Search

IMPORTANCE Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. OBJECTIVE To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. DESIGN, SETTING, AND PARTICIPANTS This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. MAIN OUTCOMES AND MEASURES Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). RESULTS The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). CONCLUSIONS AND RELEVANCE In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

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

Background and ObjectivesIn pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials.MethodsWe did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008–2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014–2018; Barcelona Plaque Study, 2015–2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed.ResultsWe included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0–1, 15.1% scoring 2–3, and 26.7% scoring 4–5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32–3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence.DiscussionThe SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain.Classification of EvidenceThis study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.

Background and Purpose: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. Methods: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. Results: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63–79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2–4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6–9] versus 6 [4–9]), similar favorable thrombus permeability (residual flow grades I–II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11–13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26–60.13]) were associated with successful recanalization among mild patients. Conclusions: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.

Background Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear. Methods A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset Results Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p p p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio [OR] 1.18, 95% CI 1.00–1.39) in patients Conclusions Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians’ suspicion of TIA/MS. Trial registration ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered.

Background: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. Methods: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. Results: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. Conclusions: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status. (Less)

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Contains fulltext : 245661.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). OBJECTIVE: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. EXPOSURES: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES: Clinical characteristics and mortality rate. RESULTS: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Background and purposePatients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects.MethodsNinety-five TIA subjects and 51 non-TIA subjects were assessed using DTI and neuropsychological batteries. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and measurements were collected from WM tracts. Adjusted mixed effects regression modelled the relationship between groups and DTI metrics.ResultsTransient ischemic attack subjects had a mean age of 67.9 ± 9.4 years, and non-TIA subjects had a mean age 64.9 ± 9.9 years. The TIA group exhibited higher MD values in the fornix (0.36 units, P < 0.001) and lower FA in the superior longitudinal fasciculus (SLF) (-0.29 units, P = 0.001), genu (-0.22 units, P = 0.016), and uncinate fasciculus (UF) (-0.26 units, P = 0.004). Compared to non-TIA subjects, subjects with TIA scored lower on the Addenbrooke's Cognitive Assessment-Revised (median score 95 vs 91, P = 0.01) but showed no differences in scores on the Montreal Cognitive Assessment (median 27 vs 26) or the Mini-Mental State Examination (median 30). TIA subjects had lower scores in memory (median 44 vs 52, P < 0.01) and processing speed (median 45 vs 62, P < 0.01) but not executive function, when compared to non-TIA subjects. Lower FA and higher MD in the fornix, SLF, and UF were associated with poorer performance on tests of visual memory and executive function but not verbal memory. Lower FA in the UF and fornix were related to higher timed scores on the TMT-B (P < 0.01), and higher SLF MD was related to higher scores on TMT-B (P < 0.01), confirming worse executive performance in the TIA group.ConclusionsDTI scans may be useful for detecting microstructural disease in TIA subjects before cognitive symptoms develop. DTI parameters, white matter hyperintensities, and vascular risk factors underly some of the altered neuropsychological measures in TIA subjects.

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

Background and Purpose— Embolic stroke of undetermined source (ESUS) constitutes a large proportion of acute ischemic stroke. It is crucial to identify possible stroke etiologies in this patient subgroup to individually tailor secondary stroke prevention strategies. This study aimed to assess the prevalence of carotid plaques causing Methods— Patients from INTERRSeCT—a multicenter prospective study of patients with acute ischemic stroke—were included in this study if their stroke etiology was not large artery atherosclerosis (>50% stenosis), and neck computed tomography angiography was obtained. Degree of stenosis ( Results— Four hundred forty-six patients were included in the study (median age, 73 years; 218 men), 138 of which were ESUS patients (median age, 70 years; 61 men). Nonstenotic carotid plaques (with P =0.004). Nonstenotic carotid plaques were significantly associated with ipsilateral strokes (adjusted odds ratio, 1.83 [95% CI, 1.05–3.18]). Conclusions— In patients with ESUS, nonstenotic carotid plaques were significantly more common on the side of the ischemic stroke, suggesting that these plaques could be a potential stroke etiology in patients in whom the ischemic stroke is classified currently as ESUS.

Background and Purpose— White matter lesions (WML) are associated with cognitive decline, increased stroke risk, and disability in old age. We hypothesized that superimposed acute cerebrovascular occlusion on chronic preexisting injury (leukoaraiosis) leads to worse outcome after minor cerebrovascular event, both using quantitative (volumetric) and qualitative (Fazekas scale) assessment, as well as relative total brain volume. Methods— WML volume assessment was performed in 425 patients with high-risk transient ischemic attack (TIA; motor/speech deficits >5 minutes) or minor strokes from the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Complete baseline characteristics and outcome assessment were available in 412 patients. Primary outcome was disability at 90 days, defined as modified Rankin Scale score of >1. Secondary outcomes were stroke progression, TIA recurrence, and stroke recurrence. Analysis was performed using descriptive statistics and regression models including interaction terms. Results— Median age was 69 years, 39.8% were female. Sixty-two patients (15%) had unfavorable outcome with disability at 90 days (modified Rankin Scale score >1). Higher Fazekas scores were strongly correlated with higher WML volume ( r =0.79). Both higher Fazekas score and higher WMH volume were associated with disability at 90 days in univariate regression (odds ratio 1.22; 95% confidence interval, 1.04–1.43 and odds ratio, 1.25 per milliliter increase; 95% confidence interval, 1.02–1.54, respectively) but not with stroke progression, TIA recurrence, or stroke recurrence. In multivariable-adjusted analyses, additive interaction terms were associated with unfavorable outcome (adjusted odds ratio 3.99, 95% confidence interval, 1.87–8.49). Conclusions— Our data suggest that quantitative and qualitative WML assessments are highly correlated and comparable in TIA/minor stroke patients. WML burden is associated with short-term outcome of patients with good prestroke function in the presence of intracranial stenosis/occlusion.

