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Background: Early reperfusion has the best likelihood for a favorable outcome in acute ischemic stroke (AIS) with large vessel occlusion (LVO). Our experience with mobile stroke unit (MSU) for direct to angiosuite (DTAS) transfer in AIS patients with suspected LVO is presented. Methods: Retrospective review of prospectively collected data from November 2019 to August 2022, of patients evaluated and transferred by the University of Alberta Hospital MSU and moved to angiosuite for endovascular thrombectomy (EVT). Result: A total of 41 cases were included. Nine were chosen for DTAS and 32 were shifted to angiosuite after stopping for computed tomography (CT) angiography of the head and neck (no-DTAS). Stroke severity measured by NIHSS (median with interquartile range (IQR)) was higher in patients of DTAS, 22 (14–24) vs 14.5 (5–25) in no-DTAS (p = 0.001). The non-contrast CT head in MSU showed hyperdense vessels in 8 (88.88%) DTAS vs 11 (34.35%) no-DTAS patients (p = 0.003). The EVT timelines (median with IQR, 90th percentile) including “door to artery puncture time” were 31 (23–50, 49.2) vs 79 (39–264, 112.8) minutes, and “door to recanalization time” was 69 (49–110, 93.2) vs 105.5 (52–178, 159.5) minutes in DTAS vs no-DTAS group, respectively. The workflow times were significantly shorter in the DTAS group (p < 0.001). Eight (88.88%) out of 9 DTAS patients had LVO and underwent thrombectomy. Conclusions: MSU for DTAS in patients with high NIHSS scores, cortical signs, and CT showing hyperdense vessel is an effective strategy to reduce the EVT workflow time.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Background In light of evidence from recent trials that endovascular thrombectomy (EVT) alone may potentially be noninferior to combined treatment, that is, with intravenous thrombolysis (IVT) with alteplase and EVT, we sought to understand physician and patient preferences around this issue. Methods We conducted a 2‐stage mixed methods study that included a structured, international, web‐based cross‐sectional survey among stroke physicians, and a focus group involving stroke survivors and caregivers. Demographic information was collected from all participants. The survey offered multiple choice questions and options to respond via free text which was analyzed quantitatively. The focus group was conducted online and analyzed qualitatively using a grounded theory approach. Results A total of 225 physicians (67% men) from 44 countries completed the survey. Most participants (70%) were between 31 and 50 years of age. Survey results showed that in current practice, 90% respondents would offer IVT to patients with large vessel occlusion stroke eligible for both IVT and EVT. When asked if their practice would change in light of recent trials, 63% responded no. When asked about the appropriate timing for IVT in the setting of large vessel occlusion stroke with EVT availability, 56% preferred to administer IVT immediately, 21% were willing to defer the decision for 30 minutes from groin puncture, and 8% were willing to defer for 60 minutes from groin puncture to assess if reperfusion was achieved with EVT. A total of 61% participants would choose to use tenecteplase over alteplase as the preferred drug for IVT if both drugs are backed by evidence. The focus group identified a need to better understand patient characteristics that may benefit from EVT‐only or combined strategies. The focus group also identified the need for more data to inform physician decision making. Conclusions Most physicians surveyed prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion, although there was some uncertainty around this issue. The need for further studies, including data on IVT with tenecteplase and among various patient subgroups to inform decision making, was apparent from both the survey and the patient focus group.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS). But occult AF is also found in some normal individuals and patients with stroke of known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal versus incidental. Methods: Through systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both CS and KS patients. We performed a random-effects meta-analyses across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients, and across age subgroups. We then applied Bayes’ theorem (method of Alsheikh-Ali et al, Stroke 2009) to determine the probability that occult AF is causal or incidental. Results: The systematic search identified 3 case-control and cohort studies enrolling 575 patients (337 CS, 238 KS). Methods of long-term monitoring were implantable loop recorder in 191 (33.2%), extended mobile external cardiac monitor in 277 (48.2%), and patch/event/Holter monitoring in 107 (18.6%). In formal meta-analysis, the summary odds ratio for occult AF in CS vs KS in all patients was 1.72 (95%CI 0.91-3.25) (Figure). With application of Bayes theorem, the corresponding probabilities indicated that, when present, occult AF in CS patients is causal in 44.4% and incidental in 55.6%. Only one study reported age-specific subgroup data: these suggested occult AF in CS patients was causal in 93% of patients Conclusions: In patients with cryptogenic stroke, when occult AF is found, it is likely causal in about 44% of patients, who may benefit from anticoagulation, and likely incidental in about 56% of patients, who may not benefit from anticoagulation. Figure

