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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: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paul, Ducroux, Correia, Daigneault, Larochelle, Stapf and Gioia.)

Background and Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial., Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times. Participants at 3 sites were invited to complete a survey of attitudes regarding consent for AcT and for acute stroke trials generally., Results: The AcT trial enrolled 1,600 participants from 22 centers across Canada of whom 1,537 were enrolled through deferral of consent (96.0%) and 63 (4.0%) were enrolled by prospective verbal consent followed by written informed consent. Of those enrolled by deferral of consent, 95% (1,454/1,537) consented to ongoing participation. Door-to-randomization times were similar regardless of method of consent, with an overall median of 30 minutes (interquartile range [IQR] 22-42): 29 minutes (IQR 22-42) in the deferral of consent group vs 32 minutes (IQR 25-44) in the prospective consent group ( p = 0.1602). Survey respondents overwhelming agreed or strongly agreed with the use of deferral of consent in AcT (86%) and in any acute stroke trial (76%)., Discussion: Deferral of consent was broadly acceptable to participants in the AcT trial as demonstrated by low rates of withdrawal and by survey results. Door-to-randomization times using deferral of consent in AcT were short, although a system of prospective verbal consent used at 1 center took only slightly longer. These results support the importance of innovation around consent for acute stroke trials.

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.

Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

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: Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion., Methods: Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes., Results: Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048)., Conclusion: In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interests., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion., Methods: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC 1 , with a coefficient > 0.60 indicating substantial to almost perfect agreement., Results: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker., Conclusion: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement., Key Points: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC 1 > 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading)., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

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.

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.

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.

Background and Purpose: The optimal management of patients with tandem lesions (TL), or cervical internal carotid artery (c-ICA) steno-occlusive pathology and ipsilateral intracranial occlusion, who are undergoing endovascular thrombectomy (EVT) remains unknown. We sought to establish the feasibility of a trial designed to address this question., Materials and Methods: The Endovascular Acute Stroke Intervention (EASI) study was a single-centre randomized trial comparing EVT to medical therapy for large-vessel occlusion stroke. Patients with TL receiving EVT were randomly allocated to acute c-ICA stenting or no stenting. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) at 24hours and mortality at 90 days., Results: Of 301 patients included in EASI between 2013 and 2018, 24 (8.0%) with TL were randomly allocated to acute stenting (n=13) or no stenting (n=11). Baseline characteristics were balanced. Eight (61.5%; 95% CI 35.5%-82.3%) and 7 (63.6%; 95% CI 35.4%-84.9%) patients, respectively, had a favorable outcome (mRS 0-2; P=1.0). One non-stented patient had a symptomatic intracerebral hemorrhage., Conclusions: This pilot trial of patients with TL undergoing EVT suggests that a sufficiently powered larger TL trial comparing acute c-ICA stenting to no stenting is feasible., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02157532., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Standard poststroke treatment monitoring protocols are made problematic during the coronavirus disease 2019 (COVID-19) pandemic by the frequency of patient assessments, requiring repeated donning and doffing procedures in a short interval of time., Methods: A streamlined poststroke treatment protocol was developed to limit frequency of patient encounters while maximizing the yield of each encounter by grouping together different components of poststroke care into single bedside visits., Results: Streamlined order sets were developed late March 2020. During the first 6 weeks following implementation, 70 patients were admitted to a geographically defined designated warm COVID-19 unit with modified poststroke care order sets. Of these, 33 (47.1%) patients received acute reperfusion therapy. All but 3 patients evolved favorably with either stable or improving National Institutes of Health Stroke Scale at 24 hours. In the 3 patients who experienced early neurological deterioration, none were found to be attributable to insufficient patient monitoring., Conclusions: Adapting preexisting poststroke care protocols may be necessary while the risk of COVID-19 infection remains high. We propose a streamlined approach to facilitate poststroke monitoring in patients with stroke with unknown COVID status.

