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Background: We evaluated the effect of persistent hyperglycemia on outcomes in 1000 patients with intracerebral hemorrhage enrolled within 4.5 hours of symptom onset. Methods: We defined moderate and severe hyperglycemia based on serum glucose levels ≥140 mg/dL— Results: In the multivariate analysis, both moderate (odds ratio, 1.8 [95% CI, 1.1–2.8]) and severe (odds ratio, 1.8 [95% CI, 1.2–2.7]) hyperglycemia were associated with higher 90-day death or disability after adjusting for Glasgow Coma Scale score, hematoma volume, presence or absence of intraventricular hemorrhage, hyperlipidemia, cigarette smoking, and hypertension (no interaction between hyperglycemia and preexisting diabetes, P =0.996). Among the patients without preexisting diabetes, both moderate (odds ratio, 1.8 [95% CI, 1.0–3.2]) and severe (odds ratio, 2.0 [95% CI, 1.1–3.7]) hyperglycemia were associated with 90-day death or disability after adjusting for above mentioned potential confounders. Among the patients with preexisting diabetes, moderate and severe hyperglycemia were not associated with 90-day death or disability. Conclusions: Persistent hyperglycemia, either moderate or severe, increased the risk of death or disability in nondiabetic patients with intracerebral hemorrhage. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01176565.

Background and Purpose: Patients with single subcortical infarctions (SSIs) have relatively a favorable prognosis, but they often experience early neurological deterioration (END). In this study, we compared the predictors for END in patients with SSI according to the location of the lesion. Methods: We included consecutive patients with SSIs within 72 hours of symptom onset presenting between 2010 and 2016. END was defined as an increase of ≥2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 in the motor NIHSS score within the first 72 hours of admission. Along with the analysis of all patients with SSI, we also analyzed the predictors for END in proximal/distal SSI patients and anterior/posterior circulation SSI patients. Results: A total of 438 patients with SSI were evaluated. In multivariable analysis, initial NIHSS score (adjusted odds ratio, 1.36 [95% CI, 1.15–1.60]), pulsatility index (adjusted odds ratio, 1.25 [95% CI, 1.03–1.52]), parent artery disease (adjusted odds ratio, 2.14 [95% CI, 1.06–4.33]), and neutrophil-to-lymphocyte ratio (adjusted odds ratio, 1.24 [95% CI, 1.04–1.49]) were positively associated with END. In patients with proximal SSI, initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio showed positive associations with END. Meanwhile, no variable related to END was found in the distal SSI group. When we compared the predictors for END based on the involved vascular territory, higher initial NIHSS score and neutrophil-to-lymphocyte ratio were significantly associated with END in patients with anterior circulation SSIs. On the contrary, higher pulsatility index values and the presence of parent artery disease were independent predictors for END in patients with SSIs in the posterior circulation. Conclusions: Initial NIHSS score, pulsatility index, parent artery disease, and neutrophil-to-lymphocyte ratio are associated with END in patients with SSIs. The frequency and predictors for END differ depending on the location of the SSI.

Supplemental Digital Content is available in the text., Background and Purpose— In the United Kingdom, mechanical thrombectomy (MT) for acute ischemic stroke patients assessed beyond 6 hours from symptom onset will be commissioned up to 12 hours provided that advanced imaging (AdvImg) demonstrates salvageable brain tissue. While the accuracy of AdvImg differs across technologies, evidence is limited regarding the proportion of patients who would benefit from late MT. We compared the cost-effectiveness of 2 care pathways: (1) MT within and beyond 6 hours based on AdvImg selection versus (2) MT only within 6 hours based on conventional imaging selection. The impact of varying AdvImg accuracy and prior probability for acute ischemic stroke patients to benefit from late MT was assessed. Methods— A decision tree and a Markov trace were developed. A hypothetical United Kingdom cohort of suspected stroke patients aged 71 years with first event was modeled. Costs, health outcomes, and probabilities were obtained from the literature. Outcomes included costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Probabilistic sensitivity analyses were performed. Various scenarios with prior probabilities of 10%, 20%, and 30%, respectively, for acute ischemic stroke patients to benefit from late MT, and with perfect accuracy, 80% sensitivity, and 70% specificity of AdvImg were studied. Results— Incremental cost-effectiveness ratios resulting from our deterministic analyses varied from $8199 (£6164) to $49 515 (£37 229) per QALY gained. AdvImg accuracy impacted the incremental cost-effectiveness ratio only when its specificity decreased. Over lifetime horizons, all scenarios including late MT improved QALYs and LYs. Depending on the scenario, the probabilistic sensitivity analyses showed probabilities varying between 46% and 93% for the late MT pathway to be cost-effective at a willingness to pay threshold of $39 900 (£30 000) per QALY. Conclusions— Late MT based on AdvImg selection may be good value for money. However, additional data regarding the implementation of AdvImg and prior probability to benefit from late MT are needed before its cost-effectiveness can be fully assessed.

Objective: Hematoma enlargement (HE) occurs after spontaneous intracerebral hemorrhage (ICH) but no studies have evaluated the frequency of HE in first 1-2 h after symptom onset. We evaluated HE in the first 2h after onset using a mobile stroke unit (MSU). Methods: Patients with spontaneous ICH within 4.5h were evaluated on the Houston MSU between 5/2014 and 4/2020. Baseline CT scans from the MSU were compared with scans repeated within 1h [median 67min (IQR 57-82 min]. Significant HE was defined as >6 ml if baseline volume was 20 ml. Kruskal-Wallis and Wilcoxon rank sum tests evaluated differences in baseline volumes and HE. Intraclass correlation coefficient (ICC) evaluated agreement between two ICH measurement techniques (ABC/2 vs semi-automated). Results: 163 patients had baseline CTs, of whom 60 had repeat 1h CTs (table 1). There was no difference between baseline volume and time of CT from symptom onset {2h median (IQR) = 14 ml (6-28) vs. 16 ml (7-32) vs. 12 ml (4-24), P=0.42)}. There was also no correlation between time from onset and difference in volume between baseline and 1 h repeat imaging. However, 9/60 patients had significant HE from baseline to 1 h repeat imaging; all of these occurred in patients initially imaged within 2 h of onset (6/24 within 1h, 3/20 within 1-2h) (P=0.03) (figure 1). High reliability was seen between the two methods measuring volumes (ICC = 0.84). Conclusion: Significant HE in the next hour occurs in 25% of ICH patients imaged within the first hour after symptom onset, and 17% imaged between 1-2 hours of onset. These patients would be a target for ultra-early hemostatic intervention.

Purpose: To compare physicians’ ability to read Alberta Stroke Program Early CT Score (ASPECTS) in patients with a large vessel occlusion within 6 hours of symptom onset when assisted by a machine learning-based automatic software tool, RAPID ASPECTS, compared with their unassisted score. Materials and Methods: 50 baseline CT scans selected from two prior studies (CRISP and GAMES-RP) were read by 3 experienced neuroradiologists who were provided access to a follow-up MRI. The average ASPECT score of these reads was used as the reference standard. Two additional neuroradiologists and 6 non-neuroradiologist readers then read the scans both with and without assistance from the RAPID ASPECTS software and reader improvement was determined. The primary hypothesis was that the agreement between typical readers and the consensus of 3 expert neuroradiologists would be improved with RAPID-assisted vs. unassisted reads. Agreement was based on the percentage of the individual ASPECT regions (50 cases, 10 regions each; N=500) where agreement was achieved. Results: Typical non-neuroradiologist readers agreed with the expert consensus read in 72% of the 500 ASPECTS regions, evaluated without software assistance. The automated software alone agreed in 77%. When the typical readers read the scan in conjunction with the software, agreement improved to 78% (P Conclusion: Typical readers had statistically significant improvement in their scoring of scans when the scan was read in conjunction with the automated RAPID ASPECTS software, achieving agreement rates that were comparable to neuroradiologists.

Introduction: Recent trials have proven safety and efficacy of mechanical thrombectomy for patients presenting with emergent large vessel occlusion beyond 6 hours of symptom onset. While evidence supports using baseline CT scan to evaluate the candidacy for mechanical thrombectomy for patients presenting in the early window, late window trials have used advanced imaging such as CT and MR perfusion. We aim to assess outcomes of MT stratified by admission Alberta Stroke Program Early CT Score (ASPECTS). Methods: We used data from the prospectively maintained registries of 28 stroke centers in the Stroke Thrombectomy and Aneurysm (STAR) collaboration. Demographics, comorbidities, LVO site, ASPECTS, MT technique, radiographic and clinical outcome data were collected. Patients with M1 or ICA occlusion were included in these analyses. Multivariable analysis was performed using a generalized linear model with logit link to assess for variables associated with favorable outcomes. Results: 3356 patients in the STAR database were reviewed and 347 (10.3%) of those underwent MT in the late window (table). Median age was 69, 189 (54.5%) were female, and 181 (52.2%) were white. 295 patients ASPECTS ≥6. In this group, 200 (68.8%) had M1 occlusion, and the remaining had ICA occlusion. Aspiration thrombectomy was used in 139 (47.1%) of patients. Successful reperfusion was achieved (mTICI≥2b) in 264 (76.1%). sICH was observed in 15 (5.1%). Excellent functional outcome (mRS 0-2) was observed in 124 (42%) patients. ASPECTS score was independently associated with favorable outcomes (aOR 1.2, 95% CI 1.1-1.4, P=0.006). Conclusion: Excellent outcomes are observed in patients with good ASPECT score presenting in the late window irrespective of perfusion criteria. Admission CT scan could be used to triage patients presenting with emergent large vessel occlusion beyond 6 hours of symptom onset.

