping (OR 3.598; 95% CI 1.894-6.836; p < 0.001), and higher aspect ratio (OR 1.310; 95% CI 1.032-1.663; p = 0.024) were independent risk factors for IPR. Patients with IPR had significantly higher rates of unfavorable clinical outcomes (mRS ≥ 3) compared to those without (18.0% vs. 3.3%, p < 0.001). However, within the ruptured aneurysm subgroup, the rate of unfavorable outcomes did not differ significantly between IPR and non-IPR groups (22.7% vs. 19.2%, p = 0.594). CONCLUSION: Ruptured aneurysms, surgical clipping, and higher aspect ratio were independently associated with IPR. IPR significantly increased the risk of unfavorable clinical outcomes regardless of treatment approach, except in the subgroup of ruptured aneurysms.

Development of a mechanical characterisation device for intracranial aneurysms: Calibration on polymeric phantom arteries.

Intracranial aneurysm is a major health issue related to biomechanical arterial wall degradation. Currently, no method allows predicting rupture risk based on in vivo quantitative mechanical data. This work is part of a large-scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool, based on the in vivo mechanical characterisation of the aneurysm wall. Thus, the primary objective of the project was to develop a deformation device prototype (DDP) of the artery wall and to calibrate it on polymeric phantom arteries. The deformations induced on the phantom arteries were quantified experimentally using a Digital Image Correlation (DIC) system. The results indicated that the DIC system was able to measure the small displacements generated by the DDP. We also observed that the flow mimicking the blood flow did not significantly disturb the measurements of the artery wall displacement caused by the DDP. Finally, a limit displacement value generated by the DDP was evaluated. This value corresponds to the lowest displacement value detectable by the clinical imaging system that will be tested on animals in the future (Spectral Photon Counting CT).

Multiomics integrated analysis and experimental validation identify TLR4 and ALOX5 as oxidative stress-related biomarkers in intracranial aneurysms.

BACKGROUND: Intracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS. METHODS: In this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence. RESULTS: Through bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs. CONCLUSIONS: Bioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.

Intracranial bypass for giant aneurysms treatment assessed by computational fluid dynamics (CFD) analysis.

Unruptured giant intracranial aneurysms (GIA) are those with diameters of 25 mm or greater. As aneurysm size is correlated with rupture risk, GIA natural history is poor. Parent artery occlusion or trapping plus bypass revascularization should be considered to encourage intra-aneurysmal thrombosis when other treatment options are contraindicated. The mechanistic background of these methods is poorly studied. Thus, we assessed the potential of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) analyses for clinical use in the preoperative stage. A CFD investigation in three patient-specific flexible models of whole arterial brain circulation was performed. A C6 ICA segment GIA model was created based on CT angiography. Two models were then constructed that simulated a virtual bypass in combination with proximal GIA occlusion, but with differing middle cerebral artery (MCA) recipient vessels for the anastomosis. FSI and CFD investigations were performed in three models to assess changes in flow pattern and haemodynamic parameters alternations (wall shear stress (WSS), oscillatory shear index (OSI), maximal time averaged WSS (TAWSS), and pressure). General flow splitting across the entire domain was affected by virtual bypass procedures, and any deficiency was partially compensated by a specific configuration of the circle of Willis. Following the implementation of bypass procedures, a reduction in haemodynamic parameters was observed within the aneurysm in both cases under analysis. In the case of the temporal MCA branch bypass, the decreases in the studied parameters were slightly greater than in the frontal MCA branch bypass. The reduction in the magnitude of the chosen area-averaged parameters (averaged over the aneurysm wall surface) was as follows: WSS 35.7%, OSI 19.0%, TAWSS 94.7%, and pressure 24.2%. FSI CFD investigation based on patient-specific anatomy models with subsequent stimulation of virtual proximal aneurysm occlusion in conjunction with bypass showed that this method creates a pro-thrombotic favourable environment whilst reducing intra-aneurysmal pressure leading to shrinking. MCA branch recipient selection for optimum haemodynamic conditions should be evaluated individually in the preoperative stage.

[Clipping via the Transsylvian Approach:From Basic to Advanced Surgical Techniques].

The transsylvian approach is one of the most commonly used approaches in neurosurgery and is essential for clipping aneurysms located in the anterior cranial circulation, such as the middle cerebral artery, internal carotid artery, and anterior communicating artery. Moreover, basilar artery aneurysms can be clipped using this approach, albeit with some modifications. Important tips for dissecting the Sylvian fissures include reliable visualization, anatomical recognition, and steady manipulation. The actual steps are as follows: determine the affiliation of the arteries and veins, gently move the brain to create a wide space, cut the arachnoid mater, and follow the course of the arteries. In case of subarachnoid hemorrhage, irrigation and flushing out the hematoma is the key step involved in recognizing the structure and safely performing surgery. Here, we describe the basic key operative techniques for performing clipping via the transsylvian approach.

