Citations

Introduction: The selection of acute ischemic stroke patients relies on the interpretation of radiological studies, commonly including noncontrast CT (ASPECTS score), CTA, and in some circumstances, CT perfusion (CTP) scans. Hypothesis: The interrater reliability between readers of noncontrast head CT will be moderate and not as good as that between readers of CT perfusion scans. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy at an academic medical center from April 2010 - November 2014. All patients underwent CT, CTA, and CTP. Images were independently reviewed by four readers (A, B, C, D) in total (2 experienced neuroradiologists, one experienced neurointensivist, and one neuroradiology fellow). Each rated half of the cohort. All readers performed online training in ASPECTS. Moderate-to-good collateral circulation was defined as filling of 50% or more of the middle cerebral artery pial arterial territory on CTA, as in ESCAPE trial. An “acceptable core” on CTP was defined as in EXTEND-IA trial with core volume < 70 mL, mismatch ratio >1.2, and absolute mismatch volume >10 mL but was qualitatively estimated. Interrater agreement was assessed for total ASPECTS, dichotomized ASPECTS (≥6 vs <6), evaluation of collaterals, and evaluation of core. Agreement was assessed using kappa statistic, which was weighted for the total ASPECTS analysis. Results: Our cohort included 119 patients with acute stroke and large vessel occlusion. Interrater agreement for total ASPECTS was very good between readers C and D (' 0.70) and good between A and B (' 0.55). For dichotomized ASPECTS, agreement was fair-to-good (' 0.30 for C/D; ' 0.41 for A/B). Agreement for grading collaterals on CTA was good to very good (' 0.64 for C /D; ' 0.54 for A/B). Agreement for rating core on CTP was very good (' 0.78 for C/D; ' 0.62 for A/D). Conclusions: Interrater reliability is good to very good for total ASPECTS score, dichotomous grading of collaterals on CTA, and subjective estimation of core size on CTP. Agreement is only fair to good for dichotomized ASPECTS.

Introduction: Numerous endovascular tools exist for the treatment of intracranial aneurysms with an increased use of flow-diverting devices in recent years. However, the biological mechanisms leading to aneurysm healing or potential complications such as delayed aneurysm ruptures after flow-diverter treatment are not yet well established. We used RNA-sequencing technology to identify genes relevant for biological impact of coils and flow-diverters in elastase-induced saccular aneurysms in rabbits and to identify genes and pathways of potential clinical interest. Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery. Aneurysms were treated with coils (n=5) or flow-diverters (Pipeline Embolic Device, Covidien, CA) (n=4). Untreated aneurysms (n=6) were used as controls. Messenger RNA and microRNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology. RNA-seq results were analyzed by using the Ingenuity Pathway Analysis tool. Results: Using RNA sequencing for coiled versus non-treated aneurysms, 464 genes were found to be differentially expressed with 58 genes down regulated and 406 genes up regulated. Using the same criteria for the flow-diverter treated aneurysms, 177 genes were found to be differentially expressed with 8 genes down regulated and 169 genes up regulated. Comparing coiled versus flow-diverter treated aneurysms, 13 genes were significantly differentially expressed with 8 down regulated and 5 up regulated genes. Genes identified with the highest interest for aneurysms healing were fibroblast growth factor-23, matrix metalloproteinases (MMP)-1, Scinderin and Basigin (implicated in MMP-2 and MMP-9 regulation). Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions. Conclusions: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and cellular migration that could explain the different biological mechanisms implicated in aneurysms healing either after coiling or flow-diverter treatments and could explain potential device-related complications.

