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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.

ObjectiveWe sought to evaluate the short- and long-term resource use and costs associated with intracerebral hemorrhage (ICH) taken from an entire population. We in addition sought to evaluate the association of oral anticoagulation (OAC) and health care costs.MethodsThis was a retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (2009–2017). We captured outcomes through linkage to health administrative databases. We used generalized linear models to identify factors associated with total cost. Analysis of OAC use was limited to patients ≥66 years of age. The primary outcome was total 1-year direct health care costs in 2020 US dollars.ResultsAmong 16,248 individuals with ICH (mean age 71.2 years, male 52.3%), 1-year mortality was 46.0%, and 24.2% required mechanical ventilation. The median total 1-year cost was $26,886 (interquartile range [IQR] $9,641–$62,907) with costs for those who died in hospital of $7,268 (IQR $4,031–$14,966) vs $44,969 (IQR $20,264–$82,414, p < 0.001) for survivors to discharge. OAC use (analysis limited to individuals ≥66 years old) was associated with higher total 1-year costs (cost ratio 1.06 [95% confidence interval 1.01–1.11]). Total 1-year costs for the entire cohort exceeded $120 million per year over the study period.ConclusionsICH is associated with significant health care costs, and the median cost of a patient with ICH is roughly 10 times the median inpatient cost in Ontario. Costs were higher among survivors than deceased patients. OAC use is independently associated with increased costs. To maximize cost-effectiveness, future therapies for ICH must aim to reduce disability, not only improve mortality.

We identified the prevalence of elevated high-sensitivity C-reactive protein and interleukin-6 in patients with recent cardiovascular (CV) events with or without prediabetes/diabetes, and in a control group of patients with remote CV events. Interleukin-6 was elevated in patients with prediabetes/diabetes and recent CV events (median, 4.84 pg/mL; interquartile range, 3.27-7.45) compared with patients with remote events (2.36 pg/mL; interquartile range, 1.09-4.00). There was a trend for elevated high-sensitivity C-reactive protein in patients with acute events and prediabetes/diabetes (P = 0.147). This supports the notion that patients with prediabetes/diabetes and recent CV events have higher inflammatory burdens than patients without recent CV events or dysglycemia. Résumé: Nous avons défini la prévalence de l’augmentation du taux de protéine C réactive à haute sensibilité et d’interleukine-6 chez des patients ayant récemment subi des événements cardiovasculaires (CV), atteints ou non de prédiabète ou de diabète, et dans un groupe témoin de patients ayant subi des événements CV antérieurement. Le taux d’interleukine-6 était élevé chez les patients atteints de prédiabète ou de diabète ayant récemment subi des événements CV (médiane de 4,84 pg/ml; écart interquartile de 3,27 à 7,45) par rapport aux patients ayant subi des événements antérieurement (2,36 pg/ml; écart interquartile de 1,09 à 4,00). Le taux de protéine C réactive à haute sensibilité avait tendance à être élevé chez les patients atteints de prédiabète ou de diabète ayant subi des événements aigus (p = 0,147). Ces données appuient la notion selon laquelle les patients atteints de prédiabète ou de diabète qui ont récemment subi des événements CV présentent des fardeaux inflammatoires supérieurs à ceux des patients qui n’ont pas récemment subi d’événements CV ou présenté de dysglycémie.

Background and Purpose: Endovascular thrombectomy (EVT) reduces 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. Patient-reported outcome measures after EVT, such as health-related quality of life and specific functional domains, are less well described. Methods: We report outcomes on the EuroQol-5D (EQ-5D) from the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized controlled trial at 90 days after stroke. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Lastly, the association between severe disability at 90 days and EQ-5D was evaluated with assessment for modification by EVT, age, and sex. Results: There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT compared with best medical management (0.80 versus 0.60; P Conclusions: Patients treated with EVT report substantially improved health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, P =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], P =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery. Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.

