Kallmes, David F.

Background & Purpose It has been hypothesized that circulating neutrophils have a direct correlation with the composition of emboli in acute ischemic stroke (AIS). The aim of this study is to evaluate the association between neutrophil-lymphocyte ratio (NLR) in peripheral blood and the expression of neutrophil extracellular traps (NETs) within stroke emboli. Methods Consecutive patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) that underwent mechanical thrombectomy (MT) were included. Patients were divided into two groups based on NLR median value. Retrieved thrombi were histologically analyzed using Martius Scarlett Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Immunohistochemistry staining for von Willebrand Factor (vWF) and anti-citrullinated H3 (H3Cit; NETs marker) was also performed. Results Samples from a total of 84 patients were included. The average percentage of RBCs, WBCs, fibrin, platelet, H3Cit, and vWF components in thrombi were 45.1%, 3.5%, 21.8%, 29.6%, 19.7% and 14.8% respectively. When stratifying by NLR group [low (≤3.94) versus high (>3.95)], high NLR group had significantly more WBCs (4.5%), fibrin (24.2%), H3Cit (22.7%) and vWF (17.1%) thrombus fractions compared to low NLR group. Additionally, RBC content (38.8%) was lower in the high NLR group. Conclusions NLR is correlated with the amounts of WBCs, fibrin, NETs and vWF within the thrombi retrieved from AIS patients due to LVO.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

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.