Search

OBJECTIVE The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%–22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%–28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%–25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%–21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%–37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%–20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%–40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%–21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%–35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%–29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%–33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%–34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%–26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%–34%). CONCLUSIONS Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

OBJECTIVE The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov)

The variable rate of infarct progression in acute ischemic stroke as assessed by various thresholds excludes a substantial proportion of patients due to time or core constraints. We evaluated 106 patients with any-type occlusion to compare these thresholds and assessed performance of hypoperfusion index (HI) for fast and slow rate of infarct progression. Seven (12.5%) were classified fast progressors and 23 (46%), 25 (50%), 12 (24%), and 33 (66%) slow progressors using different core and time criteria. In comparison, HI categorized 100% (n = 106) of cohort with optimal cutoff 0.5 for any-type occlusion (slow progressors: HI ≤ 0.5), sensitivity/specificity 100%/91%, AUC 0.94, and indicative of eligibility for reperfusion and clinical outcomes (median 90-day modified Rankin Scale; 2 for HI ≤ 0.5 versus 5). Estimation of progressors by HI seems comprehensive but needs external validation.

Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial.Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built.Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46).The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Objective:We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability.Methods:We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years).Results:EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at −$7,313 (−$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were −$1.26 (−$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively.Conclusion:The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0–2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6–92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0–15 mL, 15.1–70 mL, 70.1–200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0–15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15–200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, P =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], P =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery. Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.

Iodinated contrast media (ICM) is one of the most frequently administered pharmaceuticals. In Canada, over 5.4 million computed tomography (CT) examinations were performed in 2019, of which 50% were contrast enhanced. Acute kidney injury (AKI) occurring after ICM administration was historically considered a common iatrogenic complication which was managed by screening patients, prophylactic strategies, and follow up evaluation of renal function. The Canadian Association of Radiologists (CAR) initially published guidelines on the prevention of contrast induced nephropathy in 2007, with an update in 2012. However, new developments in the field have led to the availability of safer contrast agents and changes in clinical practice, prompting a complete revision of the earlier recommendations. This revised guidance document was developed by a multidisciplinary CAR Working Group of radiologists and nephrologists, and summarizes changes in practice related to contrast administration, screening, and risk stratification since the last guideline. It reviews the scientific evidence for contrast associated AKI and provides consensus-based recommendations for its prevention and management in the Canadian healthcare context. This article is a joint publication in the Canadian Association of Radiologists Journal and Canadian Journal of Kidney Health and Disease, intended to inform both communities of practice.

Background and purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management. Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0–2a. Proportions of good outcome (modified Rankin scale 0–2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained. Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81–2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56–2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00–22.97). Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.

BACKGROUND AND PURPOSE: Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment. MATERIALS AND METHODS: Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study. RESULTS: The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14–0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4). CONCLUSIONS: Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.

Background: During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime. Methods: Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis. Results: The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care. Conclusions: Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime. Clinical Trial Registration: NCT01778335

BackgroundThe DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.MethodsAggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics.ResultsBaseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5–11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6–16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2–12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19–146] vs median 8 mL [IQR: 0–48] in the DAWN group and 35 mL [IQR: 18–82] in DEFUSE-3), while % mRS 0–2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]).ConclusionPatients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

Background:Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.Methods and Results:Over a 3-year period (April 2015–March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI −2.74–14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94–20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.Conclusions:We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.

Background Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better. Aims We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome. Methods We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24–48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24–48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between “discrepant cases” – those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV – and “non-discrepant cases”. Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome. Results Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement ( p = 0.39, p = 0.81, respectively, for PIV ≤ 7 mL/mRS ≥ 3). Pre-treatment factors independently associated with small-PIV/mRS ≥ 3 included older age ( p = 0.010), cancer, and vascular risk-factors; post-treatment factors included 48-h NIHSS ( p = 0.007) and post-stroke complications ( p = 0.026). Absence of vascular risk-factors ( p = 0.004), CT-based lentiform nucleus sparing ( p = 0.002), lower 24-hour NIHSS ( p = 0.001), and absence of complications ( p = 0.013) were associated with large-PIV/mRS ≤ 2. Sensitivity analyses yielded similar results. Conclusions Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01778335 .

