Inflammation and obstruction of distal catheter slits in ventriculoperitoneal shunts: likely role of graphite.

OBJECTIVE: Tissue reactions that contribute to obstruction of peritoneal catheters in ventriculoperitoneal shunt systems are not well characterized. Several recent rapid obstructions in children prompted a retrospective quality assurance review. METHODS: The authors conducted a detailed investigation of 22 surgically explanted peritoneal shunt catheters and 8 autopsy cases with documented distal shunt obstruction. Patients' medical histories were reviewed, and the catheters and/or tissues were subjected to conventional histological and immunohistochemical evaluations. In addition, 3 cases were subjected to electron microscopic examination including elemental analysis. RESULTS: The majority of symptomatic obstructions were associated with distal slit catheters (17 slit, 3 open-end, and 2 unknown type). Among the autopsy cases, deaths were attributed to shunt failure in 2 cases of slit catheter obstruction, 1 case of open-end catheter obstruction, and 1 case of catheter withdrawal from the peritoneal cavity. The early tissue response consisted of a predominantly T lymphocyte accumulation with phagocytosis of graphite particles by macrophages. This is associated with proliferation of fibroblasts, mesothelial cells, and blood vessels, which can grow through the slits and occlude the catheter lumen. As the inflammation subsides after approximately 1 year, the tissue plug becomes collagenized and calcified. CONCLUSIONS: This study, supported by experimental literature in other organ systems, indicates that graphite used to coat the slit openings of distal catheters from ventriculoperitoneal shunts likely predisposes to obstruction. Neurosurgeons and manufacturers should consider the potential negative consequences of this shunt design. The authors concur with previous recommendations that slit-valve distal catheters should not be used for ventriculoperitoneal shunting unless they can be proven safe and efficacious in a controlled trial.

Stimulation of endothelial progenitor cells by microRNA-31a-5p to induce endothelialization in an aneurysm neck after coil embolization by modulating the Axin1-mediated ß-catenin/vascular endothelial growth factor pathway.

OBJECTIVE: Emerging evidence shows that frequent recurrence of intracranial aneurysms (IAs) after endovascular coiling is attributable to the lack of endothelialization across the aneurysm neck. Recently, much attention has been given to the role of microRNAs (miRs) in vascular disease, although their contributory role to IA is poorly understood. METHODS: Adult male Sprague-Dawley rats were subjected to microsurgery to create a coiled embolization aneurysm model, and were injected with miR-31a-5p agomir or a negative control agomir via the tail vein at a dose of 10 mg/kg per week for 4 weeks after IA induction. H & E staining, scanning electron microscopy, and flow cytometry were performed to evaluate the effects of miR-31a-5p agomir on endothelialization and the number of circulating endothelial progenitor cells (EPCs). The effects of miR-31a-5p on the viability and functioning of EPCs were also determined using Cell Counting Kit-8, wound-healing assay, and tube formation assays. RESULTS: The authors tested the ability of miR-31a-5p to promote EPC-induced endothelialization in a model of coiled embolization aneurysm. miR-31a-5p agomir improved endothelialization and elevated the number of circulating EPCs in the peripheral blood compared to a negative control agomir-treated group. In addition, the number of vWF- and KDR-positive cells in the aneurysm neck was increased in the miR-31a-5p agomir-treated group. Furthermore, upregulation of miR-31a-5p promoted EPC proliferation, migration, and tube formation and enhanced the expression of the proangiogenic factor vascular endothelial growth factor in vitro. Mechanistically, miR-31a-5p directly targeted the 3' untranslated region (3'UTR) of Axin1 messenger RNA and repressed its expression. Besides, miR-31a-5p exerted its effect on EPCs by regulating the Axin1-mediated Wnt/ß-catenin pathway. CONCLUSIONS: Collectively, these results indicate that miR-31a-5p is an important regulator of EPC mobilization and endothelialization and may have a positive effect on aneurysm repair.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: from hemodynamic changes to ostia surface modifications.

