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Background: The CHANCE-2 study compared 3 weeks of aspirin–ticagrelor to aspirin–clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin–ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown. Methods: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty. Results: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY. Conclusion: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin–ticagrelor compared to standard-of-care aspirin–clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine. more...

Background: Motor impairment in the arms is common after stroke and many individuals participate in therapy to improve function. It is assumed that individuals with stroke can adapt and improve their movements using feedback that arises from movement or is provided by a therapist. Here we investigated visuomotor adaptation in individuals with sub-acute and chronic stroke. Objective: We examined the impact of the stroke-affected arm (dominant or non-dominant), time post-stroke, and relationships with clinical measures of motor impairment and functional independence. Methods: Participants performed reaching movements with their arm supported in a robotic exoskeleton. We rotated the relationship between the motion of the participant’s hand and a feedback cursor displayed in their workspace. Outcome measures included the amount that participants adapted their arm movements and the number of trials they required to adapt. Results: Participants with stroke (n = 36) adapted less and required more trials to adapt than controls (n = 29). Stroke affecting the dominant arm impaired the amount of adaptation more than stroke affecting the non-dominant arm. Overall, 53% of participants with stroke were impaired in one or more measures of visuomotor adaptation. Initial adaptation was weakly correlated with time post-stroke, and the amount of adaptation correlated moderately with clinical measures of motor impairment and functional independence. Conclusion: Our findings reveal impairments in visuomotor adaptation that are associated with motor impairment and function after stroke. Longitudinal studies are needed to understand the relationship between adaptation and recovery attained in a therapy setting. more...

Introduction: The current research involved the study of chondroitin sulfate polymer to prevent moisture loss, which was formulated to treat dry eye. Method: The ophthalmic formulation was prepared with 5% liquid paraffin wax, 10% carbowax, and 1% glycerine. Furthermore, its usefulness in ophthalmology was analyzed by measuring parameters like pH, isotonicity, turbidity, viscosity, % moisture loss, vapor pressure, and in-vitro and in-vivo corneal damage. Results: We successfully adjusted the pH and osmolality of the F2 formulation to the desired physiological levels, providing the opportunity to reduce the harmful reaction as well as inflammation and dehydration. In addition, viscosity plays an important role in ophthalmic preparation. Consequently, the stability studies of optimized formulation indicated no remarkable changes in physical properties, including pH, viscosity, phase separation, and turbidity. Furthermore, a vapor pressure manometer studied the percentage of moisture loss. Interestingly, the HET-CAM test correlated properly with the findings of the Draize eye inflammation test. Moreover, the in-vivo irritation test of the optimized system showed that it was tolerable, with no signs of irritation in the rabbit eye compared to the marketed formulation. In addition, the F2 formulation demonstrated better results than the marketed corneal preparation. Thereby, from the results, it can be concluded that the simple manometer apparatus can be the best method for evaluating moisture loss prevention for dry eyes. No study or investigation has been reported before for ophthalmic preparation. Conclusion: Altogether, chondroitin sulfate with carbowax 1000 and liquid paraffin-based ophthalmic preparation can be considered a promising approach for preventing dryness of the eye. more...