Background Validation of administrative data case definitions is key for accurate passive surveillance of disease. Transient ischemic attack (TIA) is a condition primarily managed in the emergency department. However, prior validation studies have focused on data after inpatient hospitalization. We aimed to determine the validity of the Canadian 10th International Classification of Diseases (ICD-10-CA) codes for TIA in the national ambulatory administrative database. Methods We performed a diagnostic accuracy study of four ICD-10-CA case definition algorithms for TIA in the emergency department setting. The study population was obtained from two ongoing studies on the diagnosis of TIA and minor stroke versus stroke mimic using serum biomarkers and neuroimaging. Two reference standards were used 1) the emergency department clinical diagnosis determined by chart abstractors and 2) the 90-day final diagnosis, both obtained by stroke neurologists, to calculate the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the ICD-10-CA algorithms for TIA. Results Among 417 patients, emergency department adjudication showed 163 (39.1%) TIA, 155 (37.2%) ischemic strokes, and 99 (23.7%) stroke mimics. The most restrictive algorithm, defined as a TIA code in the main position had the lowest sensitivity (36.8%), but highest specificity (92.5%) and PPV (76.0%). The most inclusive algorithm, defined as a TIA code in any position with and without query prefix had the highest sensitivity (63.8%), but lowest specificity (81.5%) and PPV (68.9%). Sensitivity, specificity, PPV, and NPV were overall lower when using the 90-day diagnosis as reference standard. Conclusions Emergency department administrative data reflect diagnosis of suspected TIA with high specificity, but underestimate the burden of disease. Future studies are necessary to understand the reasons for the low to moderate sensitivity. Electronic supplementary material The online version of this article (10.1186/s12913-017-2612-6) contains supplementary material, which is available to authorized users.

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.

Background and Purpose— While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods— The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results— At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82–1.14]; P =0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53–1.01]; P =0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62–0.99]; P =0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57–0.96]; P =0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions— In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

Background and Purpose— In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18 F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18 F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods— We derived the score in a prospective cohort study of recent (18 F-fluorodeoxyglucose standardized uptake values (SUV max max 2–2.99 g/mL, 1 point; SUV max 3–3.99 g/mL, 2 points; SUV max ≥4 g/mL, 3 points) and stenosis ( Results— In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score ( P =0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5, P =0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5], P P =0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97], P =0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39], P =0.004). Conclusions— The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

Background and Purpose— Acute minor neurological deficits are a common complaint in the emergency department and differentiation of transient ischemic attack/minor stroke from a stroke mimic is difficult. We sought to assess the ability of white matter hyperintensity (WMH) volume to aid the diagnosis in such patients. Methods— This is a post hoc analysis of the previously published SpecTRA study (Spectrometry in TIA Rapid Assessment) of adult patients that presented to the emergency department with acute minor neurological deficits between December 2013 and March 2017. WMH volumes were measured if fluid-attenuated inversion recovery imaging was available. Outcomes of interest were final diagnosis, symptoms at presentation, and 90-day stroke recurrence. Results— WMH volume was available for 1485 patients. Median age was 70 years (interquartile range, 59–80), and 46.7% were female. Mean WMH volume was higher in transient ischemic attack/minor strokes compared with stroke mimics (1.71 ln mL [95% CI, 1.63–1.79 ln mL] versus 1.15 ln mL [95% CI, 1.02–1.27 ln mL], P P =0.035). Conclusions— The combination of diffusion-weighted imaging positivity and high WMH volume was associated with lower odds of focal symptoms at presentation in patients seen with minor neurological deficits in the emergency department. This suggests that WMH volume might be an important consideration and the absence of focal symptoms at presentation should not discourage clinicians from further investigating patients with suspected cerebral ischemia.

Background and Purpose- Plaque inflammation contributes to stroke and coronary events.

Background: Stroke is often preceded by transient symptoms. Although global stroke rates have been shown to be declining, previous studies have reported inconsistent temporal trends of transient ischemic attacks (TIA). The objective of the current study is to report the temporal trends of TIA admissions and outcomes in Canada over the last 11 years. Methods: We conducted a complete population cohort study using a national administrative database to study the temporal trend of age- and sex-adjusted TIA admission rates in Canada from 2003 to 2013. We also determined the rates of TIA and stroke diagnoses in the emergency department in the province of Ontario during the same period. We used multivariable analyses to study discharge location after acute hospitalization as well as 90-day stroke and/or TIA readmission rates. Results: Of 425,799 admissions to an acute care hospital for all stroke and TIA, 71,443 (16.8%) were TIA. The age- and sex-standardized rates of TIA admission decreased significantly during the study period from 30.0 to 20.6 per 100,000 (pConclusions: We show that TIA admission rates have declined in the past 11 years in Canada, reflecting improved vascular risk reduction and stroke care. Future studies to confirm our findings on improved stroke or TIA recurrence rates are necessary.

