Abstract 1122‐000107: Charles Bonnet Syndrome Secondary to Massive Dural Arteriovenous Fistula Disguised as Extensive Venous Sinus Thrombosis

Introduction : Charles Bonnet Syndrome is characterized by visual hallucinations that can occur following severe visual insult, rarely due to dural arteriovenous fistulas (DAVF) or cerebral venous sinus thrombosis (CVST). Prompt differentiation between DAVF and CVST is important since treatments may differ and inadequate treatment may result in blindness. We highlight a patient who presented with Charles Bonnet Syndrome initially misdiagnosed with CVST by MR venography and later correctly diagnosed with a massive DAVF with superimposed CVST by digital subtraction angiography and underwent DAVF embolization with complete resolution. Methods : Case Report. Results : A 78 year‐old man with hypertension and hyperlipidemia presented with three weeks of bilateral vision loss associated with formed hallucinations exacerbated by dark rooms. Neurological exam revealed decreased visual acuity of 20/400 and grade five papilledema bilaterally. Non‐Contrast (TOF) MR venogram revealed lack of flow in the superior sagittal sinus (SSS), straight sinus (SS) and deep venous system, and partial flow of the left transverse and sigmoid sinus and left jugular vein. MR brain without gadolinium was unremarkable. Cerebral angiography revealed a high‐grade DAVF predominantly supplied by the occipital branch of the left external carotid artery [Figure 1; A‐C], with retrograde flow into the left sigmoid, transverse, superior sagittal, and straight sinuses, as well as retrograde flow into the right vein of Trolard [Figure 1; A‐D]. The left distal sigmoid sinus and left jugular bulb were occluded. The left transverse and proximal left sigmoid venous sinuses were compartmentalized from non‐occlusive thrombus, while the SSS and bilateral transverse sinuses where patent [Figure 1; A, B]. Embolization using coils and onyx was performed with complete occlusion of the left transverse and sigmoid sinuses, the points of main drainage of the fistula, as there was no single trans arterial pedicle suitable for embolization. Postembolization angiography demonstrated a Cognard Grade 1 fistula with some residual fistulous shunting of the occipital artery to the torcula. Follow up angiogram at six weeks showed interval occlusion of the residual shunt. He had minimal improvement in his vision at three months of follow up. Conclusions : This case highlights a patient with Charles Bonnet Syndrome due to a high flow DAVF. The MR venogram failed to capture the DAVF since the retrograde flow was interpreted as thrombosis on MRV. DAVF and CVST have a complex cause‐effect relationship, since thrombosis may open up venous channels that can lead to a fistula and sluggish blood flow from a fistula may stimulate thrombus formation. Treatments between CVST and DAVF differ since high grade DAVF often require endovascular embolization and anticoagulation may increase the risk of intracerebral hemorrhage in a subset of patients. Digital subtraction angiography and/or contrast enhanced MRV should be considered in cases of suspected extensive thrombosis to help differentiate between thrombosis and DAVF.

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods. We develop a filament-level model of a lamellipodial actin network undergoing retrograde flow using 3D Brownian dynamics. Retrograde flow is promoted in simulations by pushing forces from the leading edge (due to actin polymerization), pulling forces (due to molecular motors), and opposed by viscous drag in cytoplasm and focal adhesions. Simulated networks have densities similar to measurements in prior electron micrographs. Connectivity between individual actin segments is maintained by permanent and dynamic crosslinkers. Remodeling of the network occurs via the addition of single actin filaments near the leading edge and via filament bond severing. We investigated how several parameters affect the stress distribution, network deformation and retrograde flow speed. The model captures the decrease in retrograde flow upon increase of focal adhesion strength. The stress profile changes from compression to extension across the leading edge, with regions of filament bending around focal adhesions. The model reproduces the observed reduction in retrograde flow speed upon exposure to cytochalasin D, which halts actin polymerization. Changes in crosslinker concentration and dynamics, as well as in the orientation pattern of newly added filaments demonstrate the model’s ability to generate bundles of filaments perpendicular (actin arcs) or parallel (microspikes) to the protruding direction.

