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Objective: To evaluate the relationship between infarct pattern, inferred stroke mechanism and risk of recurrence in patients with ischaemic stroke. The question is clinically relevant to optimise secondary stroke prevention investigations and treatment., Design: We conducted a retrospective analysis of the dabigatran treatment of acute stroke II (DATAS II) trial (ClinicalTrials.gove NCT NCT02295826), in which patients underwent diffusion-weighted imaging (DWI) at baseline and 30 days after randomisation to one of two antithrombotic therapies. Patients were classified as embolic, isolated small subcortical infarcts or transient ischaemic attack TIA (no infarct) at baseline and day 30. Stroke mechanism was determined by traditional and modified (based on DWI lesion findings) Trial of Org 10 172 in Acute Stroke Treatment (TOAST) criteria (DWI-TOAST)., Setting: Multicentre (6) tertiary acute stroke treatment hospitals., Participants: 305 adults with minor ischaemic stroke (National Institutes of Health Stroke Scale (NIHSS) score≤9)., Results: Of 305 patients, 148 had embolic pattern infarcts, 93 were isolated small subcortical infarcts and 64 had no infarct on baseline MRI (TIA). In the absence of DWI, TOAST classification indicated the mechanism was cryptogenic in 147 patients (48.2%), and small-vessel occlusion in 127 (41.6%). Using, DWI-TOAST, the number of cryptogenic strokes decreased to 123 (40.3%), and the number of small-vessel occlusion strokes increased to 151 (49.5%). Recurrent infarcts were seen in 13% of patients with an MRI-defined embolic infarct pattern and cryptogenic mechanism on DWI-TOAST. The relative risk of recurrent infarction in patients with undetermined aetiology was increased compared with other categories (standardised coefficient=1.0 (0.1, 1.9), p=0.029). The topography of recurrent infarcts was most often embolic (60.9%), but in 39.1% an isolated small subcortical infarct was seen., Conclusions: Definitive identification of infarct topography with DWI has a significant impact on infarct mechanism classification. The variable relationship between baseline infarct patterns, clinical presentation and recurrent infarct distribution is a challenge to both the lacunar and embolic stroke of uncertain source (ESUS) concepts. Irrespective of aetiological classification, patients with MRI-defined cryptogenic embolic pattern infarcts are at high risk for recurrent events., Trial Registration Number: Linked to the DATAS II trial., Clinicaltrials: gov ID NCT02295826., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days., Methods: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient ( r ) with 95% CI., Results: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase ( P =0.10). Older age ( P <0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale ( P <0.01), and longer stroke onset-to-needle time ( P =0.004) were associated with lower EQ5D index and VAS scores. There was a strong association ( r , 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index ( r , 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores ( r , 0.42 [95% CI, 0.37-0.46])., Conclusions: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249., Competing Interests: Disclosures Dr Menon reports stock in Circle NVI and patents for systems of triage in acute stroke. Dr Sajobi reports consulting fees received from Circle NVI and employment at the University of Calgary. Dr Almekhlafi reports to be on the medical advisory board of Palmera Medical, Inc. Dr Deschaintre reports being part of the Association des neurologues du Québec, the Société des Sciences Vasculaires du Québec, and the Université de Montréal. Dr Coutts reports that Boehringer Ingelheim provided a study drug (tenecteplase) for the TEMPO-2 trial. Dr Catanese reports employment with Hamilton Health Sciences and McMaster University, consulting fees from Hoffmann-La Roche Ltd, and a grant/contract from Servier Pharmaceuticals LLC. Dr Field reports consulting fees from AstraZeneca Canada, Bayer, HLS Therapeutics, and Roche; stock and being a fiduciary officer (board member) in Destine Health; grants/contracts from Boehringer Ingelheim and Bayer; and being an expert witness for the Canadian Medical Protective Association. Dr Siddiqui reports a grant/contract from Allergan and other interests from Bayer and Boehringer Ingelheim. Dr Demchuk reports stock in Circle NVI and patents for stroke imaging software; consulting fees from Servier Pharmaceuticals LLC, NovaSignal, Boehringer Ingelheim, HLS Therapeutics, Inc, Hoffmann-La Roche Ltd, and Medtronic; data and safety monitoring with Philips; and other interests from AstraZeneca Canada, Novo Nordisk AS, and Pfizer Canada, Inc. Dr Hill reports employment with the University of Calgary; consulting fees from Brainsgate Ltd; grants/contracts from Biogen, Inc, Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic, MicroVention, Inc, and NoNO, Inc; being part of the end point review committee at Merck; stock in Circle NVI; and patents for systems of triage in acute stroke. Dr Poppe reports grant funding from the Fondation Brain Canada and the Heart and Stroke Foundation of Canada and research funding from Stryker. Dr Swartz reports stock in FollowMD, Inc, and grants/contracts from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the National Institutes of Health, the Ontario Brain Institute, and the Sunnybrook Research Institute. The other authors report no conflicts.

Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS., Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI)., Results: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P  = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P  = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001)., Conclusions: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Background: 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., Methods: 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., Findings: 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., Funding: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit., Competing Interests: Declaration of interests BKM has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. SBC is principal investigator of the TEMPO-2 trial, for which Boehringer Ingelheim provides the study drug (tenecteplase). LC has received payments by Servier and consulting fees from Ischaemavie RAPID, Circle NV, and Canadian Medical Protective Association. JS has a grant from Medtronic to the University of Manitoba. AMD has received consulting fees from Medtronic and honoraria from Boehringer Ingelheim. LCG is on advisory boards for AstraZeneca and Servier and has stock options in AstraZenca. ASh has received consulting fees from Bayer, Servier Canada, Daiichi Sanyko Compan, AstraZeneca, VarmX, and Takeda; honoraria from Bayer and Daiichi Sankyo; is on an advisory board for Bayer; and has stock options in Ensho. MDH has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. DJG has received consulting fees from HSL Therapeutics. APo has received a project research grant from Stryker and honoraria from BMS-Pfizer. TTS has received consulting fees from Circle NVI. RHS has stock options in FollowMD and receives salary support for research from the Heart & Stroke Foundation of Canada, Sandra Black Centre for Brain Resilience & Recovery, and Ontario Brain Institute. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and purposes : Stroke severity scales may expedite prehospital large vessel occlusion (LVO) stroke detection, but few are validated for paramedic use. We evaluated the feasibility of introducing the Cincinnati Stroke Triage Assessment Tool (C-STAT) in the field and its capacity to detect LVO stroke. Methods : We performed a prospective paramedic-based study assessing C-STAT in the field on patients currently redirected to two comprehensive stroke centers (CSC), based on a Cincinnati Prehospital Stroke Scale (CPSS) score of 3/3. C-STAT was administered by on-site paramedics with telephone guidance from trained centralized clinical support paramedics. Results : Between October 2018 and November 2019, C-STAT scores were obtained in 188/218 (86.2%) patients, among which 118/188 (62.8%) were positive. Paramedics reported performing the C-STAT in less than 5 minutes on 170/188 (90.4%) patients and noted no difficulties administering the scale in 151/188 (80.3%). A positive C-STAT identified 51/68 (75%) LVO strokes in the cohort, demonstrating a 43% (95% CI: 38%-48%) positive and 76% (95% CI: 66%-83%) negative predictive value for LVO stroke diagnosis. In a cohort of 100 patients with CPSS 3/3, requiring a positive C-STAT for redirection would decrease CSC patient volume by 37 but miss 9 of 36 LVO strokes. Conclusion : Prehospital administration of the C-STAT was feasible, using a model of minimal paramedic training and real-time telephone guidance. A protocol based on both a CPSS 3/3 and a positive C-STAT would decrease CSC redirected patient volume by one-third but would miss one-quarter of LVO strokes when compared to a CPSS-based protocol.

Background: Stroke survivors may be at higher risk of incident cancer, although the magnitude and the period at risk remain unclear. We conducted a retrospective cohort study to compare the risk of cancer in stroke survivors to that of the general population., Methods: The Canadian Longitudinal Study on Aging is a large population-based cohort of individuals aged 45-85 years when recruited (2011-2015). We used data from the comprehensive subgroup (n = 30,097) to build a retrospective cohort with individual exact matching for age (1:4 ratio). We used Cox proportional hazards models to estimate hazard ratios of new cancer diagnosis with and without a prior stroke., Results: We respectively included 920 and 3,680 individuals in the stroke and non-stroke groups. We observed a higher incidence of cancer in the first year after stroke that declined afterward (p-value = 0.030). The hazard of new cancer diagnosis after stroke was significantly increased (hazard ratio: 2.36; 95% CI: 1.21, 4.61; p-value = 0.012) as compared to age-matched non-stroke participants after adjustments. The most frequent primary cancers in the first year after stroke were prostate (n = 8, 57.1%) and melanoma (n = 2, 14.3%)., Conclusions: The hazard of new cancer diagnosis in the first year after an ischemic stroke is about 2.4 times higher as compared to age-matched individuals without stroke after adjustments. Surveillance bias may explain a portion of post-stroke cancer diagnoses although a selection bias of healthier participants likely led to an underestimation of post-stroke cancer risk. Prospective studies are needed to confirm the potentially pressing need to screen for post-stroke cancer.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