Objective The best screening questionnaires for detecting post-stroke depression have not been identified. We aimed to validate four commonly used depression screening tools in stroke and transient ischemic attack patients. Methods Consecutive stroke and transient ischemic attack patients visiting an outpatient stroke clinic in Calgary, Alberta (Canada) completed a demographic questionnaire and four depression screening tools: Patient Health Questionnaire (PHQ)-9, PHQ-2, Hospital Anxiety and Depression Scale (HADS-D), and Geriatric Depression Scale (GDS-15). Participants then completed the Structured Clinical Interview for DSM-IV (SCID), the gold-standard for diagnosing major depression. The questionnaires were validated against the SCID and sensitivity and specificity were calculated at various cut-points. Optimal cut-points for each questionnaire were determined using receiver-operating curve analyses. Results Among 122 participants, 59.5% were diagnosed with stroke and 40.5% with transient ischemic attack. The point prevalence of SCID-diagnosed current major depression was 9.8%. At the optimal cut-points, the sensitivity and specificity for each screening tool were as follows: PHQ-9 (sensitivity: 81.8%, specificity: 97.1%), PHQ-2 (sensitivity: 75.0%, specificity: 96.3%), HADS-D (sensitivity: 63.6%, specificity: 98.1%), and GDS-15 (sensitivity: 45.5%, specificity: 84.8%). Areas under the receiver operating characteristic curves were as follows: PHQ-9 86.6%, PHQ-2 86.7%, HADS-D 85.9%, and GDS-15 66.3%. Conclusions The PHQ-2 and PHQ-9 are both suitable depression screening tools, taking less than 5 minutes to complete. The HADS-D does not appear to have any advantage over the PHQ-based scales, even though it was designed specifically for medically ill populations. The GDS-15 cannot be recommended for general use in a stroke clinic based on this study as it had worse discrimination due to low sensitivity.

Background and Purpose— Few studies have examined predictors of cognitive impairment after minor ischemic stroke and transient ischemic attack (TIA). We examined clinical and imaging features associated with worse cognitive performance at 90 days. Methods— TIA or patients with minor stroke underwent neuropsychological testing 90 days post event. Z scores were calculated for cognitive tests, and then grouped into domains of executive function (EF), psychomotor processing speed (PS), and memory. White matter hyperintensity and diffusion-weighted imaging volumes were measured on baseline magnetic resonance imaging. Ninety-day outcomes included modified Rankin Scale (mRS) and Centre for Epidemiological Studies Depression Scale (CES-D) score. Results— Ninety-two patients were included, 76% male, 54% TIA, and mean age 65.1±12.0. Sixty-four percent were diffusion-weighted imaging positive. Median domain z scores were not significantly different from published norms ( P >0.05): memory −0.03, EF −0.12, and PS −0.05. Patient performance ≥1 SD below normal was 20% on memory, 16% on PS, and 17% on EF. Cognitive scores did not differ by diagnosis (stroke versus TIA), stroke pathogenesis, presence of obstructive sleep apnea, and diffusion-weighted imaging or white matter hyperintensity volumes. In multivariable analyses, lower EF was associated with previous cortical infarct on magnetic resonance imaging ( P =0.03), mRS score of >1; P =0.0003 and depressive symptoms (CES-D ≥16; P =0.03). Lower PS scores were associated with previous cortical infarct ( P =0.02), acute bilateral positive diffusion-weighted imaging ( P =0.02), mRS score of >1 ( P =0.003), and CES-D ≥16 ( P =0.03). Conclusions— Despite average-range cognitive performance in this TIA and population with minor stroke, we found associations of EF and PS with evidence of previous stroke, postevent disability, and depression.

Leukoaraiosis regions may be more vulnerable to decreases in cerebral perfusion. We aimed to assess perfusion in leukoaraiosis regions in acute intracerebral hemorrhage (ICH) patients. We tested the hypothesis that aggressive acute BP reduction in ICH patients is associated with hypoperfusion in areas of leukoaraiosis. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), patients with ICH

Obstructive sleep apnea (OSA) is a risk factor for stroke, which is modulated by accompanying nocturnal hypoxemia. White matter hyperintensities (WMH) share many of the same risk factors as stroke. The purpose of this study was to investigate whether OSA and nocturnal hypoxemia are associated with white matter disease in patients with minor stroke and transient ischemic attack.Patients with minor stroke or TIA were recruited. Level 3 diagnostic sleep testing was used to diagnose OSA and quantify nocturnal hypoxemia. Significant OSA was defined as respiratory disturbance index ≥ 15, and nocturnal hypoxemia was defined as oxyhemoglobin saturation90% for ≥ 12% of total monitoring time. WMH were assessed and quantified on FLAIR MRI. The volume of WMH was compared between those with and without significant OSA and between those with and without nocturnal hypoxemia.One hundred nine patients were included. Thirty-four (31%) had OSA and 37 (34%) had nocturnal hypoxemia. Total WMH volume was significantly greater in the OSA than in the non-OSA groups (p = 0.04). WMH volume was also significantly higher in the hypoxic than the non-hypoxic groups (p = 0.001). Mutivariable analysis with adjustment for age, hypertension, and diabetes showed that nocturnal hypoxemia was independently associated with WMH volume (p = 0.03) but OSA was not (p = 0.29).We conclude that nocturnal hypoxemia, predominantly related to OSA, is independently associated with WMH in patients who present with minor ischemic stroke and TIA and may contribute to its pathogenesis.

