Advance consent could allow individuals at high risk of stroke to provide consent before they might become eligible for enrollment in acute stroke trials. This survey explores the acceptability of this novel technique to Canadian Research Ethics Board (REB) chairs that review acute stroke trials. Responses from 15 REB chairs showed that majority of respondents expressed comfort approving studies that adopt advance consent. There was no clear preference for advance consent over deferral of consent, although respondents expressed significant concern with broad rather than trial-specific advance consent. These findings shed light on the acceptability of advance consent to Canadian ethics regulators.

Background: Women are reported to have worse outcomes than men following ischemic stroke despite similar treatment effects for thrombolysis and endovascular treatment. Methods: We performed a post-hoc analysis of patients with acute ischemic stroke and intracranial occlusion enrolled in INTERRSeCT, an international prospective cohort study. We compared workflow times, reperfusion therapy choices, and 90-day modified Rankin scale (mRS) scores. Results: We included 575 patients, mean age 70.2 years (SD: 13.1) and 48.5% female. There were no significant sex differences in onset-to-CT (males: 115 minutes [IQR: 72-171], females: 114 minutes [IQR: 75-196] ) or CT-to-thrombolysis time (males: 24 minutes [IQR: 17-32], females: 23 minutes [IQR: 18-36]). However, female participants had a 12-minute faster CT-to-groin-puncture time, p=0.001. Reperfusion therapies did not significantly differ by sex. Reperfusion therapies included thrombolysis alone (males: 46%, females: 49%), EVT alone (males: 34%, females: 34%), thrombolysis plus EVT (males: 8%, females 9%) and conservative management (males: 12%, females: 8%). Median 90-day mRS was 2 (IQR: 1-4) in both males and females, p=0.1. Conclusions: In the INTERRSeCT cohort, rates of reperfusion therapy, workflow times and 90-day outcomes were similar between sexes, suggesting that women are not subject to any poorer performance in key quality indicators for reperfusion treatment for acute stroke.

Background: CT angiogram of the head and neck (CTA) is not part of the routine work-up of status epilepticus (SE), which could miss acute ischemic stroke (AIS) as the cause. We hypothesized that healthcare savings from early treatment of otherwise undiagnosed AIS would be greater than the cost of adding a routine CTA for work-up of SE (all comers). Methods: The total number of patients presenting to ER with SE (defined as seizure/epilepsy+hospital admission), and the subgroup who were diagnosed with a new ischemic stroke, or received a CTA were retrospectively calculated at the Ottawa Hospital between 2010-2019. CTA costs, and savings of early treatment of AIS were obtained from the Department of Radiology and literature review, respectively. Results: 727 individuals presented with SE. 3% (n=22) had a new ischemic stroke-of these, 95% (n=21) did not receive a CTA (considered missed AIS). Assuming CTA could help detect every case of ischemic stroke missed this could result in 2.27 additional strokes caught early/year, and assuming if all thrombolysis candidates this would net cost $7,967/year (vs no acute treatment), or if all thrombolysis+thrombectomy candidates would net save $19,823/year (vs thrombolysis alone). Conclusions: Routine CTA in SE in the ER has potential to result in healthcare savings.

Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

Advance consent presents a potential solution to the challenge of obtaining informed consent for participation in acute stroke trials. Clinicians in stroke prevention clinics are uniquely positioned to identify and seek consent from potential stroke trial participants. To assess the acceptability of advance consent to Canadian stroke clinic physicians, we performed an online survey. We obtained 58 respondents (response rate 35%): the vast majority (82%) expressed comfort with obtaining advance consent and 92% felt that doing so would not be a significant disruption to clinic workflow. These results support further study of advance consent for acute stroke trials.

The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Background: In Canada, it’s unknown if the prevalence of stroke survivorship differs in the population with active cancer compared to those without cancer. Methods: We analyzed the 2015-2016 iteration of the Canadian Community Health Survey. The prevalence of stroke survivorship was compared across risk factors using descriptive statistics. A multivariable logistic regression model was used to assess the association between cancer and prevalence of stroke survivorship. Covariates were assessed for effect modification and confounding using the maximum likelihood estimation method. Results: We analyzed 89,285 subjects. The prevalence of cancer and the prevalence of suffering from the effects of a stroke were 2.09% and 1.56%, respectively. Cancer was significantly associated with an increased prevalence of stroke survivorship with an odds ratio (OR) of 1.56 (95%CI: 1.24 – 1.98) after adjusting for age, sex, smoking status, education, household income, dyslipidemia, hypertension, diabetes. The association was stronger in younger age groups: the youngest age group (18 – 49 years) had the highest OR (6.49, 95%CI:2.01 – 20.94) for suffering from the effects of a stroke in association with the presence of cancer. Conclusions: In Canada, the presence of active cancer increases the odds of suffering from the effects of a stroke, particularly in the youngest age group.

Background: Dual antiplatelet therapy (DAPT) is recommended after minor ischemic stroke/ transient ischemic attack (TIA), but Clopidogrel/ Aspirin has never been compared directly to Ticagrelor/ Aspirin. Our objective is to compare these regimens in terms of efficacy and safety. Methods: Medline, Embase, and Cochrane were searched for randomized controlled trials (RCTs) that enrolled adults with minor stroke/ TIA and administered antiplatelets within 72 hours. The primary efficacy outcome is recurrent stroke or death at 90 days. We performed a Bayesian-approach NMA. Between group comparisons were presented as odds-ratios (OR) with 95% credible intervals (95%CI). Sucraplots were based on calculated probabilities of rankings for individual outcomes. Results: 9/4014 studies were included: 5 RCTs and 4 subgroup analyses. 22,098 patients were analyzed. At 90 days, both DAPT regimens were superior to Aspirin in the prevention of recurrent stroke/ death. There was no significant difference between Clopidogrel/ ASA compared to Ticagrelor/ ASA (OR 0.90 [95%CI 0.74 – 1.09]), although Clopidogrel/ Aspirin was ranked #1 using Sucraplots. There was no significant difference between the interventions for mortality, bleeding, or adverse events. Conclusions: DAPT was superior to ASA in the prevention of recurrent strokes/ death, but there was no difference between Clopidogrel/ ASA and Ticagrelor/ ASA.

