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OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. The objective of this study was to identify risk factors associated with recurrence of dAVF after putative cure. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) data were retrospectively reviewed. All patients with angiographic cure after treatment and subsequent angiographic follow-up were included. The primary outcome was recurrence, with risk factor analysis. Secondary outcomes included clinical outcomes, morbidity, and mortality associated with recurrence. Risk factor analysis was performed comparing the group of patients who experienced recurrence with those with durable cure (regardless of multiple recurrences). Time-to-event analysis was performed using all collective recurrence events (multiple per patients in some cases). RESULTS Of the 1077 patients included in the primary CONDOR data set, 457 met inclusion criteria. A total of 32 patients (7%) experienced 34 events of recurrence at a mean of 368.7 days (median 192 days). The recurrence rate was 4.5% overall. Kaplan-Meier analysis predicted long-term recurrence rates approaching 11% at 3 years. Grade III dAVFs treated with endovascular therapy were statistically significantly more likely to experience recurrence than those treated surgically (13.3% vs 0%, p = 0.0001). Tentorial location, cortical venous drainage, and deep cerebral venous drainage were all risk factors for recurrence. Endovascular intervention and radiosurgery were associated with recurrence. Six recurrences were symptomatic, including 2 with hemorrhage, 3 with nonhemorrhagic neurological deficit, and 1 with progressive flow-related symptoms (decreased vision). CONCLUSIONS Recurrence of dAVFs after putative cure can occur after endovascular treatment. Risk factors include tentorial location, cortical venous drainage, and deep cerebral drainage. Multimodality therapy can be used to achieve cure after recurrence. A delayed long-term angiographic evaluation (at least 1 year from cure) may be warranted, especially in cases with risk factors for recurrence.

There has been growing interest and insight into the histological composition of retrieved stroke emboli. One of the main focuses of the stroke clot analysis literature has been the implications of clot composition on mechanical thrombectomy procedures. However, the holy grail of clot analysis may not be in the field of clot–device interaction, but rather, in understanding mechanisms of fibrinolysis resistance. The mechanisms underlying the low response to fibrinolytic therapy, even with the newer, more powerful agents, remain poorly understood. While factors such as embolus size, location and collateral status influence alteplase delivery and recanalisation rates; compositional analyses focused on histological and ultrastructural characteristics offer unique insights into mechanisms of alteplase resistance. In this review, we strive to provide comprehensive review of current knowledge on clot composition and ultrastructural analyses that help explain resistance to fibrinolysis.

Background and Purpose: We performed a systematic review and meta-analysis comparing rates of recanalization, good neurological outcome, and mortality between patients treated with three modern devices used for endovascular treatment of acute ischemic stroke. Materials and Methods: We performed a comprehensive literature search on studies reporting outcomes of endovascular treatment of acute ischemic stroke. We selected studies including≥30 patients treated with either the Trevo stent-retriever, Penumbra aspiration system or the Solitaire stent-retriever. Outcomes studied included mrs≤2, 90-day mortality, symptomatic and intracranial hemorrhage (sICH), recanalization. Outcomes were pooled across studies using a random-effects meta-analysis. Results: 27 articles with 2666 patients were included (1514 Solitaire, 260 Trevo and 892 Penumbra). Rates of good neurological outcome (mRS≤2) were higher in the Solitaire group (54.0%, 95%CI=49.0-58.0%) than the Penumbra group (39.0%, 95%CI=31.0%-47.0%) (P<0.01). There was a trend towards higher rates of good neurological outcome in the Solitaire compared to the Trevo group (P=0.08). Rates of 90-day mortality were significantly lower in the Solitaire group (16.0%, 95%CI=11.0%-22.0%) than in the Penumbra group (27.0%, 95%CI=24.0%-30.0%) (P<0.01) and the Trevo group (23.0%, 95%CI=13.0-33.0)(P=0.01). Recanalization rates were similar between groups at 80.0% (95%CI=75.0%-84.0% for the Solitaire group, 82.0% (95%CI=75.0%-88.0%) for the Penumbra group (P=0.54) and 76.0% (95%CI=68.0-83.0) for the Trevo group (P=0.13 vs Penumbra and P=0.27 vs. Solitaire). Conclusions: Meta-analysis of incidence rates in noncomparative series reporting on over 2500 patients suggests that the Solitaire device maybe associated with superior neurological outcomes and lower rates of 90-day mortality. Comparative studies are needed to confirm these observations.

Introduction: Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke patients used differing radiological methods to select patients for treatment. Hypothesis: The percentage of patients evaluated in a non-clinical trial setting that would meet radiological criteria to be included in the five trials will differ substantially. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy based on confirmed intracranial large vessel occlusion (M1, M2, or carotid terminus) at an academic medical center from April 2010 - November 2014. All patients underwent CT perfusion and CT angiogram. Results: The table shows baseline characteristics of 119 patients. Median age was 69 years (IQR 57-79) and median NIHSS 18 (IQR 14-21). Most patients had ASPECTS score ≥ 6 (n=105, 88.2%). The M1 segment of MCA was the most common vessel occluded (n=81, 68%). All 119 patients (100%) met radiological criteria for MR CLEAN while 105 (88.2%) met criteria for SWIFT-PRIME, 96 (80.7%) for REVASCAT, 80/116 (69.0%) for EXTEND IA, and 74 (62.2%) for ESCAPE. IV TPA was given to 58 patients (48.7%) and acute endovascular stroke therapy attempted in 66 (55.5%). Any intracranial hemorrhage was more common in the patients treated with endovascular therapy than in those who were not (36% vs. 17%, p=0.025). The frequency of symptomatic ICH did not significantly differ between these two groups (6.1% vs 3.8%, p=0.691). Conclusions: The percentage of patients with acute stroke and large vessel occlusion that would qualify for endovascular stroke trials based on radiological criteria varies considerably (62%-100%) in a non-clinical trial cohort from an academic comprehensive stroke center. Additional individual patient characteristics influence treatment decisions in non-clinical trial settings.

