Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Evaluating the influence of altered cerebral hemodynamics on cognitive performance in asymptomatic carotid artery stenosis: A systematic review.

OBJECTIVE: Substantial controversy exists regarding asymptomatic carotid stenosis (ACS) and its potential role in the pathophysiology of cognitive impairment. If proven, this hypothesis may suggest an additional definition for symptomatic carotid disease that would alter current management. This study aimed to synthesize the literature evaluating the relationship between impaired cerebral hemodynamics and cognition in patients with ACS. METHODS: A literature search was performed using MEDLINE, Embase, and EBM Reviews through May 2022. We included prospective case-control studies that used validated, objective measure(s) of either global cognition or one or more domains of cognitive function and assessed cerebrovascular reserve (CVR). RESULTS: Five studies were included, comprising a total of 782 patients with moderate (50%-69%) to severe (70%-99%) ACS. Patients with ACS and impaired ipsilateral CVR demonstrated significant cognitive impairment compared with controls. Patients with unilateral or bilateral ACS and normal CVR had cognitive scores similar to controls. Those with bilateral CVR impairment demonstrated the lowest cognitive scores. CONCLUSIONS: This review lends support to the claim that cognitive impairment, likely the result of impaired cerebral hemodynamics, is an under-recognized morbidity in patients with ACS. CVR may serve as an additional tool to determine whether patients are in fact symptomatic from their carotid stenosis and warrant consideration for intervention.

Impact of the COVID-19 Pandemic on Stroke Subtype Presentation in Patients Without COVID-19 Infection.

BACKGROUND & AIMS: It is unknown if the COVID-19 pandemic and public health measures had an immediate impact on stroke subtypes and etiologies in patients not infected with COVID-19. We aimed to evaluate if the proportion of non-COVID-19-related stroke subtypes (ischemic vs. hemorrhagic) and etiologies (cardioembolic, atherosclerosis, small vessel disease, and others) during the pandemic's first wave were different from prepandemic. METHODS: For this retrospective cohort study, we included patients without COVID-19 with ischemic or hemorrhagic stroke at two large Canadian stroke centers between March-May 2019 (prepandemic cohort) and March-May 2020 (pandemic cohort). Proportions of stroke subtypes and etiologies were compared between cohorts using chi-square tests. RESULTS: The prepandemic cohort consisted of 234 stroke patients and the pandemic cohort of 207 stroke patients. There were no major differences in baseline characteristics. The proportions of ischemic versus hemorrhagic stroke were similar (ischemic stroke: 77% prepandemic vs. 75% pandemic; hemorrhagic stroke:12% prepandemic vs. 14% pandemic; p > 0.05). There were no differences in etiologies, except for a decreased proportion of ischemic stroke due to atherosclerosis in the pandemic cohort (26% prepandemic vs. 15% pandemic; difference: 10.6%, 95%CI: 1.4-19.7; p = 0.03). Notably, during the pandemic, the cause of ischemic stroke was more often unknown because of incomplete work-up (13.3% prepandemic vs. 28.2% pandemic, difference: 14.9%, 95%-CI: 5.7-24.2; p = <0.01). CONCLUSIONS: In this study, the pandemic had no clear effect on stroke subtypes and etiologies suggesting a limited impact of the pandemic on stroke triggers. However, the shift from atherosclerosis toward other causes warrants further exploration.

Fertility treatment for people with epilepsy.

Fertility treatment, including assisted reproductive technology (ART), is increasingly used. Sex hormones influence seizure control as well as interacting with antiseizure medications, and so the hormonal manipulation involved in fertility treatments has direct implications for people with epilepsy. Here, we summarise the various fertility treatments and consider their important influences on epilepsy care. While early observations raised concerns about seizure exacerbation associated with ART, there are limited data to guide best practice in people with epilepsy, and further research is needed.

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

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

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with 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. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial 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 score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

Sex Differences in Functional Outcomes Following Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND: Sex disparities have been reported across many aspects of acute ischemic stroke (AIS) care; however, there is a relative paucity of research examining sex differences in outcomes following endovascular treatment (EVT). Some studies report worse functional independence for females following EVT. Few, if any of these studies account for differences in age, baseline function, and comorbidity burden. This retrospective cohort study aimed to assess for sex differences in functional outcomes following EVT by comparing 90-day modified Rankin Scale (mRS) of males and females while controlling for baseline function and comorbidity burden. METHODS: Baseline demographic and clinical data, and stroke severity were compared for 230 consecutive patients undergoing EVT for AIS between October 2014 and July 2019 at a tertiary stroke centre in Toronto, Canada. Effect of sex on likelihood of functional independence post-EVT was assessed using regression analysis with and without correction for age, baseline mRS, and Charlson Comorbidity Index (CCI). RESULTS: Females undergoing EVT for AIS were older (75 ± 13 vs. 66 ± 15, p < 0.0001), with worse clinical and functional baselines. Unadjusted, males were more functionally independent (90-day mRS < 3) [OR = 1.831, 95%CI 1.082-3.098]. After controlling for age, baseline mRS and CCI, there was no difference between groups [OR 1.21, 95%CI 0.61-2.37]. CONCLUSIONS: This study provides evidence that prior findings of sex disparities in function after EVT may be accounted for by differences in age, baseline clinical status and functional independence between males and females when a comprehensive measure of comorbidity burden is utilized.

