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Advance consent could allow individuals at high risk of stroke to provide consent before they might become eligible for enrollment in acute stroke trials. This survey explores the acceptability of this novel technique to Canadian Research Ethics Board (REB) chairs that review acute stroke trials. Responses from 15 REB chairs showed that majority of respondents expressed comfort approving studies that adopt advance consent. There was no clear preference for advance consent over deferral of consent, although respondents expressed significant concern with broad rather than trial-specific advance consent. These findings shed light on the acceptability of advance consent to Canadian ethics regulators.
Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis.
We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts.
Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT.
Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.
Advance consent presents a potential solution to the challenge of obtaining informed consent for participation in acute stroke trials. Clinicians in stroke prevention clinics are uniquely positioned to identify and seek consent from potential stroke trial participants. To assess the acceptability of advance consent to Canadian stroke clinic physicians, we performed an online survey. We obtained 58 respondents (response rate 35%): the vast majority (82%) expressed comfort with obtaining advance consent and 92% felt that doing so would not be a significant disruption to clinic workflow. These results support further study of advance consent for acute stroke trials.
Cervico-cephalic arterial dissections (CeAD) are an important cause of stroke in young patients. This study aimed to determine the frequency and predictors of recanalization in spontaneous CeAD and to study the effect of recanalization on functional outcomes.
We identified patients presenting with acute ischemic stroke secondary to CeAD from the CT angiography (CTA) database of the Calgary Stroke Program. Dissections were diagnosed based on standard clinical and imaging findings. At the discretion of treating stroke Neurologists, the patients were either treated with single antiplatelet or dual antiplatelet or triple therapy. Follow-up imaging with CTA, magnetic resonance imaging, and DSA was completed, and a Modified Rankin scale (mRS) was performed to determine the outcome.
Fifty-six patients with CeAdD were studied. Thirty-four patients (18 VAD; vertebral artery dissection and 16 CAD; carotid artery dissection) were followed up for recanalization. Complete recanalization was observed in 27 subjects; 13 patients with VAD recanalized in comparison to 14 with CAD (p = 0.40). All non-recanalized patients had hypertension. A good clinical outcome (mRS ≤ 2) was observed in 47 patients. Interestingly, the likelihood of a good neurological outcome was not influenced by recanalization status. There was no difference in clinical outcome for different sites in VAD, whereas patients with intracranial CAD had severe strokes (NIHSS > 21).
CeAD has good recanalization rates and neurological outcomes, with recanalization seen even in vessels with initial complete occlusion. The presence of hypertension may influence recanalization. The efficacy of dual antiplatelets and heparin for early recanalization needs to be assessed in future clinical trials.
Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.
Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status.
Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0–49%), good (50–99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status.
386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78–246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8–53.0% of the observed between-patient variance in collaterals.
Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.
Methods and Results:
Over a 3-year period (April 2015–March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI −2.74–14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94–20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.
We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.
Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability.
In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions.
Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six “level-1A” scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31–0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17–1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology).
Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.
In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.
Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.
Purpose: We measured anterior cerebral artery (ACA)-middle cerebral artery (MCA) and posterior cerebral artery (PCA)-MCA pial filling on single-phase computed tomography angiograms (sCTAs) in acute ischemic stroke and correlate with the CTA-based Massachusetts General Hospital (MGH) and digital subtraction angiography (DSA)-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) score. Methods: Patients with acute stroke and M1 MCA±intracranial internal carotid artery occlusion on baseline CTA were included. Baseline sCTA was assessed for phase of image acquisition. An evaluator assessed collaterals using the Calgary Collateral (CC) Score (measures pial arterial filling in ACA-MCA and PCA-MCA regions separately), the CTA-based MGH score, and on DSA using the ASITN score. Infarct volumes were measured on 24- to 48-hour magnetic resonance imaging/ computed tomography. Results: Of 106 patients, baseline sCTA was acquired in early arterial phase in 9.9%, peak arterial in 50.7%, equilibrium in 32.4%, early venous in 5.6%, and late venous in 1.4%. Variance in ACA-MCA collaterals explained only 32% of variance in PCA-MCA collaterals on the CC score (Spearman’s correlation coefficient rho [rho]=0.56). Correlation between ACA-MCA collaterals and the MGH score was strong (rho=0.8); correlation between PCA-MCA collaterals and this score was modest (rho=0.54). Correlation between ACA-MCA collaterals and the ASITN score was modest (n=53, rho=0.43); and correlation between PCA-MCA collaterals and ASITN score was poor (rho=0.33). Of the CTA-based scores, the CC Score (Akaike [AIC] 1022) was better at predicting follow-up infarct volumes than was the MGH score (AIC 1029). Conclusion: Collateral assessments in acute ischemic stroke are best done using CTA with temporal resolution and by assessing regional variability. ACA-MCA and MCA-PCA collaterals should be evaluated separately.