Background: Tissue reperfusion is a critical determinant of outcomes after intra-arterial therapy (IAT). However, there is no standardized method for grading angiographic reperfusion. We sought to compare the two most commonly used reperfusion scales, TIMI and modified TICI (m-TICI), for predicting good long-term outcome following IAT. Methods: From a multicenter database, we evaluated acute stroke patients presenting with middle cerebral artery (MCA) M1 occlusions who underwent IAT. Clinical and angiographic data were collected. Reperfusion for each case was graded using the TIMI and m-TICI scales. The primary distinction between these scales is that partial reperfusion (TIMI 2) is sub-divided into minor (m-TICI 2A: <50%) and major (m-TICI 2B: 50-99%) grades in the m-TICI system. The performance of these scales for predicting a good 90-day outcome (mRS 0-2) was evaluated using the c-statistic. Results: There were 313 acute stroke patients with MCA M1 segment occlusions who underwent IAT at 6 academic centers; 171 (54.6%) were female. Mean age was 65.3±16.5 years. There were 157 (50.2%) right-sided strokes. Median baseline NIHSS score was 17 (IQR 15-20). Good outcome at 90 days was achieved in 32.5%. For predicting good outcome, the c-statistic was significantly higher for m-TICI (0.74 vs. 0.68; p<0.0001). The threshold that maximized predictive accuracy was m-TICI ≥2B (sensitivity 78%, specificity 65%; figure). Conclusions: The modified TICI scale is superior to the TIMI scale for predicting clinical outcome after IAT, and should be the standard tool for grading angiographic reperfusion. An m-TICI score ≥2B (≥50% reperfusion) is the optimal biomarker for successful reperfusion.

Background and Purpose: Rabbit aneurysm models are used in the testing of embolization devices as well as elucidating the mechanisms human intracranial aneurysm growth and healing. We employed ribonucleic acid sequencing (RNA-seq) technology to identify genes relevant to induced rabbit aneurysm biology and compare these with genes related to human intracranial aneurysms to identify genes of potential clinical interest. This included sequencing micro RNA, which are important regulatory non-coding RNA. Materials and Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery (CCA) in 5 rabbits. Messenger ribonucleic acid (mRNA) and micro ribonucleic acid (miRNA) was isolated from the aneurysm and the control unoperated left CCA at 12 weeks and was processed using RNA-seq technology. The results from RNA-seq were analyzed using Ingenuity Pathway Analysis. Results: 9396 genes were analyzed using RNA-seq, of which 649 (6.9%) were found to be significantly differentially expressed between aneurysm and control tissues (p < 0.05, false discovery rate 2). Of these, 500 were up-regulated in the aneurysm and 149 were down-regulated as compared to controls. Using the same criteria, 3 miRNA were identified as down regulated and 5 were identified as up regulated. Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions and pathologies. Conclusion: RNA-seq next-gen analysis of rabbit aneurysms shows similarities to human intracranial aneurysms with respect to regulation of some key pathways.

Background and Purpose: The Hydrocoil Endovascular aneurysm occlusion and Packing Study (HELPS) was a randomized controlled trial comparing Hydrocoil to bare platinum coils . We performed a subgroup analysis of angiographic and clinical outcomes of medium sized aneurysms in the HELPS trial. Methods: We selected all patients with medium sized aneurysms (5mm-9.9mm) in the HELPS trial. The following outcomes were compared between the HydroCoil and control groups: 1) any recurrence, 2) major recurrence, 3) retreatment and 4) good neurological outcome defined as mRS≤2. Outcomes of recently ruptured and non-recently ruptured aneurysms were compared separately. Comparisons between groups were performed using Fisher’s exact test. A multivariate logistic regression analysis adjusting for aneurysm neck size, shape, use of adjunctive device and rupture status was performed. Results: A total of 288 patients with medium sized aneurysms were randomized (144 in each group). At 15-18 months post-treatment, major recurrence rate was significantly lower in the HydroCoil group than the control group (18.6% versus 30.8%, P=0.03, respectively). For recently ruptured aneurysm patients, major recurrence rate was significantly lower for HydroCoil than controls (20.3% versus 47.5%, P=0.003), while rates were similar between coil types for unruptured aneurysms (16.7% versus 14.8%, P=0.80). On multivariate analysis for patients with recently ruptured aneurysms, HydroCoil was associated with lower odds of any recurrence as compared to bare platinum (OR=0.37, 95%CI=0.18-0.76, P=0.006) and major recurrence (OR=0.27, 95%CI=0.12-0.58, P=0.0007). There was a trend towards lower retreatment rates in the recently ruptured group treated with HydroCoil (OR=0.00, 95%CI=0.00-2.01, P=0.12). Conclusion: For recently ruptured, medium sized aneurysms, as compared to bare platinum coils HydroCoils were associated with lower rates of major recurrence that were both statistically significant and clinically relevant. These findings suggest that HydroCoils should be the preferred treatment for this subset of patients.