Cavitation on top of collision breaks the cover of coronary plaques and triggers acute coronary syndrome

Background Coronary injuries are hypothesized to be caused by the cavitation phenomenon (explosion of air bubbles) which is seen frequently in industrial pipes. Based on hydraulics principles applied to the coronary circulation. during distal negative suctioning in diastole, if the coronary static pressure decreases below the vapor pressure (VP), bubbles will form. They explode when the coronary static pressure recovers > the VP during systole. These explosions create jet waves weakening and rupturing the cover of the coronary plaques, triggering acute coronary syndrome (ACS). How could these events be observed, recorded and compared? Methods Coronary angiograms of patients with ACS and stable coronary artery disease (CAD) (control) were selected. The arteries were recorded at 15 frames per second and saved in the electronic health records and reviewed image by image. After the index artery was completely filled with contrast, the following images showed the blood in white moving in on a background of black contrast. The flow could be laminar, turbulent (mixing of blood in white and contrast in black), antegrade or RETROGRADE (black column traveling backward). At the same time, an artificial intelligence (AI) program was used to detect and identify the flow. Results There were 104 patients with ACS enrolled and 20 patients with stable CAD as control. First, in the ACS group, 84 lesions (80%) were in the end of the proximal segment of the left anterior descending artery (LAD) and mid-segment of the right coronary artery (RCA). 20 lesions (19%) were at the distal RCA. Second, during diastole, 95% of the flow were laminar. The flow became turbulent at the beginning of systole. The turbulence was caused by the COLLISION of the antegrade flow (end of diastole) and the retrograde flow (at the beginning of systole). These collisions were seen in 95% at the location of vulnerable plaques of patients with ACS. In the control patients, there were only 2 cases (10%) with collision. Third, in the 20 patients with lesions at the distal RCA, the lesions were seen to be located at the areas of recirculating flow, at the ostium of the posterior descending artery (PDA) or proximal to the origin of the PDA. The cause of turbulence was most likely due to cavitation on top of collision. The cavitation happened because of continuous steady forward flow (of the PDA) in the myocardium during systole, while at the proximal RCA the blood flew forward more slowly. (Fig.1) The DSICREPANCY of velocities at the proximal and distal RCA allowed the formation of an empty gap (bubble of air). When the flow reversed during systole, this retrograde flow slammed on the bubble which collapsed violently, injured, ruptured the cover of the plaque and started ACS. Conclusions Rupture of bubbles (cavitation) on top of collision was most likely the cause of injury to the cover of vulnerable plaques, triggering ACS. Understanding the mechanism will help to better manage ACS. FUNDunding Acknowledgement Type of funding sources: None. Cavity formation and collision Formation of cavitation at the PDA

Quantification of noncircular stent expansion after TAVR into a pathological annulus and its impact on paravalvular leakage

Patients undergoing transcatheter aortic valve replacement (TAVR) may suffer severe clinical complications, caused by paravalvular leakage (PVL) which is defined as leakage between TAVR and aortic annulus. PVL is often facilitated by a severely calcified annulus. This limits the expansion of a self-expandable TAVR stent. To assess TAVR performance in terms of leakage, measurement of regurgitation fraction in a pathophysiological annulus is recommended according to ISO 5840. For this purpose, a configuration of a circular annulus with a calcification nodule has been proposed in the recently published ISO 5840. The impact of the proposed pathophysiological annulus model on the expansion of self-expandable TAVR stents and on the regurgitation fraction was investigated in this study. For this purpose, two commercially available selfexpandable TAVRs (Evolut R and Portico) were implanted in a calcified annulus model. Circular expansion of the TAVR stents was investigated based on μCT scans of the implanted TAVR. The calcification-induced area in which retrograde flow can occur during diastole was detected. These results were then compared with the experimentally determined regurgitation fraction obtained from pulse duplicator tests. The results of the μCT scans showed a continuous leakage area in the region of the annulus for the Evolut R compared to a locally larger leakage area of the Portico, which, however, reattaches to the annulus in the distal inflow region. The hydrodynamic measurements confirmed a smaller leakage in the pathological annulus for the Portico. In summary, it can be assumed that a continuous leakage area in the TAVR stent inflow region encourages the PVL of TAVR.