Background: The optimal approach for cancer screening after an ischemic stroke remains unclear., Aims: We sought to summarize the existing evidence regarding the frequency and predictors of cancer after an ischemic stroke., Summary of Review: We searched seven databases from January 1980 to September 2019 for articles reporting malignant tumors and myeloproliferative neoplasms diagnosed after an ischemic stroke (PROSPERO protocol: CRD42019132455). We screened 15,400 records and included 51 articles. The pooled cumulative incidence of cancer within one year after an ischemic stroke was 13.6 per thousand (95% confidence interval [CI], 5.6-24.8), higher in studies focusing on cryptogenic stroke (62.0 per thousand; 95% CI, 13.6-139.3 vs 9.6 per thousand; 95% CI, 4.0-17.3; p = 0.02) and those reporting cancer screening (39.2 per thousand; 95% CI, 16.4-70.6 vs 7.2 per thousand; 95% CI, 2.5-14.1; p = 0.003). Incidence of cancer after stroke was generally higher compared to people without stroke. Most cases were diagnosed within the first few months after stroke. Several predictors of cancer were identified, namely older age, smoking, and involvement of multiple vascular territories as well as elevated C-reactive protein and d-dimers., Conclusions: The frequency of incident cancer after an ischemic stroke is low, but higher in cryptogenic stroke and after cancer screening. Several predictors may increase the yield of cancer screening after an ischemic stroke. The pooled incidence of post-stroke cancer is likely underestimated, and larger studies with systematic assessment of cancer after stroke are needed to produce more precise and valid estimates.

Competing Interests: Competing interests: Mark Keezer has received speaker and advisory fees for Eisai Co., Elsevier, Sunovion, Novartis and UCB, and unrestricted educational grants and research grants from UCB and Eisai Co. Laura Gioia has received speaker fees and advisory board honoraria from Bayer, BMS-Pfizer and Servier, and investigator-initiated funding from Servier. No other competing interests were declared.

Introduction: The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT., Methods: We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared., Results: During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15-23] vs. late: 17 [13-21]), as were median ASPECT scores (early: 9 [8-10] vs. late: 9 [7-9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0-2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76)., Conclusion: NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.

Background: Interest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management. Methods: In 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging. Serum levels of glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) were analyzed using a single molecule array (SIMOA®) method, according to time of symptom onset, neuroimaging, and final diagnosis. Results: Acute ischemic stroke (AIS) was diagnosed in 35 patients, 10 with large-vessel occlusion (LVO). The remaining were diagnosed with intracerebral hemorrhage (ICH) (n = 12), transient ischemic attack (n = 4), and stroke mimics (n = 11). Median (IQR) sGFAP levels were significantly higher in ICH (2,877.8 [1,002.1–10,402.5] pg./mL) compared to others diagnoses. In AIS, GFAP levels appear to increase with longer delays since symptom onset and were higher in patients with more extensive ischemic changes on baseline CT (ASPECTS ≤7) than those without, particularly in LVO stroke. NfL values were similar across groups. Conclusion: In acute stroke, serum GFAP levels show potential as an adjunct tool for the distinction between ICH and AIS. Specific to AIS, GFAP may also offer insight into time from onset, and extent of ischemic tissue injury on neuroimaging, particularly in LVO stroke. These preliminary findings merit further study. [ABSTRACT FROM AUTHOR]

Background: Interest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management. Methods: In 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging. Serum levels of glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) were analyzed using a single molecule array (SIMOA®) method, according to time of symptom onset, neuroimaging, and final diagnosis. Results: Acute ischemic stroke (AIS) was diagnosed in 35 patients, 10 with large-vessel occlusion (LVO). The remaining were diagnosed with intracerebral hemorrhage (ICH) (n = 12), transient ischemic attack (n = 4), and stroke mimics (n = 11). Median (IQR) sGFAP levels were significantly higher in ICH (2,877.8 [1,002.1–10,402.5] pg./mL) compared to others diagnoses. In AIS, GFAP levels appear to increase with longer delays since symptom onset and were higher in patients with more extensive ischemic changes on baseline CT (ASPECTS ≤7) than those without, particularly in LVO stroke. NfL values were similar across groups. Conclusion: In acute stroke, serum GFAP levels show potential as an adjunct tool for the distinction between ICH and AIS. Specific to AIS, GFAP may also offer insight into time from onset, and extent of ischemic tissue injury on neuroimaging, particularly in LVO stroke. These preliminary findings merit further study. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage is a particularly devastating type of stroke with greater morbidity and mortality compared with ischemic stroke and can account for half or more of all deaths from stroke. The seventh update of the Canadian Stroke Best Practice Recommendations includes a new stand-alone module on intracerebral hemorrhage, with a focus on elements of care that are unique or affect persons disproportionately relative to ischemic stroke. Prior to this edition, intracerebral hemorrhage was included in the Acute Stroke Management module and was limited to its management during the first 12 h. With the growing evidence on intracerebral hemorrhage, a separate module focused on this topic across the care continuum was added. In addition to topics related to initial clinical management, neuroimaging, blood pressure management, and surgical management, new sections have been introduced addressing topics surrounding inpatient complications such as venous thromboembolism, seizure management, and increased intracranial pressure, rehabilitation as well as issues related to secondary management including lifestyle management, maintaining a normal blood pressure and antithrombotic therapy, are addressed. The Canadian Stroke Best Practice Recommendations (CSBPR) are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and informal caregivers. [ABSTRACT FROM AUTHOR]