Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

Spontaneous Recanalization of Internal Carotid Artery Occlusion: A Case Report.

INTRODUCTION: Spontaneous recanalization of an occluded internal carotid artery (ICA) is thought to be unlikely. However, there has been a growing number of reports describing this phenomenon. Despite this, the frequency, time course, and mechanism of spontaneous recanalization remain unknown. In this paper, we describe a patient with a symptomatic recanalization of an occluded left ICA. CASE REPORT: A 70-year-old woman presented with transient speech arrest and right upper extremity weakness related to an occluded ICA. After 3 days, her weakness and aphasia reappeared and worsened transiently. A repeat computed tomography angiography revealed recanalization of the occluded ICA, as well as new ischemic changes in the previously hypoperfused left insular region. This finding changed the management from medical management to revascularization with a stent, after which the patient was discharged home with acetylsalicylic acid and clopidogrel. CONCLUSIONS: Although previously thought to be a rare occurrence, spontaneous recanalization is not uncommon. Further research into this phenomenon as proper identification and characterization of this phenomenon can influence follow-up and management.

Resident Match During the COVID Pandemic: How Have Neurology Programs Adapted? - A Survey.

BACKGROUND: We aimed to evaluate the perceived effectiveness of interventions implemented by Canadian neurology residency programs for the 2020-2021 iteration of the Canadian Resident Matching Service (CaRMS). METHODS: A cross-sectional survey was distributed to Canadian neurology residency programs and final-year Canadian medical students who applied to at least one neurology program during the 2020-2021 match cycle. The surveys evaluated pre-interview and interview period interventions implemented by Canadian neurology residency programs and accessed by medical students. RESULTS: Thirty-five medical students and 13 out of 15 institutions in Canada with neurology residency programs responded to the survey. Multiple adaptations were implemented, including social media advertisement, web-based platforms, pre-interview information sessions, and teaching sessions, with all surveyed programs implementing at least two virtual interventions. We found that all interventions were perceived as adequate by a majority (>60%) of medical students, with pre-interview period virtual information sessions perceived as effective by the largest proportion of respondents. All Canadian neurology residency programs held virtual interviews for the 2020-2021 cycle, and most programs utilized the same interview structure as prior years. There was discordance between residency program stakeholders and medical students on the most helpful interview period modality. Medical students found the hospital tours and information sessions most valuable, whereas program stakeholders perceived the virtual socials and interviews as most helpful. CONCLUSION: The COVID-19 pandemic has led to innovative adaptations implemented by Canadian neurology residency programs, which were seen as effective by both medical students and program stakeholders.

Aetiology of extracranial carotid free-floating thrombus in a prospective multicentre cohort.

BACKGROUND: Carotid free-floating thrombi (FFT) in patients with acute transient ischaemic attack (TIA)/stroke have a high risk of early recurrent stroke. Management depends on aetiology, which can include local plaque rupture, dissection, coagulopathy, malignancy and cardioembolism. Our objectives were to classify the underlying aetiology of FFT and to estimate the proportion of patients with underlying stenosis requiring revascularisation. METHODS: We prospectively enrolled consecutive patients presenting to three comprehensive stroke centres with acute TIA/stroke and ipsilateral internal carotid artery FFT. The aetiology of FFT was classified as: carotid atherosclerotic disease, carotid dissection, cardioembolism, both carotid atherosclerosis and cardioembolism, or embolic stroke of uncertain source (ESUS). Patients with carotid atherosclerosis were further subclassified as having ≥50% or <50% stenosis. RESULTS: We enrolled 83 patients with confirmed FFT. Aetiological assessments revealed 66/83 (79.5%) had carotid atherosclerotic plaque, 4/83 (4.8%) had a carotid dissection, 10/83 (12%) had both atrial fibrillation and carotid atherosclerotic plaque and 3/83 (3.6%) were classified as ESUS. Of the 76 patients with atherosclerotic plaque (including those with atrial fibrillation), 40 (52.6%) had ≥50% ipsilateral stenosis. CONCLUSIONS: The majority of symptomatic carotid artery FFT are likely caused by local plaque rupture, more than half of which are associated with moderate to severe carotid stenosis requiring revascularisation. However, a significant number of FFTs are caused by non-atherosclerotic mechanisms warranting additional investigations.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Canadian Stroke Best Practice Recommendations: Virtual Stroke Rehabilitation Interim Consensus Statement 2022.