BackgroundThe endovascular clip system (eCLIPs) is a novel device with both neck bridging and flow-diversion properties that make it suitable for the treatment of wide-necked bifurcation aneurysms.ObjectiveTo describe the clinical and radiologic outcomes of the eCLIPs device, including the first-in-man use of the latest version of the device.MethodsThis is a retrospective case series on all the wide-necked bifurcation aneurysms treated with the eCLIPs device in our center. The immediate and latest radiologic and clinical outcomes were assessed.ResultsThe device was successfully implanted in 12 of 13 patients. After a median follow-up period of 19 months (range 3–64 months), all patients with available data (11/12) had a good radiologic outcome (modified Raymond-Roy classification scores of 1 or 2). Two patients (18.2%) underwent re-treatment with simple coiling through the device. One of these had a subarachnoid hemorrhage prior to re-treatment. There were no major complications (death or permanent neurologic deficits) associated with use of the device.ConclusionOur series demonstrates occlusion rates that are similar to those of standard stent-assisted coiling and intrasaccular flow diversion for wide-necked bifurcation aneurysms. Larger registry-based studies are necessary to support our findings.

Background and purpose Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. Methods The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS > 2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. Results An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS > 2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%–53%), and 10/34 patients allocated to coiling (29%; 17%–46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%–94%), and 18/27 patients allocated to coiling (67%; 47%–81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%–60%]) than EVT (9/48 [19%; 10%–31%]). Conclusion Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

Background and Purpose— Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT. Methods— Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT. Results— Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8–10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2–3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without ( P =0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was U -shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold 4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up. Conclusions— Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.

OBJECTIVEFreehand insertion of external ventricular drains (EVDs) using anatomical landmarks is considered the primary method for placement, although alternative techniques have shown improved accuracy in positioning. The purpose of this study was to retrospectively evaluate which features of the baseline clinical history and preprocedural CT scan predict EVD positioning into suboptimal and unsatisfactory locations when using the freehand insertion technique.METHODSA retrospective chart review was performed evaluating 189 consecutive adult patients who received an EVD via freehand technique through an anterior burr hole between January 1, 2014, and December 31, 2015, at a Level 1 trauma facility in Edmonton, Alberta, Canada. The primary outcome measures included features associated with suboptimal positioning (Kakarla grade 1 vs Kakarla grades 2 and 3). The secondary outcome measures were features associated with unsatisfactory positioning (Kakarla grades 1 and 2 vs Kakarla grade 3).RESULTSFifty-one EVDs (27%) were suboptimally positioned. Fifteen (8%) EVDs were placed into eloquent cortex or nontarget CSF spaces. Admitting diagnosis, head height-to-width ratio in axial plane, and side of predominant pathology were found to be significantly associated with suboptimal placement (p = 0.02, 0.012, and 0.02, respectively). A decreased height-to-width ratio was also associated with placement into only eloquent cortex and/or nontarget CSF spaces (p = 0.003).CONCLUSIONSFreehand insertion of an EVD is associated with significant suboptimal positioning into parenchyma and nontarget CSF spaces. The likelihood of inaccurate EVD placement can be predicted with baseline clinical and radiographic features. The patient’s height-to-width ratio represents a novel potential radiographic predictor for malpositioning.

