Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa.

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa. Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis. Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα. Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

Comparing Occlusive Balloon Performance Using 3-Dimensional Printed Models of Intracranial Aneurysmal Defects.

OBJECTIVE: Balloon remodeling microcatheters are essential in assisting endovascular coiling of brain aneurysms, but the performance and pressure requirements of different balloon types when used in aneurysmal defects are currently unknown. METHODS: We used Tinkercad (Autodesk, Montreal, Quebec) to create model vessels with aneurysmal defects and 3-dimensionally printed these designs with polylactic acid using the Ultimaker2 (Ultimaker, Geldermalsen, Netherlands). We constructed a pressurized box capable of reaching physiologic pressures that housed our vessels and then tested compliant remodeling balloons under fluoroscopy from 3 manufacturers: Hyperglide (Medtronic, Minneapolis, Minnesota, USA), Transform (Stryker Neurovascular, Fremont, California, USA), and Scepter C (Microvention, Tustin, California, USA). Each balloon was inflated to a nominal and supranominal point at each defect, and at each inflation the maximum diameter of the balloon and internal balloon pressure were recorded. The Phillips Intellivue (Phillips, Amsterdam, The Netherlands) monitor was adapted for internal balloon pressure monitoring. A multivariate linear regression analysis was performed to model balloon compliance (balloon diameter divided by pressure). RESULTS: Multivariate regression modeling demonstrated the Scepter balloon had significantly greater compliance compared with both the Hyperglide and Transform balloons (P < 0.001). In addition, we found that Scepter balloons had higher compliance in larger defects compared with the other types of balloons and performance differences based on vessel size. CONCLUSIONS: Scepter balloons require less pressure compared with their counterparts to adequately deform through model defects, specifically in larger aneurysm necks in smaller vessel diameters. This result could inform operators of optimal balloon type and size when trying to minimize balloon pressure in fragile brain aneurysms.

Follow-up of incidental pulmonary nodules and association with mortality in a safety-net cohort.

Background Though incidental pulmonary nodules are common, rates of guideline-recommended surveillance and associations between surveillance and mortality are unclear. In this study, we describe adherence (categorized as complete, partial, late and none) to guideline-recommended surveillance among patients with incidental 5-8 mm pulmonary nodules and assess associations between adherence and mortality. Methods This was a retrospective cohort study of 551 patients (≥35 years) with incidental pulmonary nodules conducted from September 1, 2008 to December 31, 2016, in an integrated safety-net health network. Results Of the 551 patients, 156 (28%) had complete, 87 (16%) had partial, 93 (17%) had late and 215 (39%) had no documented surveillance. Patients were followed for a median of 5.2 years [interquartile range (IQR), 3.6-6.7 years] and 82 (15%) died during follow-up. Adjusted all-cause mortality rates ranged from 2.24 [95% confidence interval (CI), 1.24-3.25] deaths per 100 person-years for complete follow-up to 3.30 (95% CI, 2.36-4.23) for no follow-up. In multivariable models, there were no statistically significant associations between the levels of surveillance and mortality (p > 0.16 for each comparison with complete surveillance). Compared with complete surveillance, adjusted mortality rates were non-significantly increased by 0.45 deaths per 100 person-years (95% CI, -1.10 to 2.01) for partial, 0.55 (95% CI, -1.08 to 2.17) for late and 1.05 (95% CI, -0.35 to 2.45) for no surveillance. Conclusions Although guideline-recommended surveillance of small incidental pulmonary nodules was incomplete or absent in most patients, gaps in surveillance were not associated with statistically significant increases in mortality in a safety-net population.

Depression in Patients with Tinnitus: A Systematic Review.

OBJECTIVE: Tinnitus is a condition that causes distress and impairment across cognitive, functional, and psychiatric spectra. In the psychiatric realm, tinnitus has long been associated with depression. To better characterize the co-occurrence of depression and tinnitus, we performed a systematic review of the prevalence of depression among patients with tinnitus. DATA SOURCES: We comprehensively examined original studies reporting the prevalence of depression in adult populations with tinnitus, as indexed in the PubMed and Web of Science databases and published from January 2006 to August 2016. REVIEW METHODS: All identified articles were reviewed independently by 2 researchers, with a third reviewer for adjudication. Included studies were evaluated for threats to validity across 3 domains-representativeness, response rate, and ascertainment of outcome-on a 4-point modified Newcastle-Ottawa Quality Assessment Scale. RESULTS: Twenty-eight studies were included, representing 15 countries and 9979 patients with tinnitus. Among the included studies, the median prevalence of depression was 33%, with an interquartile range of 19% to 49% and an overall range of 6% to 84%. Studies were high quality overall, with a mean score of 3.3 (SD = 0.76), and 89% utilized a validated tool to ascertain depression. CONCLUSIONS: We conducted one of the largest contemporary comprehensive reviews, which suggests a 33% prevalence of depression among patients with tinnitus. Our review reaffirms that a substantial proportion of patients with tinnitus have depression, and we recommend that all who treat tinnitus should screen and treat their patients for depression, if present.

Endovascular Biopsy: In Vivo Cerebral Aneurysm Endothelial Cell Sampling and Gene Expression Analysis.