Introduction: Predicting the course of aneurysms after treatment with flow diverters is important to prognosticate long term outcomes and optimize interventions. Hypothesis: Aneurysm occlusion after flow diversion can be predicted using post-treatment flow information. Methods: Flows in experimental aneurysms in rabbits (n=15) and clinical cases (n=23) were evaluated with computational fluid dynamics. Subject-specific models were created from 3D angiographies. Flow conditions were measured with ultrasound in the rabbits, and derived from measurements in normal subjects in the clinical cases. Models of the devices were virtually deployed into the anatomical models. Experimental aneurysms were assigned to either a “complete” occlusion group if completely occluded at 4 weeks follow up, or to an “incomplete” occlusion group if still open at 8 weeks. Similarly, clinical cases were classified as “complete” occlusions if completely occluded at 3 months, or as “incomplete” occlusions if still patent at 6 months. Flow variables were then statistically compared between these groups for both the experimental and clinical series, and the predictive power of different variables to discriminate between aneurysms in each group was assessed by calculating the area under the receiving operating characteristics curves. Results: In the clinical (experimental) series, the aneurysm inflow rate was 4.02 (3.29) times larger in the incomplete occlusion group than in the completely occluded group, p=0.0210 (0.0239). Similarly, the mean aneurysm velocity was 2.75 (2.29) times larger, p=0.0044 (0.0582), and the shear rate was 1.57 (1.78) times larger, p=0.0210 (0.0722). Inflow rate could discriminate complete and incomplete occlusions with a 77% (90%) accuracy in the clinical (experimental) series. Similarly, mean velocity had a predictive power of 84% (83%) and shear rate of 76% (76%) in the clinical and experimental series. Conclusions: Flow conditions created immediately after treatment, in particular aneurysm inflow rate and mean aneurysm velocity, can prognosticate the future occlusion of aneurysms treated with flow diverters.

Backgound and Purpose: Mechanisms of both healing and complications, including spontaneous aneurysm rupture, remain unclear following flow diverter treatment. The aim of the current study was to compare the gene expression of various key molecules involved in the healing of aneurysms between aneurysms treated with microcoils and flow diverters. Methods: Saccular aneurysms were created in rabbits (n=12). Aneurysms were either treated with coils (n=6) or with flow diverters (n=6). Aneurysm tissue was harvested at four weeks following treatment and used for gene expression and zymography experiments. Genes with a fold change of 1.2 or greater were considered up regulated, whereas those with a fold change of 0.8 or less were considered down regulated. Results: All coil embolized aneurysms were completely occluded at follow up. Two aneurysms were occluded and the remaining four samples were incompletely occluded in the flow diverter treated group. The following genes were expressed at lower levels in the flow diverter group as compared to the coiled aneurysm group: genes encoding proteinases (matrix metalloproteinases -2 and -9), cellular markers (endothelial nitric oxide synthase and smooth muscle actin), and structural proteins (collagens and fibronectin). Genes related to inflammation (tumor necrosis factor-α and monocyte chemoattractant protein -1) were up regulated in flow diverter treated aneurysms compared to coil embolized aneurysms. Notably, the enzymatic activity of active MMP-9 was high in aneurysms treated with flow diverters. Conclusion: As compared to coiled aneurysms, the molecular milieu surrounding aneurysms treated with flow diverters is characterized by higher levels of activated proteases, elevated expression of genes encoding inflammatory proteins, and diminished expression of genes encoding structural proteins. These data may provide improved understanding of rupture risk and healing following aneurysm treatment, and inform development of therapies aimed at lowering rupture risk and accelerating healing.