BackgroundThe Alteplase compared to Tenecteplase (AcT) randomized controlled trial (RCT) showed that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known, however the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase.MethodsPatients included were from AcT, a pragmatic, registry linked, phase 3 RCT comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4·5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin scale(mRS) 0-1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality rates. Mixed effects logistic regression was used to assess a)the association of stroke symptom onset to needle time (ONT), b)door (hospital arrival) to needle time(DNT) with outcomes and c)if these associations were modified by type of thrombolytic administered (tenecteplase vs. alteplase), after adjusting for age, sex, baseline stroke severity and site of intracranial occlusion.ResultsOf the 1538 patients included in this analysis, 1146(74.5%)[591: tenecteplase, 555 alteplase] presented within 3 hours vs. 392 (25.5%)[196: TNK, 196 alteplase] who presented within 3-4.5 hours of symptom onset. Baseline patient characteristics in the 0-3 hour versus 3-4.5-hour time window were similar, except patients in the 3-to-4.5-hour window had lower median baseline NIHSS (10 vs 7 respectively) and lower proportion of patients with large vessel occlusion on baseline CT Angiography (26.9% vs 18.7% respectively). Type of thrombolytic agent (tenecteplase vs. alteplase) did not modify the association between ONT(pinteraction= 0.161) or DNT(pinteraction= 0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-min reduction in ONT was associated with a 1.8% increase while every 10 min reduction in DNT was associated with a 0.2% increase in the probability of achieving 90-day mRS 0-1 respectively.ConclusionThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.Key points:QuestionIn patients with acute ischemic stroke, does the effect of time to thrombolysis on clinical outcomes differ with tenecteplase vs. alteplase administration?FindingsIn this analysis from the alteplase compared to tenecteplase (AcT) trial, a pragmatic, registry linked, phase 3 randomized controlled trial, each 30-min reduction in stroke onset to thrombolysis start time was associated with a 1.8% increase in the probability of achieving excellent functional outcome, which means that for every 30-minute reduction in onset to needle time two more of a 100 people achieved an excellent outcome. This effect was not modified by type of thrombolytic used (alteplase versus tenecteplase)MeaningThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. more...

Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial.Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built.Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46).The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion. more...

Introduction: Age is a predictor of functional outcome after acute ischemic stroke (AIS). Frailty increases with age and comorbidities, and imaging markers of brain-frailty (e.g. atrophy, small-vessel-disease) are associated with outcomes. However, the extent to which the association of age and 90-day outcome is mediated by brain-frailty is unknown. We explored this mediation in AIS patients receiving endovascular therapy (EVT), with a particular interest in neuroimaging. Methods: In this post-hoc analysis of the ESCAPE-NA1 trial, in which all patients underwent EVT, we assessed brain atrophy (subcortical/cortical), white-matter disease (periventricular/deep) and the number of lacunes and chronic infarctions. Structural equation modelling (SEM) was used to create 3 latent variables: “imaging-frailty” (above-mentioned markers), “clinical-frailty” (e.g. pre-stroke mRS, cardiovascular risk factors, cancer) and “total-frailty” (imaging + clinical markers). We created 3 models ( figure1) including each latent variable as a potential mediator of the association of age and 90-day outcome, adjusting for baseline ASPECTS, NIHSS, onset-to-puncture-time, nerinetide and alteplase. Results: Among 1,092 patients, the indirect effect of age on 90-day outcome, mediated by imaging-frailty, contributed 96% of the total effect(β=0.047;p=0.02), while the indirect effect through clinical-frailty accounted for only 21%(β=0.01;p=0.001) of the total effect. When including both frailty constructs, the indirect pathway accounted for 86% of the total effect(β=0.06;p Conclusions: Brian frailty mediates the association of age and 90-day outcome after EVT, with most of the effect mediated by imaging as opposed to clinical markers of frailty. This work underscores the importance of considering brain-frailty, as opposed to chronological age alone, in predicting post-stroke outcomes. more...

