Kallmes, David F.

Background and purpose Vertebrobasilar dolichoectatic and fusiform aneurysms (VBDAs) are known to have a poor natural history, with high rates of growth, rupture, and stroke. The purpose of this study was to identify hemodynamic characteristics that differ between VBDAs associated with growth, rupture, and stroke. Materials and methods VBDAs with CT angiography or MR angiography followed longitudinally without treatment were studied. Unstable aneurysms were defined as those that grew or ruptured during follow-up. Aneurysms associated with stroke were defined as those associated with posterior circulation infarct at follow-up. Baseline data, including demographics, comorbidities, and aneurysm morphology and size were collected. Image based computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups (stable vs unstable and no stroke vs stroke) using the Wilcoxon test. Results A total of 37 VBDAs were included (24 stable, 13 unstable; 30 no stroke, 7 stroke). Unstable aneurysms had lower shear rates (P=0.05), blood flow velocity (P=0.03), and lower vorticity (P=0.049) than stable aneurysms. In addition, unstable aneurysms had higher mean oscillatory shear indices (P=0.001). There were no differences in the hemodynamic characteristics of aneurysms in the stroke group compared with the non-stroke group. Conclusion This small study suggests there may be hemodynamic differences between unstable and stable VBDAs. Unstable VBDAs appear to be under lower flow conditions with lower velocity, vorticity, and shear rates, and have more oscillatory flow. There was no difference in the hemodynamic characteristics of aneurysms in the stroke and no stroke group.

Background Intracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations within the aneurysm early after creation in a rabbit model. Methods Elastase induced saccular aneurysms were created in rabbits and harvested on day 1 (n=3) and after 2 (n=5), 4 (n=4), 8 (n=5), and 12 (n=6) weeks. Sham operated controls (n=3) were harvested on the same day. Aneurysm and control tissue samples were subjected to en face whole mount CD31 staining for endothelial cells. Semiquantitative scoring was performed on the basis of endothelial coverage of the vessel wall (proximal, middle, and distal portions of the aneurysm dome). Mixed effects models were used to assess the effect of time and aneurysm section on endothelial coverage. Results Aneurysmal segments were near completely de-endothelialized at 4 and 8 weeks but had re-endothelialized by 12 weeks. Compared with controls, aneurysms at all time points showed decreased endothelialization, but the difference was only significant compared with the 4 and 8 week groups. Both time (P=0.03) and aneurysm section (P=0.07) were significantly associated with the degree of endothelialization. Proximal locations showed increased endothelialization compared with distal locations (P=0.03). Conclusion In experimental aneurysms of rabbits, endothelial cells regress during the first month after creation, followed by ascending re-endothelialization that stays incomplete. These findings suggest that re-population of endothelial cells comes from resident cells in the adjacent parent artery and that deranged hemodynamics may affect full reconstitution of endothelial cells long term.