ObjectiveThe concept of the ‘self-fulfilling prophecy’ is well established in intracerebral haemorrhage (ICH). The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care. We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality. However, delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.Design, setting and participantsWe analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days. 276 patients were included.Interventions and measurementsWe calculated the original ICH score (oICH), modified-ICH score (MICH), max-ICH score and the FUNC score on presentation (baseline), and on day 4 (delayed). Outcomes assessed were mortality and poor functional outcome in survivors (defined as modified Rankin Scale of 4–5) at 180 days. We generated receiver operating characteristic curves, and measured the area under the curve values (AUC) for mortality and functional outcome. We compared baseline and delayed AUCs with non-parametric methods.ResultsAt 180 days, 21 of 276 (7.6%) died. Out of the survivors, 54 of 255 had poor functional outcome (21.2%). The oICH, MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents ((0.74 vs 0.83, p=0.005), (0.73 vs 0.80, p=0.036), (0.74 vs 0.83, p=0.008), respectively). The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.ConclusionDelaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.Trial registration numberClinicalTrials.gov Registry (NCT02175225).

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N=528 subjects for ICV, N=501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer), as well as a ventricular segmentation tool (FreeSurfer). Our multi-contrast models outperformed other methods across all evaluation metrics, with average Dice coefficients of 0.98 and 0.94 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies.

Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0–3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2–3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0–1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0–2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72–20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21–5.51]). Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Background and Purpose: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. Methods: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. Results: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2–8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6–1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2–2.9]). Conclusions: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01778335.

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

Background and Purpose: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. Methods: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. Results: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5–12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase ( P =0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23–4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88–3.25]). Conclusions: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in

Background and Purpose: Research suggests that women and men may present with different transient ischemic attack (TIA) and stroke symptoms. We aimed to explore symptoms and features associated with a definite TIA/stroke diagnosis and whether those associations differed by sex. Methods: We completed a retrospective cohort study of patients referred to The Ottawa Hospital Stroke Prevention Clinic in 2015. Exploratory multinomial logistic regression was used to evaluate candidate variables associated with diagnosis and patient sex. Backwards elimination of the interaction terms with a significance level for staying in the model of 0.25 was used to arrive at a more parsimonious model. Results: Based on 1770 complete patient records, sex-specific differences were noted in TIA/stroke diagnosis based on features such as duration of event, suddenness of symptom onset, unilateral sensory loss, and pain. Conclusions: This preliminary work identified sex-specific differences in the final diagnosis of TIA/stroke based on common presenting symptoms/features. More research is needed to understand if there are biases or sex-based differences in TIA/stroke manifestations and diagnosis.

International guidelines recommend carotid revascularization within 14 days for patients with a symptomatic transient ischemic attack (TIA) or stroke event. However, significant delays in care persist, with only 9% of outpatients and 36% of inpatients in Ontario meeting this target. The study objective was to explore the influence of health system factors on carotid revascularization timelines.We conducted a retrospective chart review of all symptomatic TIA/stroke patients undergoing carotid endarterectomy or stenting at The Ottawa Hospital (2015-2016). The primary outcome was time from TIA/stroke to carotid revascularization. Health system variables of interest included location and timing of patient presentation, timelines to vascular imaging, and same-day collaboration between key services such as emergency, neurology, and surgery. Descriptive statistics and univariate analysis were used to determine statistically significant differences between groups.A total of 228 records met the inclusion criteria. The median time from TIA/stroke to carotid revascularization was 10 days, with 58% of patients meeting the 14-day guideline. Prompt patient presentation to emergency demonstrated significantly shorter timelines to surgery (7 days; P .001). Early vascular imaging was strongly correlated with early revascularization (4-5 days; P .001). In addition, collaboration from two or more care services enhanced timelines to surgery ranging from 2.0 to 6.5 days (P .001-.008).Early/emergency response to stroke symptoms was pivotal in achieving best practice recommendations for rapid carotid revascularization, emphasizing the need for ongoing public awareness. Emergency and ambulatory strategies to facilitate urgent vascular imaging, as well as mechanisms for same-day communication between teams require optimization to promote early revascularization.