Introduction: Patients with major bleeding (e.g. gastrointestinal bleeding, and intracranial hemorrhage [ICH]) are commonly encountered in the Emergency Department (ED). A growing number of patients are on either oral or parenteral anticoagulation (AC), but the impact of AC on outcomes of patients with major bleeding is unknown. With regards to oral anticoagulation (OAC), we particularly sought to analyze differences between patients on Warfarin or Direct Oral Anticoagulants (DOACs). Methods: We analyzed a prospectively collected registry (2011-2016) of patients who presented to the ED with major bleeding at two academic hospitals. “Major bleeding” was defined by the International Society on Thrombosis and Haemostasis criteria. The primary outcome, in-hospital mortality, was analyzed using a multivariable logistic regression model. Secondary outcomes included discharge to long-term care among survivors, total hospital length of stay (LOS) among survivors, and total hospital costs. Results: 1,477 patients with major bleeding were included. AC use was found among 215 total patients (14.6%). Among OAC patients (n = 181), 141 (77.9%) had used Warfarin, and 40 (22.1%) had used a DOAC. 484 patients (32.8%) died in-hospital. AC use was associated with higher in-hospital mortality (adjusted odds ratio [OR]: 1.50 [1.17-1.93]). Among survivors to discharge, AC use was associated with higher discharge to long-term care (adjusted OR: 1.73 [1.18-2.57]), prolonged median LOS (19 days vs. 16 days, P = 0.03), and higher mean costs ($69,273 vs. $58,156, P = 0.02). With regards to OAC, a higher proportion of ICH was seen among patients on Warfarin (39.0% vs. 32.5%), as compared to DOACs. No difference in mortality was seen between DOACs and Warfarin (adjusted OR: 0.84 [0.40-1.72]). Patients with major bleeding on Warfarin had longer median LOS (11 days vs. 6 days, P = 0.03) and higher total costs ($51,524 vs. $35,176, P < 0.01) than patients on DOACs. Conclusion: AC use was associated with higher mortality among ED patients with major bleeding. Among survivors, AC use was associated with increased LOS, costs, and discharge to long-term care. Among OAC patients, no difference in mortality was found. Warfarin was associated with prolonged LOS and costs, likely secondary to higher incidence of ICH, as compared to DOACs.

Introduction: Elevated intracranial pressure (ICP) is a devastating complication of brain injury, such as traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and other conditions. Delay to diagnosis and treatment are associated with increased morbidity and mortality. For Emergency Department (ED) physicians, invasive ICP measurement is typically not available. We sought to summarize and compare the accuracy of physical examination, imaging, and ultrasonography of the optic nerve sheath diameter (ONSD) for diagnosis of elevated ICP. Methods: We searched Medline, EMBASE and 4 other databases from inception through August 2018. We included only English studies (randomized controlled trials, cohort and case-control studies). Gold standard was ICP≥20 mmHg on invasive ICP monitoring. Two reviewers independently screened studies and extracted data. We assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Hierarchical Summary Receiver Operating Characteristic model generated summary diagnostic accuracy estimates. Results: We included 37 studies (n = 4,768, kappa = 0.96). Of exam signs, pooled sensitivity and specificity for increased ICP were: mydriasis (28.2% [95% CI: 16.0-44.8], 85.9.0% [95% CI: 74.9-92.5]), motor posturing (54.3% [95% CI: 36.6-71.0], 63.6% [95% CI: 46.5-77.8]) and Glasgow Coma Scale (GCS) ≤8 (75.8% [95% CI: 62.4-85.5], 39.9% [95% CI: 26.9-54.5]). Computed tomography findings: compression of basal cisterns had 85.9% [95% CI: 58.0-96.4] sensitivity and 61.0% [95% CI: 29.1-85.6] specificity; any midline shift had 80.9% [95% CI: 64.3-90.9] sensitivity and 42.7% [95% CI: 24.0-63.7] specificity; midline shift≥1cm had 20.7% [95% CI: 13.0-31.3] sensitivity and 89.2% {95% CI: 77.5-95.2] specificity. Finally, pooled area under the ROC curve describing accuracy for ONSD sonography for ICP was 0.94 (95% CI: 0.91-0.96). Conclusion: The absence of any one physical exam feature (e.g. mydriasis, posturing, or decreased GCS) is not sufficient to rule-out elevated ICP. Significant midline shift is highly suggestive of elevated ICP, but absence of shift does not rule it out. ONSD sonography may be useful in diagnosing elevated ICP. High suspicion of elevated ICP may necessitate treatment and transfer to a centre capable of invasive ICP monitoring.

Thirty-three patients admitted to hospital with severe early onset puerperal psychiatric disorders were compared with matched normal puerperal controls. Interviews, which were administered after recovery, covered life events in the previous thirteen months and detailed assessment of previous and personal history, pregnancy and labour, other aspects of stress, social support, and marital relationships. No differences, except for previous history of psychiatric disorder, were found between patients and controls or between patients with depressive and with other diagnoses. These findings of absence of social stress contrast with previous studies of milder post-partum depression and of disorders with onset during pregnancy, and suggest that the aetiology of severe post-partum disorders is predominantly biological.