Background and Purpose— Multiple studies have shown the 90-day risk of stroke following an emergency department (ED) diagnosis of transient ischemic attack (TIA) or minor stroke is significant, with the greatest risk of recurrence being within the first 24 to 48 hours following initial symptom onset. This study explored regional differences in ED disposition, neuroimaging, and subsequent 90-day stroke risk of patients diagnosed with TIA or minor stroke in Alberta. Methods— We used administrative databases to identify ED visits, neuroimaging, and 90-day return visits for TIA or minor stroke in Alberta from April 2011 to March 2016 among adults ≥20 years of age and stratified them based on regions of presentation (Edmonton, Calgary, or nonmajor urban). Results— During the 5-year study period, 22 421 patients had index ED visits for TIA or minor stroke. All 3 regions had a similar number of ED visits for TIA/minor stroke; however, on index ED visit, Calgary had a higher proportion of computed tomographic angiography imaging (48.8%; P P P =0.002). Conclusions— This study demonstrates regional variation in computed tomographic angiography for neurovascular imaging of patients presenting to the ED for TIA/minor stroke and a possible association with frequency of index visit admission and 90-day readmission for the same problem.

Background and Purpose— MRproANP (midregional proatrial natriuretic peptide) is known to be independently associated with cardioembolic stroke cause and to improve risk stratification for 90-day mortality when measured within 24 to 72 hours after symptom onset in patients with acute ischemic stroke. However, the optimal time point for assessment remains unclear. This study aimed to evaluate prognostic utility of MRproANP at different time points during the first 5 days of hospitalization in patients with acute ischemic stroke. Methods— Samples of MRproANP were collected on admission ( Results— MRproANP levels modestly decease over the initial 5 days but remain highly predictive for cardioembolic stroke cause (odds ratio, 9.75 [95% CI, 3.2–29]; 10.62 [95% CI, 3.4–33.3]; 10.8 [95% CI, 3.1–37.1]; 19.4 [95% CI, 5.49–68.7] on admission, day 1, 3 and 5) and 90-day mortality (odds ratio, 59.4 [95% CI, 7.4–480.7]; 78.3 [95% CI, 7.9–772.6]; 14.5 [95% CI, 1.4–145]; 19.81 [95% CI, 2.7–143.4] on admission, day 1, 3, and 5). Change over time does not significantly modify the prognostic value of MRproANP ( P =0.65 and P =0.56 for the interaction term in the multivariate model). Conclusions— Independent prognostic value of MRproANP remains unaltered in the acute phase of stroke at least up to 5 days; repeated measurements do not improve the prognostic value.

Introduction: Recently, two randomized controlled trials proved the safety and efficacy of mechanical thrombectomy in patients presenting up to 24 hours from symptom onset. While the number of patients receiving mechanical thrombectomy has increased following the publication of the extended time window trials, the literature on acute stroke calls over telestroke is relatively scant. In this study we evaluate the volume of telestroke calls, rate of transfers to the thrombectomy center and MT receipt before and after the extended window MT trials publication. Methods: We interrogated the prospectively collected data from a major telestroke network in Southeast the United States to include patients who received a telestroke consult between January 2015 and July 2019. We compared the demographical and clinical characteristics and the outcomes between patients who presented before and after the publication of the extended window mechanical thrombectomy trials. Results: Total of 7,438 patients were evaluated during the study period. Of those, 3392 were after February 2018. There was no difference in age, race, or sex between the two groups (table 1). Patients in the post extended window group had lower National Institute of Health stroke scale (NIHSS) on presentation (3 vs. 4, P Conclusion: The number of telestroke consults almost doubled since the publication of the extended thrombectomy trials without increase in the rate of MT receipt. These findings have important operational implications for hospitals implementing telestroke call coverage.

Introduction: Recent trials have demonstrated the benefit of endovascular therapy (EVT) beyond 6 hours of symptom onset. However, the importance of time to reperfusion (TTR) in the extended time window has recently been questioned. Given the variability of infarct growth rate (IGR), the time delay until reperfusion may have greater consequences for those with rapidly progressing infarcts, and identifying such patients is essential for improving outcomes. We tested the hypothesis that TTR is more closely associated with functional outcome in patients with rapidly progressing infarcts compared to their slow-progressing counterparts. Methods: We retrospectively identified 106 patients at our center’s prospectively collected stroke database with anterior circulation large-vessel occlusion stroke and known time of symptom onset. Patients underwent initial CT perfusion imaging (CTP), EVT and and follow-up MRI at 24 hours. Core infarct volumes at presentation (CBF Results: 35 fast progressors (age 71±14, 17 F, TTR 288±91 minutes, mean IGR 21±24 mL/hour) and 71 slow progressors (age 71±17, 48 F, TTR 374±211 minutes, mean IGR 1.0±1.5 mL/hour) were identified. Fast progressors had higher admission NIHSS scores (18±6 vs 13±7, p Conclusions: In patients with rapidly progressing infarcts (≥5 mL/hour), TTR was associated with worse functional outcomes at 90 days compared to slow progressors. Identifying such patients may be critical for appropriate triage and rapid delivery of acute stroke care.

Study Objectives: Tissue plasminogen activator (tPA) may improve ischemic stroke outcomes if administered soon after symptom onset. A computed tomography (CT) scan is required to exclude hemorrhagic stroke. The purpose of this study was to evaluate the feasibility of using an experimental, non-invasive, point-of-care electroencephalography (EEG)-based platform to identify hemorrhage in suspected stroke subjects presenting to the emergency department (ED). Methods: During a study that took place between May 2018 and July 2019, a sensor was added to the EEG-based platform that was hypothesized could differentiate between hemorrhagic and ischemic stroke. Eligible subjects presented within 24 hours of symptom onset and had a National Institute of Health Stroke Score (NIHSS) greater than 1. The performance of an artificial intelligence (AI) algorithm was assessed using five-fold cross validation. Results: Starting in December 2018, 88 subjects were enrolled with the additional sensor. The median (IQR) age was 68 (56 - 78), 56 subjects (64%) were male, and the distribution in terms of ethnicity was 44% white, 38% African American, and 18% non-black latino. There were 14 (16%) intracerebral hemorrhages (ICH) and 52 (59%) ischemic strokes. Median (IQR) time last known well time was 430 (193 - 574) minutes. Performance is shown in Table 1. Conclusion: Preliminary results from a small sample are encouraging. More hemorrhagic stroke patients are expected to improve performance.

Background: The RESILIENT randomized trial of endovascular therapy for anterior circulation stroke within 8 hours of symptom onset excluded subjects with poor collaterals. We analyzed the relationship of CTA collateral grade with respect to subsequent infarct growth over 24 hours, with and without revascularization. Methods: The independent RESILIENT imaging and angiography core lab scored baseline CTA Tan collateral grade (0-3) and CT ASPECTS scores at baseline and 24 hours in both arms. ASITN collateral grade (0-4) was adjudicated prior to revascularization in the interventional arm. Descriptive statistics, univariate, multivariate and ANOVA related CTA collateral grade with 24-hour infarct growth. Results: 210/221 (95%) subjects (median age 67 (53-76) years; 48% women) in RESILIENT had baseline single-phase CTA available to the core lab evaluation. CTA collateral grade was complete (grade 3) in 106 (50.5%), grade 2 (50-99%) in 68 (32.4%), grade 1 (1-49%) in 36 (17.1%), with no collaterals in 0. The extent of collaterals was more robust in the medical arm (55.0% grade 3, 31.4% grade 2, 13.3% grade 1) compared to the interventional arm (45.7% grade 3, 33.3% grade 2, 21.0% grade 1), although this finding was not statistically significant (p=0.11). In the interventional arm, the extent of CTA collaterals had a strong correlation with ASITN grade (ρ=0.59, p Conclusions: In RESILIENT, CTA collateral grade was linked with higher ASPECTS and less infarct growth over 24 hours. Despite more robust collaterals in the medical arm, greater infarct growth occurred without revascularization or endovascular therapy.

