Citations

Introduction: Outcomes of mechanical thrombectomy (MT) are influenced by the composition of thrombi. Amongst the risk factors affecting clot composition, diabetes mellitus (DM) may be associated with more thrombus structural and mechanical alterations resulting in fibrinolysis-resistant thrombi. However, extensive analysis of the composition of thrombi obtained from patients is needed to elucidate this relationship. Hypothesis: Thrombi retrieved from patients with DM may have different compositions compared to that of patients with no history of DM. Methods: MT retrieved-thrombi from patients suffering from large vessel occlusion (LVO) stroke were included. Thrombi sections were stained with Martius Scarlet Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Additionally, immunohistochemistry (IHC) was performed to identify neutrophil extracellular traps (NETs) (anti-citrulinated H3; CitH3; NETs-specific marker) and von Willebrand Factor (vWF) in thrombi. Slides were then scanned and analyzed and the thrombus composition was compared between patients with or without a DM diagnosis at the time of stroke presentation. Results: A total of 140 patients were included of which 35 had a diagnosis of DM at stroke presentation. Baseline characteristics (excluding age), IV-tPA use prior to MT, and MT outcomes (number of device passes and final mTICI score) were similar between DM and non DM patients. The overall average percentage of RBCs, WBCs, fibrin, platelet, NETs (CitH3), and vWF components in thrombi were 47.4%, 3.2%, 27.4%, 21.8%, 25.9% and 17.6%, respectively. Thrombi from patients with DM were not statistically significant different from those of patients with no DM in terms of RBCs (44.3 vs 48.4 p=0.37), WBCs (2.7 vs 3.3 p=0.05), fibrin (29.5 vs 26.7 p=0.37), platelet (23.3 vs 21.3 p=0.57), NETs (25.6 vs 22.3 p=0.54), and vWF (17.5 vs 17.7 p=0.96). Conclusion: DM has no effect on the composition of thrombi as no significant difference was found in thrombi obtained from patients with and without DM.

Background and Purpose: Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients 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 (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results: Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MEDT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 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 to MEDT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40). Conclusions: EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MEDT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in PC-LVO patients.

Introduction: Ample evidence exists in support of the anti-inflammatory properties of statins which in turn could affect arterial thrombosis. Compositional analysis of thrombi retrieved by MT may provide us with knowledge useful for evaluating the effect of current Statin therapy on thrombus composition. Methods: Consecutive AIS-LVO patients were included. Histopathological evaluation of thrombi retrieved during MT was performed using Martius Scarlet Blue staining (MSB) and immunohistochemistry for von Willebrand Factor (vWF) and anti-citrulinated H3 (CitH3; NETs marker) and the composition of thrombi was determined using image analysis software. Thrombus was considered rich in a given composition if that composition was higher than its overall mean. We reviewed patient’s medication records and cataloged any statin therapy prior to MT. Results: 117 patients were included in this study. The mean density of red blood cells (RBCs), white blood cells (WBCs), platelets (PLT), fibrin (FIB), vWF and NETs (CitH3) in thrombi was 43.4%, 3.7%, 23.6%, 29.3%, 14.3% and 21.1% respectively. Twenty-seven patients were taking Statins at the time of MT. Statins were not associated with pre-thrombectomy IV-tPA, and stroke etiology (p values: >0.05). There was no association between Statins and thrombi composition and type (p values: >0.05 for all thrombus components and type). Additionally, Statins were not associated with MT outcomes including number of device passes and final mTICI score. Conclusion: Pre-stroke Statin therapy was not associated with differences in thrombus composition.

Introduction: Selection criteria for endovascular thrombectomy (EVT) for emergent large-vessel occlusion (ELVO) stroke increasingly rely on CT perfusion (CTP) findings at presentation. While perfusion imaging is used to estimate the likelihood of deriving long-term functional benefit from EVT, there is comparatively little data on how perfusion deficits relate to domains of neurological function. Here, we investigated region-specific hypoperfusion as a driver of neurological dysfunction through correspondence between NIHSS items and CTP. Methods: We included 169 patients with ELVO presenting to Mayo Clinic Rochester or Jacksonville, who had baseline CTP and itemised NIHSS data. Perfusion was quantified as mean transit time using e-CTP (Brainomix Ltd., Oxford, UK) and thresholded to ≥5 s for lesion masking. Voxel-wise lesion-symptom mapping (VLSM) was performed using sparse canonical correlations analysis (Lesymap package, R). Results: Total NIHSS was most strongly predicted by left MCA territory hypoperfusion, corresponding to language-eloquent cortical areas and dominant hemisphere motor tracts (figure 1). Contralateral limb motor deficits (NIHSS 5 and 6) were mainly associated with subcortical and white matter hypoperfusion; there was an additional strong signal for left frontal cortex in language function (NIHSS 9). The remaining NIHSS items were less well localised. Conclusions: Expanding on previous pilot data, our results provide further evidence for the feasibility of hypoperfusion-to-symptom mapping in ELVO. This could allow for more nuanced clinical-imaging mismatch determination, and selection of patients based on specific neurological deficits that may be reversible.

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.

OBJECTIVE Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time. RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001). CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

OBJECTIVE The risk-to-benefit profile of treating an unruptured high-grade dural arteriovenous fistula (dAVF) is not clearly defined. The aim of this multicenter retrospective cohort study was to compare the outcomes of different interventions with observation for unruptured high-grade dAVFs. METHODS The authors retrospectively reviewed dAVF patients from 12 institutions participating in the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR). Patients with unruptured high-grade (Borden type II or III) dAVFs were included and categorized into four groups (observation, embolization, surgery, and stereotactic radiosurgery [SRS]) based on the initial management. The primary outcome was defined as the modified Rankin Scale (mRS) score at final follow-up. Secondary outcomes were good outcome (mRS scores 0–2) at final follow-up, symptomatic improvement, all-cause mortality, and dAVF obliteration. The outcomes of each intervention group were compared against those of the observation group as a reference, with adjustment for differences in baseline characteristics. RESULTS The study included 415 dAVF patients, accounting for 29, 324, 43, and 19 in the observation, embolization, surgery, and SRS groups, respectively. The mean radiological and clinical follow-up durations were 21 and 25 months, respectively. Functional outcomes were similar for embolization, surgery, and SRS compared with observation. With observation as a reference, obliteration rates were higher after embolization (adjusted OR [aOR] 7.147, p = 0.010) and surgery (aOR 33.803, p < 0.001) and all-cause mortality was lower after embolization (imputed, aOR 0.171, p = 0.040). Hemorrhage rates per 1000 patient-years were 101 for observation versus 9, 22, and 0 for embolization (p = 0.022), surgery (p = 0.245), and SRS (p = 0.077), respectively. Nonhemorrhagic neurological deficit rates were similar between each intervention group versus observation. CONCLUSIONS Embolization and surgery for unruptured high-grade dAVFs afforded a greater likelihood of obliteration than did observation. Embolization also reduced the risk of death and dAVF-associated hemorrhage compared with conservative management over a modest follow-up period. These findings support embolization as the first-line treatment of choice for appropriately selected unruptured Borden type II and III dAVFs.

OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120–1038.5 days). CONCLUSIONS With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.