Background and Purpose: First pass effect (FPE), or effective reperfusion with a single pass of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), is strongly associated with good functional outcome (mRS≤2) and can aid in optimal device selection for EVT. We aim to investigate the arterial tortuosity from great vessel origin to the intracranial occlusion location and predict first pass effect, automatically by a novel neural network, on computed tomographic angiography (CTA). Materials and Methods: Patients with thin-slice (≤2.5 mm) neck CTA from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of AIS) were included. Arterial centerlines from the aortic arch to the intracranial occlusion site were manually traced by three experienced readers on CTA. The centerlines were modeled and organized by tortuosity. A model based on graph neural network (GNN) was proposed to predict FPE on the processed data. Model performance was compared to manual annotations and traditional classification algorithms using diagnostic statistics. Results: 539 patients were included, with a 429/110 training/testing-ratio. FPE was observed in 136(31.7%, training set) and 35 (31.8%, testing set). The suggested model showed an overall good performance with an area under the receiver operating characteristic curve (AUC-ROC) of 0.66 (95% CI=0.65-0.67), precision of 0.46(17/37), sensitivity of 0.71(17/35), specificity of 0.61(55/75) and accuracy of 0.65(72/110), whereas the manually annotated features with traditional classification methods had an AUC-ROC of 0.54 (95%CI=0.53, 0.55), precision of 0.42(8/19), sensitivity of 0.23(8/35), specificity of 0.85(64/75) and accuracy of 0.65(72/110). Conclusion: An automated model for FPE prediction on CTA had better performance and higher sensitivity as compared to manual annotations and traditional machine learning algorithms, suggesting that it could be used in routine clinical practice prior to EVT. more...

Introduction: Brain-selective hypothermia is a promising neuroprotectant in acute ischemic stroke. However, a non-invasive bedside method to monitor brain temperature during cooling is lacking. We tested the feasibility and accuracy of measuring brain temperature non-invasively using sensors designed to monitor core body temperature. Methods: In this prospective single-center study, 20 patients with large or medium vessel occlusion strokes were enrolled. Patients underwent a 3T MR spectroscopy imaging (MRSI, the reference standard) and zero heat flux (ZHF) core temperature sensor measurements (3M TM Bair Hugger TM ) within 12-72 hours from admission. Two ZHF sensors were placed on each side of the forehead on the side of stroke and contralateral side and the temperatures were checked before and after MRSI. A 2x2x2 cm voxel was centered on the infarct and matching contralateral location using diffusion weighted imaging. Brain temperature on MRSI was calculated using the relative chemical shifts of water and N-acetyl aspartate. Temperature measurements of the ZHF sensors were compared to MRSI measurements. Results: The brain temperature of stroke and contralateral sides were similar using MRSI or using ZHF sensors when each modality was compared to itself by hemisphere (all p>0.05). However, there was a significant difference for the ipsilateral side: median (SD) temperatures using MRSI was 36.0°C (1.8) vs 36.8°C (0.5) for sensor measurement. Bland-Altman plots showed that 95% of the observations fell within upper and lower limits of agreement of -2.1 to +3.7°C while 61% of observations fell within an agreement limit of +/- 1°C. There was an indication of an overall higher temperature measurements using the ZHF sensors compared to MRSI (Figure 1). Conclusions: More studies are needed to validate the use of ZHF thermometry in ischemic stroke including studies implementing hypothermia. Figure 1. Boxplot of stroke side MRSI compared to zero-heat-flux sensors. more...

BACKGROUND AND PURPOSE: Thrombus embolization during mechanical thrombectomy occurs in up to 9% of cases, making secondary medium vessel occlusions of particular interest to neurointerventionalists. We sought to gain insight into the current endovascular treatment approaches for secondary medium vessel occlusion stroke in an international case-based survey because there are currently no clear recommendations for endovascular treatment in these patients. MATERIALS AND METHODS: Survey participants were presented with 3 cases involving secondary medium vessel occlusions, each consisting of 3 case vignettes with changes in the patient’s neurologic status (improvement, no change, unable to assess). Multivariable logistic regression analyses clustered by the respondent’s identity were used to assess factors influencing the decision to treat. RESULTS: In total, 366 physicians (56 women, 308 men, 2 undisclosed) from 44 countries provided 3294 responses to 9 scenarios. Most (54.1%, 1782/3294) were in favor of endovascular treatment. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio = 2.62; 95% CI, 2.27–3.03) or A3 (59.7%; risk ratio = 2.11; 95% CI, 1.83–2.42) segment compared with the M3/4 segment (28.3%; reference). Physicians were less likely to pursue endovascular treatment in patients who showed neurologic improvement than in patients with an unchanged neurologic deficit (49.9% versus 57.0% responses in favor of endovascular treatment, respectively; risk ratio = 0.88, 95% CI, 0.83–0.92). Interventionalists and more experienced physicians were more likely to treat secondary medium vessel occlusions. CONCLUSIONS: Physicians’ willingness to treat secondary medium vessel occlusions endovascularly is limited and varies per occlusion location and change in neurologic status. More evidence on the safety and efficacy of endovascular treatment for secondary medium vessel occlusion stroke is needed. more...