Background: Recent endovascular treatment (EVT) trials suggest the presence of target mismatch profiles up until 24 hours after stroke symptom onset. We aim to a) demonstrate the presence of target mismatch in patients presenting beyond these recent time thresholds and b) potential benefit with EVT in these patients. Methods: Between 01/2012 and 12/2018, patients with AIS with ICA or MCA occlusion and baseline NIHSS score ≥6 arriving ≥16 hours from last known well were identified. CT or MR perfusion images at presentation were evaluated using RAPID software; ischemic core was defined as rCBF Results: Of 154 patients [55% male, mean age 70 ± 13 years, median baseline NIHSS 13 [IQR 8 - 18], 76 (49%) had unwitnessed onset. Median last known well to arrival in hospital time was 42.2 [22.8 - 76.9]. CTP or MR perfusion were obtained in 115 (75%). Median ischemic core volume i.e., 11.0 ml [iqr 0 - 40 ml], and penumbra volume (Tmax >6 s) i.e., 57 ml [16 - 133 ml] and a median mismatch ratio 4.0 [iqr 0.9 - 18.0] were noted. When inclusion criteria of the following trials, namely, ESCAPE, DAWN and DEFUSE3 trial were applied, DAWN-eligible patients were n=45 (29%), DEFUSE3 n= 61 (40%) and ESCAPE n=59 (43%). Figure 1a shows trial eligibility by time from last known well. 24 (16%) patients had EVT. EVT was associated with better functional recovery at 3 months (Figure 1b) for 90-day mRS 0-2 (adjusted OR [95% CI], 8.11 [2.49 - 30.44]) and 90-day mRS shift (common adjusted OR 5.50 [2.33 - 13.29]). Treatment effect with EVT was seen from 16 to 240 hours since last known well (Figure 1c). Parenchymal Hemorrhage type 2 was seen in 13 % offered EVT vs. 3% (adjusted OR 4.11 [0.73 - 21.72]). Conclusions: Patients with anterior circulation LVO presenting very late, even days from last known well, may potentially benefit from EVT.

Introduction: Recent data suggests stenting of symptomatic intracranial atherosclerotic disease (ICAD) in the hyper-acute period (< 8 days of symptom onset) is associated with a high incidence of early postoperative morbidity and mortality. We assessed the efficacy and safety of this select group of patients at our institutions. Methods: Between December 2017 to May 2019, anterior circulation stroke patients who underwent acute stenting of symptomatic intracranial atherosclerotic disease with the Atlas stent (Stryker) were identified from a prospectively maintained database of stroke patients at two comprehensive stroke centres. Baseline characteristics, imaging, and clinical outcomes are reported. Results: Nine cases were identified (mean age 71years, 44.4% male, median NIHSS 9 (range 5-18)). All patients had baseline mRS of 3 or less. Median time from symptom onset to groin puncture was 10hours (range 4-96hours). All patients received dual-antiplatelet therapy with Aspirin and Prasugrel(DAPT) either immediately before or after the procedure. In patients who did not receive pre-procedure loading with DAPT (55.6%), a single intravenous dose of Abciximab (mean 9mg +/- 4mg) or Tirofiban (1mg) was given intra-operatively. No thromboembolic complications or mortality occurred in the early postoperative period (within 72hours). All patients showed improvement in target vessel perfusion on day-one CT-perfusion. At 90-days, 7 (77.8%) patients were either functionally independent (mRS 0-2) or at their pre-operative baseline. No symptomatic intracranial haemorrhage occurred. No recurrent target vessel strokes were recorded. One patient died of medical complications unrelated to intracranial stenting and one patient was mRS 3 at 90-days. Conclusion: Hyper-acute stenting of symptomatic ICAD may be safe and effective. Antiplatelet treatment strategies and advances in stent devices may be critical in the success of this approach.

Background and Purpose: Efficacy of mechanical thrombectomy for acute cerebral large vessel occlusion depends on time from symptom onset to reperfusion. While time to treatment in hospital has been optimized in these days, it is not well-known about improving time in pre-hospital when suspected stroke. We sought to analyze time from emergency medical services (EMS) dispatch to arterial puncture in stroke patients eligible for mechanical thrombectomy. Methods: We analyzed time components from EMS dispatch to puncture in patients with acute large vessel occlusion within 6 hours from onset treated with mechanical thrombectomy between April 2015 and December 2018. We assessed the associated factors with each time component and patient outcomes. Results: Consecutive 195 patients were included in this analysis. The median EMS dispatch-to-scene, on-scene, transport, door-to-puncture (DTP), and scene-to-puncture (STP) times were 4, 16, 12, 40, and 70 minutes, respectively. Percentage of favorable outcomes were significantly higher in patients with STP within 60 minutes (57.5% vs 35.8%, p Conclusions: Reducing time in pre-hospital and in-hospital interact with each other. Education program and use of direct call from EMS contributed to reducing these times.

Background and Purpose— Knowledge on a natural history of untreated ruptured intracranial aneurysms is based on a small historical cohort from 1960s. We calculated mortality rates for patients with untreated ruptured intracranial aneurysms using a more recent and relatively large hospital cohort. Methods— Patients admitted to the study hospital between 1968 and 2007 with saccular but untreated ruptured intracranial aneurysms were identified from the hospital aneurysm registry of 6850 patients. The study cohort included only patients who were followed up until death and for whom the date of symptom onset and the date of hospital admission were available. Results— For 510 patients identified, the median survival time from symptom onset to death was 20 days. The 1-year mortality rate was 65%, but varied substantially by admission delays and clinical status on admission, being lowest (13%) for patients admitted later than a month after symptom onset and highest (89%) for poor-grade patients. The 1-year mortality rate was 75% for good-grade patients admitted within a week. Conclusions— Mortality rates for patients with untreated ruptured intracranial aneurysms are even worse than presented in the historical study. When discussing with subarachnoid hemorrhage patients and their relatives about treatment options, the presented natural history figures are of use.

Background and Purpose— There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods— Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results— Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49–0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50–0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, −0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, −0.08 to 0.78]). Conclusions— Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.

Background and Purpose— With the lack of confirmatory examinations, the distinction of a transient ischemic attack (TIA) from various TIA-mimicking diseases is difficult, particularly in diffusion-weighted imaging (DWI)-negative TIAs. In this study, we aimed to evaluate the relationship between arterial spin labeling (ASL) perfusion defects and early ischemic recurrence (FU-DWI [+]) in patients with DWI-negative TIAs. Methods— We assessed consecutive patients with a DWI-negative TIA within 24 hours of symptom onset, who underwent both ASL images and follow-up magnetic resonance imaging during the acute period. As markers of the ASL images, we evaluated the ASL perfusion defects in each hemisphere. Arterial transit artifact (ATA) and intraarterial high-intensity signal (IAS) were also rated as markers of collateral status and blood stagnation due to large vessel occlusion, respectively. Results— Among the 136 patients with a DWI-negative TIA, 33 patients had FU-DWI (+) lesions in 36 hemispheres. In the multivariable analysis, ASL defects remained an independent predictor of FU-DWI (+) (adjusted odds ratio, 13.94 [95% CI, 5.77–33.70], P P Conclusions— We demonstrated that ASL perfusion defects were associated with ipsilateral FU-DWI (+) in patients with a DWI-negative TIA. Furthermore, this association was enhanced with IASs and attenuated with ATAs.

Background and Purpose— NEUROSQUAD (Stroke Treatment: Quality and Efficacy in Different Referral Systems) is a prospective, observational, bi-center study comparing 3 triage pathways in endovascular stroke treatment: mothership (MS), drip and ship (DS) and transferring a neurointerventionalist to a remote hospital for thrombectomy (drive the doctor [DD]). Methods— Between February and October 2018, all stroke patients undergoing thrombectomy at 2 university hospitals and 2 associated remote hospitals were included. Primary outcome measures were time from onset to groin puncture and time from imaging to groin puncture. Secondary outcome measures were time from onset to imaging and time from onset to thrombolysis. Results— In total, 440 patients were included (mothership 32.3%, DS 55.9%, DD 11.8%). Median time from onset to groin puncture (168 minutes) and time from imaging to groin puncture (51 minutes) were the shortest in the mothership group. Time from onset to groin puncture (DD median 225 versus DS median 300 minutes; P =0.001) and time from imaging to groin puncture (DD median 118 versus DS median 172 minutes; P P =0.363). In patients receiving thrombolysis, time from onset to needle was similar among the groups ( P =0.620). Conclusions— The NEUROSQUAD study adds evidence that DD may be a feasible alternative to DS, leading to shorter delay between symptom onset and groin puncture. Both are time-wise inferior compared with mothership, though.