Sex differences and predictors of completion of a 6-month exercise-based cardiac rehabilitation program in 1,536 people following stroke.

OBJECTIVE: To retrospectively examine sex-differences and predictors of completion in consecutively-referred patients to a 6-month exercise-based cardiac rehabilitation program (CRP) from 2006 to 2017. MATERIALS/METHODS: People with hemiplegic gait participated in stroke-adapted-CRP; otherwise, traditional-CRP. Reasons for non-completion were ascertained by interview. Regression-analyses were conducted to determine non-completion in all patients and women and men separately. RESULTS: There were 1536 patients (30.3% women), mean age 64.5 ± 12.5 with 23% initiating the stroke-adapted-CRP. Overall, 75.1% completed the CRP (87.3% stroke-adapted-CRP vs 71.5% traditional-CRP; p < .001). There was no difference in completion between women and men (74.5% vs 75.4%; p=0.7), or in attendance to pre-scheduled sessions (p=0.6) or reasons for non-completion (p > .05, all). The only sex difference in completion by age (decade) occurred in those <41 years (59% women vs 85% men; p=.02). Baseline predictors of non-completion among all patients included not being enrolled in the stroke-adapted-CRP, lower V̇O2peak, smoking, diabetes (prescribed insulin) and depression but not sex (p=.5) or age (p=.15). Unique predictors in women vs men were younger age, lower V̇O2peak, smoking, diabetes (prescribed insulin), depression, and cancer diagnoses. Unique to men was having >1 stroke and diabetes (any anti-diabetes medication). The strongest predictor of non-completion among all models was not being enrolled in stroke-adapted-CRP. CONCLUSIONS: While there were no sex-differences in adherence to the CRP, women and men have mostly unique predictors of non-completion. Younger women are at greatest risk for non-completion. Practitioners should provide sex-specific, tailored strategies for enhancing completion with a focus on younger women and offering a stroke-adapted-CRP with close attention to those with diabetes.

Health-Related Quality of Life Among Patients With Acute Ischemic Stroke and Large Vessel Occlusion in the ESCAPE Trial.

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<0.001). After accounting for the greater number of deaths in the elderly, there was evidence of modification of treatment effect by age, with older age associated with a larger effect size difference in EQ-5D with EVT. Those receiving EVT had higher odds of symptom-free status in self-care, usual activities, mobility for those aged 60 to 79 years, and pain/discomfort for women, but there was no association with anxiety/depression. Severe disability at 90 days was associated with lower EQ-5D in older compared with younger individuals, and the association was not modified by EVT. 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.

In-Hospital Delays for Acute Stroke Treatment Delivery During the COVID-19 Pandemic.

BACKGROUND: We investigated the impact of regionally imposed social and healthcare restrictions due to coronavirus disease 2019 (COVID-19) to the time metrics in the management of acute ischemic stroke patients admitted at the regional stroke referral site for Central South Ontario, Canada. METHODS: We compared relevant time metrics between patients with acute ischemic stroke receiving intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy (EVT) before and after the declared restrictions and state of emergency imposed in our region (March 17, 2020). RESULTS: We identified a significant increase in the median door-to-CT times for patients receiving intravenous tPA (19 min, interquartile range (IQR): 14-27 min vs. 13 min, IQR: 9-17 min, p = 0.008) and/or EVT (20 min, IQR: 15-33 min vs. 11 min, IQR: 5-20 min, p = 0.035) after the start of social and healthcare restrictions in our region compared to the previous 12 months. For patients receiving intravenous tPA treatment, we also found a significant increase (p = 0.005) in the median door-to-needle time (61 min, IQR: 46-72 min vs. 37 min, IQR: 30-50 min). No delays in the time from symptom onset to hospital presentation were uncovered for patients receiving tPA and/or endovascular reperfusion treatments in the first 1.5 months after the establishment of regional and institutional restrictions due to the COVID-19 pandemic. CONCLUSION: We detected an increase in our institutional time to treatment metrics for acute ischemic stroke patients receiving tPA and/or endovascular reperfusion therapies, related to delays from hospital presentation to the acquisition of cranial CT imaging for both tPA- and EVT-treated patients, and an added delay to treatment with tPA.