Abstract Objective : Blood flow waveforms—essential data for hemodynamic modeling—are often in practice unavailable to researchers. The objectives of this work were to assess the variability among the waveforms for a clinically relevant older population, and develop data-based methods for addressing the missing waveform data for hemodynamic studies. Approach : We analyzed 272 flow waveforms from the internal carotid arteries of older patients (73 ± 13 yr) with moderate cardiovascular disease, and used these data to develop methods to guide new approaches for hemodynamic studies. Main results : Profound variations in waveform parameters were found within the aged population that were not seen in published data for young subjects. Common features in the aged population relative to the young included a larger systole-to-diastole flow rate ratio, increased flow during late systole, and absence of a dicrotic notch. Eight waveforms were identified that collectively represent the range of waveforms in the older population. A relationship between waveform shape and flow rate was obtained that, in conjunction with equations relating flow rate to diameter, can be used to provide individualized waveforms for patient-specific geometries. The dependence of flow rate on diameter was statistically different between male and female patients. Significance : It was shown that a single archetypal waveform cannot well-represent the diverse waveforms found within an aged population, although this approach is frequently used in studies of flow in the cerebral vasculature. Motivated by these results, we provided a set of eight waveforms that can be used to assess the hemodynamic uncertainty associated with the lack of patient-specific waveform data. We also provided a methodology for generating individualized waveforms when patient gender, age, and cardiovascular disease state are known. These data-driven approaches can be used to devise more relevant in vitro or in silico intra-cranial hemodynamic studies for older patients.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P <0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Background The angiographic evaluation of previously coiled aneurysms can be difficult yet remains critical for determining re-treatment. Objective The main objective of this study was to determine the inter-rater reliability for both the Raymond Scale and per cent embolization among a group of neurointerventionalists evaluating previously embolized aneurysms. Methods A panel of 15 neurointerventionalists examined 92 distinct cases of immediate post-coil embolization and 1 year post-embolization angiographs. Each case was presented four times throughout the study, along with alterations in demographics in order to evaluate intra-rater reliability. All respondents were asked to provide the per cent embolization (0–100%) and Raymond Scale grade (1-3) for each aneurysm. Inter-rater reliability was evaluated by computing weighted kappa values (for the Raymond Scale) and intraclass correlation coefficients (ICC) for per cent embolization. Results 10 neurosurgeons and 5 interventional neuroradiologists evaluated 368 simulated cases. The agreement among all readers employing the Raymond Scale was fair (κ=0.35) while concordance in per cent embolization was good (ICC=0.64). Clinicians with fewer than 10 years of experience demonstrated a significantly greater level of agreement than the group with greater than 10 years (κ=0.39 and ICC=0.70 vs κ=0.28 and ICC=0.58). When the same aneurysm was presented multiple times, clinicians demonstrated excellent consistency when assessing per cent embolization (ICC=0.82), but moderate agreement when employing the Raymond classification (κ=0.58). Conclusions Identifying the per cent embolization in previously coiled aneurysms resulted in good inter- and intra-rater agreement, regardless of years of experience. The strong agreement among providers employing per cent embolization may make it a valuable tool for embolization assessment in this patient population.

Background and Purpose— There is currently controversy on the ideal anesthesia strategy during mechanical thrombectomy for acute ischemic stroke. We performed a systematic review and meta-analysis of studies comparing clinical and angiographic outcomes of patients undergoing general anesthesia (GA group) and those receiving either local anesthesia or conscious sedation (non-GA group). Methods— A literature search on anesthesia and endovascular treatment of acute ischemic stroke was performed. Using random-effects meta-analysis, we evaluated the following outcomes: recanalization rate, good functional outcome at 90 days (modified Rankin Score≤2), symptomatic intracranial hemorrhage, death, vascular complications, respiratory complications, procedure time, and time to groin puncture. Results— Twenty-two studies (3 randomized controlled trials and 19 observational studies), including 4716 patients (1819 GA and 2897 non-GA) were included. In the nonadjusted analysis, patients in the GA group had higher odds of death (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.66–2.45) and respiratory complications (OR, 1.70; 95% CI, 1.22–2.37) and lower odds of good functional outcome (OR, 0.58; 95% CI, 0.48–0.64) compared with the non-GA group. There was no difference in procedure time between the 2 primary comparison groups. When adjusting for baseline National Institutes of Health Stroke Scale, GA was still associated with lower odds of good functional outcome (OR, 0.59; 95% CI, 0.29–0.94). When considering studies performed in the stent-retriever/aspiration era, there was no significant difference in good neurological outcome rates (OR, 0.84; 95% CI, 0.67–1.06). Conclusions— Acute ischemic stroke patients undergoing intra-arterial therapy may have worse outcomes when treated with GA as compared with conscious sedation/local anesthesia. However, major limitations of current evidence (ie, retrospective studies and selection bias) indicate a need for adequately powered, multicenter randomized controlled trials to answer this question.