POINTS CLES En 2016, au Canada (a l’exclusion du Quebec), 270 204 personnes ont ete admises a l’hopital pour un trouble cardiaque, un accident vasculaire cerebral (AVC) ou un deficit cognitif d’origine vasculaire; de ce nombre, 107 391 etaient des femmes, 162 813 etaient des hommes

Objective: We sought to map the landscape of trials investigating hydroxychloroquine (HCQ) for SARS-CoV-2 in order to draw conclusions about how clinical trials have been conducted in the pandemic environment and offer potential regulatory recommendations. Study Design and Setting: We identified and captured data related to registered studies using HCQ to treat SARS-CoV-2 registered with the publicly available National Institutes of Health (NIH) Clinical Trials Registry between February and November 2020. Results: Between February and November 2020, 206 studies investigating HCQ in SARS-CoV-2 were registered with the NIH Clinical Trials Registry. As of November 2020, 135 studies were listed as ongoing, 22 have been completed, and 46 are either suspended or have been terminated. Reasons for suspension or termination included difficulties with patient recruitment (n=9), emerging evidence showing a lack of benefit of HCQ (n=7), and recommendations by regulatory boards to discontinue (n=10). Conclusion: Many clinical trials of HCQ were launched in the first months of the pandemic, and a significant proportion of them remained active as of November 2020. The medical community appears to have responded very quickly to political interest in HCQ, while responding much more slowly to the evolving medical evidence of its lack of efficacy.

ObjectiveTo undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature.MethodsWe pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0–1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0–2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation.ResultsAmong 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] −8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%–41.6%) higher risk of neurologic deterioration at 24 hours.ConclusionsEVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days.Classification of evidenceThis study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.

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.

Background. Understanding potential sex differences in stroke recovery is important for prognosis, ensuring appropriate allocation of health care resources, and for stratification in research studies. Previously, functional measures have shown poorer outcomes for females, however, little is known about sex differences that may exist in specific motor and sensory impairments. Objective. The aim of this study was to utilize robotic assessments of motor and sensory impairments to determine if there are sex differences at the impairment level in stroke recovery over the first 6 months poststroke. Methods. We used robotic and clinical assessments of motor and sensory impairments at 1, 6, 12, and 26 weeks poststroke in 108 males and 52 females. Linear mixed models were used to examine the effect of sex on recovery poststroke, controlling for age and lesion volume. Results. In general, we did not find significant sex differences across a range of assessments. The exception to this was a sex × age interaction for the Purdue Pegboard Assessment, where we found that females had better performance than males at younger ages (

Background and Purpose— Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods— Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results— Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition ( P =0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]). Conclusions— In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods— We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results— The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76–0.87) compared with 0.78 at baseline (95% CI, 0.72–0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79–0.89) compared with 0.76 at baseline (95% CI, 0.70–0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76–0.88) compared with 0.74 at baseline (95% CI, 0.67–0.81) for modified ICH Score. Conclusions— Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

KEY POINTS In 2016, 270 204 people in Canada (excluding Quebec) were admitted to hospital for heart conditions, stroke and vascular cognitive impairment, including 107 391 women and 162 813 men, of whom 91 524 died.[1][1] This equates to 1 out of every 3 deaths in Canada and outpaces other diseases