OBJECTIVE The outcome for jailing arterial branches that emerge near intracranial aneurysms during flow-diverting stent (FDS) deployment remains controversial. In this animal study, the authors aimed to elucidate the role of collateral supply with regard to the hemodynamic changes and neointimal modifications that occur from jailing arteries with FDSs. To serve this purpose, the authors sought to quantify 1) the hemodynamic changes that occur at the jailed arterial branches immediately after stent placement and 2) the ostia surface values at 3 months after stenting; both parameters were investigated in the presence or absence of collateral arterial flow. METHODS After an a priori power analysis, 2 groups (Group A and Group B) were created according to an animal flow model for terminal and anastomotic arterial circulation; each group contained 7 Large White swine. Group A animals possessed an anastomotic-type arterial configuration to supply the territory of the right ascending pharyngeal artery (APhA), while Group B animals possessed a terminal-type arterial configuration to supply the right APhA territory. Subsequently, all animals underwent FDS placement, thereby jailing the right APhAs. Mean flow rates and velocities inside the jailed branches were quantified using time-resolved 3D phase-contrast MR angiography before and after stenting. Three months after stent placement, the jailed ostia surface values were quantified on scanning electron micrographs. The data were analyzed using descriptive statistics and group comparisons with parametric and nonparametric tests. RESULTS The endovascular procedures were feasible, and there were no findings of in situ thrombus formation on postprocedural optical coherence tomography or ischemia on postprocedural diffusion-weighted imaging. In Group A, the mean flow rate values at the jailed right APhAs were reduced immediately following stent placement as compared with values obtained before stent placement (p = 0.02, power: 0.8). In contrast, the mean poststenting flow rates for Group B remained similar to those obtained before stent placement. Three months after stent placement, the mean ostia surface values were significantly higher for Group B (527,911 ± 306,229 µm2) than for Group A (89,329 ± 59,762 µm2; p < 0.01, power: 1.00), even though the initial dimensions of the jailed ostia were similar between groups. A statistically significant correlation was found between groups (A or B), mean flow rates after stent placement, and ostia surface values at 3 months. CONCLUSIONS When an important collateral supply was present, the jailing of side arteries with flow diverters resulted in an immediate and significant reduction in the flow rate inside these arteries as compared with the prestenting values. In contrast, when competitive flow was absent, jailing did not result in significant flow rate reductions inside the jailed arteries. Ostium surface values at 3 months after stent placement were significantly higher in the terminal group of jailed arteries (Group B) than in the anastomotic group (Group A) and strongly correlated with poststenting reductions in the velocity value.

Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: animal flow model evaluation and preliminary results.

OBJECTIVE The authors describe herein the creation of an animal model capable of producing quantifiable data regarding blood flow rate and velocity modifications in terminal and anastomotic types of cerebrofacial circulation. They also present the preliminary results of a translational study aimed at investigating the role of terminal and anastomotic types of circulation in arterial branches jailed by flow-diverting stents as factors contributing to arterial patency or occlusion. METHODS Two Large White swine were used to validate a terminal-type arterial model at the level of the right ascending pharyngeal artery (APhA), created exclusively by endovascular means. Subsequently 4 Large White swine, allocated to 2 groups corresponding to the presence (Group B) or absence (Group A) of terminal-type flow modification, underwent placement of flow-diverting stents. Blood flow rates and velocities were quantified using a dedicated time-resolved 3D phase-contrast MRA sequence before and after stenting. Three months after stent placement, the stented arteries were evaluated with digital subtraction angiography (DSA) and scanning electron microscopy (SEM). Patent (circulating) ostia quantification was performed on the SEM images. RESULTS Terminal-type flow modification was feasible; an increase of 75.8% in mean blood velocities was observed in the right APhAs. The mean blood flow rate for Group A was 0.31 ± 0.19 ml/sec (95% CI -1.39 to 2.01) before stenting and 0.21 ± 0.07 ml/sec (95% CI -0.45 to 0.87) after stenting. The mean blood flow rate for Group B was 0.87 ± 0.32 ml/sec (95% CI -1.98 to 3.73) before stenting and 0.76 ± 0.13 ml/sec (95% CI -0.41 to 1.93) after stenting. Mean flow rates after stenting showed a statistically significant difference between Groups A and B (Welch test). Mean and maximal blood velocities were reduced in Group A cases and did not decrease in Group B cases. Control DSA and SEM findings showed near occlusion of the jailed APhAs in both cases of anastomotic circulation (mean patent ostium surface 32,776 µm2) and patency in both cases of terminal-type circulation (mean patent ostium surface 422,334 µm2). CONCLUSIONS Terminal-type arterial modification in swine APhAs is feasible. Sufficient data were acquired to perform an a priori analysis for further research. Flow diversion at the level of the APhA ostium resulted in significant stenosis in cases of anastomotic circulation, while sufficient patency was observed in terminal-type circulation.