Introduction: The DAWN and DEFUSE 3 studies established thrombectomy as standard care for patients with emergent large vessel occlusions (ELVO) presenting 6-24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3 we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN. Methods: Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 Non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large (CTL), NIHSS 6-9 and mRS 2. Subgroups were compared to the DEFUSE 3 Non-Dawn and entire DEFUSE 3 cohorts. Results: There were 71 DEFUSE 3 Non-DAWN patients; 31 patients with NIHSS 6-9, 33 with CTL, and 13 with pre-morbid mRS 2 (some patients met multiple criteria). For CTL patients, median 24-hour infarct volume was 119ml (IQR 74.6-180) versus 31.5ml (IQR 17.6-64.3) for Core Not Too Large (CNTL) patients, p= Conclusions: Patients with pretreatment core infarct volumes

Background: The efficacy and safety of endovascular treatment for proximal large vessel occlusion after 6 hours of symptom onset have recently been studied in randomized controlled trials. We performed this meta-analysis to identify the combined effect of endovascular treatment on various outcomes in this patient population. Methods: We performed this meta-analysis of all available randomized controlled clinical studies that involved the use of endovascular treatment in after 6 hours of symptom onset. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) of 0 (no symptoms), 1 (no significant disability), or 2 (slight disability) at 90 days post-randomization. Other outcome variables included symptomatic intracerebral hemorrhage, excellent outcome (mRS 0-1), and mortality at 90 days post-randomization. Results: Three trials were identified that included 447 patients. The proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to endovascular treatment compared with best medical treatment (445 subjects analyzed; OR 4.34; 95% CI, 2.65-7.14; P < .001). Excellent outcome was also significantly greater among those randomized to endovascular treatment (445 subjects analyzed; odds ratio, 3.29; 95% CI, 1.98-5.46, P < .001). Risk of symptomatic intracranial hemorrhage and mortality were similar between endovascular treatment and best medical treatment with p-value of 0.320 and 0.375, respectively. No risk of heterogeneity was observed in any of outcome variables. Conclusion: We found a prominent benefit (4 times higher odds) with endovascular treatment in appropriately selected patients with large vessel occlusion ischemic stroke presenting after 6 hours of symptom onset

Background: Recent data have demonstrated robust efficacy for endovascular thrombectomy in acute large vessel occlusion (LVO) up to 24h after symptom onset. Given the overwhelming benefit of this intervention in a highly selective, clinical trial population, it is plausible that a benefit may also be observed in some trial-ineligible patients. Methods: Using the BEST multi-center prospective cohort of consecutive patients who underwent thrombectomy for LVO, we compared DAWN and DEFUSE 3 trial-ineligible patients treated within 6-24 hours after last known normal (LKN) to trial-eligible patients, and to untreated controls from those trials. The co-primary outcomes were an early therapeutic response (decrease in NIHSS ≥10, or NIHSS 0-1 by 24h) and good functional outcome (90-day mRS 0-2). Secondary outcomes included change in NIHSS at 24h, intracerebral hemorrhage within 72h, and discharge to home or acute rehab. Results: Of 443 patients in the BEST cohort, 159 (36%) underwent endovascular therapy between 6-24 hours after LKN, of whom 71 (45%) were trial-ineligible. The most common trial exclusion criteria were M2 (53%) and multivessel occlusions (30%). Compared to trial-eligible patients, trial-ineligible patients were younger (median 63 vs. 72y, p=0.02) but had similar baseline NIHSS (median 14 vs. 15, p=0.28), ASPECTS scores (median 8 v. 8, p=0.69), times to recanalization (median 627 vs. 682 min, p=0.08), and rates of successful recanalization (TICI 2b/3, 83% v. 86%, p=0.57). Compared to DAWN untreated controls, BEST trial-ineligible patients were more likely to have an early therapeutic response (OR 2.02, 95%CI 1.00-4.06, p=0.049) and good functional outcome (OR 3.02, 95%CI 1.33-6.86, p=0.001). Compared to trial-eligible patients in BEST, trial-ineligible patients had similar improvements in 24h NIHSS (-2 vs. -4, p=0.33), rates of intracerebral hemorrhage (28% vs. 24%, p=0.54), and rates of discharge to home or rehab (77% vs. 73%, p=0.49). Conclusion: This multicenter prospective cohort demonstrates that thrombectomy for acute LVO within 24 hours in DAWN and DEFUSE 3 trial-ineligible patients is safe and may be effective. Treating these patients may be reasonable but our findings should be confirmed by additional randomized data trials.

Background: Recent extended window (EW) trials support the benefit of mechanical thrombectomy (MT) in anterior circulation emergent large vessel occlusions (ELVO). However, only up to 1.7% of consecutive acute ischemic strokes (AIS) were eligible for EW-MT using clinical trial selection criteria. We examined eligibility and outcomes of EW-MT in consecutive ELVOs using pragmatic selection criteria. Methods: We prospectively evaluated consecutive patients presenting between 6-24 hours that underwent MT using selection criteria consisting of only non-contrast CT (ASPECTS > 6), CTA occlusion + good collateral scores (JNIS 2016;8:559-562). Effectiveness outcomes included TICI 2b-3 and 3-month modified Rankin Scores (mRS); safety outcomes included in-hospital mortality and symptomatic intracerebral hemorrhage (sICH). Results: 767 consecutive AIS patients presented within 6-24 hour window, and of these 48 (6%) anterior circulation ELVOs underwent MT (mean age 63±17 years; 56% men; median NIHSS 16 [IQR 10-19]; median groin puncture to recanalization 53 minutes [IQR 41-85]). Median ASPECTS was 9 (IQR 8-10), and 79% (n=38) of patients had good CTA collateral grade. Occlusions were primarily M1 MCA (46%), with 29% tandem occlusions. Successful recanalization (mTICI 2b or 3) was achieved in 73% (n=35), while 6% (n=3) of patients developed sICH. In-hospital mortality was 25% (n=12), however 40% (n=19) achieved 3-month mRS 0-2. Conclusions: The use of standard of care CT/CTA yields an acceptable rate of MT eligibility, allowing a group of patients facing likely death or severe disability to obtain reasonable safety and effectiveness outcomes.

Background: Shorter time from symptom onset to thrombectomy is associated with better stroke patient outcomes. Despite this urgency, stroke patients transferred from PSC to CSCs experience treatment delays of 1-2 hours. Objective: We aimed to reduce door-in-door-out (DIDO) times at a spoke PSC serviced by a telestroke CSC hub using failure mode, effects, and criticality analysis (FMECA) of the current state process of care, implementation of an improved workflow, and deployment of a HIPAA-compliant real-time communication technology to all service providers (including transport EMS). Methods: Process mapping and FMECA was used to identify and rank delays and opportunities for reducing DIDO times. Multidisciplinary teams involved in acute stroke patient evaluation, transfer, and treatment participated in moderated sessions at both the PSC and CSC. Resulting process maps were used to streamline processes of care as well as identify opportunity for implementing a real-time communication technology (Pulsara™). A streamlined workflow was adopted which included early simultaneous activation of transferring EMS with telestroke neurology, direct to CT care, standardized documentation handoff, and real-time communication between CSC stroke neurologists and spoke hospital nursing, pharmacy, and transferring EMS. DIDO was measured prospectively after implementation and compared to the previous year’s data. Results: Process mapping identified 6 issues impacting DIDO time: delay in symptom identification and stroke code activation, delay in door to CT time, delay in EMS handoff, delay in requesting transfer ambulance, delays in contacting multiple providers at CSC hub, and redundant communication between providers. Ten key changes were proposed and implemented. Prior to implementation, 28 stroke patients with an average DIDO of 269m (SD 112m) were transferred. To date following implementation, 7 patients were transferred with an average DIDO of 104m (SD 25m). Only 4% of patients had DIDO Conclusions: Rigorous analysis of the transfer process and implementation of process improvements can reduce DIDO times for acute stroke patients in a hub-spoke telestroke system.

Background and Purpose— Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. Methods— We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. Results— Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245–435]) and 120 minutes longer in group C (350 minutes [284–408]) compared with group A (230 minutes [160–407]; P Conclusions— Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.

