Sherif Rashad

Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization

Background and Purpose— Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms. Methods— We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a follow-up of >1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics. Results— Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density <30% were independent and significant predictors for the recanalization of coiled aneurysms. Additional investigation revealed that a small branch angle formed by the basilar artery and the posterior cerebral artery increased blood flow into the aneurysm. Conclusions— The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.

Daughter Sac Formation Related to Blood Inflow Jet in an Intracranial Aneurysm

OBJECTIVE We performed a hemodynamic study of an intracranial aneurysm with a newly developed daughter sac during observation to investigate the role of hemodynamics on the formation of a daughter sac. METHODS A 75-year-old man underwent magnetic resonance angiography that revealed a large internal carotid artery aneurysm with inflow jet inside the aneurysm. The aneurysm was stable for 18 months, but a new daughter sac developed at the tip of the aneurysm during the next 6 months. The daughter sac seemed to be related to the inflow jet on magnetic resonance angiography. Aneurysm geometries before and after daughter sac formation were reconstructed using the longitudinal data of magnetic resonance angiography. Computational fluid dynamic simulations were conducted under the patient-specific pulsatile inlet conditions measured by magnetic resonance velocimetry. RESULTS The hemodynamic simulation revealed that the inflow jet impinged on 2 sites of the aneurysm: the right side of the aneurysmal dome and the tip of the aneurysm. The flow impingement caused elevation of pressure at both sites. However, the daughter sac formed at the latter site surrounded by the basal cistern but did not form at the former site that was in contact with the right temporal lobe. CONCLUSIONS Blood inflow jet caused local elevation of pressure, and the formation of the daughter sac occurred at the site with high pressure but without the surrounding structure, which may cancel the perpendicular wall tension.

Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms

OBJECTIVE Risk factors for aneurysm rupture have been extensively studied, with several factors showing significant correlations with rupture status. Several studies have shown that aneurysm shape and hemodynamics change after rupture. In the present study the authors investigated a static factor, the bifurcation angle, which does not change after rupture, to understand its effect on aneurysm rupture risk and hemodynamics. METHODS A hospital database was retrospectively reviewed to identify patients with cerebral aneurysms treated surgically or endovascularly in the period between 2008 and 2015. After acquiring 3D rotational angiographic data, 3D stereolithography models were created and computational fluid dynamic analysis was performed using commercially available software. Patient data (age and sex), morphometric factors (aneurysm volume and maximum height, aspect ratio, bifurcation angle, bottleneck ratio, and neck/parent artery ratio), and hemodynamic factors (inflow coefficient and wall shear stress) were statistically compared between ruptured and unruptured groups. RESULTS Seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Univariate analysis showed aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with a ruptured status. Logistic regression analysis showed that aspect ratio and bifurcation angle were significant predictors of a ruptured status. Bifurcation angle was inversely correlated with inflow coefficient (p < 0.0005), which in turn correlated directly with mean (p = 0.028) and maximum (p = 0.014) wall shear stress (WSS) using Pearsons correlation coefficient, whereas aspect ratio was inversely correlated with mean (0.012) and minimum (p = 0.018) WSS. CONCLUSIONS Bifurcation angle and aspect ratio are independent predictors for aneurysm rupture. Bifurcation angle, which does not change after rupture, is correlated with hemodynamic factors including inflow coefficient and WSS, as well as rupture status. Aneurysms with the hands-up bifurcation configuration are more prone to rupture than aneurysms with other bifurcation configurations.

Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia

Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on five G-protein-coupled cell membrane receptors. Following transient global cerebral ischemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. In this study, we evaluated S1P levels and S1P-processing enzyme expression in different hippocampal areas following tGCI in rats. We found that S1P was upregulated earlier in CA3 than in CA1. This was associated with upregulation of SphK1 in both regions; however, SphK2 was downregulated quickly in CA3. S1P lyase was also downregulated in CA3, but not in CA1. Spinster 2, the S1P exporter, was upregulated early in both regions, but was quickly downregulated in CA3. Together, these effects explain the variable levels of S1P in the CA1 and CA3 areas and indicate that S1P levels play a role in the preferential resistance of the CA3 subregion to tGCI-induced ischemia. FTY720 did not improve neuronal survival in the CA1 subregion, indicating that these effects were due to intracellular S1P accumulation. In conclusion, the findings suggest that intracellular S1P levels affect neuronal cell fate following tGCI.

Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge

PurposeImage-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline.Methods3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods, boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters.ResultsA total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability.ConclusionsWide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters.

Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex

The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS); however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited. Our objective was to address this critical issue, and we investigated Rnf213 mRNA expression in rat brains after 5 minutes of transient global cerebral ischemia (tGCI) by occluding the common carotid arteries coupled with severe hypotension. Rnf213 gene expression patterns were investigated with in situ RNA hybridization and a real-time polymerase chain reaction (PCR) from 1 to 72 hours after tGCI. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the hippocampus CA1 sub-region 48 hours after tGCI. The significant induction of the Rnf213 gene was also evident in the ischemic cortex. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression exclusively in neurons. The real-time PCR analysis confirmed the induction of the Rnf213 gene after tGCI. The up-regulation of the Rnf213 gene in vulnerable neurons in the hippocampus CA1 after tGCI suggests its involvement in forebrain ischemia, which is an underlying pathology of MMD. Further investigations are needed to elucidate its exact role in the pathophysiology of ICAS including MMD.

De Novo Giant Partially Thrombosed Aneurysm Complicating STA-MCA Bypass Site in 3 Years: Case Report With Review of the Literature

Background and Importance:Aneurysm formation after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is a rare condition with only a handful of cases reported in the literature with various presentations and management strategies. Various theories have been postulated to explain such rare complication and to determine whether it is a de novo pathology or related to operative techniques. Clinical Presentation:We report on a 33-year-old man who had undergone STA-MCA bypass and parent vessel occlusion for a giant cavernous internal carotid artery aneurysm 3 years ago. He presented to us with headache and on follow-up radiologic investigations a giant aneurysm was found at the bypass site. We present this rare case and discuss its troublesome management. Conclusions:This is the first case reported with unruptured giant partially thrombosed aneurysm developing on the site of STA-MCA bypass. We discuss its management and possible etiologies for its formation with review of similar cases in the literature for future prevention and/or management of similar cases.

Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is a rare form of cerebral stroke that causes a variety of symptoms, ranging from mild headache to severe morbidity or death in the more severe forms. The use of anti-coagulant or thrombolytic agents is the classical treatment for CVT. However, the development of new therapies for the treatment of the condition has not been the focus. In this study, we aimed to analyze the pathophysiology of CVT and to identify the pathways associated with its pathology. Moreover, mechanisms that are potential drug targets were identified. Our data showed the intense activation of immune cells, particularly the microglia, along with the increase in macrophage activity and NLRP3 inflammasome activation that is indicated by NLRP3, IL-1β, and IL-18 gene and caspase-1 upregulation and cleavage as well as pyroptotic cell death. Leukocytes were observed in the brain parenchyma, indicating a role in CVT-induced inflammation. In addition, astrocytes were activated, and they induced glial scar leading to parenchymal contraction during the subacute stage and tissue loss. MMP9 was responsible primarily for the BBB breakdown after CVT and it is mainly produced by pericytes. MMP9 activation was observed before inflammatory changes, indicating that BBB breakdown is the initial driver of the pathology of CVT. These results show an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be targeted by pharmaceutical agents to improve the neuroinflammation that follows CVT, such as MMP9, NLRP3, and IL-1β. Some of these pharmaceutical agents are already in clinical practice or under clinical trials indicating a good potential for translating this work into patient care.

Therapeutic Clip Occlusion of the Anterior Choroidal Artery Involved with Partially Thrombosed Fusiform Aneurysm: A Case Report

BACKGROUND We describe a rare case with partially thrombosed fusiform anterior choroidal artery (AchA) aneurysm successfully treated with therapeutic occlusion of the AchA. CLINICAL PRESENTATION A 58-year-old man presented with transient mild hemiparesis of the right side. Magnetic resonance imaging (MRI) showed an ischemic lesion in the posterior limb of the left internal capsule. Digital subtraction angiography (DSA) revealed a left internal carotid artery saccular aneurysm (14.5-mm diameter) arising from the supraclinoid segment. The left AchA was not detected in the initial DSA, and MRI showed the aneurysm to be partially thrombosed. The second DSA performed 2 weeks after the onset showed recanalization of the thrombosed portion of the aneurysm with the left AchA apparently arising from its tip. The aneurysm was diagnosed as a partially thrombosed fusiform AchA aneurysm. RESULTS Open surgery was performed and a titanium clip was applied to the base of the fusiform aneurysm under motor evoked potential monitoring, which remained unchanged after clipping. Occlusion of the aneurysm was confirmed by Doppler ultrasound and intraoperative fluorescence angiography. Furthermore, Doppler ultrasound and fluorescence angiography showed that the blood flow supplying the pyramidal tract was reconstituted by the retrograde collateral flow from the choroidal segment. The aneurysm was completely obliterated in postoperative DSA, which demonstrated retrograde filling of the AchA through the posterior circulation. The patient manifested transient weakness of the right side postoperatively, which was completely recovered after short-term rehabilitation. CONCLUSIONS This case illustrates the unique clinical course of a rare partially thrombosed fusiform AchA aneurysm, successfully treated with therapeutic clip occlusion of the AchA under the multimodal monitoring.