There is limited data describing endothelial cell (EC) gene expression between aneurysms and arteries partly because of risks associated with surgical tissue collection. Endovascular biopsy (EB) is a lower risk alternative to conventional surgical methods, though no such efforts have been attempted for aneurysms. We sought (1) to establish the feasibility of EB to isolate viable ECs by fluorescence-activated cell sorting (FACS), (2) to characterize the differences in gene expression by anatomic location and rupture status using single-cell qPCR, and (3) to demonstrate the utility of unsupervised clustering algorithms to identify cell subpopulations. EB was performed in 10 patients (5 ruptured, 5 non-ruptured). FACS was used to isolate the ECs and single-cell qPCR was used to quantify the expression of 48 genes. Linear mixed models and exploratory multilevel component analysis (MCA) and self-organizing maps (SOMs) were performed to identify possible subpopulations of cells. ECs were collected from all aneurysms and there were no adverse events. A total of 437 ECs was collected, 94 (22%) of which were aneurysmal cells and 319 (73%) demonstrated EC-specific gene expression. Ruptured aneurysm cells, relative controls, yielded a median p value of 0.40 with five genes (10%) with p values < 0.05. The five genes (TIE1, ENG, VEGFA, MMP2, and VWF) demonstrated uniformly reduced expression relative the remaining ECs. MCA and SOM analyses identified a population of outlying cells characterized by cell marker gene expression profiles different from endothelial cells. After removal of these cells, no cell clustering based on genetic co-expressivity was found to differentiate aneurysm cells from control cells. Endovascular sampling is a reliable method for cell collection for brain aneurysm gene analysis and may serve as a technique to further vascular molecular research. There is utility in combining mixed and clustering methods, despite no specific subpopulation identified in this trial.

Improving mechanical thrombectomy time metrics in the angiography suite: Stroke cart, parallel workflows, and conscious sedation.

Purpose Earlier reperfusion of large-vessel occlusion (LVO) stroke improves functional outcomes. We hypothesize that use of a stroke cart in the angiography suite, containing all commonly used procedural equipment in a mechanical thrombectomy, combined with parallel staff workflows, and use of conscious sedation when possible, improve mechanical thrombectomy time metrics. Methods We identified 47 consecutive LVO patients who underwent mechanical thrombectomy at our center, retrospectively and prospectively from implementation of these three workflow changes (19 pre- and 28 post-). For each patient, last known normal, NIHSS, angiography suite in-room time, type of anesthesia, groin puncture time, on-clot time, recanalization time, LVO location, number of passes, device(s) used, mTICI score, and outcome (mRS) were recorded. Between-group comparisons of time metrics and multivariate regression were performed. Results Stroke cart, parallel workflows, and primary use of conscious sedation decreased in-room time to groin puncture (-21.3 min, p < 0.0001), in-room to on-clot time (-24.1 min, p = 0.001), and in-room to reperfusion time (-29.5 min, p = 0.01). In a multivariate analysis, endotracheal intubation and general anesthesia were found to significantly increase in-room to on-clot time ( p = 0.01), in-room to reperfusion time ( p = 0.01), and groin puncture to on-clot time ( p = 0.05). The number of patients achieving a good outcome (mRS 0-2), however, did not significantly differ between the two groups (9/18 (47%) vs 14/28 (50%), p = 0.60). Conclusions Use of a stroke cart, parallel workflows by neurointerventionalists, technologists, and nursing staff, and use of conscious sedation may be useful to other institutions in efforts to improve procedural times.

Intra-Arterial MR Perfusion Imaging of Meningiomas: Comparison to Digital Subtraction Angiography and Intravenous MR Perfusion Imaging.

BACKGROUND AND PURPOSE: To evaluate the ability of IA MR perfusion to characterize meningioma blood supply. METHODS: Studies were performed in a suite comprised of an x-ray angiography unit and 1.5T MR scanner that permitted intraprocedural patient movement between the imaging modalities. Patients underwent intra-arterial (IA) and intravenous (IV) T2* dynamic susceptibility MR perfusion immediately prior to meningioma embolization. Regional tumor arterial supply was characterized by digital subtraction angiography and classified as external carotid artery (ECA) dural, internal carotid artery (ICA) dural, or pial. MR perfusion data regions of interest (ROIs) were analyzed in regions with different vascular supply to extract peak height, full-width at half-maximum (FWHM), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT). Linear mixed modeling was used to identify perfusion curve parameter differences for each ROI for IA and IV MR imaging techniques. IA vs. IV perfusion parameters were also directly compared for each ROI using linear mixed modeling. RESULTS: 18 ROIs were analyzed in 12 patients. Arterial supply was identified as ECA dural (n = 11), ICA dural (n = 4), or pial (n = 3). FWHM, rCBV, and rCBF showed statistically significant differences between ROIs for IA MR perfusion. Peak Height and FWHM showed statistically significant differences between ROIs for IV MR perfusion. RCBV and MTT were significantly lower for IA perfusion in the Dural ECA compared to IV perfusion. Relative CBF in IA MR was found to be significantly higher in the Dural ICA region and MTT significantly lower compared to IV perfusion.