Background and Purpose: The diagnosis of transient ischemic attack (TIA) is largely dependent on a process of clinical decision-making that remains poorly characterized in the absence of a validated and accessible biomarker or imaging test. We performed a retrospective chart review to identify variables associated with a final neurologist diagnosis of TIA/stroke. Methods: Records for all patients seen in The Ottawa Hospital’s Stroke Prevention Clinic in 2015 were analyzed for patient and referral characteristics, features of the presenting neurological event, and final diagnosis by a stroke neurologist (classified as definite, possible, or definite not TIA/stroke). Multinomial logistic regression analysis with backward elimination was used to identify variables associated with the final diagnosis. Results: Our inclusion criteria were met by 1894 patients. After backward elimination, 23 potentially important variables were identified, including monocular vision loss (odds ratio [OR]: 30.4, 95% confidence interval [CI]: 14.6-63.3), symptoms of sudden onset (OR: 28.3, 95% CI: 14.2-56.2), unilateral weakness affecting 2 or 3 of face, arm, or leg (OR: 17.7, 95% CI: 9.8-31.7), and homonymous hemianopia (OR: 16.6, 95% CI: 8.1-34.0). Conclusions: Accurate diagnosis of TIA is essential to initiating appropriate secondary stroke prevention therapies. A focus on elements of the patient history most commonly associated with a final diagnosis of TIA/stroke may help to identify patients in greatest need of urgent SPC assessment and allow for the provision of effective and efficient stroke prevention services.

Arterial recanalization to restore the blood supply and limit the brain damage is the primary goal in the management of acute ischemic stroke (AIS). Since the publication of pivotal randomized clinical trials in 2015, endovascular thrombectomy has become part of the standard of care in selected cases of AIS from large-vessel occlusions up to 6 hours after the onset of symptoms. However, the association between endovascular reperfusion and improved functional outcome is not strictly time dependent. Rather than on rigid time windows, candidates should be selected based on vascular and physiologic information. This approach places imaging data at the center of treatment decisions. Advances in imaging-based management of AIS provide crucial information about vessel occlusion, infarct core, ischemic penumbra, and degree of collaterals. This information is invaluable in identifying patients who are likely to benefit from reperfusion therapies and excluding those who are unlikely to benefit or are at risk of adverse effects. The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work-up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from "Time is Brain" to "Imaging is Brain." This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS.

The sixth update of the Canadian Stroke Best Practice Recommendations: Rehabilitation, Recovery, and Reintegration following Stroke. Part one: Rehabilitation and Recovery Following Stroke is a comprehensive set of evidence-based guidelines addressing issues surrounding impairments, activity limitations, and participation restrictions following stroke. Rehabilitation is a critical component of recovery, essential for helping patients to regain lost skills, relearn tasks, and regain independence. Following a stroke, many people typically require rehabilitation for persisting deficits related to hemiparesis, upper-limb dysfunction, pain, impaired balance, swallowing, and vision, neglect, and limitations with mobility, activities of daily living, and communication. This module addresses interventions related to these issues as well as the structure in which they are provided, since rehabilitation can be provided on an inpatient, outpatient, or community basis. These guidelines also recognize that rehabilitation needs of people with stroke may change over time and therefore intermittent reassessment is important. Recommendations are 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. Unlike the previous set of recommendations, in which pediatric stroke was included, this set of recommendations includes primarily adult rehabilitation, recognizing many of these therapies may be applicable in children. Recommendations related to community reintegration, which were previously included within this rehabilitation module, can now be found in the companion module, Rehabilitation, Recovery, and Community Participation following Stroke. Part Two: Transitions and Community Participation Following Stroke.

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.

Introduction: Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage. Methods: We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution. Results: Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, P = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], P < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], P < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], P < .001). Conclusions: Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage.

There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapy using in vivo animal models of subacute or chronic stroke were included. Measures of safety and efficacy were assessed. Eleven clinical and 76 preclinical studies were included. Preclinically, MSC therapy was associated with significant benefits for multiple measures of motor and neurological function. Clinically, MSC therapy appeared to be safe, with no increase in adverse events reported (with the exception of self-limited fever immediately following injection). However, the efficacy of treatment was less apparent, with significant heterogeneity in both study design and effect size being observed. Additionally, in the only randomized phase II study to date, efficacy of MSC therapy was not observed. Preclinically, MSC therapy demonstrated considerable efficacy. Although MSC therapy demonstrated safety in the clinical setting, efficacy has yet to be determined. Future studies will need to address the discordance in the continuity of evidence as MSC therapy has been translated from "bench-to-bedside".