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 and Purpose- Patients with transient ischemic attack (TIA) and minor ischemic stroke are at risk for early recurrent cerebral ischemia. Anticoagulants are associated with reduced recurrence but also increased hemorrhagic transformation (HT). The safety of the novel oral anticoagulant dabigatran in acute stroke has not been evaluated. Methods- DATAS II (Dabigatran Treatment of Acute Stroke II) was a phase II prospective, randomized open label, blinded end point trial. Patients with noncardioembolic stroke/transient ischemic attack (National Institutes of Health Stroke Scale score, ≤9; infarct volume, ≤25 mL) were randomized to dabigatran or aspirin. Magnetic resonance imaging was performed before randomization and repeated at day 30. Imaging end points were ascertained centrally by readers blinded to treatment. The primary end point was symptomatic HT within 37 days of randomization. Results- A total of 305 patients, mean age 66.59±13.21 years, were randomized to dabigatran or aspirin a mean of 42.00±17.31 hours after symptom onset. The qualifying event was a transient ischemic attack in 21%, and ischemic stroke in 79% of patients. Median National Institutes of Health Stroke Scale (interquartile range) was 1 (0-2), and mean infarct volume 3.2±6.5 mL. No symptomatic HT occurred. Asymptomatic petechial HT developed in 11/142 (7.8%) of dabigatran-assigned patients and 5/142 (3.5%) of aspirin-assigned patients (relative risk, 2.301 [95% CI, 0.778-6.802]). Baseline infarct volume predicted incident HT (odds ratio, 1.07 [95% CI, 1.03-1.12]; P =0.0026). Incident covert infarcts on day 30 imaging occurred in 9/142 (6.3%) of dabigatran-assigned and 14/142 (9.8%) of aspirin-assigned patients (relative risk, 0.62 [95% CI, 0.26, 1.48]). Conclusions- Dabigatran was associated with a risk of HT similar to aspirin in acute minor noncardioembolic ischemic stroke/transient ischemic attack. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02295826.

Introduction: Prehospital identification of large vessel occlusion (LVO) stroke may expedite treatment by direct transport to comprehensive stroke centers (CSCs) with endovascular capabilities. The Cincinnati Prehospital Stroke Scale (CPSS) is commonly used for prehospital stroke detection. We aimed to assess whether (1) a high CPSS score can identify LVO and (2) an Emergency Medical Service (EMS) redirection protocol based on high CPSS accelerated endovascular treatment (EVT)., Methods: A retrospective comparison of patients transported by EMSs for suspected stroke to a high-volume CSC over a 16-month period, before and after implementation of an EMS redirection protocol based on high CPSS score (3/3). Charts were reviewed to determine the presence of LVO. Time to EVT and 3-month outcomes were compared before and after implementation., Results: A prehospital CPSS 3/3 score was found in 223 (59%) patients, demonstrating positive and negative predictive values for LVO of 29% and 94%, respectively. CPSS-based EMS redirection increased the proportion of EVT performed after direct transport to CSC [before: 21 (36%), after: 45 (63%), p < 0.01] and decreased median first door-to-groin puncture time by 28 minutes [109 (interquartile range (IQR) 64-116) versus 81 (IQR 56-130), p = 0.03]. At 3 months, the proportion of patients achieving functional independence (modified Rankin score 0-2) went from 20/57 (35%) to 29/68 (43%) (p = 0.39) following implementation., Conclusions: CPSS-based EMS redirection accelerated identification of LVO strokes in the out-of-hospital setting and decreased time to EVT. Nevertheless, this protocol was also associated with high rates of non-LVO stroke. Impact on clinical outcomes should be evaluated in a larger cohort.