Délais dans le traitement en milieu hospitalier des AVC aigus dans le contexte de la pandémie de COVID-19. CONTEXTE: Nous nous sommes penchés, dans le contexte de la pandémie de COVID-19, sur l'impact de restrictions régionales imposées dans le domaine social et dans les soins de santé sur les délais de prise en charge de patients victimes d'un AVC aigu. À noter que ces patients ont été admis dans un centre régional de traitement des AVC situé dans le centre-ouest de l'Ontario (Canada). MÉTHODES: Nous avons comparé entre eux les délais de prise en charge de patients ayant bénéficié d'activateurs tissulaires du plasminogène par intraveineuse (tPA) et/ou d'une procédure de thrombectomie endovasculaire (TE) avant et après la mise sur pied de restrictions et l'imposition d'un état d'urgence sanitaire dans notre région (17 mars 2020). RÉSULTATS: Après la mise sur pied de ces restrictions, nous avons identifié, par rapport aux 12 mois précédent, une augmentation notable des délais médians entre l'arrivée à l'hôpital et un examen de tomodensitométrie dans le cas de patients bénéficiant de tPA (19 minutes, EI : 14­27 minutes contre 13 minutes, EI : 9­17 minutes ; p = 0,008) et/ou d'une procédure de TE (20 minutes, EI : 15­33 minutes contre 11 minutes, EI : 5­20 minutes ; p = 0,035). Pour ce qui est des patients bénéficiant de tPA, nous avons également observé une augmentation importante (p = 0,005) des délais médians entre leur arrivée à l'hôpital et l'injection d'un traitement (61 minutes, EI : 46­72 minutes contre 37 minutes, EI : 30­50 minutes). Enfin, dans le premier mois et demi suivant la mise sur pied des restrictions régionales et institutionnelles attribuables à la pandémie de COVID-19, aucun délai supplémentaire entre l'apparition des premiers symptômes d'un AVC et l'arrivée à l'hôpital n'a été remarqué pour des patients bénéficiant de tPA et/ou d'une procédure de TE. CONCLUSION: En somme, nous avons détecté une augmentation de nos délais de traitement dans le cas de patients victimes d'un AVC aigu ayant bénéficié de tPA et/ou d'une procédure de TE. Cela peut être attribué à une augmentation des délais de présentation à l'hôpital mais aussi à des délais dans l'obtention d'images de tomodensitométrie pour des patients traités avec des tPA et une procédure de TE, sans compter des délais accrus pour bénéficier d'un traitement de tPA.

Endovascular Therapy of Acute Ischemic Stroke in Patients with Large-Vessel Occlusion Associated with Active Malignancy.

PURPOSE: There is limited data on the effectiveness of endovascular therapy (EVT) in stroke patients with active malignancy. In this study, we investigated the outcome of EVT for acute ischemic stroke for patients with active malignancy compared to those without malignancy. METHODS: We selected patients who underwent EVT for acute ischemic stroke between January 2015 and July 2019. Patients were divided into two groups, those with active malignancy (oncology group - OG) and those without (non-oncology group, NOG). RESULTS: 300 patients were included in this study. There were 19 EVT procedures (18 patients) in the OG and 285 procedures (282 patients) in the NOG. There was no difference in recanalization success rate (mTICI 2b & 3) between the groups: 94.7% versus 80.9% in OG and NOG respectively (p = 0.13). Success rate using the direct aspiration (ADAPT) technique of EVT was not different between compared groups (42.9% versus 67.7%; p = 0.18). However, when using smaller-caliber aspiration devices, ADAPT was less successful in OG (0.0% versus 64.7%, p < 0.05). There was no difference in recanalization success rate of EVT when using a stent-retriever or combined technique. Patients in the OG had a less favorable functional outcome than in the NOG group (mRS 0-2 at 90-days post event: 22.2% versus 48.2%, p < 0.05) CONCLUSION: The technical success rate of EVT in patients with active malignancy is similar to the general population of stroke patients. Interestingly, the success rate of EVT using the ADAPT technique was lower in the OG when using smaller caliber aspiration devices.

How to Be Savvy About Gender Disparities in Academic Stroke Medicine: Five Practical Strategies.