Objective: Controversy exists as to whether platelet inhibition testing is necessary prior to aneurysm treatment in patients premedicated with antiplatelet agents. Using the IntrePED ( Int ernational Re trospective Study of P ipeline E mbolization D evice) registry, we studied complication rates in platelet-testing and non-platelet testing groups to determine if platelet testing is associated with improved outcomes. Materials and Methods: Patients with unruptured intracranial aneurysms from the INTREPED registry were divided into those who received platelet testing (testing group) and those who did not (nontesting group). Morbidity, mortality and thrombotic and hemorrhagic complication rates were studied. Comparisons between groups for continuous variables were evaluated using t -tests and Fisher’s exact test or Pearson’s chi-square for binary categorical variables. Multivariate logistic regression analysis was performed to determine if platelet function testing was independently associated with poor outcomes adjusting for age, number of devices, aneurysm location, size, and use of multiple exchange wires. Results: When compared to the non-testing group, the platelet testing group suffered higher rates of ipsilateral intracranial hemorrhage (12/511, 2.3% versus 0/187, 0.0%, P=0.04), neurological morbidity (42/511, 8.2% versus 4/187, 2.1%, P=0.01), and combined neurological morbidity and mortality (45/511, 8.8% versus 6/187, 3.2%, P=0.01). More patients in the testing group were treated with multiple PEDs (228 patients, 38.1% versus 57 patients, 28.4%, P=0.01). On multivariate analysis, the platelet testing group had a higher odds of total major morbidity (OR=3.80, 95%CI=1.30=11.08, P=0.01) and total major morbidity and neurological mortality (OR=2.74, 95%CI=1.11-6.79). Conclusion: Our findings caution against blind acceptance of platelet testing in Pipeline patients. Further prospective studies are needed to determine if and when platelet testing in Pipeline patients is appropriate.

Background and Purpose: The HydroSoft coil was developed to be placed along the aneurysm neck to enhance intracranial aneurysm healing. In order to better understand the safety and efficacy of Hydrosoft coils in treating the aneurysm neck, the GEL THE NEC multicenter registry was developed. We report immediate angiographic and clinical results of this prospective registry. Methods: The GEL THE NEC study was undertaken at 30 centers in 5 countries. Patients aged 21-90 years with a ruptured or unruptured aneurysm 3-15 mm in size were eligible for enrollment. For each patient the following data were obtained: demographics and comorbidities, aneurysm geometry, use of adjunctive devices, immediate angiographic outcomes, and early (<30 days) adverse events. Postoperative anatomic results were graded by on-site neuroradiologists using the Modified Raymond Scale (Raymond 1=complete obliteration of aneurysm including the neck, Raymond 2=contrast filling the neck of the aneurysm without opacification of the aneurysm sac, Raymond 3=contrast filling the sac of the aneurysm). Predictors of good angiographic outcome were studied using chi-squared and t-tests. Results: A total of 571 patients with 571 aneurysms have been treated thus far in the study (196 ruptured, 375 unruptured). HydroSoft coils were successfully deployed in 549 (96.3%) of these patients. Adjunctive devices were used in 307 cases (53.8%) (212 balloon assistance, 89 stent). Aneurysmal occlusion rates were the following: 261 patients (47.3%) exhibited Raymond 1 occlusion, 257 patients (47.0%) had Raymond 2, and 29 patients (5.3%) had Raymond 3. Early post-operative stroke occurred in 10 patients (1.8%). Aneurysm perforation occurred in 11 patients (1.9%). Coil prolapse/migration occurred in 8 patients (1.4%). Early post-operative death occurred in 3 patients, all of whom presented with SAH (0.5%). Small aneurysm neck size was a significant predictor of good angiographic outcome (P=0.0003). Conclusions: Endovascular treatment of intracranial aneurysms with HydroSoft coils resulted in high rates of satisfactory occlusion (94.3%) and low rates of major clinical complications. Aneurysm neck size was a significant predictor of angiographic outcomes.

Aims The objective of this systematic review is to determine with the highest accuracy the average radial artery (RA) diameter overall and in certain subgroups. The aim of this study is to provide assistance in the development of fitting transradial devices, an increasingly popular intervention. Methods Several databases were used to extract appropriate studies highlighting RA diameter. Databases used in the generation of this study were Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science Core Collection. RA diameter was determined overall, in males versus females, adults only, adults+children, in the presence of comorbidities, and finally RA diameter in the context of various vasodilators. Results A total of 71 studies were included. The average RA diameter overall was determined to be 2.62±0.15 mm in children+adults and 2.70±0.15 mm in adults only. In comparison to an RA diameter of 2.68±0.24 mm in adult males, the diameter was found to be 2.27±0.27 mm in adult females (p=0.028). As for comorbidities, the mean RA diameter in adult patients with hypertension and congestive heart failure was 2.72±0.37 mm and 2.80±0.25 mm, respectively. Finally, the mean RA diameter with nitrate and angiotensin-converting enzyme (ACE) inhibitor use was 2.97±0.53 mm and 2.82±0.29 mm respectively. For comparison, the average outer diameter of a 5 French introducer sheath is 2.29 mm and a 6 French introducer sheath is 2.62 mm. Conclusions The findings presented in this study will help determine the most appropriate transradial device to use in several different populations in the context of vasodilator usage or the absence thereof.