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 Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared using the area under the receiver operating characteristic curve (AUC). Shapley values were used to determine marginal contributions of variables to outcome variance in the regression models. Results Among 1105 patients, functional independence was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95% CI, 0.71–0.77); this iteratively improved when treatment and posttreatment variables were added to the models (model 2: AUC, 0.77; 95% CI, 0.74–0.80; model 3: AUC, 0.80; 95% CI, 0.77–0.83; model 4: AUC, 0.82; 95% CI, 0.79–0.85). With baseline variables alone, 26% of patients who achieved functional independence were erroneously classified as not achieving functional independence. Even with the most comprehensive model, 19.8% of patients were misclassified as such. Patient age contributed most to outcome variance (Shapley value, 0.28), followed by severe adverse events including pneumonia (0.16) and intracranial hemorrhage at 24‐hours imaging (0.13). Conclusions A substantial contribution to outcomes after endovascular therapy comes from factors unrelated to currently collected baseline patient variables. One‐fifth of patients achieving functional independence were misclassified as not achieving independence, even with the most comprehensive model. Our findings suggest that the achievable accuracy of current outcome prediction models is limited, and caution should be used when applying them in clinical practice.

Introduction Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset. Methods Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries. Discussion In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

White matter hyperintensities (WMH) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI-based segmentation methods are often sensitive to acquisition protocols, scanners, noise-level, and image contrast, failing to generalize to other populations and out-of-distribution datasets. Given these concerns, we propose a novel Bayesian 3D Convolutional Neural Network (CNN) with a U-Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. 432 subjects were recruited to train the CNNs from four multi-site imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multi-site study. We compared our model to two established state-of-the-art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U-Net achieved the highest Dice similarity coefficient of 0.89 ± 0.08 and the lowest modified Hausdorff distance of 2.98 ± 4.40 mm. We further validated our models highlighting their robustness on ‘clinical adversarial cases’ simulating data with low signal-to-noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases.Methods: 513 participants with Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinson’s Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness.Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH.Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.

[Figure: see text].

Background and purpose Recovery after intracerebral haemorrhage (ICH) is often slower than ischemic stroke. Despite this, ICH research often quantifies recovery using the same outcome measures obtained at the same timepoints as ischemic stroke. The primary objective of this scoping review is to map the existing literature to determine when and how outcomes are being measured in prospective studies of recovery after ICH. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception to November 2019, for prospective studies that included patients with ICH. Two investigators independently screened the studies and extracted data around timing and type of outcome assessment. Results Among the 9761 manuscripts reviewed, 395 met inclusion criteria, of which 276 were observational studies and 129 were interventional studies that enrolled 66274 patients. Mortality was assessed in 93% of studies. Functional outcomes were assessed in 85% of studies. The most frequently used functional assessment tool was the modified Rankin Scale (mRS) (60%), followed by the National Institute of Health Stroke Severity Scale (22%) and Barthel Index (21%). The most frequent timepoint at which mortality was assessed was 90 days (41%), followed by 180 days (18%) and 365 days (12%), with 2% beyond 1 year. The most frequent timepoint used for assessing mRS was 90 days (62%), followed by 180 days (21%) and 365 days (17%). Conclusion While most prospective ICH studies report mortality and functional outcomes only at 90 days, a significant proportion do so at 1 year and beyond. Our results support the feasibility of collecting long-term outcome data to optimally assess recovery in ICH.