Background and Purpose— Prehospital stroke code activations help reducing workflow times during in-hospital triage. We aim to identify predictors of endovascular treatment (EVT) among stroke codes (SC) activated within 6 hours from symptom onset. Methods— CICAT (Codi Ictus Catalunya) is a prospective official mandatory registry of all SC in Catalunya. We studied all CICAT entries from 6 comprehensive stroke centers for 18 months. We recorded demographic, clinical, and imaging variables on admission. We explored the relationship between these variables and EVT Results— From 3944 SC, 2778 (70.4%) were admitted within 6 hours from symptom onset. Mean age was 72±15.3 years, median Rapid Arterial Occlusion Evaluation scale score 4 (interquartile range [IQR], 2–6), median onset-to-door time 89 minutes (IQR, 54–158), median National Institutes of Health Stroke Scale score 9 (IQR, 4–18), median Alberta Stroke Program Early CT Score 10 (IQR, 8–10). Final diagnosis was ischemic stroke in 1762 patients (63.4%), hemorrhagic stroke in 359 (13.0%), transient ischemic attack in 164 (5.9%), and stroke-mimic in 493 (17.7%). A large vessel occlusion was confirmed in 720 (25.6%) patients. Of all SC, 16% (n=444) received EVT, with a median door-to-groin time of 77 minutes (IQR, 55–102). Baseline variables associated with EVT were premorbid modified Rankin Scale score P 4 ( P =0.003), and National Institutes of Health Stroke Scale on admission >8 ( P P 90% along time (0–3 hours, 95.1% versus 3–6 hours, 94.0%; P =0.25) and did not decrease over time. The chances to receive EVT and the presence of large vessel occlusion decreased over time. However, the rate of EVT was not different between patients admitted 0 to 3 hours (26.1%) and those admitted 3 to 6 hours (22.9%; P =0.2). Conclusions— Among SC within 6 hours from symptom onset, National Institutes of Health Stroke Scale on admission was the only factor independently associated with EVT. Only 5% of these patients show an Alberta Stroke Program Early CT Score

Background: The AHA/ASA guideline recommends endovascular therapy for patients with acute ischemic stroke within 6 hours from symptom onset. Identification of the patients most likely to benefit (and those most likely to be harmed) from reperfusion plays a pivotal role in decision-making. We applied the MR PREDICTS tool (clinical decision making tool derived from MR CLEAN clinical trial) on a real-world sample of patients with acute ischemic stroke to assess its utility in predicting clinical benefit from endovascular therapy. Methods: We identified all patients with acute ischemic stroke with occlusion of the distal internal carotid artery, proximal M1, or M2 segment of the middle cerebral artery who underwent endovascular reperfusion procedure (thrombectomy and/or intra-arterial thrombolysis) from July 2016 to June 2017. Patients were divided into two groups; those with a good outcome (90 Day mRS 0-2) and those with a poor outcome (90 Day mRS 3-6). The MR PREDICTS tool was used to determine absolute treatment benefit for each patient. This predicted outcome was compared to actual patient outcome. Results: A total of 22 patients were identified. Eight patients had a good outcome and 14 patients had a poor outcome. The calculated absolute treatment benefit from endovascular therapy using the MR PREDICTS tool was consistently higher among patients in the good outcome group, with an average absolute treatment benefit of 12% greater among these patients compared to those in the poor outcome cohort (19% versus 7%). Of note, patients with a poor outcome had a higher rate of prior stroke, higher baseline NIHSS, longer symptom onset to groin puncture time, less favorable collaterals and lower rate of successful recanalization defined as TICI 2b or 3 (100% versus 64%). Conclusion: There is a strong correlation between predicted treatment benefit by MR PREDICTS tool and actual patient outcomes which supports broader use of this tool during the decision-making process for endovascular therapy in patients with acute ischemic stroke.

Introduction: Data are scarce regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset, termed the “golden hour” (GH) window. We present systematic review and meta-analysis of outcomes between AIS patients treated within (+) and outside (-) the GH. Methods: We performed a systematic review in MEDLINE and SCOPUS databases for observational studies providing unadjusted rates or adjusted odds ratios (OR) for the following outcomes: symptomatic intracranial hemorrhage (sICH), mortality and favourable functional outcome (FFO), defined as mRS-scores of 0-1. Results: We identified 3 eligible studies (range of median NIHSS-scores: 10-11 points), including a total of 72,662 IVT-treated patients (1.5% treated within the GH. GH(+) patients had higher FFO rates (42%, 95%CI:35%-48%) compared to GH(-) patients (31%, 95%CI:30%-31%). In adjusted analyses, IVT within the GH was associated with a two-fold increase in the odds of FFO (OR=2.02, 95%CI: 1.55-2.63, p2 =0, p for Cochran Q=0.93; Figure). No significant differences on the risk of both sICH (OR=0.77, 95%CI: 0.53-1.13, p=0.180; I 2 =0, p for Cochran Q=0.63) and mortality (OR=0.61, 95%CI: 0.29-1.28, p=0.190; I 2 =72, p for Cochran Q=0.03) were documented between the two groups in adjusted analyses. Conclusions: AIS treated within the GH have substantially higher odds of FFO compared to IVT administered later during conventional time window independent of potential confounders. Improvement of care systems to achieve the earliest onset to treatment times should remain the goal of the front line stroke treatment.

Introduction: Prehospital stroke code activations help reducing wokflow times during in-hospital triage. We aim to identify predictors of endovascular treatment among activated stroke codes (ASC) within 6 hours from symptom onset. Methods: CICAT is a prospective official mandatory registry of all ASC in Catalunya. We studied all CICAT entries from 5 comprehensive stroke centers during 18 months. We recorded demographic, historic, clinical and imaging variables on admission. We explored the relationship between these variables and endovascular treatment (EVT) Results: From 3944 ASC, 2818 (71.5%) were admitted < 6 hours from symptom onset. Mean age was 72±15.3 years, median RACE scale 4 (IQR 2-6), median onset-to-door time (OTDT) was 87 minutes (IQR 54-158), median NIHSS score 9 (IQR 4-18), median ASPECTS 10 (IQR 8-10. Final diagnosis was ischemic stroke in 1767 patients (62.7%), hemorrhagic stroke in 364 (12.9%), TIA in 167 (5.9%), stroke-mimic in 500 (17.7%). After admision a large vessel occlusion (LVO) was confirmed in 916 (23.2%) patients. While the rate of ASPECTS ≥ 9 among ischemic strokes progressively decreased over time (0-3h: 73.2% vs 3-6h: 57.1%: p2 (p4 (p=0.003) and NIHSSon admission >8 (p4 had 26.0% probability to receive EVT Conclusion: Among ACS within 6 hours from symptom onset, time from onset to arrival is not associated with the probability of receiving EVT. Only 5% of these patients show an ASPECTS

Purpose: We hypothesized that two-phase (the arterial phase and the phase between the peak and late venous phases) CTA may work comparably with 3-phase CTA, and sought to compare a simulated 3-phase CTA with a simulated 2-phase CTA for assessment of collaterals. Methods: We enrolled 155 patients (76 male; median, 72 years) who underwent 9.6-cm, 70-kVp perfusion CT (PCT) for 60 seconds within 8 hours after symptom onset and had occlusion in the ICA (ICA with/without M1; n=63) or M1 segment (with/without M2 segment; n=92). PCT data were reconstructed with a section width of 1 mm, and were used to create the simulated 3-phase CTA (3-CTA; peak arterial, peak venous, and late venous phase; 3 seconds each) with an increment of 4.5 seconds. Another 3-second CTA immediately after peak venous phase was additionally generated, which consisted of the second CTA of the simulated 2-phase CTA (2-CTA) with the peak arterial CTA. Each CTA was reconstructed into 25-mm axial maximum intensity projections, and was assessed by 2 independent reviewers at a separate session. For the 2-CTA, good collaterals were determined when the ipsilateral side showed both similar vascular filling and enhancement (ASPECT>7) compared to the contralateral brain on the peak arterial CTA. For the 3-CTA, we followed the published criteria to determine good/poor collaterals. Results: Interobserver agreements were excellent (k=0.931 for 3-CTA; k=0.929 for 2-CTA). Consensus review determined good and poor collaterals in 97 and 58 patients, respectively, on 3-CTA. All 97 patients with good collaterals on 3-CTA showed good collaterals on 2-CTA; 2 out of 58 patients with poor collaterals on 3-CTA were determined to have good collaterals on 2-CTA, showing no significant difference (P=0.5, McNemar test). Conclusion: Compared to the simulated 3-phase CTA, the simulated 2-phase CTA has comparable diagnostic performance for determining the status of collateral circulation.

Background: Most studies recruiting patients with acute ischemic stroke ascertain the final functional status at 3 months post symptom onset. The rates and predictors of late functional improvement (>3 months) in acute ischemic stroke patients has not been systemically studied. Methods: We analyzed data from three phase-III randomized multicenter clinical trials that recruited acute ischemic stroke patients within 3 or within 5 hours of symptoms onset. Late improvement was defined by an improvement of 1 or more grade in modified Rankin scale between ascertainments performed at 3 and 12 months post randomization. We analyzed the rates of late improvement in three groups of patients; patients treated with IV (recombinant tissue plasminogen activator [rt-PA], those treated with endovascular treatment, and those not treated with any acute reperfusion treatment. Multivariate analysis was performed to identify predictors’ of late functional improvement. Results: A total of 2555 patients (mean age ± SD; 66.4 ± 12.9 years) with acute ischemic stroke were analyzed.Late functional improvement was observed in 447 (17.5%, 95% confidence interval [CI] 15.9 to 19.2]) of 2555 patients analyzed. The rates of late functional improvement according to acute reperfusion treatment were as follows: 248 (22.4%) of 1106 in IV rt-PA treated; 108 (23.9%) of 452 in endovascular treated; and 91 (19.1%) of 477 in patients without any treatment (p= 0.179). In multivariate analysis, patients with age ≥65 years (odds ratio [OR], 0.53; 95 % CI 0.35 to 0.80; P = 0.002), and severity of baseline neurological deficits with National Institutes of Health Stroke Scale [NIHSS] score at 24 hours ≥ 20 (OR, 0.40; 95 % CI, 0.28 to 0.58; P = Conclusions: Late functional improvement occurs in one fourth of acute ischemic stroke patients and should be considered in estimation of functional recovery in future clinical studies.