Background and ObjectivesThe rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset.MethodsCore progression was assessed in 106 patients with acute stroke and CT perfusion. Using reperfusion trial core time criteria, fast progressors had core >70 mL within 6 hours of stroke onset and slow progressors had core ≤70 mL, mismatch ≥15 mL, and mismatch to core ratio ≥1.8 within 6 to 24 hours. The relationship between HI and infarct core progression (core/time) was examined using receiver operating characteristics to determine optimal HI cutoff. The HI cutoff was then tested in the overall cohort, compared between MeVO and LVO, and evaluated in patients up to 24 hours from stroke onset to differentiate fast from slow rate of core progression. HI threshold was assessed in a second independent cohort of 110 patients with acute ischemic stroke.ResultsIn 106 patients with acute stroke, 6.6% were fast progressors, 27.4% were slow progressors, and 66% were not classified as fast or slow progressor by reperfusion trial core time criteria. HI >0.5 was associated with fast progression and able to distinguish fast from slow progressors (area under the curve [AUC] 0.94; 95% confidence interval [CI] 0.80–0.99). In MeVO (n = 26) HI >0.5 had a core progression of 0.30 mL/min compared to 0.03 mL/min for HI ≤0.5 (p < 0.001). In LVO (n = 80), HI >0.5 had a core progression of 0.26 mL/min compared to 0.02 mL/min for HI ≤0.5 (p < 0.001). In patients not classified as fast or slow progressor by reperfusion trial criteria, those with HI >0.5 had progression rate of 0.21 mL/min compared to 0.03 mL/min for those with HI ≤0.5 (p < 0.001). Validation in a second cohort of patients with acute ischemic stroke (n = 110; MeVO = 42, LVO = 68) yielded similar results for HI >0.5 to distinguish fast and slow core progression with an AUC of 0.84 (95% CI 0.72–0.97).DiscussionHI can differentiate fast from slow core progression in MeVO and LVO within the first 24 hours of acute ischemic stroke. Consideration of core progression rate at time of stroke evaluation may have implications in the selection of patients with MeVO and LVO stroke for reperfusion therapy that warrant further study.

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.ResultsAmong 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0–2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0–2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).ConclusionsTandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Objective There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. Methods Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. Results There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02–0.19) for clipping and 13/48 (27%; 95% CI, 0.17–0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09–0.33) cases, and 8/33 (24%; 95% CI, 0.13–0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60–0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22–0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54–0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36–0.70) patients with RA allocated coiling. Conclusions Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Guidelines are lacking for management of acute ischemic stroke and stroke prevention in patients with immune thrombocytopenia (ITP). Our aim is to highlight the dilemma inherent in managing patients with both significant bleeding and thrombotic risk factors. In this review, we present two patients with history of ITP who presented with acute ischemic stroke and received tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT), a rare management strategy in this patient population. In addition, we identified 27 case reports of ischemic stroke in patients with ITP; none of them received tPA or EVT. Furthermore, there are 92 patients with significant thrombocytopenia with no available data regarding the cause of thrombocytopenia, who were acutely treated with tPA or EVT. Conclusive evidence cannot be determined based on these limited number of cases. Future multicenter prospective cohort studies in patients with ITP are needed to provide better evidence-based treatment plans. At present, treatment of acute ischemic stroke in patients with ITP requires close collaboration between hematology and vascular neurology experts to find a balance between the benefit and risk of hemorrhagic complications.

In the absence of randomized evidence, the optimal management of patients with unruptured intracranial aneurysms (UIA) remains uncertain.Comprehensive Aneurysm Management (CAM) is an all-inclusive care trial combined with a registry. Any patient with a UIA (no history of intracranial hemorrhage within the previous 30 days) can be recruited, and treatment allocation will follow an algorithm combining clinical judgment and randomization. Patients eligible for at least 2 management options will be randomly allocated 1:1 to conservative or curative treatment. Minimization will be used to balance risk factors, using aneurysm size (≥7 mm), location (anterior or posterior circulation), and age60 years.The CAM primary outcome is survival without neurologic dependency (modified Rankin Scale [mRS] score3) at 10 years. Secondary outcome measures include the incidence of subarachnoid hemorrhage during follow-up and related morbidity and mortality; morbidity and mortality related to endovascular treatment or surgical treatment of the UIA at 1 year; overall morbidity and mortality at 1, 5, and 10 years; when relevant, duration of hospitalization; and, when relevant, discharge to a location other than home. The primary hypothesis for patients randomly allocated to at least 2 options, 1 of which is conservative management, is that active UIA treatment will reduce the 10-year combined neurologic morbidity and mortality (mRS score2) from 24% to 16%. At least 961 patients recruited from at least 20 centers over 4 years will be needed for the randomized portion of the study.Patients with unruptured intracranial aneurysms can be comprehensively managed within the context of an all-inclusive care trial.