The effect of blood pressure (BP) reduction on cerebral blood flow (CBF) in acute ischemic stroke is unknown. We measured regional CBF with perfusion-weighted MRI before and after BP treatment in a three-armed non-randomized prospective controlled trial. Treatment arm assignment was based on acute mean arterial pressure (MAP). Patients with (MAP) >120 mmHg ( n  = 14) were treated with intravenous labetalol and sublingual (SL) nitroglycerin (labetalol group). Those with MAP 100-120 mmHg ( n  = 17) were treated with SL nitroglycerin (0.3 mg) ('NTG Group') and those with baseline MAP<100 mmHg ( n  = 18) were not treated with antihypertensive drugs (untreated group). Forty-nine patients (18 female, mean age 65.3 ± 12.9 years) were serially imaged. Labetalol reduced MAP by 12.5 (5.7-17.7) mmHg, p  = 0.0002. MAP remained stable in the NTG (6.0 (0.4-16, p  = 0.3) mmHg and untreated groups (-0.3 (-2.3-7.0, p  = 0.2) mmHg. The volume of total hypoperfused tissue (CBF<18 ml/100 g/min) did not increase after labetalol (-1.1 ((-6.5)-(-0.2)) ml, p  = 0.1), NTG (0 ((-1.5)-4.5) ml, p  = 0.72), or no treatment 0.25 ((-10.1)-4.5) ml, p  = 0.87). Antihypertensive therapy, based on presenting BP, in acute stroke patients was not associated with an increased volume of total hypoperfused tissue.

Background Subacute ischemic lesions in intracerebral hemorrhage ( ICH ) have been hypothesized to result from hypoperfusion. Although studies of cerebral blood flow ( CBF ) indicate modest hypoperfusion in ICH , these investigations have been limited to early time points. Arterial spin labeling ( ASL ), a magnetic resonance imaging technique, can be used to measure CBF without a contrast agent. We assessed CBF in patients with ICH using ASL and tested the hypothesis that CBF is related to systolic blood pressure ( SBP ). Methods and Results In this cross-sectional study, patients with ICH were assessed with ASL at 48 hours, 7 days, and/or 30 days after onset. Relative CBF ( rCBF ; ratio of ipsilateral/contralateral perfusion) was measured in the perihematomal regions, hemispheres, border zones, and the perilesional area in patients with diffusion-weighted imaging hyperintensities. Twenty-patients (65% men; mean± SD age, 68.5±12.7 years) underwent imaging with ASL at 48 hours (N=12), day 7 (N=6), and day 30 (N=11). Median (interquartile range) hematoma volume was 13.1 (6.3-19.3) mL. Mean± SD baseline SBP was 185.4±25.5 mm Hg. Mean perihematomal rCBF was 0.9±0.2 at 48 hours at all time points. Baseline SBP and other SBP measurements were not associated with a decrease in rCBF in any of the regions of interest ( P≥0.111). r CBF did not differ among time points in any of the regions of interest ( P≥0.097). Mean perilesional rCBF was 1.04±0.65 and was unrelated to baseline SBP ( P=0.105). Conclusions ASL can be used to measure rCBF in patients with acute and subacute ICH . Perihematomal CBF was not associated with SBP changes at any time point. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.

Background and Purpose- In patients with acute stroke caused by tandem occlusion, the benefit of immediate revascularization (stenting) of the cervical internal carotid artery lesion during endovascular thrombectomy is uncertain. We sought to determine current practice patterns and whether consensus existed among physicians with stroke expertise. Methods- We distributed an online survey to stroke experts affiliated with the Canadian Stroke Consortium, the Canadian Interventional Neuro Group, the Society of Vascular and Interventional Neurology, and international ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) collaborators. Questions were based on clinical scenarios, and multiple choice responses across a Likert-type scale were provided. The survey was sent out in September 2017. After 2 months, data were extracted and then analyzed using descriptive statistics. Results- Responses from 162 stroke experts were analyzed; most were stroke physicians (n=65, 40.1%) and neurointerventionalists (n=74, 45.7%), from Canada (n=95, 58.6%), the United States (n=42, 25.9%), and other countries (n=25, 15.4%). Over half (n=96, 59.3%) of respondents consider acute stenting of the cervical internal carotid artery as a treatment option, whereas 40.7% (n=66) would never use it. Most respondents (n=113, 69.8%) agree that there exists uncertainty about the optimal acute management of patients with tandem occlusion. A majority (n=88, 54.3%) of physicians surveyed would include patients in a randomized trial addressing this question. Conclusions- This survey shows high variability in practice about acute management of tandem occlusion. The existence of community equipoise underscores the importance of a randomized trial evaluating the benefit of acute internal carotid artery stenting in patients with tandem occlusion undergoing endovascular thrombectomy.