ABSTRACT: The seventh edition of the Canadian Stroke Best Practice Recommendations for Rehabilitation and Recovery following Stroke includes a new section devoted to the provision of virtual stroke rehabilitation. This consensus statement uses Grading of Recommendations, Assessment, Development and Evaluations methodology and Appraisal of Guidelines for Research & Evaluation II principles. A literature search was conducted using PubMed, Embase, and Cochrane databases. An expert writing group reviewed all evidence and developed recommendations, as well as consensus-based clinical considerations where evidence was insufficient for a recommendation. All recommendations underwent internal and external review. These recommendations apply to hospital, ambulatory care, and community-based settings where virtual stroke rehabilitation is provided. This guidance is relevant to health professionals, people living with stroke, healthcare administrators, and funders. Recommendations address issues of access, eligibility, consent and privacy, technology and planning, training and competency (for healthcare providers, patients and their families), assessment, service delivery, and evaluation. Virtual stroke rehabilitation has been shown to safely and effectively increase access to rehabilitation therapies and care providers, and uptake of these recommendations should be a priority in rehabilitation settings. They are key drivers of access to high-quality evidence-based stroke care regardless of geographical location and personal circumstances in Canada.

Differentiating Carotid Free-Floating Thrombus From Atheromatous Plaque Using Intraluminal Filling Defect Length on CTA: A Validation Study.

OBJECTIVE: To validate a previously proposed filling defect length threshold of >3.8 mm on CT angiography (CTA) to discriminate between free-floating thrombus (FFT) and plaque of atheroma. METHODS: This was a prospective multicenter observational study of 100 participants presenting with TIA/stroke symptoms and a carotid intraluminal filling defect on initial CTA. Follow-up CTA was obtained within 1 week and at weeks 2 and 4 if the intraluminal filling defect was unchanged in length. Resolution or decreased length was diagnostic of FFT, whereas its static appearance after 4 weeks was indicative of plaque. Diagnostic accuracy of FFT length was assessed by receiver operating characteristic analysis. RESULTS: Ninety-five participants (mean [SD] age 68 [13] years, 61 men, 83 participants with FFT, 12 participants with a plaque) were evaluated. The >3.8-mm threshold had a sensitivity of 88% (73 of 83) (95% confidence interval [CI] 78%-94%) and specificity of 83% (10 of 12) (95% CI 51%-97%) (area under the curve 0.91, p < 0.001) for the diagnosis of FFT. The optimal length threshold was >3.64 mm with a sensitivity of 89% (74 of 83) (95% CI 80%-95%) and specificity of 83% (10 of 12) (95% CI 51%-97%). Adjusted logistic regression showed that every 1-mm increase in intraluminal filling defect length is associated with an increase in odds of FFT of 4.6 (95% CI 1.9-11.1, p = 0.01). CONCLUSION: CTA enables accurate differentiation of FFT vs plaque using craniocaudal length thresholds. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02405845. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with TIA/stroke symptoms, the presence of CTA-identified filling defects of lengths >3.8 mm accurately discriminates FFT from atheromatous plaque.

Decreased Stroke Presentation Rates at a Comprehensive Stroke Center during COVID-19.

We reviewed stroke care delivery during the COVID-19 pandemic at our stroke center and provincial telestroke system. We counted referrals to our prevention clinic, code strokes, thrombolysis, endovascular thrombectomies, and activations of a provincial telestroke system from February to April of 2017-2020. In April 2020, there was 28% reduction in prevention clinic referrals, 32% reduction in code strokes, and 26% reduction in telestroke activations compared to prior years. Thrombolysis and endovascular thrombectomy rates remained constant. Fewer patients received stroke services across the spectrum from prevention, acute care to telestroke care in Ontario, Canada, during the COVID-19 pandemic.

Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.

Distribution and predictive performance of the temporal phase of dynamic spot sign appearance in acute intracerebral hemorrhage.

BACKGROUND: Dynamic CT angiography (dCTA) contrast extravasation, known as the "dynamic spot sign", can predict hematoma expansion (HE) in intracerebral hemorrhage (ICH). Recent reports suggest the phase of spot sign appearance is related to the magnitude of HE. We used dCTA to explore the association between the phase of spot sign appearance and HE, clinical outcome, and contrast extravasation rates. METHODS: We assessed consecutive patients who presented with primary ICH within 4.5 hours from symptom onset who underwent a standardized dCTA protocol and were spot sign positive. The independent variable was the phase of spot sign appearance. The primary outcome was significant HE (either 6 mL or 33% growth). Secondary outcomes included total absolute HE, mortality, and discharge mRS. Mann-Whitney U, Fisher's exact test, and logistic regression were used, as appropriate. RESULTS: Of the 35 patients with spot signs, 27/35 (77%) appeared in the arterial phase and 8/35 (23%) appeared in the venous phase. Thirty patients had follow-up CT scans. Significant HE was seen in 14/23 (60.87%) and 3/7 (42.86%) of arterial and venous cohorts, respectively (p = 0.67). The sensitivity and specificity in predicting significant HE were 82% and 31% for the arterial phase and 18% and 69% for the venous phase, respectively. There was a non-significant trend towards greater total HE, in-hospital mortality, and discharge mRS of 4-6 in the arterial spot sign cohort. Arterial spot signs demonstrated a higher median contrast extravasation rate (0.137 mL/min) compared to venous spot signs (0.109 mL/min). CONCLUSION: Our exploratory analyses suggest that spot sign appearance in the arterial phase may be more likely associated with HE and poorer prognosis in ICH. This may be related to higher extravasation rates of arterial phase spot signs. However, further studies with larger sample sizes are warranted to confirm the findings.

A Delayed Modified ICH Score Outperforms Baseline Scoring in Acute Intracerebral Hemorrhage.

The Modified Intracerebral Hemorrhage (MICH) score is a simple tool created to provide prognostication in basal ganglia hemorrhages. Current prognostic scores, including the MICH, are based on the assessment of baseline patient characteristics, failing to account for significant developments, such as intraventricular extension and clinical deterioration, which may occur over the first 72 hours. We propose to validate the MICH in all hemorrhage locations and hypothesize that its calculation at 72 hours will outperform its baseline counterpart with respect to predicting mortality and functional outcome. We performed a retrospective analysis of collated data from the Virtual International Stroke Trials Archive database. Primary outcome was 90-day mortality. Secondary outcome was poor outcome (modified Rankin Scale 4-6) at 90 days. Receiver operating characteristic curves were generated looking at the predictive ability of the MICH score for mortality and poor outcome, at baseline and at 72 hours. Competing curves were assessed with nonparametric methods. A total of 226 patients were included, with a 90-day mortality of 22.5%. The MICH scores calculated at 72 hours were more predictive of mortality than at baseline (area under the curve [AUC]: 0.89 [95% confidence interval [CI]: 0.83-0.94] vs 0.78 [95% CI: 0.70-0.85]), P < .01. The MICH scores at 72 hours similarly better predicted functional outcome (AUC: 0.78 [95% CI: 0.72-0.84] vs AUC: 0.72 [95% CI: 0.66-0.78]), P = .047. The MICH score has positive prognostic value for mortality and poor functional outcome in all hemorrhage locations. Delaying its calculation resulted in higher predictive values for both and suggests that delaying discussions around withdrawal of care may result in more accurate prognostication in acute intracerebral hemorrhage.

Best practice interprofessional stroke care collaboration and simulation: The student perspective.