Introduction: Endovascular therapy(EVT) is proven effective for patients with acute ischemic stroke with proximal vessel occlusion, treated within 6 hours since symptom onset. However, up to 30% of stroke patients wake up with their symptoms (“wake-up stroke” (WUS)) or have an unknown time of onset. Canadian guidelines suggest that EVT may also be effective up to 12 hours after onset and yet-to-be published data from the DAWN trial also suggest a strong benefit of EVT for these patients if selected by perfusion imaging. We aimed to examine the real-world effectiveness of EVT in late-presenting stroke patients selected for EVT with a simple non-contrast CT (NCCT) and simple phase CT angiogram (CTA). Methods: We analyzed a prospectively collected registry of epidemiological, clinical and imaging data of patients treated for acute ischemic stroke ≥6 hours since symptom onset or WUS in a tertiary stroke center (Hôpital Notre-Dame, Montréal) between 2016 and 2017. Eligibility for EVT was based on a combination of disabling neurological deficit, a NCCT with salvageable brain tissue (ASPECTS >5), and presence of a LVO on CTA. Results: Over a 16-month period, a total of 366 patients were treated with IV thrombolysis and/or EVT. Of these, 46 had WUS or presented ≥ 6 hours since symptom onset and received EVT. Median age was 70, median baseline mRS score 1, median NIHSS at arrival 17 and median ASPECTS 9. Good collaterals on CTA were noted in 63%(29) of patients. 5 patients had posterior circulation stroke with basilar occlusion. Median time from last time seen normal to admission was 9h17(IQR, 6h44-12h46). 31 (67.4%) NCCTs were done at a referent center and not repeated locally to avoid treatment delays. At 3-month follow-up, functional autonomy(mRS ≤ 2) was found in 15 (32.6%) patients while 15 (32,6%) died (mRS=6). Symptomatic hemorrhagic transformation occurred in 3(6.5%) patients. Conclusions: In a real-world setting, EVT is feasible in late-presenting stroke patients selected by NCCT and yields favorable outcomes similar to those seen in the more pragmatic EVT trials.

Purpose: The ASTER trial (contact Aspiration versus Stent Retriever for revascularization in patients presenting with acute ischemic stroke and a large vessel occlusion in the anterior circulation within six hours of symptom onset) did not show superiority of contact aspiration over stent retriever regarding successful revascularization (TICI 2B/3) result at the end of the procedure and clinical results at 3 months. Objective: To assess whether patient admission modes, directly to a comprehensive stroke center (CSC) versus to a primary stroke center (PSC), impacted the rate of patients with functional independence at 3 months and the rate of favorable angiographic outcome in the ASTER trial. Methods: Primary outcomes included degree of functional independence (modified Rankin scale ≤2) at 90 days, the change in National Institute of Health Stroke Scale (NIHSS) at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events. Secondary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis In Cerebral Infarction [mTICI] score of 2b or 3 at the end of procedure. Results: Among 381 patients who were randomized in the ASTER trial, 138 were directly admitted to a CSC (Mothership paradigm) and 243 were admitted first in a PSC (Drip-and-Ship paradigm). Aspiration as first strategy was performed in 50.7% of the patients in the Mothership paradigm group, versus 50.2% in the Drip-and-Ship. Onset to groin puncture time was 170 minutes (IQR, 142 to 207) in the Mothership group versus 262 minutes (IQR, 216 to 295) in the Drip-and-Ship group (p Conclusions: The Mothership treatment paradigm did not result in better functional neurological outcome at 3 months compared to the Drip-and-Ship paradigm, whatever the first line treatment strategy.

Background and Purpose— Shorter delays between symptom onset and treatment translate into better outcomes after ischemic stroke thrombolysis. There are considerable intercenter variations in treatment delivery. We analyzed the trends of door-to-needle times (DNTs) in the Safe Implementation of Thrombolysis in Stroke registry between 2003 and 2011. Methods— We extracted from the Safe Implementation of Thrombolysis in Stroke registry (n=45 079) year of treatment, center code, DNT, sex, age, National Institutes of Health Stroke Scale, and comorbidity. For each center, the year they joined the registry and the annual volume of patients were determined ( Results— DNT was not available for 720 (1.6%) patients. The overall mean (SD) DNT was 73 (37) minutes with a median (interquartile range) of 67 (47–91) minutes. The DNT was 65 (46–90), 68 (50–92), and 72 (51–98) minutes for centers joined early (2003–2005), later (2006–2009), and recently (2009–2011), respectively. Center volume had more robust effect on DNT than year of treatment, and the shortest DNTs were seen in centers with volumes ≥100 patients/y. Earlier enrollment period was also associated with shorter delays. Conclusions— Centers that joined the registry earlier and those with high annual volume achieved shorter DNT than centers that joined later and low-volume centers. However, in most of the centers, DNT did not change much during the registry period. A multicenter project aiming to reduce DNT is warranted.

Background and Purpose— Interhospital transfer after use of intravenous tissue-type plasminogen activator (tPA) in acute stroke (drip and ship) is increasingly frequent. Small studies have suggested that drip and ship tPA is safe and increases rates of tPA use; however, little is known about real-world practice patterns. We sought to evaluate temporal trends in drip and ship tPA use and to compare the patient and hospital characteristics with that of conventional (front door) thrombolysis. Methods— We analyzed data from 44 667 patients with ischemic stroke treated with intravenous tPA ≤3 hours of symptom onset in the Get With The Guidelines-Stroke program from April 2003 to October 2010 in 1440 hospitals. The main outcomes were the frequency of drip and ship tPA use over time, the characteristics of patients treated, and in-hospital outcomes, treatments, and complications. Results— Among 44 667 patients treated with tPA, the drip and ship method was a common method (n=10 475; 23.5%), the use of which increased in parallel with the traditional tPA method over time. Patients treated by the drip and ship method differed significantly from front-door patients, with lower National Institutes of Health Stroke Scale scores when recorded (n=35 467). Crude in-hospital mortality (10.9%) and symptomatic intracranial hemorrhage (5.7%) in patients treated by the drip and ship method were slightly higher compared with those in front-door patients, and these differences persisted after risk adjustment. Conclusions— Drip and ship tPA is common, used in 1 in 4 patients treated with tPA in the United States. Modest differences in mortality and symptomatic intracranial hemorrhage may be because of patient selection bias, post-tPA care differences, or unmeasured confounding. The drip and ship paradigm may facilitate widespread tPA use in patients with acute stroke.

Background: IV tPA is the only drug approved for the initial treatment of acute ischemic stroke, and can only be given within 3-4.5 hours from stroke symptom onset. Studies demonstrate that for every 15-minute reduction in door to needle time (DTN) there is a 5% lower odds of mortality. The faster tPA is administered, the better the patient’s chance for a meaningful recovery. Purpose: As part of an ongoing initiative to decrease DTN times, we applied the concept of “mobile mixing” to our stroke alert process. Typically, tPA is mixed in the main pharmacy and delivered to the CT scanner, which occasionally resulted in a delay in care. The mobile mixing process gives the pharmacist the resources necessary to compound tPA for immediate use while the patient is still in CT. Methods: We began work on this quality improvement project in August 2015. Our multidisciplinary team, consisting of advanced practice providers, pharmacists, nurses, and our stroke medical director, met monthly to design and evaluate our pilot process. Pharmacy created tackle boxes containing the medications and supplies required to mix and administer tPA. We addressed staffing challenges, held mock stroke alerts; collected data on response times for a six-week period, and evaluated the impact this intervention made on our times. Results: During the pilot period, we treated 10 patients with tPA with a median DTN of 23.5 minutes. Further, as of July 2016, we gave tPA 60 times with a pharmacist present with a median DTN of 23.5 minutes. This has translated into a 2016 year-to-date DTN of 23.5 minutes. Members of the stroke team acknowledge that this process has also contributed to an increased sense of patient safety and team collaboration. Conclusions: The mobile mixing project has had a direct positive impact on patient care. The faster we give tPA, the faster the patient is then ready for the angiography suite if he or she is candidate for mechanical thrombectomy. In stroke, every minute counts and the mobile mixing project is one piece of the well-oiled machine that achieves a positive outcome for patients every day.