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

Purpose We aim to characterize infarct volume evolution within the first month post-ischemic stroke and to determine the effect of recanalization status on early infarct volume estimation. Methods Ischemic stroke patients recruited for the MONITOR and VISION studies were retrospectively screened and patients who had infarcts on diffusion-weighted imaging (DWI) at baseline and had at least two follow-up MR scans (n = 56) were included. Pre-defined target imaging time points, obtained on a 3-T MR scanner, were 12 hours (h), 24 h, 7 days, and ≥30 days post-stroke. Infarct tissue was manually traced blinded to the images at the other time points. Infarct expansion index was calculated by dividing infarct volume at each follow-up time point by the baseline DWI infarct volume. Recanalization was assessed within 24 h post-stroke. Correlation and statistical comparison analysis were done using the Spearman, Mann–Whitney, and Kruskal–Wallis tests. Results Follow-up infarct volumes were positively correlated with the baseline infarct volume (ρ > 0.81; p, Highlights • We characterize infarct volume evolution within the first month post-stroke. • We show that final infarct volume can be approximated 7 days post-stroke. • Nonrecanalized patients had a stronger correlation in 7-day vs final infarct volume.

A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single “troponin.” Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within

Background Late-life cognitive decline, caused by progressive neuronal loss leading to brain atrophy years before symptoms are detected, is expected to double in Canada over the next two decades. Cognitive impairment in late life is attributed to vascular and lifestyle related risk factors in mid-life in a substantial proportion of cases (50%), thereby providing an opportunity for effective prevention of cognitive decline if incipient disease is detected earlier. Patients presenting with transient ischemic attack (TIA) commonly display some degree of cognitive impairment and are at a 4-fold increased risk of dementia. In the Predementia Neuroimaging of Transient Ischemic Attack (PREVENT) study, we will address what disease processes (i.e., Alzheimer’s vs. vascular disease) lead to neurodegeneration, brain atrophy, and cognitive decline, and whether imaging measurements of brain iron accumulation using quantitative susceptibility mapping predicts subsequent brain atrophy and cognitive decline. Methods A total of 440 subjects will be recruited for this study with 220 healthy subjects and 220 TIA patients. Early Alzheimer’s pathology will be determined by cerebrospinal fluid samples (including tau, a marker of neuronal injury, and amyloid β1–42) and by MR measurements of iron accumulation, a marker for Alzheimer’s-related neurodegeneration. Small vessel disease will be identified by changes in white matter lesion volume. Predictors of advanced rates of cerebral and hippocampal atrophy at 1 and 3 years will include in vivo Alzheimer’s disease pathology markers, and MRI measurements of brain iron accumulation and small vessel disease. Clinical and cognitive function will be assessed annually post-baseline for a period of 5-years using a clinical questionnaire and a battery of neuropsychological tests, respectively. Discussion The PREVENT study expects to demonstrate that TIA patients have increased early progressive rates of cerebral brain atrophy after TIA, before cognitive decline can be clinically detected. By developing and optimizing high-level machine learning models based on clinical data, image-based (quantitative susceptibility mapping, regional brain, and white matter lesion volumes) features, and cerebrospinal fluid biomarkers, PREVENT will provide a timely opportunity to identify individuals at greatest risk of late-life cognitive decline early in the course of disease, supporting future therapeutic strategies for the promotion of healthy aging.

Rationale Patients with transient ischemic attack or minor stroke are at high risk of early recurrent cerebrovascular events. Anticoagulation with heparin or warfarin acutely after ischemic stroke is at least as efficacious as aspirin for preventing recurrent events but is associated with an increased risk of clinical worsening due to hemorrhagic transformation. Aim and hypothesis We aim to demonstrate the safety of early anticoagulation with dabigatran, an oral direct thrombin inhibitor, in acute cerebrovascular syndrome patients. The primary hypothesis is that symptomatic hemorrhagic transformation rates in dabigatran and aspirin-treated patients will be similar. Sample size estimates At least 136 participants in two groups required to demonstrate an absolute between-group difference in the rate of hemorrhagic transformation of 5.6% with 80% power, assuming alpha = 5%. Methods and design A randomized, multicenter open-label clinical trial (NCT02295826). Three-hundred participants with a transient ischemic attack/ischemic stroke (National Institutes of Health Stroke Scale ≤ 9) will undergo magnetic resonance imaging within 72 h of symptom onset and will be randomized to aspirin 81 mg daily or dabigatran 150 mg twice daily for 30 days. Participants undergo repeat magnetic resonance imaging at 30 days and clinical assessment to 90 days. Study outcomes The primary outcome is the symptomatic hemorrhagic transformation rate. Secondary outcomes include recurrent stroke and new ischemic lesions on repeat magnetic resonance imaging. Discussion This study will determine the safety of early anticoagulation with dabigatran in patients with acute transient ischemic attack/ischemic stroke and will inform the design of a phase III randomized trial aimed at demonstrating reduced recurrent early ischemic events after acute transient ischemic attack/stroke.