Background: A heterogeneous patient population receives endovascular treatment (EVT) for acute ischemic stroke due to proximal large vessel occlusion every day. We aimed to conduct a population-based study of EVT in the province of Alberta, Canada, to understand the effectiveness in a complete population and how the magnitude of effect differs from the artificial world of clinical trials. Methods and Results: Within a three year period (April 2015 - March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. Primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at pre-morbid living situation without increase in level of care within 90 days of index stroke event. Median age of patients was 70 years (interquartile range (IQR) 59 - 81) and 47.8% were female. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13 - 20). EVT was associated with an increased 90-day home-time by an average of 8.5 days compared to medical treatment alone using Cragg hurdle regression (p = 0.009). Age and higher NIHSS score were associated with decreased 90-day home-time (both p = 0.001). Multivariable logistic regression showed no association between EVT and mortality at 90 days (odds ratio 0.76, 95% confidence interval 0.47 - 1.24). Conclusions: EVT for acute ischemic stroke due to proximal large vessel occlusion was effective in our province-wide population-based study and results in increased 90-day home-time by ~8.5 days. Home-time is a novel and patient-centered outcome that reflects health circumstances that are easy to understand and meaningful to patients and their caregivers.

BACKGROUND AND PURPOSE The purpose of this study was to compare Doppler ultrasound (DUS) to other angiographic modalities: computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). METHODS All DUS studies performed at Stroke Prevention Clinic (SPC) from 2011 to 2013 and referred for further angiographic modalities were included. Patients were excluded if the corresponding angiographic modality was not performed within 6 months of DUS. Patients were also excluded if they underwent interventions before DUS or between the time of DUS and the corresponding angiographic modality. The degree of stenosis was classified as mild (

BackgroundOptimal technical approaches of large-vessel anterior circulation acute ischemic strokes with concomitant extracranial internal carotid artery tandem occlusions is controversial.PurposeThis systematic review and meta-analysis evaluates: the overall outcomes of patients with tandem occlusions treated with second-generation mechanical thrombectomy devices; differences in outcomes of extracranial versus intracranial first approaches; and differences in outcomes of extracranial stenting at time of procedure versus angioplasty alone.MethodsMEDLINE, EMBASE, and the Web of Science was searched through September 2017 for studies evaluating patients presenting with acute tandem occlusions of the extracranial ICA and intracranial ICA, and/or proximal MCA treated with second-generation mechanical thrombectomy devices. Outcomes were pooled across studies using the random-effects model and expressed as cumulative incidence (event rate) and 95% CI.ResultsThirty-three studies were included in analysis. Overall mRS≤0–2 at 90 days was 47% (95% CI 42% to 51%). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial versus intracranial first approaches, 53% (95% CI 44% to 61%) vs 49% (95% CI 44% to 57%) (P=0.58). No statistical difference was seen in 90-day mRS≤0–2 for patients treated with extracranial stenting versus angioplasty alone, 49% (95% CI 42% to 56%) vs 49% (95% CI 33% to 65%) (P=0.39). No other statistical differences in outcome or safety were identified.ConclusionsNearly half of all tandem occlusion patients treated with mechanical thrombectomy have good neurological outcomes. No statistical differences in outcome are identified between extracranial first versus intracranial first approaches, nor extracranial stenting versus angioplasty alone.

BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial. MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0–2, mRS 0–1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses. RESULTS: There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0–2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage. CONCLUSIONS: Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.

Background and purposeFlow diversion is a relatively new strategy used to treat complex cerebral aneurysms. The optimal method for radiographic follow-up of patients treated with flow diverters has not been established. The rate and clinical implications of in-stent stenosis for these devices is unclear. We evaluate the use of transcranial Doppler ultrasound (TCD) for follow-up of in-stent stenosis.Materials and methodsWe analyzed 28 patients treated with the Pipeline embolization device (PED) over the course of 42 months from January 2009 to June 2012. Standard conventional cerebral angiograms were performed in all patients. TCD studies were available in 23 patients.ResultsAngiographic and TCD results were compared and found to correlate well.ConclusionsTCD is a potentially useful adjunct for evaluating in-stent stenosis after flow diversion.