Background and Purpose: It is unclear whether it is clinically necessary or cost-effective to routinely obtain a transthoracic echocardiogram (TTE) during inpatient admission for ischemic stroke. Methods: We assessed consecutive patients presenting with acute ischemic stroke at a comprehensive stroke center from 2015 to 2017 who underwent TTE. We assessed for findings on TTE that would warrant urgent intervention including cardiac thrombus, atrial myxoma, mitral stenosis, valve vegetation, valve dysfunction requiring surgery, and low ejection fraction. Subsequent changes in management included changes in anticoagulation, antibiotics, or valve surgery. We calculated in-hospital resource utilization and associated costs for inpatient TTE using individual direct cost details within a case-costing system. Results: Of 695 patients admitted with acute ischemic stroke, 516 (74%) had a TTE and were included in our analysis. TTE findings were potentially clinically significant in 30 patients (5.8%) and changed management in 17 patients (3.3%). Inpatient admission was prolonged to expedite TTE in 24 patients, while TTE occurred after discharge in 76 patients. After correcting for the cost of TTE, the mean difference in cost to prolong an admission for TTE was $555.52 (USD), or $16 832 per change in management. Conclusions: Given the low clinical utility of inpatient TTE after acute ischemic stroke and the costs associated with prolonging admission, discharge from hospital should not be delayed solely to obtain TTE.

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.

A 1DOF lower limb rehabilitation robot is presented for delivering leg extension therapy to bed-bound stroke patients. Such a compact and minimal system may be beneficial in terms of compatibility with pre-existing hospital equipment, ease-of-use, safety, and cost. A set of design criteria was created based on the literature and on previous field work at a local hospital. The device uses admittance control to apply assistive or resistive forces, and can also use haptic feedback to increase user engagement. A pilot study on six healthy participants was used to determine the feasibility of such a minimal system in administering assistance or resistance through the leg extension exercise. Results indicate that a single DOF is capable of decreasing trajectory error with assistance and increasing user effort with resistance. Observations confirm that the minimal system is effective; however, extending the robot with additional DOFs so that it can target multiple bed-bound exercises may help to increase therapy duration.

The 2019 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Mood, Cognition and Fatigue following Stroke is a comprehensive set of evidence-based guidelines addressing three important issues that can negatively impact the lives of people who have had a stroke. These include post-stroke depression and anxiety, vascular cognitive impairment, and post-stroke fatigue. Following stroke, approximately 20% to 50% of all persons may be affected by at least one of these conditions. There may also be overlap between conditions, particularly fatigue and depression. If not recognized and treated in a timely matter, these conditions can lead to worse long-term outcomes. The theme of this edition of the CSBPR is Partnerships and Collaborations, which stresses the importance of integration and coordination across the healthcare system to ensure timely and seamless care to optimize recovery and outcomes. Accordingly, these recommendations place strong emphasis on the importance of timely screening and assessments, and timely and adequate initiation of treatment across care settings. Ideally, when screening is suggestive of a mood or cognition issue, patients and families should be referred for in-depth assessment by healthcare providers with expertise in these areas. As the complexity of patients treated for stroke increases, continuity of care and strong communication among healthcare professionals, and between members of the healthcare team and the patient and their family is an even bigger imperative, as stressed throughout the recommendations, as they are critical elements to ensure smooth transitions from acute care to active rehabilitation and reintegration into their community.

The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01–1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57–0.71). Youden’s method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09–3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61–5.42) were similar to HEP scores ≥ 4. The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Background Identifying and treating patients with transient ischemic attack is an effective means of preventing stroke. However, making this diagnosis can be challenging, and over a third of patients referred to stroke prevention clinic are ultimately found to have alternate diagnoses. Aims We performed a systematic review to determine how neurologists diagnose transient ischemic attack. Summary of review A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE, Embase, and the Cochrane Library databases. Publications eligible for inclusion were those that included information on the demographic or clinical features neurologists use to diagnose transient ischemic attacks or transient ischemic attack–mimics. Of 1666 citations, 210 abstracts were selected for full-text screening and 80 publications were ultimately deemed eligible for inclusion. Neurologists were more likely to diagnose transient ischemic attack based on clinical features including negative symptoms or speech deficits. Patients with positive symptoms, altered level of consciousness, or the presence of nonfocal symptoms such as confusion or amnesia were more likely to be diagnosed with transient ischemic attack–mimic. Neurologists commonly include mode of onset (i.e. sudden versus gradual), recurrence of attacks, and localizability of symptoms to a distinct vascular territory in the diagnostic decision-making process. Transient ischemic attack diagnosis was more commonly associated with advanced age, preexisting hypertension, atrial fibrillation, and other vascular risk factors. Conclusions Neurologists rely on certain clinical and demographic features to distinguish transient ischemic attacks from mimics, which are not currently reflected in widely used risk scores. Clarifying how neurologists diagnose transient ischemic attack may help frontline clinicians to better select patients for referral to stroke prevention clinics.