Introduction: The timing of direct oral anticoagulant (DOAC) after atrial fibrillation (AF)-related stroke is unknown. Most guidelines are inconsistent and based on expert opinion. We conducted a survey to evaluate the global practice patterns of this common clinical scenario. Methods: We used an electronic survey with practice-related demographic and clinical questions of 10 cases with different stroke severities and sizes: transient ischemic attack, small, medium, large, and strokes with hemorrhagic infarction and parenchymal hematoma. Results: A total of 242 clinicians from 21 countries completed at least one clinical scenario. The majority of the respondents were from Australia (36.4%) or Canada (22.7%). Stroke-specific sub-specialty training was self-reported in 82.2% of the respondents. Median (IQR) time spent dedicated to stroke patient care/research was 70 (60) % of total working hours. Only 14% of responding clinicians reported current participation in a randomized trial of DOAC initiation timing after AF-related stroke. Stroke size, severity, and the grade of hemorrhage if present seem to be determinants of the decisions. Lack of consensus was observed in moderate stroke, multi-territory infarcts, large stroke, and in the presence of HT. The majority of respondents would be willing to randomize patients with different stroke sizes and severities with/without HT in a clinical trial of early versus delayed initiation of DOAC after AF-related stroke. Conclusions: Decisions related to the timing of DOAC initiation after AF-related stroke vary globally. The variability in clinical practice will continue until randomized controlled trials are completed.

Background: Atrial fibrillation (AF) is a common cause of ischemic stroke; however, it is often difficult to detect. It is unclear whether specific infarct topography on magnetic resonance imaging (MRI) is associated with underlying AF. We aimed to objectively assess the infarct patterns on MRI in patients with acute ischemic stroke and determine imaging characteristics that are associated with AF. Methods: We conducted a subgroup analysis on patients randomized in Post-Embolic Rhythm Detection with Implantable vs External Monitoring trial (PER DIEM; NCT02428140) who had brain MRI. Two raters blinded to clinical details reviewed the MRI findings. Patients were divided to two groups (AF and non-AF) and descriptive statistics were used to characterize findings. Variables associated with new AF were analyzed using logistic regression and reported as odds ratios (OR) with 95% confidence interval (CI) and p -values. Results: Of the 300 patients who were randomized in the trial, 249 (83%) patients (59.4% male) with a mean age of 64.3 ± 13.1 years had MRI brain and were included in the analysis. Median (IQR) NIHSS was 0 (0 - 1), number of lesions was 2 (1 - 3), and diameter of lesion (mm) was 10.4 (5.8 - 21.1) mm. In this cohort of patients, imaging characteristics were not significantly associated with the detection of AF. Conclusions: Association between infarct topography and AF detection was not found in this study. Imaging characteristics cannot be relied upon to predict or exclude an underlying AF. Large prospective studies are suggested to examine the link between infarct topography and underlying AF.