Microtubule retrograde flow retains neuronal polarization in a fluctuating state

In developing vertebrate neurons, a neurite is formed by more than a hundred microtubules. While individual microtubules are dynamic, the microtubule array itself has been regarded as stationary. Using live cell imaging in combination with photoconversion techniques and pharmacological manipulations, we uncovered that the microtubule array flows retrogradely within neurites to the soma. This microtubule retrograde flow drives cycles of microtubule density, a hallmark of the fluctuating state before axon formation. Shortly after axon formation, microtubule retrograde flow slows down in the axon, which stabilizes microtubule density cycles and thereby functions as a molecular wedge to enable axon extension. We propose microtubule retrograde flow and its specific slowdown in the axon to be the long-sought mechanism to single one neurite out to drive neuronal polarization.

Comparison of Prospective and Retrospective Gated 4D Flow Cardiac MR Image Acquisitions in the Carotid Bifurcation

The superior temporal coverage of retrospective versus prospective gating in 4D flow cardiac MRI (cMRI) imaging offers advantages in comprehensively evaluating the hemodynamic environment across the complete cardiac cycle; however, retrospective acquisitions may result in temporal smoothing. Thus, the purpose of this study was to evaluate the agreement of 4D flow cMRI-derived bulk flow features and fluid (blood) velocities in the carotid bifurcation using prospective and retrospective gating techniques. Prospective and retrospective ECG-gated three-dimensional (3D) cine phase-contrast cardiac MRI with three-direction velocity encoding (i.e., 4D flow cMRI) data were acquired in ten carotid bifurcations from men (n = 3) and women (n = 2) that were cardiovascular disease-free. Velocity magnitude data were extracted from the fluid domain within the image volumes and evaluated across the entire volume or at defined anatomic planes (common, internal, external carotid arteries). Vector magnitudes were decomposed into components to quantify flow direction and disturbances, including retrograde flow. Flow streamlines encoded for velocity magnitude and velocity profiles were generated. Qualitative and quantitative agreement was observed in bulk flow features and fluid velocity magnitudes derived from either prospective or retrospective ECG-gated 4D flow cMRI. No significant differences in velocity magnitudes or components (υr, υθ, υz) were observed. Importantly, retrospective acquisitions captured increased retrograde flow in the internal carotid artery (i.e., carotid sinus) compared to prospective acquisitions. Prospective and retrospective ECG-gated 4D flow cMRI acquisitions provide comparable evaluations of the hemodynamic environment in the carotid bifurcation. However, the increased temporal coverage of retrospective acquisitions depicts disturbed blood flow patterns not captured by the prospective gating technique.

The Actin-Disassembly Protein Glia Maturation Factor γ Enhances Actin Remodeling and B Cell Antigen Receptor Signaling at the Immune Synapse

Signaling by the B cell antigen receptor (BCR) initiates actin remodeling. The assembly of branched actin networks that are nucleated by the Arp2/3 complex exert outward force on the plasma membrane, allowing B cells to form membrane protrusions that can scan the surface of antigen-presenting cells (APCs). The resulting Arp2/3 complex-dependent actin retrograde flow promotes the centripetal movement and progressive coalescence of BCR microclusters, which amplifies BCR signaling. Glia maturation factor γ (GMFγ) is an actin disassembly-protein that releases Arp2/3 complex-nucleated actin filaments from actin networks. By doing so, GMFγ could either oppose the actions of the Arp2/3 complex or support Arp2/3 complex-nucleated actin polymerization by contributing to the recycling of actin monomers and Arp2/3 complexes. We now show that reducing the levels of GMFγ in human B cell lines via transfection with a specific siRNA impairs the ability of B cells to spread on antigen-coated surfaces, decreases the velocity of actin retrograde flow, diminishes the coalescence of BCR microclusters into a central cluster at the B cell-APC contact site, and decreases APC-induced BCR signaling. These effects of depleting GMFγ are similar to what occurs when the Arp2/3 complex is inhibited. This suggests that GMFγ cooperates with the Arp2/3 complex to support BCR-induced actin remodeling and amplify BCR signaling at the immune synapse.