Objective:To describe home-time, stratified by stroke type, in a complete population and to determine its correlation with modified Rankin Scale (mRS) scores.Methods:We used linked administrative data to derive home-time in all patients admitted for a cerebrovascular event in Alberta, Canada, between 2012 and 2016. Home-time is the number of days spent outside a health institution in the first 90 days after index hospitalization. We used negative binomial regression, adjusted for age, sex, Charlson comorbidity index, and hospital location, to determine the association between home-time and stroke type. In 552 patients enrolled in 4 acute ischemic stroke clinical trials, we used multivariable ordinal logistic regression analysis to determine the association between home-time and mRS score at 90 days.Results:Among 15,644 patients (n = 10,428 with ischemic stroke, n = 1,415 with intracerebral hemorrhage, n = 760 with subarachnoid hemorrhage, n = 3,041 with TIA), patients with TIA have the longest home-time, almost triple the number of days at home compared to patients with intracerebral hemorrhage (incidence rate ratio 2.85, 95% confidence interval [CI] 2.58–3.15). Among clinical trial ischemic stroke patients, longer home-time was associated with a lower mRS score at 90 days (adjusted common odds ratio 1.04, 95% CI 1.04–1.05).Conclusions:We showed that home-time is an objective and graded indicator that is correlated with disability after stroke. It is obtainable from administrative data, applicable to different stroke types, and a valuable outcome indicator in population-based health services research.

Rationale Stroke risk after transient ischaemic attack is high and, it is a challenge worldwide to provide urgent assessment and preventive services to entire populations. Aims To determine whether a province-wide transient ischaemic attack Triaging algorithm and transient ischaemic attack hotline (the Alberta Stroke Prevention in transient ischaemic attacks and mild strokes intervention) can reduce the rate of stroke recurrence following transient ischaemic attack across the population of Alberta, Canada (population 3·7 million, 90-day rate of post-stroke transient ischaemic attack currently 9·5%). It also seeks to improve upon current transient ischaemic attack triaging rules by incorporating time from symptom onset as a predictive variable. Design The transient ischaemic attack algorithm and hotline were developed with a broad consensus of clinicians, patients, policy-makers, and researchers and based on local adaptation of the work of others and research and insights developed within the province. Because neither patient-level nor region-level randomization was possible, we conducted a quasi-experimental design examining changes in the post-transient ischaemic attack rate of stroke recurrence before and after the 15-month implementation period using an interrupted time-series regression analysis. The design controls for changes in case-mix, co-interventions, and secular trends. A prospective transient ischaemic attack cohort will also be concurrently created with telephone follow-up at seven-days and 90 days as well as passive follow-up over the longer term using linkages to provincial healthcare administrative databases. Study Outcomes The primary outcome measure is the change in recurrence rate of stroke following transient ischaemic attack at seven-days and 90 days, comparing a period of two-years before vs. two-years after the intervention is implemented. All cases of recurrent stroke will be validated. Secondary outcomes include functional status, hospitalizations, morbidity, and mortality. Conclusions We are undertaking a rigorous evaluation of a population-based approach to improving quality of transient ischaemic attack care. Whether positive or negative, our work should provide important insights for all potential stakeholders.

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 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 P P =0.78) or P =0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP 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.

Objectives To determine the diagnostic yield of echocardiography and its utility in changing medical management; and to derive a risk score to guide its use in patients with in-hospital stroke or transient ischaemic attack (TIA). Methods We carried out a retrospective chart review from January 2009 to June 2010 of patients with acute ischaemic stroke or TIA who had undergone transthoracic echocardiography (TTE) or transoesophageal echocardiography (TOE). Clinical and imaging findings at baseline were noted and ‘potential clinically relevant findings’ identified on TTE and TOE. A multivariable logistic regression was used to identify predictors of potential clinically relevant findings on TTE or TOE and derive a risk score. Results Of 370 patients, 307 (83.0%) had TTE and 63 (17.0%) had additional TOE. Potential clinically relevant findings on echocardiography were noted in 28 (7.6%) patients. Change in medical management was noted in 19/307 (6.2%) patients on TTE and in 7/63 (11.1%) patients on TOE. Male sex (OR 3.05, 95% CI 1.19 to 7.84; p=0.021), abnormal admission ECG (OR 4.39, 95% CI 1.79 to 10.79; p=0.001), and embolic pattern imaging at baseline (OR 2.38, 95% CI 1.05 to 5.40; p=0.038) were independent predictors of findings on TTE or TOE. A risk score including these three variables had modest discrimination (c-statistic 0.69, 95% CI 0.59 to 0.80). Conclusions Echocardiography detected potential clinically relevant findings in a minority of patients (7.6%), but these findings changed medical management 90.5% of the time. A risk score using sex, ECG abnormality, and embolic pattern imaging at baseline could help predict which patients are more likely to have these echo findings.