Background: Despite the use of validated prehospital stroke scales, stroke mimics are frequent among patients transported by Emergency Medical Services to the Emergency Department. We aimed to describe the frequency and characteristics of neurological and non-neurological mimics transported to a comprehensive stroke center for acute stroke evaluation., Methods: This was a retrospective analysis of a database consisting of all consecutive patients with suspected stroke transported to the Emergency Department of a comprehensive stroke center during an 18-month period. Hospital charts and neuroimaging were utilized to adjudicate the final diagnosis (acute stroke, stroke mimic, and specific underlying diagnoses)., Results: Nine hundred fifty patients were transported with suspected stroke, among whom 405 (42.6%) were stroke mimics (age 66.9 ± 17.1 years; 54% male). Neurological mimics were diagnosed in 223 (55.1%) patients and mimics were non-neurological in 182. The most common neurological diagnoses were seizures (19.7%), migraines (18.8%), and peripheral neuropathies (11.2%). Cardiovascular (14.6%) and psychiatric (11.9%) diagnoses were common non-neurological mimics. Patients with neurological mimics were younger (64.1 ± 17.3 years versus 70.5 ± 16.1 years, P < .001) and had less vascular risk factors than non-neurological mimics. The proportion of non-neurological mimics remained high (38%) despite the use of a prehospital stroke identification scale., Conclusions: Stroke mimics are common among patients transported by Emergency Medical Services to a comprehensive stroke center for suspected stroke, with a considerable proportion being non-neurological in origin. Studies refining triage and transport of suspected acute stroke may be warranted to minimize the number of mimics transported by to a comprehensive stroke center for acute stroke evaluation., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Purpose To follow the evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM). Materials and Methods Thirty-six patients with ICH confirmed at CT were enrolled to follow ICH evolution on day 2, 7, and 30 after symptom onset between August 2013 and April 2017. QSM was reconstructed from MRI gradient-echo phase images acquired at 1.5 T or 3.0 T. ICH regions were manually drawn on two-dimensional sections of co-registered CT and MR images independently by two raters. The ICH areas and mean values were compared between CT and MRI by using Bland-Altman plots and Pearson correlation. QSM time evolution of ICH was assessed by using paired t tests and was compared with conventional T2-weighted fluid-attenuated inversion recovery, or T1-weighted or T2*-weighted magnitude intensities. Results Significant reductions in ICH susceptibility were found between day 2 and day 7 (P < .001) and between day 7 and day 30 (P = .003), corresponding to different disease stages. The ICH areas measured at CT and QSM were linearly correlated (r 2 = 0.98). The mean CT attenuation and mean susceptibility of ICH were linearly correlated (r 2 = 0.29). Excellent intra- and interobserver reproducibility were found for QSM (intraclass correlation coefficient, 0.987 and 0.966, respectively). Conclusion Longitudinal evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM) demonstrated susceptibility differences in different disease stages, which was not found at conventional MRI; therefore, QSM may assist in quantitatively following ICH iron content., (© RSNA, 2018 Online supplemental material is available for this article.)

Background and Purpose: Thrombolysis >4.5 hours after ischemic stroke onset is unproven. We assessed the feasibility of tenecteplase (TNK) treatment in patients with evidence of an ischemic penumbra 4.5 to 24 hours after onset., Methods: Acute ischemic stroke patients underwent perfusion computed tomography (CT)/magnetic resonance imaging. Patients with cerebral blood volume (CBV) or diffusion weighted imaging Alberta Stroke Program Early CT Scores (ASPECTS) >6 and mismatch score >2 (defined as >2 ASPECTS regions with delay on mean transit time maps and normal CBV) were eligible for treatment with TNK (0.25 mg/kg). Patients with mismatch patterns enrolled in non-endovascular/non-thrombolysis trials and those without mismatch patterns served as comparators., Results: The median (interquartile range) baseline National Institutes of Health Stroke Scale (NIHSS) in TNK treated patients (n=16) was 12 (range, 8 to 15). In the untreated mismatch (n=18) and nonmismatch (n=23) groups, the baseline NIHSS was 12 (range, 7 to 12) and 16 (range, 8 to 20; P =0.09) respectively. There was one symptomatic hemorrhage each in the TNK group (parenchymal hematoma [PH] 2) and non-mismatch group (PH 2). Penumbral salvage volumes were higher in TNK treated patients (48.3 mL [range, 24.9 to 80.4]) than the non-mismatch (-90.8 mL [range, -197 to -20]; P <0.0001) patients., Conclusions: This prospective, non-randomized study supports the feasibility of TNK therapy in patients with evidence of ischemic penumbra 4 to 24 hours after onset.