In the past decade, stroke medicine has evolved from discovery of innovative diagnostic tools to implementation of new treatments. These advances are projected to increase the demand for stroke neurologists in academic and clinical practices, but hopefully with equitable opportunities for everyone across the gender spectrum. Academic medicine provides opportunities to participate in clinical care, teaching, research, and administration. The early career stage is short-focused on finding an academic niche and developing new skills that will help you navigate the academic environment. A recent InterSECT article emphasized the critical role of women's leadership in stroke medicine. In this article, we reflect on workforce gender disparities and provide 5 practical strategies that may help women overcome barriers and advance their work mission.

Comparison of multimodal CT scan protocols used for decision-making on mechanical thrombectomy in acute ischemic stroke.

PURPOSE: Different CT-based protocols are being used in acute ischemic stroke. We aimed to assess the added value of delayed-phase CT angiography (CTA) and CT perfusion (CTP) to a basic protocol using non-contrast computerized tomography (NCCT) with arterial-phase CTA in patient selection for mechanical thrombectomy. METHODS: We retrospectively included consecutive acute ischemic stroke patients with a symptomatic intracranial arterial occlusion between January 2015 and November 2016 who underwent NCCT, arterial and delayed-phase CTA, and CTP. These imaging studies were grouped into five protocols: (1) NCCT and arterial-phase CTA; (2) NCCT, arterial-phase CTA, and CTP; (3) NCCT, arterial- and delayed-phase CTA; (4) NCCT, arterial- and delayed-phase CTA, and CTP; and (5) NCCT and delayed-phase CTA. Two interventional neuro-radiologists independently decided on mechanical thrombectomy for each patient based on the protocols. They reached consensus for discrepant decisions. We assessed the raters' confidence level, inter-rater agreement, and compared treatment decisions for the different protocols. RESULTS: We included 73 patients (44% male, mean age 74). The inter-rater agreement was substantial for protocols with three or more modalities (Ò¡ = 0.613-0.704) and moderate for two-modality protocols (Ò¡ = 0.506-0.529). The highest agreement and confidence level was achieved for the combination of NCCT, arterial-phase CTA, and CTP. Adding CTP to NCCT and arterial-phase CTA resulted in a 10% increase of recommendations for mechanical thrombectomy and adding delayed-phase CTA resulted in a 4% increase. These management changes did not reach statistical significance (p = 0.07; p = 0.25, respectively). CONCLUSION: Adding CTP and/or a delayed-phase CTA to NCCT with arterial-phase CTA improves the decision-maker's confidence level and creates a trend towards a lower threshold for mechanical thrombectomy.

Revised Framingham Stroke Risk Profile to Reflect Temporal Trends.

BACKGROUND: Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies. METHODS: We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks. RESULTS: The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ2 of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks. CONCLUSIONS: A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

BACKGROUND AND PURPOSE: Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. METHODS: We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. RESULTS: During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P=0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke (P<0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P=0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P=0.031) lower risk of incident ischemic stroke, respectively. CONCLUSIONS: IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.

High Prevalence of Cerebral Microbleeds in Inner City Young Stroke Patients.

BACKGROUND: Data on cerebral microbleeds (CMBs) in younger populations are lacking, particularly in young stroke patients. We sought to characterize CMBs in an inner city cohort of young adults with stroke. METHODS: CMB presence, count, and topography were assessed on magnetic resonance imaging (MRI) scans of 104 young stroke patients (≤49 years) presenting to Boston Medical Center between January 2006 and February 2010. Subsequent MRIs were assessed for the occurrence of new microbleeds in 29 patients. We performed cross-sectional analysis comparing baseline characteristics between patients with and without microbleeds, and between predefined microbleed burden and topography categories. We performed additional analysis to assess the determinants of new microbleeds on repeat MRI. RESULTS: Microbleeds were present in 17% of the sample. Male sex (odds ratio [OR] 5.7, 95% confidence interval [CI] 1.0-32.6, P = .049), hypertension (OR 6.2, 95% CI 1.2-32, P = .03), moderate-severe white matter hyperintensities on MRI (OR 5.8, 95% CI 1.6-29.0, P = .01), and intracerebral hemorrhage (ICH; OR 5.0, 95% CI 1.2-20, P = .03) were over-represented in patients with microbleeds. Patients who developed new microbleeds on repeat MRI (14%) had higher microbleed counts on baseline MRI (50% versus 0% ≥ 3 CMBs, P = .02), history of illicit drug use (75% versus 24%, P = .08), positive serum toxicology for cocaine (67% versus 13%, P = .11), ICH as their presenting stroke subtype (50% versus 8%, P = .08), and over-representation of moderate-severe white matter hyperintensities (75% versus 20%, P = .05). CONCLUSIONS: Results from this inner city cohort suggest that microbleeds are prevalent in young stroke patients and are largely associated with modifiable risk factors.