Importance Early treatment of patients with transient ischemic attack (TIA) reduces the risk of stroke. However, many patients present with symptoms that have an uncertain diagnosis. Patients with motor, speech, or prolonged symptoms are at the highest risk for recurrent stroke and the most likely to undergo comprehensive investigations. Lower-risk patients are much more likely to be cursorily investigated. Objective To establish the frequency of acute infarct defined by diffusion restriction detected on diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) scan (DWI positive). Design, Setting, and Participants The Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study was a prospective, observational, international, multicenter cohort study of 1028 patients with low-risk transient or minor symptoms referred to neurology within 8 days of symptom onset. Patients were enrolled between June 1, 2010, and October 31, 2016. Included patients were 40 years or older and had experienced nonmotor or nonspeech minor focal neurologic events of any duration or motor or speech symptoms of short duration (≤5 minutes), with no previous stroke. Exposures Patients underwent a detailed neurologic assessment prior to undergoing a brain MRI within 8 days of symptom onset. Main Outcomes and Measures The primary outcome was restricted diffusion on a brain MRI scan (acute stroke). Results A total of 1028 patients (522 women and 506 men; mean [SD] age, 63.0 [11.6] years) were enrolled. A total of 139 patients (13.5%) had an acute stroke as defined by diffusion restriction detected on MRI scans (DWI positive). The final diagnosis was revised in 308 patients (30.0%) after undergoing brain MRI. There were 7 (0.7%) recurrent strokes at 1 year. A DWI-positive brain MRI scan was associated with an increased risk of recurrent stroke (relative risk, 6.4; 95% CI, 2.4-16.8) at 1 year. Absence of a DWI-positive lesion on a brain MRI scan had a 99.8% negative predictive value for recurrent stroke. Factors associated with MRI evidence of stroke in multivariable modeling were older age (odds ratio [OR], 1.02; 95% CI, 1.00-1.04), male sex (OR, 2.03; 95% CI, 1.39-2.96), motor or speech symptoms (OR, 2.12; 95% CI, 1.37-3.29), ongoing symptoms at assessment (OR, 1.97; 95% CI, 1.29-3.02), no prior identical symptomatic event (OR, 1.87; 95% CI, 1.12-3.11), and abnormal results of initial neurologic examination (OR, 1.71; 95% CI, 1.11-2.65). Conclusions and Relevance This study suggested that patients with transient ischemic attack and symptoms traditionally considered low risk carry a substantive risk of acute stroke as defined by diffusion restriction (DWI positive) on a brain MRI scan. Early MRI is required to make a definitive diagnosis.

Importance The NAVIGATE ESUS randomized clinical trial found that 15 mg of rivaroxaban per day does not reduce stroke compared with aspirin in patients with embolic stroke of undetermined source (ESUS); however, it substantially reduces stroke risk in patients with atrial fibrillation (AF). Objective To analyze whether rivaroxaban is associated with a reduction of recurrent stroke among patients with ESUS who have an increased risk of AF. Design, Setting, and Participants Participants were stratified by predictors of AF, including left atrial diameter, frequency of premature atrial contractions, and HAVOC score, a validated scheme using clinical features. Treatment interactions with these predictors were assessed. Participants were enrolled between December 2014 and September 2017, and analysis began March 2018. Intervention Rivaroxaban treatment vs aspirin. Main Outcomes and Measures Risk of ischemic stroke. Results Among 7112 patients with a mean (SD) age of 67 (9.8) years, the mean (SD) HAVOC score was 2.6 (1.8), the mean (SD) left atrial diameter was 3.8 (1.4) cm (n = 4022), and the median (interquartile range) daily frequency of premature atrial contractions was 48 (13-222). Detection of AF during follow-up increased for each tertile of HAVOC score: 2.3% (score, 0-2), 3.0% (score, 3), and 5.8% (score, >3); however, neither tertiles of the HAVOC score nor premature atrial contractions frequency impacted the association of rivaroxaban with recurrent ischemic stroke (P for interaction = .67 and .96, respectively). Atrial fibrillation annual incidence increased for each tertile of left atrial diameter (2.0%, 3.6%, and 5.2%) and for each tertile of premature atrial contractions frequency (1.3%, 2.9%, and 7.0%). Among the predefined subgroup of patients with a left atrial diameter of more than 4.6 cm (9% of overall population), the risk of ischemic stroke was lower among the rivaroxaban group (1.7% per year) compared with the aspirin group (6.5% per year) (hazard ratio, 0.26; 95% CI, 0.07-0.94;Pfor interaction = .02). Conclusions and Relevance The HAVOC score, left atrial diameter, and premature atrial contraction frequency predicted subsequent clinical AF. Rivaroxaban was associated with a reduced risk of recurrent stroke among patients with ESUS and moderate or severe left atrial enlargement; however, this needs to be independently confirmed before influencing clinical practice.

Background and Purpose— Transient or minor ischemic stroke is associated with an early risk of deterioration. Baseline perfusion–diffusion mismatch may predict clinical deterioration and infarct growth in this population. Methods— High-risk transient ischemic attack and minor stroke (National Institutes of Health Stroke Scale ≤3) subjects were prospectively enrolled and imaged with MRI within 24 hours of symptom onset as part of sequential derivation and validation cohorts. Baseline diffusion-weighted imaging, perfusion-weighted imaging ( T max ≥4 s), mismatch ( T max ≥4 s-diffusion-weighted imaging), and follow-up fluid-attenuated inversion recovery infarct volumes were measured. Primary outcome was infarct growth on fluid-attenuated inversion recovery, and secondary outcome was symptom progression. Results— One hundred thirty-seven and 281 subjects were included in the derivation and validation cohorts, respectively. Infarct growth occurred in 18.5% of the derivation and 5.5% of the validation cohorts. Symptom progression occurred in 9.5% of the derivation and 4.5% of the validation cohorts. In the derivation cohort, subjects with baseline mismatch were significantly more likely to show infarct growth on fluid-attenuated inversion recovery (relative risk [RR], 13.5; 95% confidence interval [CI], 4.2–38.9) and symptom progression (RR, 7.0; 95% CI, 2.0–7.3). A baseline mismatch volume of 10 mL in the derivation cohort was the optimal threshold to predict infarct growth (area under the curve, 0.89; 95% CI, 0.80–0.98). This threshold was highly predictive of infarct growth in the validation cohort ( P =0.001). Baseline mismatch was associated with clinical deterioration in the derivation (area under the curve, 0.81; 95% CI, 0.67–0.96) and validation cohorts (area under the curve, 0.66; 95% CI, 0.46–0.85). Conclusions— Among subjects with high-risk transient ischemic attack and minor stroke, diffusion-weighted imaging–perfusion-weighted imaging mismatch predicts infarct growth and clinical deterioration. These findings suggest that reperfusion strategies would be beneficial in this population.