ObjectiveNo systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients.Design, setting and participantsWe systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis.ResultsFrom 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex.ConclusionsOnly half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.

Introduction There is an increased risk of stroke in patients with cancer–this risk is particularly heightened around the time of cancer diagnosis, although no studies have systematically quantified this risk in the literature. Patients newly diagnosed with cancer without prior stroke represent a highly susceptible population in whom there is a window of opportunity to study and implement primary prevention strategies. Therefore, the objective of this systematic review and meta-analysis is to identify the cumulative incidence of ischemic and hemorrhagic strokes during the first year after a diagnosis of cancer. Methods and analysis MEDLINE, EMBASE, and PubMed will be searched with the assistance from a medical information specialist, from 1980 until present. Eligible studies will include observational studies that have enrolled adult patients newly diagnosed with cancer and report outcomes of stroke during the first year of cancer diagnosis. We will exclude all randomized and non-randomized interventional studies. Data on participant characteristics, study design, baseline characteristics, and outcome characteristics will be extracted. Study quality will be assessed using the Newcastle-Ottawa Scale for cohort studies, and heterogeneity will be assessed using the I2 statistic. Pooled cumulative incidence will be calculated for ischemic and hemorrhagic strokes separately using a random-effects model. Ethics and dissemination No formal research ethics approval is necessary as primary data collection will not be done. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will inform clinicians and patients regarding the risk of stroke in patients newly diagnosed with cancer by quantifying the cumulative incidence of each subtype of stroke during the first year after a diagnosis of cancer. This represents a window of opportunity to implement prevention strategies in a susceptible population. Registration ID with Open Science Framework osf.io/ucwy9.

Background and Purpose: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Recent epidemiological data on incidence, mortality, and association with oral anticoagulation are needed. Methods: Retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (April 1, 2009–March 30, 2019). We captured outcome data using linked health administrative databases. The primary outcome was mortality during hospitalization, as well as at 1 year following ICH. Results: We included 20 738 patients with ICH. Mean (SD) age was 71.3 (15.1) years, and 52.6% of patients were male. Overall incidence of ICH throughout the study period was 19.1/100 000 person-years and did not markedly change over the study period. In-hospital and 1-year mortality were high (32.4% and 45.4%, respectively). Mortality at 2 years was 49.5%. Only 14.5% of patients were discharged home independently. Over the study period, both in-hospital and 1-year mortality reduced by 10.4% (37.5% to 27.1%, P P Conclusions: Both short- and long-term mortality have decreased in the past decade. Most survivors from ICH are likely to be discharged to long-term care. Oral anticoagulation is associated with both short- and long-term mortality following ICH. These findings highlight the devastating nature of ICH, but also identify significant improvement in outcomes over time.