Purpose: To investigate gradient-echo phase errors caused by intracranial hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts from phase errors in quantitative susceptibility mapping (QSM) of ICH., Methods: Two QSM methods are proposed: (1) mask-inversion that masks the phase of low signal magnitude regions, and (2) ICH magnetic dipole field isolation followed by susceptibility superposition using multiple boundaries for background field removal. The reconstruction methods were tested in eight subjects with ICH using standard single-echo susceptibility-weighted imaging at 1.5 Tesla with 40 ms echo time. Different phase unwrapping algorithms were also compared., Results: Significant phase errors were evident inside ICHs with low signal magnitude. The mask-inversion method recovered susceptibility of ICH in numerical simulation and minimized phase error propagation in patients with ICH. The additional superposed dipole inversion process substantially suppressed and constrained streaking artifacts in all subjects. Using the proposed superposition method, ICH susceptibilities measured from long and short echo times were similar. Laplacian based phase unwrapping substantially underestimated the ICH dipole field as compared to a path-based method., Conclusion: The proposed methods of mask-inversion as well as ICH isolation and superposition can substantially reduce artifacts in QSM of ICH. Magn Reson Med 76:781-791, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack., Methods: A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7., Results: Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7., Conclusions: These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT., (© 2016 American Heart Association, Inc.)

Objective: To assess the natural history of prehospital blood pressure (BP) during emergency medical services (EMS) transport of suspected stroke and determine whether prehospital BP differs among types of patients with suspected stroke (ischemic stroke, TIA, intracerebral hemorrhage [ICH], or stroke mimic)., Methods: A retrospective, cross-sectional, observational analysis of a centralized EMS database containing electronic records of patients transported by EMS to the emergency department (ED) with suspected stroke during an 18-month period was conducted. Hospital charts and neuroimaging were utilized to determine the final diagnosis (ischemic stroke, TIA, ICH, or stroke mimic)., Results: A total of 960 patients were transported by EMS to ED with suspected stroke. Stroke was diagnosed in 544 patients (56.7%) (38.2% ischemic stroke, 12.2% TIA, 5.3% ICH) and 416 (43.2%) were considered mimics. Age-adjusted mean prehospital systolic BP (SBP) was higher in acute stroke patients (155.6 mm Hg; 95% confidence interval [CI]: 153.4-157.9 mm Hg) compared to mimics (146.1 mm Hg; 95% CI: 142.5-148.6 mm Hg; p < 0.001). Age-adjusted mean prehospital SBP was higher in ICH (172.3 mm Hg; 95% CI: 165.1-179.7 mm Hg) than in either ischemic stroke or TIA (154.7 mm Hg; 95% CI: 152.3-157.0 mm Hg; p < 0.001). Median (interquartile range) SBP drop from initial prehospital SBP to ED SBP was 4 mm Hg (-6 to 17 mm Hg). Mean prehospital SBP was strongly correlated with ED SBP (r = 0.82, p < 0.001)., Conclusions: Prehospital SBP is higher in acute stroke relative to stroke mimics and highest in ICH. Given the stability of BP between initial EMS and ED measurements, it may be reasonable to test the feasibility and safety of prehospital antihypertensive therapy in patients with suspected acute stroke., (© 2016 American Academy of Neurology.)

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume.