BACKGROUND AND PURPOSE: There is a paucity of evidence regarding the safety of endovascular treatment for patients with acute ischemic stroke due to primary medium-vessel occlusion. The aim of this study was to examine the willingness among stroke physicians to perform endovascular treatment in patients with mild-yet-disabling deficits due to medium-vessel occlusion. MATERIALS AND METHODS: In an international cross-sectional survey consisting of 7 primary medium-vessel occlusion case scenarios, participants were asked whether the presence of personally disabling deficits would influence their decision-making for endovascular treatment despite the patients having low NIHSS scores (100 endovascular treatments per year (risk ratio = 1.63; 95% CI, 1.22–2.17). CONCLUSIONS: The presence of a patient-relevant deficit in low-NIHSS acute ischemic stroke due to medium-vessel occlusion is an important factor for endovascular treatment decision-making. This may have relevance for the conduct and interpretation of low-NIHSS endovascular treatment in randomized trials. more...

Endovascular therapy (EVT) is an effective treatment for ischemic stroke due to large vessel occlusion (LVO). Unlike intravenous thrombolysis, EVT enables visualization of the restoration of blood flow, also known as successful reperfusion in real time. However, until successful reperfusion is achieved, the survival of the ischemic brain is mainly dependent on blood flow from the leptomeningeal collaterals (LMC). It plays a critical role in maintaining tissue perfusion after LVO via pre-existing channels between the arborizing pial small arteries or arterioles overlying the cerebral hemispheres. In the ischemic territory where the physiologic cerebral autoregulation is impaired and the pial arteries are maximally dilated within their capacity, the direction and amount of LMC perfusion rely on the systemic perfusion, which can be estimated by measuring blood pressure (BP). After the EVT procedure, treatment focuses on mitigating the risk of hemorrhagic transformation, potentially via BP reduction. Thus, BP management may be a key component of acute care for patients with LVO stroke. However, the guidelines on BP management during and after EVT are limited, mostly due to the scarcity of high-level evidence on this issue. In this review, we aim to summarize the anatomical and physiological characteristics of LMC to maintain cerebral perfusion after acute LVO, along with a landscape summary of the literature on BP management in endovascular treatment. The objective of this review is to describe the mechanistic association between systemic BP and collateral perfusion after LVO and thus provide clinical and research perspectives on this topic. more...

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

Background and purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management. Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0–2a. Proportions of good outcome (modified Rankin scale 0–2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained. Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81–2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56–2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00–22.97). Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management. more...

Patients with pre-morbid disability have been generally excluded from randomized controlled trials of mechanical thrombectomy for acute ischemic stroke. However, stroke physicians commonly encounter such patients in practice, and face challenging treatment decisions when caring for them.We review the literature on the safety and efficacy of thrombectomy in patients with pre-morbid disability. Recent clinical-epidemiological studies have highlighted the adverse outcomes that come with each increment of additional post-stroke disability in these patients. Several observational studies - both case series and registry-based studies - have helped demonstrate the comparable safety of thrombectomy in patients with pre-morbid disability as in those without, complementing similar data on thrombolysis. These data also suggest similar rates of successful recanalization, symptomatic intracerebral hemorrhage, and return to pre-stroke level of disability when treated with mechanical thrombectomy, although they have higher mortality.In the absence of high-quality evidence, we recommend pursuing shared decision-making with patients or family members and being upfront about the uncertain evidence. Available observational data underline the potential for a substantial proportion of these patients to return to their pre-morbid state, do not indicate a greater rate of treatment-related complications, and do not support routinely excluding these patients from thrombectomy. more...