Accurate and timely prehospital stroke diagnosis and detection of large vessel occlusion (LVO) are essential to ensure stroke patients are transported to hospitals that offer emergent reperfusion therapies. However, symptom based prehospital stroke scales often fail to identify LVO. Thus, a need exists for cost-effective and portable diagnostic tools, such as portable electroencephalography (EEG) to improve the accuracy of prehospital stroke diagnosis. Hypotheses: 1) Quantitative EEG measures will differ between LVO and non-LVO stroke patients, particularly in regards to brain slowing (ratio of low to high frequency oscillatory brain power) and brain asymmetry (ratio between oscillations in the affected and unaffected hemisphere) 2) Combining EEG with prehospital stroke scales will improve the accuracy of LVO detection. We enrolled patients with acute suspected stroke on presentation to an emergency department at a comprehensive stroke centre. Patients were rapidly evaluated with the Los Angeles Motor Scale followed by a 3-minute resting-state EEG recording using a modified Muse EEG headband (InteraXon). The LVO diagnosis and the extent of cerebral blood flow abnormalities were determined from CT angiography and CT perfusion imaging performed in close temporal proximity to the EEG recording. The study enrolled 74 patients (n= 8 LVO, n=66 non-LVO, including stroke mimics). Initial analysis suggests that LVO patients have trends towards brain slowing, as measured by the delta alpha ratio (LVO: mean = 1.21, SEM = 0.03; non-LVO: mean = 1.19, SEM = 0.01; p-value = 0.34). Additionally, LVO patients showed a trend towards increased brain asymmetry from 6-8 Hz, suggesting physiological differences between hemispheres specific to the theta frequency (LVO: mean = 0.02, SEM = 0.006; non-LVO: mean = 0.01, SEM = 0.002; p-value = 0.13). Quantitative measures will be assessed using classification trees to determine which combination of EEG and clinical features is most predictive of LVO. In conclusion, acute differences in brain activity between LVO and non-LVO patients can be detected with portable EEG, which when combined with clinical stroke scales, have the potential to improve the diagnosis and triage of suspected stroke patients in a prehospital setting.

Introduction: Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC) initiation within 48 hours vs. > 48 hours in the post-stroke period. Methods: A pooled analysis of five studies of DOAC initiation within 14 days of ischemic stroke onset was conducted. The primary endpoint was incident radiographic HT on follow-up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage (PH1 or asymptomatic PH2), recurrent systemic events, systemic hemorrhagic complications, mortality within the study period, final modified Rankin Scale score. The results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 468 patients were enrolled. Median infarct volume was 1.35 (0-7.5) ml, and National Institutes of Health Stroke Scale was 1 (0-3). Incident radiographic HT was seen on follow-up scan in 29 patients. DOAC initiation within 48 hours from index event onset was not associated with incident HT (adjusted OR 0.67, [0.31 - 1.50] P =0.34). No patients developed symptomatic HT. Conversely, 25 patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating DOAC within 48 hours of onset was not associated with a reduction in the risk of recurrent ischemic events (OR 0.47, [0.19 - 1.20] P =0.12). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.95 - 15.63], p Conclusions: Early DOAC initiation after stroke was not associated with increased incident HT risk. Recurrent ischemic events were common and associated with poor outcomes. These data may be useful for estimating outcome rates and sample size calculations in future trials of early versus late DOAC initiation after AF-related stroke.

Background and Purpose— MRI permeability imaging is a promising approach to identify patients with acute ischemic stroke with an increased propensity for hemorrhagic transformation (HT). Permeability imaging provides direct visualization of blood–brain barrier derangements in ischemic fields. Methods— We retrospectively analyzed clinical and MRI data on patients with acute cerebral ischemia within the middle cerebral artery territory to identify the frequency, patterns, and predictors of permeability derangements and their association with HT types. Results— A total of 179 permeability scans was obtained in 127 patients (59 men; mean age, 66.8 years). Among 179 image sets (82 pre-/no treatment and 97 posttreatment), permeability derangements were present in 29 images, frequently at the basal ganglia (n=23) and rarely at the juxta-cortical area (n=6). After adjusting for covariates, diastolic pressure (OR, 1.12, per 1-mm Hg increase; 95% CI, 1.02 to 1.22) and s-glucose (OR, 1.04, per 1-mg/dL increase; 95% CI, 1.01 to 1.07) were independently associated with pretreatment permeability derangements, whereas low-density lipoprotein cholesterol (OR, 0.97, per 1-mg/dL increase; 95% CI, 0.94 to 0.99), malignant MRI profile (OR, 24.84; 95% CI, 1.50 to 412.93), and time from onset to recanalization therapy (OR, 1.47, per 1-hour increase; 95% CI, 1.10 to 1.96) were independently associated with permeability derangements after recanalization therapy. Types of HT varied among the patients with permeability derangements (no HT, 4; hemorrhagic infarct type, 12; and parenchymal hematoma, 13) and transient derangements (without subsequent HT) and normalization of derangements (in the presence of HT) on permeability images was observed in several cases. Conclusions— Permeability derangements, a dynamic process associated with ischemic stroke pathophysiology and recanalization therapy, vary in pattern and evolution toward HT. Several prognostic and therapeutic predictors for HT are independently associated with pre- and posttreatment permeability derangements.