Background and Purpose: Diffusion-weighted imaging (DWI) lesions have been identified both inside and outside the perihematoma region. We tested the hypotheses that larger hematoma volumes and blood pressure reduction are associated with DWI lesions., Methods: Hematoma and perihematoma edema volumes were measured using planimetric techniques in 117 intracerebral hemorrhage (ICH) patients who underwent DWI. Perihematoma and remote DWI lesion volumes were measured using apparent diffusion coefficient thresholds for moderate (<730×10(-6) mm/s) and severe (<550×10(-6) mm/s) ischemia. Acute blood pressure change over the first 24 hours was calculated., Results: The median (interquartile range) time to magnetic resonance imaging was 2 (1-5) days. Median hematoma volume was 9.8 (2.6-23.0) mL, and median perihematoma edema volume was 7.0 (2.9-18.6) mL. A small portion of the perihematoma region contained tissue below the thresholds for moderate (8.0 [2.9-14.5]%) and severe ischemia (1.1 [0.3-3.5]%). Ischemic perihematoma tissue volumes were correlated with hematoma volumes (R=0.52, P<0.001), but not maximal systolic blood pressure drop at 24 hours (R=-0.09, P=0.38). Remote DWI lesions were found in 17 (14.5%) patients (mean volume=0.44±0.3 mL). Patients with remote DWI lesions had higher rates of antiplatelet use (P=0.01), prior ICH (P=0.03), lobar ICH (0.04), and larger leukoaraiosis volumes (P=0.02). Maximal systolic blood pressure drop at 24 hours was similar in patients with (-20.5 [-55, -10] mm Hg) and without remote DWI lesions (-27 [-46, -13] mm Hg, P=0.96)., Conclusions: Small DWI lesions within and outside the perihematoma region are common in primary ICH. Perihematoma DWI lesions were independently associated with larger hematoma volumes. Remote DWI lesions may be an epiphenomenon associated with the underlying microvascular pathogenesis. These data do not support a hemodynamic mechanism of ischemic injury after primary ICH., (© 2015 American Heart Association, Inc.)

Purpose of Review: Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of morbidity and mortality. Although treatment options are limited, a potential acute medical intervention is blood pressure (BP) reduction. The review will summarize the current evidence and remaining knowledge gaps with respect to acute BP management in acute ICH., Recent Findings: More than 3000 patients were enrolled in seven prospective randomized-controlled clinical trials assessing the safety and efficacy of intensive BP reduction (target <140-150 mmHg systolic) compared with current guideline-recommended BP target (<180 mmHg) in acute ICH. Overall, these trials demonstrated that intensive BP reduction is well tolerated and may be associated with a modest improvement in functional outcomes. There is still no conclusive evidence that aggressive BP reduction is associated with attenuation of hematoma growth or mortality rates. Delayed time to enrolment and difficulty in achieving intensive BP targets in a timely fashion without stringent antihypertensive protocols may partially account for the absence of proven benefit., Summary: Recent trials have shown that BP lowering (<140 mmHg systolic) is well tolerated and may improve functional outcomes. Ongoing trials will provide insight into the overall benefit of early aggressive BP reduction in acute ICH.

Background and Purpose: The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated blood pressure (BP) reduction does not affect mean perihematoma or hemispheric cerebral blood flow. Nonetheless, portions of the perihematoma and borderzones may reach ischemic thresholds after BP reduction. We tested the hypothesis that BP reduction after intracerebral hemorrhage results in increased critically hypoperfused tissue volumes., Methods: Patients with Intracerebral hemorrhage were randomized to a target systolic BP (SBP) of <150 or <180 mm Hg and imaged with computed tomographic perfusion 2 hours later. The volumes of tissue below cerebral blood flow thresholds for ischemia (<18 mL/100 g/min) and infarction (<12 mL/100 g/min) were calculated as a percentage of the total volume within the internal and external borderzones and the perihematoma region., Results: Seventy-five patients with intracerebral hemorrhage were randomized a median (interquartile range) of 7.8 (13.3) hours from onset. Acute hematoma volume was 17.8 (27.1) mL and mean SBP was 183±22 mm Hg. At the time of computed tomographic perfusion (2.3 [1.0] hours after randomization), SBP was lower in the <150 mm Hg (n=37; 140±18 mm Hg) than in the <180 mm Hg group (n=36; 162±12 mm Hg; P<0.001). BP treatment did not affect the percentage of total borderzone tissue with cerebral blood flow<18 (14.7±13.6 versus 15.6±13.7%; P=0.78) or <12 mL/100 g/min (5.1±5.1 versus 5.8±6.8%; P=0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP<150 mmHg) did not predict borderzone tissue volume with cerebral blood flow<18 mL/100 g/min (β=0.023 [-0.073, 0.119])., Conclusions: BP reduction does not increase the volume of critically hypoperfused borderzone or perihematoma tissue. These data support the safety of early BP reduction in intracerebral hemorrhage., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00963976., (© 2014 American Heart Association, Inc.)