Background and Purpose— Endovascular therapy has been shown to be highly efficacious based on 90-day modified Rankin Scale score. We examined actual daily healthcare utilization from stroke onset to 1 year afterward from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Time) and registry data. Methods— We examined patients from Alberta, Canada, that was enrolled into the ESCAPE trial and the Quality Improvement and Clinical Research registry in the 2016/2017 fiscal year. Through data linkages to several administrative data sets, the daily location of each patient was assessed in various healthcare settings. Results— A total of 286 patients were analyzed, 52 patients were in the treatment arm, and 47 patients were in the control arm of the ESCAPE trial while 187 patients received endovascular therapy as usual care (2016/2017 fiscal year). The odds of a patient being out of a healthcare setting over 1 year was significantly higher when they received endovascular therapy: 3.46 (1.68–7.30) in ESCAPE trial patients and 2.00 (1.08–3.75) in the Quality Improvement And Clinical Research patients. Conclusions— Endovascular therapy significantly reduces healthcare utilization up to 1 year after a stroke.

OBJECTIVEIn this study the authors sought to compare the proportion of patients with lumbar spondylolisthesis detected to have dynamic instability based on flexion and extension standing radiographs versus neutral standing radiograph and supine MRI.METHODSThis was a single-center retrospective study of all consecutive adult patients diagnosed with spondylolisthesis from January 1, 2013, to July 31, 2018, for whom the required imaging was available for analysis. Two independent observers measured the amount of translation, in millimeters, on supine MRI and flexion, extension, and neutral standing radiographs using the Meyerding technique. Interobserver and intraobserver correlation coefficients were calculated. The difference in amount of translation was compared between 1) flexion and extension standing radiographs and 2) neutral standing radiograph and supine MRI. The proportion of patients with dynamic instability, defined as a ≥ 3 mm difference in the amount of translation measured on different imaging modalities, was reported. Correlation between amount of dynamic instability and change in back pain and leg pain 1 year after decompression and instrumented fusion was analyzed using multivariate regression analysis.RESULTSFifty-six patients were included in this study. The mean patient age was 57.1 years, and 55.4% of patients were female. The most commonly affected levels were L4–5 (60.7%) and L5–S1 (30.4%). The average translations measured on flexion standing radiograph, extension standing radiograph, neutral standing radiograph, and supine MRI were 12.5 mm, 11.9 mm, 10.1 mm, and 7.2 mm, respectively. The average difference between flexion and extension standing radiographs was 0.58 mm, with dynamic instability detected in 21.4% of patients. The average difference between neutral standing radiograph and supine MRI was 3.77 mm, with dynamic instability detected in 60.7% of patients. The intraobserver correlation coefficient ranged from 0.77 to 0.90 mm. The interobserver correlation coefficient ranged from 0.79 to 0.86 mm. In 44 patients who underwent decompression and instrumented fusion, the amount of dynamic instability between standing and supine imaging was significantly correlated with change in back pain (p < 0.001) and leg pain (p = 0.05) at the 12-month postoperative follow-up. There was no correlation between amount of dynamic instability between flexion and extension standing radiographs and postoperative back pain and leg pain.CONCLUSIONSMore patients were found to have dynamic instability by using neutral standing radiograph and supine MRI. In patients who received decompression and instrumented fusion, there was a significant correlation between dynamic instability on neutral standing radiograph and supine MRI and change in back pain and leg pain at 12 months.

Background— The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. Methods and Results— Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% ( P =0.006). Symptom onset-to-imaging time was not associated with outcome ( P >0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). Conclusions— Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01778335.

Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29–5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. Conclusions— Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups.