Introduction: Early treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset is associated with neurologic improvement. A risk of rtPA is hemorrhagic conversion, which has a higher incidence in patients with elevated blood pressure at presentation. Current literature supports the use of blood pressure goals ( Hypothesis: AIS patients requiring anti-HTN medications (anti-HTN group) before rtPA have a poorer outcome at 90 days compared to those that do not need anti-HTN medications (control group). Methods: This was a retrospective cohort study of patients >18 years diagnosed with AIS from January 2011 through December 2015 who received one or multiple anti-HTN medication(s) prior to rtPA administration, compared to control patients who did not. Primary endpoint was poor outcome at 90 days, defined as a modified Rankin Scale (mRS) of ≥3. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Multivariate analysis was conducted. Results: Of 235 patients evaluated for AIS, 145 (61.7%) were included. Baseline demographics were well matched, though more patients in the anti-HTN group had a history of HTN (86.7% vs. 62.5%, p Conclusion: No difference was observed in poor outcomes, hemorrhagic conversion, or 90-day mortality in patients receiving anti-HTN medications prior to rtPA compared to those that did not. These results suggest that aggressive blood pressure management should be used to control hypertension in AIS who may qualify for rtPA, though larger, randomized trials are needed to confirm this finding.

Introduction: It is well documented that a Prehospital Stroke Alert (PHSA) protocol leads to decreased treatment times for stroke patients. Outcomes measured typically include Door to Physician (DTP), Door to CT (DTCT), and Door to Needle (DNT) times. Our comprehensive stroke center’s PHSA system has been in place since 2012. This study evaluates 3 specific endpoints. First, Emergency Medical Services (EMS) improve their recognition of stroke symptoms as they gain experience with PHSA. Second, a PHSA protocol decreases intervention times of DTP, DTCT, and DNT over a study period of 3 years. Third, when patients present to our Neurologic Emergency Department (Neuro ED) as a PHSA, rather than a non-PHSA, the intervention times are markedly decreased, and acute ischemic stroke care is significantly expedited. Methods: A retrospective chart review was conducted for patients who presented to our hospital with an admitting diagnosis of stroke from 2012-2014. Patients were screened for presentation to the Neuro ED and further stratified based on whether a PHSA was called. PHSA was called if EMS deemed the patient’s Cincinnati Stroke Scale score as positive, and symptom onset was within 6 hours. We recorded DTCT, DTP, and DTN times over the years for all patients meeting these inclusion criteria. Results: Three hundred and five patients with an admission diagnosis of stroke were seen in the Neuro ED (Hours are 0700-1800, 7 days a week) from 2012 to 2014, 128 of which presented as PHSAs. EMS responders accurately diagnosed stroke in 82% of cases. Previously, EMS assessment of stroke was accurate only 66% of the time. PHSA patients had decreased DTP, DTCT, and DTN times over the 3 year period. When comparing the PHSA group to non-PHSA group, statistically significant differences were found in DTP and DTCT times within each year (p≤0.0001). Discussion: In conclusion, gaining experience with a PHSA protocol did in fact lead to EMS better recognizing stroke symptoms, reduction in the times of delivery of care for acute ischemic stroke patients over the years 2012-2014, and a markedly statistically significant difference in intervention times if patients were seen as a PHSA as opposed to a non-PHSA.

Introduction: Early hospital arrival form symptom onset has been related to the good outcome. However, it has been unknown whether in hyperacute recanalization therapy, early hospital arrival improves outcome in patients with and without large artery occlusion (LAO). We evaluated the association of onset-to-door (OTD) time with clinical outcome after hyperacute recanalization therapy in patients with and without LAO. Methods: Consecutive stroke patients treated using hyperacute recanalization therapy including intravenous thrombolysis using tissue-plasminogen activator (tPA) and endovascular therapy (EVT) were studied. Good outcome was defined as mRS ≤2 at hospital discharge. All patients were divided into patient with and without LAO. Results: From 2014 September to 2016 July, 129 (median age, 73 [64-82] years; 86 [67%] males) patients were analyzed. tPA alone was administered in 65 (50%) patients, EVT alone in 33 (26%), and tPA and EVT in 31 (24%). At discharge, 67 (52%) patients achieved the good outcome. Ninety-one patients (71%) were classified into the LAO group and 38 (29%) were into the non-LAO group. The OTD was similar between the LAO and the non-LAO groups (1.57 [0.87-3.42] h vs. 1.38 [0.76-2.68], p=0.420). Forty-six (51%) patients in the LAO and 21 (55%) patients in the non-LAO groups had good outcome (p=0.701). Regarding patients with LAO, age, OTD, and NIHSS score were significantly associated with good outcome (p=0.021, 0.014, and 0.001). Multivariate regression analysis also showed the OTD was the independent negative factor for good outcome (OR 0.77, 95%CI: 0.65-0.91, p=0.003). On the other hand, when we analyzed patients without LAO, OTD and NIHSS score were also significantly associated with good outcome (p=0.009, and 0.004). However, multivariate regression analysis did not show the OTD was the independent factor for good outcome (OR 0.83, 95%CI: 0.58-1.18, p=0.299). Only NIHSS score was independently related to it (OR 0.80, 95%CI: 0.67-0.96, p=0.018). Conclusion: Impact of early hospital arrival on clinical outcome after hyperacute recanalization therapy differed between patients with and without LAO. In hyperacute recanalization therapy, early hospital arrival should improve outcome in patients with LAO but not without it.

Background: There is very limited data on the use of advanced neuroimaging to select patients with acute ischemic stroke and large vessel occlusion for intraarterial therapy beyond 6 hours from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6 hours from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. Methods: This is a single institution retrospective study between December 1st, 2015, and July 30 th , 2016 with acute ischemic stroke and anterior circulation large vessel occlusion (LVO) with ASPECTS of 6 or more and beyond 6 hours from symptoms onset. Favorable imaging profile was defined as 1) DWI lesion volume (as defined as apparent diffusion coefficient < 620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined by volume of tissue with Tmax >6 sec) of 15 mL or greater AND 3) A mismatch ratio of 1.8 or more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. Good outcome was defined as a 90 day mRS≤2. Results: In the study period, 41 patients met the inclusion criteria; 22 (53.6%) had favorable imaging profile and underwent mechanical embolectomy. The median age was 75 years (59-92), 68.2% were females; the median time from last known normal to groin puncture was 684.5 minutes (range 363-1628) and the median admission NIHSS score was 17.5 (range 4-28). The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (68.2% vs. 46.0%, p=0.07). The rate of good outcome matches that of the EXTEND-IA trial that selected patients using perfusion imaging (68.2% vs. 71.0%, p = 1.00). None of the patients in our cohort had symptomatic intracereberal hemorrhage. Conclusion: Advanced MR imaging may help select patients with acute ischemic stroke and anterior circulation large vessel occlusion for embolectomy beyond the treatment window used in most endovascular trials.

Background & Purpose: There are scarce data regarding outcomes of AIS patients treated with IVT within 60 min from symptom onset (“golden hour”). We sought to compare outcomes between AIS patients treated within (OTT≤60 min) and outside (OTT: 61-270min) the “golden hour” [GH(+) & GH (-)] using a propensity score matching approach. Methods: Patients were evaluated during a 12-year period in a large, international, prospective registry of IVT (SITS-EAST). They underwent serial NIHSS-score assessments at baseline, 2 hrs and 24 hrs following tPA-bolus. Clinical recovery (CR) at 2 and 24 hrs was defined as a reduction of ≥10 points in NIHSS-score compared with baseline, or a NIHSS-score of ≤3 at 2 and 24 hrs respectively. A relative reduction in NIHSS-score of ≥40% at 2 hrs was predictive of complete recanalization (CREC). sICH was defined using SITS-MOST criteria; 3-month favourable functional outcome (FFO) was defined as a mRS-score of 0-1. The two groups were matched for demographics, risk factors, baseline NIHSS, admission blood pressure and serum glucose. Results: Out of 19.077 tPA-treated AIS patients, 71 patients in GH(+) group [mean age 67±13 years; median NIHSS-score 12 points (IQR 10); median onset to treatment time (OTT) 55min, (IQR 10)] were matched to 6882 patients in GH(-) group (mean age 67±12 years; median NIHSS-score 11 points (IQR 9); median OTT 155min (IQR 55)]. The two groups did not differ in any of the matched characteristics (p>0.1). GH(+) had significantly (p0.2) in the two groups. GH(+) was independently (p Conclusions: AIS patients treated with IVT within the GH have substantially higher odds of early CR and FFO. These findings highlight the potential of mobile stroke units to further improve AIS outcomes by increasing the rates of tPA delivery within the GH.