People with MS (pwMS) have higher prevalence of comorbidities at disease onset and face increased risk of developing cardiovascular disorders. Stroke is of particular concern for this population with previous neurological disability. However, data on stroke outcomes and resource utilization in those pwMS remains scarce.To assess the risk of adverse stroke outcomes and hyperacute treatment utilization for pwMS in a U.S. population-based sample of hospitalized patients.This study identified patients discharged with a diagnosis of ischemic stroke in the 2018 National Inpatient Sample. We compared the discharge outcomes and hyperacute stroke treatment utilization in MS (n = 2,795) versus non-MS patients (n = 682.730). Regression models adjusted for cardiovascular risk factors and hospital characteristics were used to account for the complex sampling design.The odds of a good discharge were 32% less likely to occur in pwMS (adj.OR 0.68 [95%CI 0.58-0.81], p0.001). However, this was not associated with an increased risk of mortality. PwMS had a 57% reduction in the risk of receiving endovascular thrombectomy (EVT) (adj.OR 0.43 [95%CI 0.22-0.83], p = 0.01) but no difference in rates of thrombolysis.Patients with MS have lower rates of good discharge outcomes and EVT with ischemic stroke, despite similar rates of thrombolysis. more...

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an astrocytopathy with a predilection for the optic nerve, spinal cord, and brainstem. In this ambispective study, we evaluate clinical characteristics, responses to therapy, and disability outcomes in patients with NMOSD. Methods: Patients diagnosed as NMOSD and following up for at least 1 year at a tertiary care center in India were recruited. Patient data were collected ambispectively from January 2012 until December 2018. Results: A total of 106 patients (29M/77F) with NMOSD were evaluated. The mean age of onset was 29 (±11.6) years. About 77 patients (72.64%) were positive for the AQP4 antibody. Age of onset was higher for those presenting with an opticospinal syndrome (34.2 years) as compared to either isolated longitudinally extensive transverse myelitis (LETM) (30 years) or optic neuritis (ON) (25.3 years). The most common syndrome at onset was LETM in 57 patients (53.77%) followed by ON in 31 patients (29.24%). Azathioprine was the most common immunotherapy (83.96%) prescribed followed by rituximab (7.54%) and mycophenolate mofetil (1.88%). There was a significant decrease in the number of relapses post-azathioprine (P < 0.001). Out of 67 patients with ON, 21 (31.34%) had complete recovery while 17 (25.37%) patients had a severe deficit at a 3-month follow-up. Out of 92 patients with a motor deficit, 49 (53.26%) patients had a partial motor deficit at a 6-month follow-up. The severe visual deficit at baseline and female gender predicted poor visual and motor recovery, respectively. Conclusion: This is the largest descriptive study on patients with NMOSD from India. Relapse rates were similar irrespective of the clinical presentation, age, gender, and disease course. Treatment with immunosuppressive treatment significantly affected the disease course. more...

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. more...

The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions. Ultimately, the approach we outline here could become the foundation for a general justification for deferral of consent. more...