Six recent trials and a patient-level meta-analysis have demonstrated the superiority of endovascular therapy (EVT) compared with standard care (including intravenous alteplase) among patients with large-artery anterior circulation strokes.1–7 The absolute benefit of EVT was substantial in these trials, and EVT now requires careful implementation and optimization in real-world settings to provide all eligible patients with this new standard of care. Parallel rather than serial workflow, with team members having well-defined roles, is a crucial element in providing rapid and effective delivery of acute stroke care.8 There is little or no literature on the division of labor or the expected role for each individual in this setting, and existing stroke guidelines do not elaborate on this issue. Although each system may require customization, it is clear is that there must be physician leadership outside of the angiography suite, a physician in addition to the neurointerventionalist (who is most commonly a radiologist, but who may be a neurosurgeon or neurologist) in the angiography suite, and a physician to coordinate care between the other stroke team members throughout the periprocedural period. We suggest that it is necessary to designate a physician to fulfill these roles during the EVT process, and we have termed herein the individual fulfilling this role the stroke physician. The stroke physician must work in close collaboration with the neurointerventionalist to optimize the speed, efficiency, and safety of EVT, elements which are critical to enhancing patient outcomes. A proposed division of physician roles is shown in Table, with emphasis on parallel rather than serial workflow. The administration of intravenous alteplase is ideally performed under the guidance of a stroke physician with specialized training in stroke care. This is most often a neurologist but may also be an emergency physician, geriatrician, internist, or family physician, …

Vertebral hemangiomas are common lesions usually restricted to the vertebral body. They are characterized by proliferation of endothelial cells and subsequent expansion of vascular spaces within the bone. These lesions are usually clinically silent and are discovered incidentally. Only rarely are vertebral hemangiomas symptomatic. Here, we present the case of a 68-year-old female with an aggressive hemangioma causing neurologic deficit. The lesion was localized within the posterior spinal elements, with no involvement of the vertebral body. Transarterial embolization was deemed unsafe due to the close proximity of a prominent radiculomedullary artery. The patient was treated with posterior decompression at T4-T6.

Introduction: Multiphase CT angiography (mCTA) has been proposed as an alternative to CT Perfusion (CTP) for identification of acute stroke patients with the potential for salvage after reperfusion therapy. We tested the hypothesis that poor collateral patterns on mCTA are predictive of large CTP defined ischemic cores. Methods: Multiphase CTA was generated from CTP source images (peak arterial, +8 and +16 s). Two expert raters assessed the collateral pattern on mCTA (absent/moderate/good). An Alberta Stroke Program Early CT (ASPECT) score was also assessed on the first and last phase of the mCTA as well as the non-contrast CT (NCCT). Hypoperfused regions were defined as those without vessel enhancement on the first phase. Core regions were defined as those without vessel enhancement on the final phase and/or NCCT changes. An ASPECTS mismatch score was calculated as a penumbral estimate. Penumbral tissue on CTP was defined as regions with a Delay Time (DT) >3 seconds, and ischemic core was defined as a combination of DT>3 seconds and relative CBF Results: Of 141 patients, 79(56%) had penumbral patterns on CTP. Of these, 71(90%) had moderate/good collaterals. The mean penumbral volume in all patients was 20.8±26.6 ml and that in patients with large vessel occlusions (LVO; n=40) was 44.0±30.5 ml. At an ASPECTS mismatch score threshold of 2, mCTA predicted CTP defined penumbral patterns with a sensitivity of 77% and specificity of only 10%. The positive and negative predictive values were 57.7% and 61.5% respectively. In large vessel occlusion patients, mCTA predicted penumbra with 95.8% sensitivity and 43.8% specificity. The positive predictive value for penumbral patterns was 71.7%, and the negative predictive value was 87.5%. Eight patients were found to have a large core (>70 ml) on CTP, 3 of whom had moderate/good collaterals and 2 of whom also had a NCCT ASPECTS>5. Four large core patients had a mCTA penumbral score ≥ 2. Discussion: mCTA predicts penumbra with relatively high sensitivity, particularly in LVO patients. In some patients, however, mCTA can incorrectly classify penumbral patterns despite the presence of large cores on CTP. In non-LVO patients, mCTA is neither sensitive, nor specific for penumbral patterns.