Background: Usually early infarct signs on imaging take a few hours to develop in ischemic stroke. There may be a subset of patients manifesting early infarct signs on imaging hyperacutely. Objective: To determine the prevalence and factors associated with very early infarct signs on ASPECTS among patients with cerebral ischemia who were imaged Methods: Subjects participating in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) phase 3 clinical trial with a final diagnosis of cerebral ischemia (TIA or Stroke) and initial imaging performed Results: There were 566 cases imaged a mean of 71 (SD 11) minutes after LKWT. Mean age was 69 (SD 13), 43% women, 93% ischemic stroke, 7% TIA, median emergency department NIHSS 8 (IQR 3-16), median ASPECTS score of 10 (IQR 7-10, range 1-10). There were 200 cases with early ischemic findings (35%). Early ischemic changes were not related to age, blood pressure, history of hypertension, diabetes, dyslipidemia, coronary artery disease, or time to imaging (71 vs. 71 mins). Early ischemic changes were more commonly noted in women (50% vs. 39%, p=0.015) and associated higher presenting NIHSS (14 [IQR 7-20] vs 5 [IQR 2-11], p Conclusions: Early ischemic changes were noted on about 1/3 rd of imaging obtained

Background and Purpose— It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. Methods— We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: Results— A total of 919 patients were enrolled. Among them, 9 had P =0.695) and symptomatic intracranial hemorrhage (0% versus 3.82% versus 1.46%; P =0.106). The 0.5 to 0.7 mg/kg group had less excellent recovery outcome (modified Rankin scale, 0–1) than 0.85 to 0.95 mg/kg group (41.89% versus 53.83%; odds ratio=0.58; P =0.031) at 90 days. The 0.70 to 0.85 mg/kg group had less functional independence outcome (modified Rankin scale, 0–2) than 0.85 to 0.95 mg/kg group (54.33% versus 64.51%; odds ratio=0.66; P =0.036) at 90 days. Conclusions— Our study suggests that standard-dose intravenous tPA for stroke had more favorable outcome without increasing the risk of symptomatic intracranial hemorrhage than low-dose tPA. For Asian people, 0.9 mg/kg should be the optimal dose of tPA to treat acute ischemic stroke.

Background and Purpose— The Interventional Management of Stroke (IMS)-III trial randomized patients with acute ischemic stroke to intravenous tissue-type plasminogen activator (tPA) plus endovascular therapy versus intravenous tPA therapy alone within 3 hours from symptom onset. A predefined secondary hypothesis was that subjects with significant early ischemic change on the baseline scan would not respond to endovascular therapy. Methods— The primary outcome was 90-day modified Rankin Scale score 0 to 2. The baseline and follow-up computed tomographic (CT) scan images were reviewed centrally and blinded to any clinical information. We assessed whether the baseline Alberta Stroke Program Early CT Score (ASPECTS) predicted outcome and interacted with study treatment. We analyzed subgroups defined by time from onset to intravenous tPA initiation and baseline occlusion status at a prespecified α=0.01. Results— Baseline demographic and clinical characteristics of 656 randomized patients were similar between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus 0 to 7. Subjects with ASPECTS 8 to 10 were almost twice as likely (relative risk, 1.8; 99% confidence interval, 1.4–2.4) to achieve a favorable outcome. There was insufficient evidence of a treatment-by-ASPECTS interaction. In those treated with onset to intravenous tPA Conclusions— ASPECTS is a strong predictor of outcome and a predictor of reperfusion. ASPECTS did not identify a subpopulation of subjects that particularly benefitted from endovascular therapy immediately after routine intravenous tPA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00359424.

Background and Purpose— Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. Methods— Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. Results— In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year ( P R 2 =−0.12; P R 2 =−0.75; P P Conclusions— DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods— In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results— One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions— In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Background and Purpose— The use of magnetic resonance imaging (MRI) after transient ischemic attack (TIA) or minor stroke may be affected by the relative timing of imaging. We measured the impact of scanning an individual patient late versus early after TIA and minor stroke. Methods— Two hundred sixty-three TIA or minor stroke (National Institute of Health Stroke Scale score ≤3) patients with a baseline MRI completed within 24 hours of symptom onset and a follow-up MRI at 90 days were included. Baseline and 90-day scans were assessed independently for the presence of any stroke lesions that could explain the presenting symptoms. The presence and pattern of any stroke lesions were compared at the 2 time points. Results— The presence of a stroke (acute or chronic) in any location was more common on baseline MRI versus 90-day MRI (68% vs 56%; P =0.005). Thirty percent of subjects with negative scans at 90 days had a clearly identifiable stroke at baseline. When interpreted blinded to the baseline scan, the presumed relevant lesion on the 90-day MR scan was the correct lesion in only 53% patients. One-third (34%) of patients had a different lesion pattern on the baseline scan compared with the 90-day scan. Ninety percent (80/89) of these patients had more lesions on the baseline MRI and 10% (9/89) had new lesions on the 90-day MRI. Conclusions— Delayed MRI after TIA or minor stroke reduces the diagnostic yield and results in missed understanding of the lesion pattern. MRI of minor stroke and TIA patients should occur early after symptom onset, and delayed imaging should be interpreted with caution.

Background and Purpose— The relationship between smoking and the outcome in patients received thrombolysis is undetermined. The outcome could be influenced by different stroke subtypes. This study aimed to explore whether smoking had any impact on the outcome in patients with stroke of different subtypes who received intravenous thrombolysis. Methods— All patients who received intravenous thrombolysis within 4.5 hours after symptom onset from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) database were eligible to be entered into this analysis. Smokers were considered if they smoked at least 1 cigarette/d for >6 months before stroke. Ischemic stroke subtype was classified by using the Trial of Org 10172 in Acute Stroke Treatment criteria. Outcome measurements included post–intravenous thrombolysis symptomatic intracranial hemorrhage within 7 days, mortality, and functional independence at 90 days. The relationship between smoking and thrombolysis was analyzed by using univariate and multivariate logistic regression models. Results— Of 1118 patients enrolled, we identified 454 smokers and 664 nonsmokers. After stratifying for ischemic stroke subtypes, multivariate analysis revealed a significant relationship between smoking and functional independence in patients with noncardioembolism stroke subtypes (large artery atherosclerosis: odds ratio [OR], 1.452; 95% confidence interval [CI], 1.053–2.264; small artery occlusion: OR, 4.275; 95% CI, 1.098–16.649; other: OR, 3.120; 95% CI, 1.162–8.373). Furthermore, smoking was specially related to lower rates of symptomatic intracranial hemorrhage (OR, 0.316; 95% CI, 0.120–0.832) and mortality (OR, 0.272; 95% CI, 0.128–0.577) in patients with large artery atherosclerosis subtype. Conclusions— In patients treated with intravenous thrombolysis, smoking could be related to a better chance of functional independence if their subtype of stroke was noncardioembolic, and a lower risk of symptomatic intracranial hemorrhage and mortality in those with large artery atherosclerosis.

Background: Neuroprotective can be administered soon after symptom onset may preserve brain tissue potentially leading to better outcomes after endovascular treatment. We describe prehospital treatment with magnesium sulfate among endovascular treated cases. Methods: Subjects enrolled in the NIH Phase 3 Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial of prehospital treatment with magnesium or placebo initiated Results: Of 1235 subjects with cerebral ischemia, 76 (6%) underwent endovascular therapy (38 magnesium, 38 placebo), mean age 69 (SD13), 50% women, median NIHSS 17 (IQR 11-23). Median (IQR) time from onset to study drug initiation was 39 (33-46) minutes, to TPA (N=49) 135 (114-175) and to groin puncture was 247 (169-287) minutes. There were no significant differences in baseline demographics or times. Assignment to Mg was not associated with improved NIHSS at 24 hours (12 vs.13.5, p=0.904) or disability at 3-months (mRS 3 vs. 3, p=0.867). Conclusions: Although treatment with magnesium was neutral, the strategy of prehospital Neuroprotection initiation strategy exposed subjects to 3 hours and 28 minutes of potential brain stabilizing therapy prior to groin puncture. With more recent groin puncture times prehospital Neuroprotection could provide 3 hours of stabilization prior to endovascular therapy initiation.

We read the article by Flores et al1 with great interest but are concerned about some issues. The effect of decompressive hemicraniectomy in malignant middle cerebral artery infarction (MMI) is time dependent. Therefore, early predictors of a malignant course are needed to allow timely selection of patients suitable for decompressive hemicraniectomy.2 At present, the gold standard for defining and predicting MMI is diffusion-weighted imaging. Thomalla et al3,4 described a lesion volume of >82 mL within 6 hours of symptom onset as highly specificity and predictive for MMI. Souza et al4 described that poor collateral status is associated with admission diffusion-weighted imaging and defined a malignant profile of collateral circulation that was highly specific …