Background: A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions., Aim: To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients., Materials and Methods: Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine., Results: Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of Fabry disease. Investigation results suggestive of Fabry disease (idiopathic hypertrophic cardiomyopathy, proteinuria, vertebrobasilar dolichoectasia, and the pulvinar sign) were found only in subjects with normal α-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke., Conclusions: Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the association between silent ischemic lesions (SILs) on baseline brain MRI and recurrent stroke in young adults with first-ever ischemic stroke., Methods: This was a single-center retrospective study of adult patients aged 18-50 years with first-ever ischemic stroke investigated by brain MRI between 2002 and 2009. Silent brain infarcts (SBIs) were defined as focal T2 hyperintensities ≥ 3 mm without corresponding focal symptoms, and leukoaraiosis was defined as focal, multifocal, or confluent hyperintensities on T2-weighted sequences. The primary outcome was recurrent stroke. A forward stepwise Cox regression model was used to determine whether SILs were independently associated with recurrent stroke., Results: A total of 271 eligible patients were identified in the database: 89 did not undergo MRI imaging and 12 patients had inadequate follow-up, leaving a study population of 170 patients. MRI demonstrated SILs in 48 of 170 (28.2) patients. No patients had isolated leukoaraiosis. Hypertension (p = 0.049), migraine with aura (p = 0.02), and cardiovascular disease (p = 0.04) were associated with SIL. Mean follow-up duration was 25 ± 7 months. Among patients with SILs, 11 of 48 (23%) had a recurrent stroke vs 8 of 122 (6.5%) patients without SIL (p = 0.003). After multivariate Cox regression, SILs remained independently associated with recurrent stroke (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.2-8.6, p = 0.02), as did the combination of SBIs and leukoaraiosis (HR 7.3, 95% CI 2.3-22.9, p = 0.003)., Conclusions: In adults ≤ 50 years old with first-ever ischemic stroke, SILs are common and independently predict recurrent stroke.

The benefits of angiotensin-converting enzyme (ACE) inhibitors for the treatment of congestive heart failure (CHF) are well-established. A newer class of medications, angiotensin II receptor blockers (ARBs), may be a suitable replacement for ACE inhibitors as a result of a more complete inhibition of angiotensin II and better tolerability among patients. To examine the current literature on the efficacy and safety of ARBs in the setting of CHF, a Medline search was conducted of the English language literature for the years 1987 to 2005. Clinical trials that reported data on cardiac outcomes were reviewed. The earlier trials were direct ARB to ACE inhibitor comparisons (ELITE I and ELITE II). These studies indicated that ARBs do not confer an improvement in cardiac outcomes over ACE inhibitors. RESOLVD, Val-HeFT, and the 3 separate trials of the CHARM program investigated the addition of an ARB to standard therapy. The RESOLVD trial showed no significant differences in clinical events among ACE inhibitor, ARB, and their combination. Although no mortality benefit was evident in the Val-HeFT trial, a substantial reduction in CHF rehospitalizations was reported among patients who were not receiving ACE inhibitor therapy. The CHARM-Overall program demonstrated a significant benefit in cardiovascular death and hospital admissions for CHF with the addition of ARB to standard therapy, a benefit that was more pronounced in patients with depressed left ventricular ejection fraction. In the setting of CHF, rates of cardiac outcomes do not differ substantially between ARBs and ACE inhibitors. However, their combination may improve outcomes for patients with CHF.

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR = 2.83, 95% CI = 1.25-6.40, p = 0.01; OR = 6.60, 95% CI = 1.02-42.4, p = 0.047, respectively). For each readmission, the mean length of stay was 10.7 +/- 2.5 days and the mean cost was dollar 13,397 +/- 3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7 +/- 3.5 days for each readmitted patient and the mean per-patient total cost was dollar 23,262 +/- 5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients' index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.