Background: In the ESCAPE trial, patients with large vessel occlusions and small infarct cores identified with CT/CT angiography were randomized to endovascular therapy or standard of care. CT Perfusion (CTP) was obtained in some cases, but was not utilized to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. Methods: All CTP data acquired in ESCAPE patients was analyzed centrally using a semi-automated perfusion threshold based approach. A penumbral pattern was defined as an infarct core15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was a good functional outcome at 90 days (mRS 0-2). Results: CTP was acquired in 138 of 316 ESCAPE patients. Motion degraded CTP images from 9 patients were excluded. Penumbral patterns were present in 110/129 (85.3%) of patients. The rate of good functional outcome in penumbral pattern patients (53/108; 49.1%) was higher than that in non-penumbral patients (3/19; 15.8%, p=0.011). In penumbral patients, endovascular therapy increased the likelihood of good outcome (35/58; 60.3%) over those in the control group (18/50; 36%, OR=2.71, p=0.013). Only 4 of 19 non-penumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. Conclusion: The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Non-penumbral patients were much less likely to achieve good outcomes.

Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. Methods We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). Results The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8–10 vs. 6–7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0–1; mRS 0–2; Barthel 95–100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days.

Background and Purpose— In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. Methods— All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core 15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0–2). Results— CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P =0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25–5.76; P =0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. Conclusions— The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes.

OBJECTIVERuptured intracranial aneurysms (RIAs) can be managed surgically or endovascularly. In this study, the authors aimed to measure the interobserver agreement in selecting the best management option for various patients with an RIA.METHODSThe authors constructed an electronic portfolio of 42 cases of RIA in which an angiographic image along with a brief clinical vignette for each patient were displayed. Undisclosed to the responders was that the RIAs had been categorized as International Subarachnoid Aneurysm Trial (ISAT) (small, anterior-circulation, non–middle cerebral artery location, n = 18) and non-ISAT (n = 22) aneurysms; the non-ISAT group also included 2 basilar apex aneurysms for which a high number of endovascular choices was expected. The portfolio was sent to 132 clinicians who manage patients with RIAs and circulated to members of an American surgical association. Judges were asked to choose between surgical and endovascular management, to indicate their level of confidence in the choice of treatment on a quantitative 0–10 scale, and to determine whether they would include the patient in a randomized trial in which both treatments are compared. Eleven clinicians were asked to respond twice at least 1 month apart. Responses were analyzed using kappa statistics.RESULTSEighty-five clinicians (58 cerebrovascular surgeons, 21 interventional neuroradiologists, and 6 interventional neurologists) answered the questionnaire. Overall, endovascular management was chosen more frequently (n = 2136 [59.8%] of 3570 answers). The proportions of decisions to clip were significantly higher for non-ISAT (50.8%) than for ISAT (26.2%) aneurysms (p = 0.0003). Interjudge agreement was only fair (kappa 0.210, 95% CI 0.158–0.276) for all cases and judges, despite high confidence levels (mean score > 8 for all cases). Agreement was no better within subgroups of clinicians with the same specialty, years of experience, or location of practice or across capability groups (ability to clip or coil, or both). When agreement was defined as > 80% of responders choosing the same option, agreement occurred for only 7 of 40 cases, all of which were ISAT aneurysms, for which coiling was preferred.CONCLUSIONSAgreement between clinicians regarding the best management option was infrequent but centered around coiling for some ISAT aneurysms. Surgical clipping was chosen more frequently for non-ISAT aneurysms than for ISAT aneurysms. Patients with such an aneurysm might be candidates for inclusion in randomized trials.

BackgroundTandem occlusions of the extracranial carotid and intracranial carotid or middle cerebral artery have a particularly poor prognosis without treatment. Several management strategies have been used with no clear consensus recommendations. We examined subjects with tandem occlusions enrolled in the ESCAPE trial and their outcomes.MethodsData are from the ESCAPE trial. Additional data were sought on interventions for each subject.ResultsThere were 54 (17%) subjects with tandem extracranial and intracranial occlusions. Patients in the endovascular treatment arm (n=30) were more likely to be younger (median age 66 years, pConclusionsTandem occlusions occurred in one-sixth of patients and were treated highly variably within the ESCAPE trial. While outcomes were similar, the best method to treat the carotid artery in patients with tandem occlusion awaits further randomized data.Trial registration numberNCT01778335.