Background Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke attributable to the anterior circulation large‐vessel occlusion. Randomized trials of patients with posterior circulation large‐vessel occlusion (PC‐LVO) have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta‐analysis to understand better whether EVT is beneficial for PC‐LVO. Methods Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC‐LVO treated with EVT versus MEDT. The primary outcome variable was 90‐day modified Rankin scale score of 0 to 3, and secondary outcome variables included 90‐day modified Rankin scale score of 0 to 2, 90‐day mortality, and rate of symptomatic intracranial hemorrhage. A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results Three studies with 1248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta‐analysis. The favorable outcome rate (modified Rankin scale score of 0–3) in patients undergoing EVT was 39.9% (95% CI, 30.6%–50.1%) versus 24.5% in patients undergoing MEDT (95% CI, 9.6%–49.8%). Patients undergoing EVT had higher modified Rankin scale score of 0 to 2 rates (31.8% [95% CI, 25.7%–38.5%] versus 19.7% [95% CI, 7.4%–42.7%]) and lower mortality (42.1% [95% CI, 35.9%–48.6%] versus 52.8% [95% CI, 33.3%–71.5%]) compared with patients undergoing MEDT, but neither result was statistically significant. Patients undergoing EVT were more likely to develop symptomatic intracranial hemorrhage (odds ratio, 10.36; 95% CI, 3.92–27.40). Conclusions EVT treatment of PC‐LVO trended toward superior functional outcomes and reduced mortality compared with MEDT despite a trend toward increased symptomatic intracranial hemorrhage in patients undergoing EVT. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in patients with PC‐LVO.

Introduction: Mechanical thrombectomy (MT) has become the standard of care for acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). Clinical outcome of successful recanalization (mTICI 2b or higher) varies greatly and is associated with some baseline characteristics. Many studies have reported the relation of thrombus composition with MT outcomes however the association of thrombus composition with the prognosis of successful recanalization remains to be elucidated. Hypothesis: thrombi retrieved from patients with good clinical outcome may have different compositions compared to that of patients with poor clinical outcome. Methods: Thrombi retrieved from AIS-LVO patients with successful recanalization were included. Patients were divided according to modified Rankin Scale at 90 days (mRS-90days) into good clinical outcome (mRS-90days 0-2) and poor clinical outcome (mRS-90 days 3-6). Representative slide for each thrombus was stained with Martius Scarlet Blue (MSB) for red blood cells (RBCs), white blood cells (WBCs), fibrin (FIB), and platelet (PLT). Immunohistochemistry (IHC) was also performed for NETs (anti-citrullinated H3; CitH3) and vWF in thrombi. The overall mean value of each thrombus composition was calculated. Thrombus was considered rich in given composition if that composition was higher than its overall mean. We compared the thrombus composition and type between patients with good and poor clinical outcomes. Results: A total of 94 patients were included. Fifty-six patients had good clinical outcome. The overall average percentage of RBCs, WBCs, fibrin, platelet, NETs (CitH3), and vWF components in thrombi were 44.3%, 3.6%, 29.3%, 22.8%, 20.3% and 12.5% respectively. There was no association between thrombus type (including RBC-rich, FIB-rich, PLT-rich, vWF-rich, and NETs-rich) and clinical outcomes (P values>0.05). Multivariate logistic regression analysis showed no association between thrombus composition and clinical outcome (good vs poor) while adjusting for age, initial NIHSS score, ASPECT score, pre-MT IV-tPA, and MT technique and number of the device passes. Conclusion: we found no association between thrombus composition and clinical outcome after successful recanalization.