We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA).
Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA.
A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006).
Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.
Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center.
We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups.
Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster.
CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.
We describe the internal cerebral vein (ICV) sign, which is a hypo-opacification of the ICV on computed tomogram angiography (CTA) as a new marker of increased cerebral blood transit-time in ipsilateral internal carotid artery occlusions (ICAO).
A retrospective analysis of 153 patients with acute unilateral M1 middle cerebral artery (MCA) occlusions ± ICAOs was performed. The degree of contrast opacification of the ICV on the ipsilesional side was compared to that of the unaffected side.
Of 153 patients in our study, 135 had M1 MCA occlusions ± intra-cranial ICAO (M1±iICAO) and 18 had isolated extracranial ICAO (eICAO). In the patients with proximal M1±iICAO, 57/65 (87.1%) showed the ICV sign. Of the 8 patients without the ICV sign in this group, 6 had prominent lenticulostriate arteries arising from the non-occluded M1 segment, 1 had a recurrent artery of Huebner, and 1 had filling of distal ICA/M1 segment through prominent Circle of Willis collaterals. For the 70 patients with isolated distal M1±iICAO, 7/70 (10%) showed the ICV sign, with all 7 showing occluded lenticulostriate arteries. Of the patients with eICAO, 8/18 showed the ICV sign, all 8 with the ICV sign had poor Circle of Willis collaterals.
The ICV sign correlates well with presence of proximal M1±iICAO in patients with either occluded lenticulostriate arteries or poor Circle of Willis collaterals. In patients with eICAO, the sign correlates with reduced Circle of Willis collaterals and may be a marker of increased ipsilateral cerebral blood transit time.
We studied the safety of use of acute reperfusion therapies in patients with stroke- on- awakening using a computed tomographic angiography (Cta) based large vessel occlusion-good scan paradigm in clinical routine.
the Cta database of the Calgary stroke program was reviewed for the period January 2003-March 2010. patients with stroke-on-awakening with large artery occlusions on Cta, who received conservative, iV thrombolytic and/or endovascular treatment at discretion of the attending stroke neurologist were analyzed. time of onset was defined by the time last seen or known to be normal. Baseline non-contrast Ct scan (nCCt) alberta Stroke program early Ct Score (aSpeCtS) > 7 was considered a good scan. hemorrhage was defined on follow-up brain imaging using eCaSS 3 criteria. independence (mrS≤2) at three months was considered a good clinical outcome. Standard descriptive statistics and multivariable analysis were done.
among 532 patients with large artery occlusions, 70 patients with stroke-on-awakening (13.1%) were identified. the median age was 69.5 (iQr 24) and 41 (58.6%) were female; 41 (58.6%) received anti-platelets only and 29 (41.4%) received thrombolytic treatment [iV-12 (17.1%), iV/ia-12 (17.1%) and ia-5(7.1%)]. unadjusted analysis showed that baseline nCCt aSpeCtS ≤ 7 (p=0.002) and higher nihSS scores (p=0.018) were associated with worse outcomes. there were no ph2 hemorrhages in the iV thrombolytic or endovascular treated group. functional outcome was not different by treatment.
When carefully selected using Ct –Cta, by a good scan (aSpeCtS > 7) occlusion paradigm, acute reperfusion therapies in patients with stroke-on-awakening can be performed safely in clinical routine.
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