Introduction Endovascular treatment of acute ischemic stroke is more effective when performed quickly. In this report, we describe quality interventions to ensure fast endovascular treatment times in the ESCAPE (Endovascular Treatment for Small Core and Anterior circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times) trial. Methods An “audit and feedback” intervention using webinar and letter was used to improve treatment time over the course of the trial. The time metrics were computed tomography-to-groin-puncture (target Results There were 165 patients enrolled into the endovascular arm from 22 sites. The computed tomography-to-groin-puncture time dropped from 57 to 47 min (p = 0.14) while computed tomography-to-reperfusion time dropped from 89 to 81 min (p = 0.48). Over the course of the trial, the absolute treatment benefit increased by 7.8% (p Conclusions An “audit and feedback” intervention throughout the conduct of the ESCAPE trial was a feasible way to ensure fast treatment times. Quality improvement processes should continue as standard practice beyond the trial to encourage good patient selection and the best clinical outcomes.

Background and Purpose— Multimodal imaging in acute ischemic stroke defines the extent of arterial collaterals, resultant penumbra, and associated infarct core, yet limitations abound. We identified superficial and deep venous drainage patterns that predict outcomes in patients with a proximal arterial occlusion of the anterior circulation. Methods— An observational study that used computed tomography (CT) angiography to detail venous drainage in a consecutive series of patients with a proximal anterior circulation arterial occlusion. The principal veins that drain the cortex (superficial middle cerebral, vein of Trolard, vein of Labbé, and basal vein of Rosenthal) and deep structures were scored with a categorical scale on the basis of degree of contrast enhancement. The Prognostic Evaluation based on Cortical vein score difference In Stroke score encompassing the interhemispheric difference of the composite scores of the veins draining the cortices (superficial middle cerebral+vein of Trolard+vein of Labbé+basal vein of Rosenthal) was analyzed with respect to 90-day modified Rankin Scale outcomes. Results— Thirty-nine patients were included in the study. A Prognostic Evaluation based on Cortical vein score difference In Stroke score of 4 to 8 accurately predicted poor outcomes (modified Rankin Scale, 3–6; odds ratio, 20.53; P P =0.009) and an elevated admission National Institutes of Health Stroke Scale (odds ratio, 1.423; P =0.023) were independent predictors of poor outcome. Conclusions— The Prognostic Evaluation based on Cortical vein score difference In Stroke score, a novel measure of venous enhancement on CT angiography, accurately predicts clinical outcomes. Venous features on computed tomography angiography provide additional characterization of collateral perfusion and prognostication in acute ischemic stroke.

Background and Purpose— The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. Methods— The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject’s infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). Results— Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P P P P P P >0.05). Post-treatment infarct volume ( P P Conclusions— These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01778335.

Background and Purpose: The goal of reperfusion therapy in acute ischemic stroke is to limit the extension of the ischemic core. The objectives of the present study were to assess the relationship between endovascular treatment and final infarct volume. Methods and Results: ESCAPE is a multicenter prospective randomized open-label trial with blinded outcome evaluation that enrolled 315 patients (endovascular treatment n=165; control n=150). Of these, 314 patient infarct volumes at 24 hours on CT or MRI were measured blinded to clinical data. Because infarct volumes were non-normally distributed, final infarct volumes were analysed by quartiles. Final infarct volumes were compared by treatment assignment and recanalization/reperfusion status measured by 2-8h CT angiogram in the control group and by formal angiography in the intervention arm. Results: Median final infarct volume among all study participants was 21 mL (IQR: 7 to 72). Median final infarct volume in endovascular treatment arm at 15.5 mL (IQR: 5 to 46.5) was significantly lower than median final infarct volume in control arm 33.5 mL (IQR: 11 to 95; P=0.0004). Small infarcts, defined as 1st quartile of infarct volumes were more common in the endovascular group compared to control (relative risk [RR] 1.5, CI95 1.02-2.3). Successful recanalization and reperfusion was highly associated with small infarcts (RR 2.2, CI95 1.4-3.4). The proportion of large hemispheric stroke (defined as an infarct volume in the 4th quartile) was much less frequent in the endovascular treatment arm (RR 0.6, CI95 0.3-0.8). Conclusions: This analysis supports the primary results of ESCAPE trial as endovascular treatment was associated with significantly smaller final infarct volumes. Recanalization/reperfusion was associated with smaller final infarct volume.