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

Background: Warfarin-associated intracerebral hemorrhage (WAICH) is a devastating disease with increasing incidence. In this setting, treatment with prothrombin complex concentrates (PCC) is essential to correct coagulopathy. Yet despite the availability of coagulopathy correction strategies, significant treatment delays can occur in emergency departments (EDs), which may be overcome using stroke prenotification strategies. To explore this, we compared arrival-to-treatment times with PCC for WAICH between two different stroke response systems that used the same international normalized ratio (INR) correction protocol. Methods: We established a registry of consecutive patients presenting with WAICH and treated with PCC presenting to two Canadian tertiary-care academic stroke centers: one with a stroke prenotification system, and one with a traditional ED assessment, treatment and referral system. In this comparative cohort design, we defined the WAICH diagnosis time as the earliest time point where both INR and CT were available. We compared median times from arrival to treatment, as well as arrival to diagnosis, and diagnosis to treatment. Results: Between 2008 and 2010, we collected data from 123 consecutive patients with intracranial hemorrhage who received PCC for INR correction (79 from ED referral, and 44 prenotification). Onset-to-arrival times, demographics, Glasgow Coma Scale scores, and baseline INR were similar between the two systems. Arrival-to-treatment times were significantly shorter in the prenotification system as compared to the traditional ED referral system (135 vs. 267 min; p = 0.001), which was driven by both decreased arrival-to-diagnosis time (49 vs. 117 min; p = 0.006), as well as decreased diagnosis-to-treatment time (56 vs. 112 min; p < 0.001). Arrival-to-scan times and arrival-to-INR times were similarly shorter in the prenotification system (68 vs. 118 min and 20.5 vs. 47 min, respectively). Conclusion: Stroke prenotification was associated with shorter arrival-to-treatment times for emergent INR correction in patients with WAICH, which was driven by both faster diagnosis and treatment. Our results are consistent with those seen in ischemic stroke, suggesting that prenotification systems present an opportunity to optimize acute intracerebral hemorrhage therapy.

Background and Purpose— Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. Methods— Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models. Results— Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models ( P P >0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score ( P P P Conclusions— Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.

Background and Purpose— Only a small percentage of stroke patients are treated with thrombolytic therapy. We sought to determine whether vessel occlusion in mild strokes represented a new target population for interventional therapy. Methods— We imaged 106 acute stroke patients with MRI. Patients were identified with evidence of middle cerebral artery (MCA) occlusion and mild or no stroke signs (National Institutes of Health Stroke Scale [NIHSS] ≤3). They were compared with patients with signs of stroke, NIHSS >3, and MCA occlusion. Results— We identified 5 patients with absent flow on MRA in the MCA and mild or no stroke signs (NIHSS ≤3). All 5 were functionally independent at 3 months. Conclusions— Caution should be exercised in considering thrombolytic therapy in these patients. Quantification of perfusion imaging is required to identify “at risk” mild stroke populations.

Contexte et objectif: La precision de l'angiographie par resonance magnetique intracrânienne (ARM) et la fiabilite de son interpretation sont mal etablies par rapport a l'angiographie selective conventionnelle par catheter. L'objectif de cette etude etait de determiner la precision de l'ARM pour l'evaluation des vaisseaux intracrâniens dans l'accident vasculaire cerebral (AVC) aigu et l'accident ischemique transitoire (AIT). Methodes: Vingt-neuf patients, (sept femmes et 22 hommes - âge median 53 ans) atteints d'AVC aigu ou d'AIT ont participe a l'etude. Tous les patients ont subi une ARM utilisant un aimant 3T et une angiographie conventionnelle en dedans de 48 heures de l'evenement. Le temps median entre l'ARM et l'angiographie etait de 263 minutes. L'angiographie conventionnelle a precede l'ARM chez 15 patients. Quatorze patients ont subi une thrombolyse pendant l'ARM ou l'angiographie. Le score au National Institutes of Health Stroke Scale a ete determine avant de faire l'ARM. Un neuroradiologiste a lu tous les angiogrammes conventionnels qui ont ete utilises comme examen de reference. Cinq observateurs qui ignoraient les resultats de l'angiographie conventionnelle ainsi que l'information clinique sauf la lateralite des symptomes, ont lu les angiogrammes par resonance magnetique. La fiabilite a ete evaluee au moyen de l'analyse statistique kappa; la precision de l'ARM non rehaussee et rehaussee a ete evaluee au moyen de tables de contingence. Resultats: Deux cent cinquante-deux vaisseaux intracrâniens ont ete evalues. La concordance entre les evaluateurs etait bonne tant pour les images non rehaussees (k = 0,50) que pour les images rehaussees au gadolinium (k = 0,46). A l'angiographie numerique, 26 vaisseaux etaient occlus. En tout, l'ARM avait une sensibilite de 84,2% (IC 95%: 60,4 a 96,6) et une specificite de 84,6% (IC 95%: 78,6 a 89,4). L'ARM rehaussee avait une sensibilite de 69,2% (IC 95%: 38,6 a 90,9) et une specificite de 73.6% (IC 95%: 65,5 a 80.7). Conclusions: L'angiographie par resonance magnetique est un bon outil de depistage non effractif pour evaluer l'etat des vaisseaux intracrâniens dans l'AVC aigu. L'angiographie demeure l'examen de reference pour l'evaluation de la circulation intracrânienne.

