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BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.
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Fibrinolíticos , AVC Isquêmico , Tenecteplase , Humanos , Tenecteplase/uso terapêutico , Tenecteplase/administração & dosagem , Masculino , Feminino , AVC Isquêmico/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Estudos Prospectivos , Padrão de Cuidado , Ativador de Plasminogênio Tecidual/uso terapêutico , Ativador de Plasminogênio Tecidual/administração & dosagem , Terapia Trombolítica/métodosRESUMO
BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. METHODS: Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. RESULTS: Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. CONCLUSIONS: Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.
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BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.
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Procedimentos Endovasculares , AVC Isquêmico , Ativador de Plasminogênio Tecidual , Humanos , Procedimentos Endovasculares/métodos , Masculino , Feminino , Idoso , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Pessoa de Meia-Idade , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Angiografia por Tomografia Computadorizada , Circulação Colateral/fisiologia , Fibrinolíticos/uso terapêutico , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Isquemia Encefálica/cirurgia , Isquemia Encefálica/tratamento farmacológicoRESUMO
Endovascular treatment (EVT) for acute ischemic stroke is one of the most efficacious and effective treatments in medicine, yet globally, its implementation remains limited. Patterns of EVT underutilization exist in virtually any health care system and range from a complete lack of access to selective undertreatment of certain patient subgroups. In this review, we outline different patterns of EVT underutilization and possible causes. We discuss common challenges and bottlenecks that are encountered by physicians, patients, and other stakeholders when trying to establish and expand EVT services in different scenarios and possible pathways to overcome these challenges. Lastly, we discuss the importance of implementation research studies, strategic partnerships, and advocacy efforts to mitigate EVT underutilization.
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Procedimentos Endovasculares , AVC Isquêmico , Trombectomia , Humanos , Trombectomia/métodos , Procedimentos Endovasculares/métodos , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Amyloid-beta and brain atrophy are hallmarks for Alzheimer's Disease that can be targeted with positron emission tomography (PET) and MRI, respectively. MRI is cheaper, less-invasive, and more available than PET. There is a known relationship between amyloid-beta and brain atrophy, meaning PET images could be inferred from MRI. PURPOSE: To build an image translation model using a Conditional Generative Adversarial Network able to synthesize Amyloid-beta PET images from structural MRI. STUDY TYPE: Retrospective. POPULATION: Eight hundred eighty-two adults (348 males/534 females) with different stages of cognitive decline (control, mild cognitive impairment, moderate cognitive impairment, and severe cognitive impairment). Five hundred fifty-two subjects for model training and 331 for testing (80%:20%). FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted structural (T1w). ASSESSMENT: The testing cohort was used to evaluate the performance of the model using the Structural Similarity Index Measure (SSIM) and Peak Signal-to-Noise Ratio (PSNR), comparing the likeness of the overall synthetic PET images created from structural MRI with the overall true PET images. SSIM was computed in the overall image to include the luminance, contrast, and structural similarity components. Experienced observers reviewed the images for quality, performance and tried to determine if they could tell the difference between real and synthetic images. STATISTICAL TESTS: Pixel wise Pearson correlation was significant, and had an R2 greater than 0.96 in example images. From blinded readings, a Pearson Chi-squared test showed that there was no significant difference between the real and synthetic images by the observers (P = 0.68). RESULTS: A high degree of likeness across the evaluation set, which had a mean SSIM = 0.905 and PSNR = 2.685. The two observers were not able to determine the difference between the real and synthetic images, with accuracies of 54% and 46%, respectively. CONCLUSION: Amyloid-beta PET images can be synthesized from structural MRI with a high degree of similarity to the real PET images. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.
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Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons , Masculino , Adulto , Feminino , Humanos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética/métodos , Atrofia , Processamento de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Estenose das Carótidas , Endarterectomia das Carótidas , Médicos , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/tratamento farmacológico , Estenose das Carótidas/cirurgia , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Stents , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Ensaios Clínicos como AssuntoRESUMO
INTRODUCTION: Despite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. METHODS: The survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. RESULTS: A total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. CONCLUSIONS: Pharmacologic interactions result in major uncertainty about cytoprotective treatment choices.