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

Background : Intravenous thrombolysis with alteplase is widely used in acute ischemic stroke patients presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared to alteplase. This study investigates whether intravenous tenecteplase is non‐inferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods : This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non‐inferior to intravenous alteplase (0.9 mg/kg body weight, max dose 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a non‐inferiority margin of 5%, assuming incidence of 90‐day mRS 0–1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate < 5%. Results : The blinded primary endpoint is the proportion of subjects achieving a 90‐day mRS (modified Rankin scale) of 0–1. Key safety outcomes include 24‐hour symptomatic intracerebral hemorrhage and 90‐day all‐cause mortality. All serious adverse events within 24‐hour period will be reported and coded using MedDRA. Outcomes are collected either centrally (primary, key secondary and safety endpoints) or through ongoing Canadian stroke registries. The primary analysis is a simple unadjusted comparison of proportions. Conclusion : Results from the trial will provide real‐world evidence of the effectiveness of intravenous tenecteplase vs. alteplase in patients with acute ischemic stroke presenting early after stroke onset. Clinical Trial Registration: NCT03889249 https://clinicaltrials.gov/ct2/show/NCT03889249 This article is protected by copyright. All rights reserved more...

BackgroundThe benefit of endovascular thrombectomy (EVT) in stroke patients with a low baseline Alberta Stroke Program Early CT Score (ASPECTS, ≤5) is uncertain. We aim to use random forest regression modeling to predict 90 day home time in patients with low ASPECTS.MethodsWe used the Quality Improvement and Clinical Research (QuICR) provincial stroke registry and administrative data from southern Alberta to identify patients who underwent EVT in our center from July 2015 to November 2020. Baseline ASPECTS on non-contrast CT and CT angiography data were scored by a two physician consensus. The primary outcome was the predicted 90 day home time (the number of nights a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using random forests regression. Estimates were generated using 200 bootstrapped datasets. Covariate contribution to home time was determined using partial dependence plots.ResultsOf 657 EVT patients, 85 (12.9%) had baseline ASPECTS ≤5 (mean age 70.9 years, 44.7% women, 93.9% good–moderate collaterals, 60% M1–middle cerebral artery occlusion). Using partial dependence estimates, mean predicted home times were similar in the low ASPECTS (44.3 days) versus higher ASPECTS (43.1) groups. Factors predicting lower 90 day home time in this population were diabetes mellitus (−8.8 days), hypertension (−5.7 days), and atrial fibrillation (−3.6 days). There was no meaningful difference in predicted 90 day home time by sex, baseline National Institutes of Health Stroke Severity Scale score, occlusion site, tandem lesion, collateral grade or thrombolysis.ConclusionsPatients with low ASPECTS who are selected for EVT using demographic and clinical profiles similar to higher ASPECTS patients achieved comparable outcomes. more...

Background: 90-day home-time, the number of days a patient is back at their premorbid living situation without an increase in level of care in the first 90 days post stroke, is routinely collected in administrative data. We evaluated the prediction of 90-day home-time using machine learning modelling in patients undergoing endovascular treatment (EVT). Methods: We used the QuICR provincial stroke registry and administrative data from Southern Alberta from Jan 2015-Dec 2019 to identify patients who underwent EVT. Imaging data were scored by 2-physician consensus. The primary outcome was 90 day home-time, which has a highly non-normal distribution with excess zero’s. We modelled using generalized boosting machine model with Gaussian distribution. Contribution of different covariates to hometime was determined using partial dependence plots. Results: We identified 659 EVT patients from Jan 2015 to Dec 2019 treated in Calgary, Alberta. Overall,median predicted 90d home-time was 41days (IQR 5.5 to 77.8) with good model accuracy (Root mean square error 6.96). Holding other covariates constant, factors predicting lower 90d-hometime were diabetes mellitus(-14.1d), hypertension (-7d), low baseline ASPECTS (≤5) (-5.6d) and symptomatic intracerebral hemorrhage (sICH) on follow up scan (-13.8d). There was a consistent improvement in the predicted home-time over the last 5 years. There was no meaningful difference in predicted 90d-home-time by age, baseline NIHSS, sex, atrial fibrillation, occlusion site, tandem occlusion, thrombolysis, or successful reperfusion (Figure 1) Conclusions: Predicting 90-d hometime using boosting machine learning modelling is useful to assess complex relationships between predictors and home-time. Hypertension, diabetes, low ASPECTS and sICH were predictors of lower 90-d home-time in this registry. more...