Interprofessional practice (IPP) is the accepted standard of care for clients following a stroke. A brief, embedded and evidence-based IPP team simulation was designed to address stroke care knowledge and IPP competencies for students within limited curriculum space. Each team was required to construct a collaborative care plan for their patient during the simulation and submit the care plan for evaluation of best practice stroke care knowledge and implementation with evidence of interprofessional collaboration (IPC). A total of 302 students (274 on-site, 28 by distance technology) representing four professions comprised of 55 teams took part in this experience. Post-simulation, voluntary and anonymous programme evaluations were completed using the standardised interprofessional collaborative competency assessment scale (ICCAS) and open-ended free-text responses to five questions. There was a significant improvement for all pre-post ratings on the ICCAS regardless of profession or previous interprofessional experience. Additionally, the open-ended responses indicated perceived changes to role clarification, communication, and teamwork. The combined interpretation of the programme evaluation results supports interprofessional team simulation as an effective and efficient learning experience for students regardless of previous interprofessional experience, and demonstrated positive changes in stroke best-practice knowledge and IPC competencies.

Canadian Stroke Best Practice Recommendations: Telestroke Best Practice Guidelines Update 2017.

Every year, approximately 62,000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2016 update of the Canadian Stroke Best Practice Recommendations Telestroke guideline is a comprehensive summary of current evidence-based and consensus-based recommendations appropriate for use by all healthcare providers and system planners who organize and provide care to patients following stroke across a broad range of settings. These recommendations focus on the use of telemedicine technologies to rapidly identify and treat appropriate patients with acute thrombolytic therapies in hospitals without stroke specialized expertise; select patients who require to immediate transfer to stroke centers for Endovascular Therapy; and for the patients who remain in community hospitals to facilitate their care on a stroke unit and provide remote access to stroke prevention and rehabilitation services. While these latter areas of Telestroke application are newer, they are rapidly developing, with new opportunities that are yet unrealized. Virtual rehabilitation therapies offer patients the opportunity to participate in rehabilitation therapies, supervised by physical and occupational therapists. While not without its limitations (e.g., access to telecommunications in remote areas, fragmentation of care), the evidence-to-date sets the foundation for improving access to care and management for patients during both the acute phase and now through post stroke recovery.

Fast-Track Systems Improve Timely Carotid Endarterectomy in Stroke Prevention Outpatients.

BACKGROUND: For optimal stroke prevention, best practices guidelines recommend carotid endarterectomy (CEA) for symptomatic patients within two weeks; however, 2013 Ontario data indicated that only 9% of eligible patients from outpatient Stroke Prevention Clinics (SPCs) achieved this target. The goal of our study was to identify modifiable system factors that could enhance the quality and timeliness of care among patients needing urgent CEA. METHODS: We conducted a retrospective chart review of transient ischemic attack/stroke patients assessed in Champlain Local Health Integrated Network SPCs between 2011 and 2014 who subsequently underwent CEA. Descriptive statistics were used to define patient characteristics, timelines from symptom onset to CEA, and system factors that contributed to delays or improvements in care. Multivariate analysis was used to determine statistically significant variations between groups. RESULTS: Seventy-five records were eligible for study inclusion. Median time from initial symptoms to CEA was 31 days, with 21.3% of patients undergoing surgery within 2 weeks. Significant delays were common in patient presentation and assessment following symptom onset, wait times for vascular imaging and neurological assessment, and time from surgical assessment to CEA completion. Rapid testing and triage, coupled with collaborative initiatives among SPC, surgical, and radiology teams were associated with significantly improved timelines. CONCLUSIONS: Success factors for rapid CEA are multifaceted, including system changes that address public awareness of stroke and 911 response, improvements in vascular imaging access, and redesign of clinical services to promote collaboration and fast-tracking of care. Implementation of performance measures to monitor and guide clinical innovations is recommended.

Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant Hematoma Expansion.

BACKGROUND AND PURPOSE: Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available. METHODS: Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan. RESULTS: Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (P=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%-71%), whereas margin irregularity had the highest negative predictive value (78%; 71%-85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive. CONCLUSIONS: Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.