Background: Endovascular thrombectomy (EVT) improves 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. However, the effect of EVT on health-related quality of life and specific functional domains, and whether this effect differs by age or sex is less studied. Methods: We used data from the ESCAPE randomized controlled trial to obtain EuroQol-5D-3L (EQ-5D) at 90 days after acute stroke in patients randomized to EVT or standard care. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores, and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Results: There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT (0.80 versus 0.60; p Conclusions: EVT substantially improves health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Background and Purpose: In present-day intracerebral hemorrhage (ICH) trials, hematoma expansion (HE) is often analyzed as a binary variable - present or absent. However, dichotomizing intrinsically wide-ranging variables discards substantial information reflective of treatment effect and can reduce the ability to detect relationships between the exposure and outcome of interest. We explored the concept of a “HE shift analysis” as a novel analytic mode for ICH treatment trials using previously published clinical trial data. Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, patients were stratified by treatment status (intensive vs. standard blood pressure lowering with IV nicardipine) and HE shift was evaluated by generating strata based on a) previously established HE definitions, b) quartiles of 24-hour total hematoma volume, and c) quartiles of 24-hour total hematoma volume (THV) change. The relationship between blood pressure treatment and hematoma expansion shift was explored using proportional odds models and adjusted Wilcoxon testing. Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no hematoma growth. Using a conventional threshold, significant intraparenchymal expansion (≥33%) was reduced by 5.8% in those assigned to the intensive therapy arm (aOR: 0.77 [95% CI: 0.60-0.99], Figure 1A). The stratified quartiles of 24-hour total hematoma volumes were associated with a 5% shift within the highest and lowest strata in the intensive arm, (aOR: 0.83 [0.66-1.05], Figure 1B). Intensive therapy was associated with a 5.2% reduction from > 3 mL to 0.5-3 mL (aOR: 0.86 [0.68-1.09], Figure 1C). Conclusions: A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an alternate way to assess hemostatic agents in future hemorrhage trials.

Background and Purpose: No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in women. In this scoping review, we aimed to identify all randomized controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularization, and determine whether sufficient information is reported within these studies to assess women’s short and long-term outcomes. Methods: We systematically searched Medline, Embase, Pubmed, and Cochrane libraries for RCTs published between 1991 and 2020 that included women and compared either endarterectomy with stenting, or any revascularization (endarterectomy or stenting) with medical therapy in patients with symptomatic high grade (greater than 50%) carotid stenosis. Results: From 1,537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled women were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment were limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex. Conclusions: Half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analysis on the benefits of carotid artery intervention for women with symptomatic stenosis is limited . Further analysis with individual patient data and a network meta-analysis is the necessary next step to better assess the treatment effects of carotid management in women.

Background: Hematoma expansion (HE) is an important therapeutic target in intracerebral hemorrhage. Recently proposed HE definitions have not been validated, and no previous definition has accounted for withdrawal of care (WOC). Objective: To compare conventional and revised definitions of hematoma expansion (HE), while accounting for WOC. Methods: We analyzed data from the ATACH-2 trial, comparing revised definitions of HE incorporating intraventricular hemorrhage (IVH) expansion to the conventional definition of “≥6 mL or ≥33%”. The primary outcome was modified Rankin Scale of 4-6 at 90-days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and c- statistic for all definitions of HE. Definitions were compared using non-parametric methods. Secondary analyses were performed after removing patients who experienced WOC. Results: Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition “≥6 mL or ≥33% or any IVH”, with increased c -statistic from 60.2% to 65.9% (p < 0.001). Secondary analysis excluded 46 participants who experienced WOC. The revised definitions outperformed the conventional definition in this population as well, with the greatest improvement in c -statistic using “≥6 mL or ≥33% or any IVH” (58.1% vs 64.1%, p < 0.001). Conclusions: HE definitions incorporating intraventricular expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.

IntroductionInsulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.Methods and analysisThe authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by I².Ethics and disseminationNo human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.PROSPERO registration numberCRD42020173608.

ObjectiveHematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose an HE shift analysis model as a method to improve the evaluation of candidate ICH therapies.MethodsUsing data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on previously established HE definitions, percentile/absolute quartiles of hematoma volume change, and quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored with proportional odds models.ResultsThe primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. With the use of a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.60–0.99). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy (aOR 0.73, 95% CI 0.57–0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (>21.9 mL) were most notable.ConclusionsOur findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies.Trial Registration InformationClinicalTrials.govIdentifier:NCT01176565.

Objectives Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior. Methods We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index. Results Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018). Conclusions Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.