[Interhemispheric Approach for Ruptured Anterior Communicating Artery Aneurysms].

The interhemispheric approach is very useful for the safe and reliable clipping of ruptured anterior communicating aneurysms. This approach enables surgeons to directly visualize the aneurysm and the surrounding vessels, including perforators, and provides a wide surgical corridor for clip insertion from multiple directions. Furthermore, in challenging situations, this approach facilitates vascular reconstruction without the need for graft harvesting. However, because of the procedural difficulty, many young and inexperienced neurosurgeons may hesitate to perform this technique. Therefore, this study aimed to provide useful tips, based on intraoperative photography, for skin and dural incisions, prevention of cerebrospinal fluid leakage and olfactory impairment, and fundamental steps for opening tight interhemispheric fissures. Finally, representative challenging cases that were adequately managed using the advantages of this approach are presented.

[Molecular Mechanisms Underlying Intracranial Aneurysm Rupture].

Intracranial aneurysms, a major cause of subarachnoid hemorrhage(SAH), pose a significant social burden due to their poor patient outcomes. Recent studies, including those using animal models, have shed light on a new disease concept: intracranial aneurysms as a chronic inflammatory disease. This process is triggered by abnormal hemodynamic forces and mediated by immune cells like macrophages and neutrophils. The initiation of intracranial aneurysms is a two-step process. First, high wall shear stress and mechanical stretch work together to promote macrophage infiltration into the arterial walls. This infiltration is facilitated by endothelial cells and fibroblasts, which are activated to produce chemoattractants. Once the lesions enlarge, low wall shear stress and turbulent flow take over, maintaining macrophage infiltration. As the disease progresses towards rupture, infiltration creates hypoxic conditions that exacerbate the situation. These conditions, in turn, induce the formation of neovessels at the weakest point of the aneurysm and promote specific inflammatory microenvironments rich in neutrophils. The excessive tissue destruction caused by neutrophil-mediated inflammation ultimately leads to lesion rupture. Therefore, intracranial aneurysm rupture requires not only structural changes but also qualitative alterations within the chronic inflammatory environment. This suggests that factors mediating chronic inflammation could be potential targets for predicting or preventing aneurysm rupture.

[Association Between Intracranial Aneurysms and Genes].

Ruptured intracranial aneurysm(IA) leads to aneurysmal subarachnoid hemorrhage(aSAH), which is the most severe type of stroke. Besides age, sex, and alcohol consumption, family history is considered an important risk factor. Approximately 5% of the Japanese population is affected by unruptured cerebral aneurysms. However, their developmental processes and pathologies remain unclear. Familial cerebral aneurysms account for 10% of all cerebral aneurysm cases, and somatic gene mutations are believed to be involved in their development. This review summarizes the recent findings from family-based, genome-wide association, sequencing, and somatic gene mutation studies on IA.

[Microsurgery for Vertebral and Posterior Inferior Cerebellar Artery Aneurysms via Lateral Suboccipital Craniotomy].

Among ruptured intracranial aneurysms, aneurysms of the vertebral artery(VA) and posterior inferior cerebellar artery(PICA) are relatively rare, and they exhibit distinct characteristics. These include: 1) a high frequency of diverse aneurysmal morphologies, such as fusiform or dissecting aneurysms; 2) proximity to the lower cranial nerves; 3) the presence of perforators to the medulla oblongata; and, 4) obstruction to the surgical approach by specific bony structures, such as the occipital condyle and jugular tubercle. Consequently, these aneurysms often require interventions that are more complex than simple clipping or coiling, which is typical for anterior circulation aneurysms. Interventions include skull base techniques such as the far-lateral approach and revascularization procedures such as occipital artery(OA)-PICA bypass. Despite these complexities, the rarity of these aneurysms and the recent advancements in endovascular procedures pose challenges for young neurosurgeons in acquiring adequate microsurgical experience. This narrative review addresses the clinical features of VA and PICA aneurysms, the history and variations in the lateral suboccipital approach for these aneurysms, and several bypass techniques for reconstructing the PICA. Lastly, we illustrate our current microsurgical practices through a case presentation accompanied by a surgical video showcasing both the far-lateral approach and the OA-PICA bypass.