Background and Purpose— The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD 2 score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD 2 I). Methods— Twelve centers provided unpublished data on ABCD 2 scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD 2 I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis. Results— Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD 2 score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD 2 score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P 2 I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD 2 score to 0.78 (0.72 to 0.85) for the ABCD 2 I score. Conclusions— In secondary care, incorporation of brain infarction into the ABCD system (ABCD 2 I score) improves prediction of stroke in the acute phase after transient ischemic attack.

Background There is an increasing trend to treating proximal vessel occlusions with intravenous–inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy. Methods Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2–3 flow on angiography. Results Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27–0·84) and favourable outcome (RR 2·14 confidence interval95 1·3–3·5). Conclusions Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified.

Background and Purpose— Definitions for chronic lacunar infarcts vary. Recent retrospective studies suggest that many acute lacunar strokes do not develop a cavitated appearance. We determined the characteristics of acute lacunar infarcts on follow-up MRI in consecutive patients participating in prospective research studies. Methods— Patients with acute lacunar infarction on diffusion-weighted imaging were selected from 3 prospective cohort studies of minor stroke imaged within Results— Probable or definite cavitation on any sequence was more common at 90 days compared with 30 days ( P ≤0.001 for all sequences). At 90 days, evidence of cavitation was seen on at least 1 sequence in 33 of 34 patients (97%). The T1-weighted sequence was most sensitive to the presence of cavitation (94% at 90 days). By contrast, the fluid-attenuated inversion recovery sequence frequently failed to show evidence of cavitation in the brain stem or thalamus (only 10 of 18 [56%] showed cavitation). Conclusions— MRI scanning at 90 days with T1-weighted imaging reveals evidence of cavitation in nearly all cases of acute lacunar infarction. By contrast, reliance on fluid-attenuated inversion recovery alone will miss many cavitated lesions in the thalamus and brain stem. These factors should be taken into account in the development of standardized criteria for lacunar infarction on MRI.

Background and Purpose— The Penumbra Pivotal Stroke Trial reported a 25% good outcome (modified Rankin scale score ≤2) despite an 81% recanalization rate. We evaluated the association of a favorable initial noncontrast CT and a short time to recanalization in predicting good outcome. Methods— Data were from the Penumbra Pivotal Stroke Trial. Baseline scans were evaluated by 2 experienced readers blinded to outcomes using ASPECTS. ASPECTS scores were dichotomized into >7 and ≤7 for primary analysis. Data on degree of recanalization based on thrombolysis in myocardial infarction scores, stroke onset to recanalization, and CT to recanalization times were obtained. Primary outcome was modified Rankin scale score ≤2 at 3 months. Results— Median baseline NIHSS was 18 (range, 8–34) and median baseline ASPECTS score was 6 (range, 0–10); 81.2% achieved recanalization (thrombolysis in myocardial infarction, 2–3) and (27.7%) achieved good outcome. Good outcome was significantly higher in the ASPECTS score >7 group when compared to the ASPECTS score ≤7 group (50% vs 15%; RR, 3.3; 95% CI, 1.6–6.8; P =0.0001). No patient with an ASPECTS score ≤4 (n=28) or without recanalization (n=16) had a good outcome. There was an interaction between baseline ASPECTS score (>7 and ≤7) and onset to recanalization time (≤300 minutes and >300 minutes) in predicting good outcome ( P =0.06). Conclusion— Patients with baseline CT ASPECTS score ≤4 do not benefit from recanalization. Fast recanalization may benefit patients with evident damage on the CT scan (ASPECTS score >4). Overall, patients benefit the most with early recanalization and a favorable baseline CT scan (ASPECTS score >7).

Background and Purpose— In children with stroke, poor motor outcome is associated with early Wallerian degeneration of the corticospinal tract that is seen on diffusion-weighted MRI. In this study we test the hypothesis that early diffusion changes also occur in the corticospinal tract (CST) of adults after stroke and that these lesions are associated with poor outcome. Methods— In this retrospective study, we assessed images from a serial MRI study of adults with acute middle cerebral/internal carotid artery stroke. MRI-negative TIA patients served as controls. Custom software measured signal along the CST on different sequences, including the apparent diffusion coefficient (ADC). Visual detection of abnormal signal by blinded neuroradiologists was also evaluated. We then determined associations between CST signal changes and 3-month motor outcome (NIHSS score). Results— Thirty-eight patients (20 stroke/18 control) were included. ADC measures were much more accurate than other MRI sequences for detection of degeneration in the CST. The ADC decreased in a time-dependent fashion in the CST of patients with poor motor outcome but not in those with good outcome. Changes in ADC were maximal at 7 days. Neuroradiologists could visually detect these changes with accuracy comparable to the software method. Conclusion— CST ADC decreases after acute stroke in patients with poor motor outcome and may represent early Wallerian degeneration. Recognition of this imaging marker may improve early outcome prediction and patient selection for rehabilitation and neuroprotection trials.