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Tomada de Decisão Clínica , Fibrinolíticos , AVC Isquêmico , Padrões de Prática Médica , Terapia Trombolítica , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/diagnóstico , AVC Isquêmico/terapia , AVC Isquêmico/fisiopatologia , Terapia Trombolítica/efeitos adversos , Padrões de Prática Médica/tendências , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Incerteza , Trombectomia/efeitos adversos , Pesquisas sobre Atenção à Saúde , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Adulto , Fatores de Tempo , Fármacos Neuroprotetores/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Gastrointestinal (GI) complications are seen in over 50% of ischemic stroke survivors; the most common complications are dysphagia, constipation, and GI bleeding. The bidirectional relationship of the gut-brain axis and stroke has recently gained traction, wherein stroke contributes to gut dysbiosis (alterations in the normal host intestinal microbiome) and gut dysbiosis perpetuates poor functional neurologic outcomes in stroke. It is postulated that the propagation of proinflammatory cells and gut metabolites (including trimethylamine N-oxide and short-chain fatty acids) from the GI tract to the central nervous system play a central role in gut-brain axis dysfunction. In this review, we discuss the known GI complications in acute ischemic stroke, our current knowledge from experimental stroke models for gut-brain axis dysfunction in stroke, and emerging therapeutics that target the gut-brain axis.
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Gastroenteropatias , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Disbiose , Acidente Vascular Cerebral/complicações , Sistema Nervoso Central , Gastroenteropatias/etiologiaRESUMO
BACKGROUND: Despite the high proportion of stroke patients with a pre-existing impairment, patients with disabilities are often excluded from stroke treatment trials. Trials are designed for "perfect patients": patients who are functionally independent and thus generally younger with fewer comorbidities; ironically, such patients are less likely to experience stroke than those with premorbid disability. Exclusionary practices in trials may translate into disparities in stroke care in practice. Through a review of literature, our purpose is to illuminate how people with disabilities are treated across the care continuum following a stroke. METHODS: We completed a qualitative systematized review of articles pertaining to the care of patients with premorbid disability and stroke and their outcomes. Using a critical disability studies' theoretical lens, we analyzed inequity across the stroke care continuum. FINDINGS: Among 24 included studies, we found evidence that people with disabilities did not receive equitable access to treatment ranging from being admitted to stroke units to receiving post-stroke rehabilitation. However, observational studies suggest that stroke therapies may be beneficial in selected patients with disabilities when measures of success are framed more achievable (e.g. return to pre-stroke status). This leaves us concerned about how people with pre-existing impairments might be structurally disabled within current systems of stroke care. CONCLUSION: We use our critical disability studies' theoretical lens to argue that an intersectional approach to stroke treatment is much needed if we are to remedy structural inequities embedded throughout the care continuum.
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BACKGROUND: Although age-standardized stroke occurrence has been decreasing, the absolute number of stroke events globally, and in Canada, is increasing. Stroke surveillance is necessary for health services planning, informing research design, and public health messaging. We used administrative data to estimate the number of stroke events resulting in hospital or emergency department presentation across Canada in the 2017-18 fiscal year. METHODS: Hospitalization data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database and the Ministry of Health and Social Services in Quebec. Emergency department data were obtained from the CIHI National Ambulatory Care Reporting System (Alberta and Ontario). Stroke events were identified using ICD-10 coding. Data were linked into episodes of care to account for readmissions and interfacility transfers. Projections for emergency department visits for provinces/territories outside of Alberta and Ontario were generated based upon age and sex-standardized estimates from Alberta and Ontario. RESULTS: In the 2017-18 fiscal year, there were 108,707 stroke events resulting in hospital or emergency department presentation across the country. This was made up of 54,357 events resulting in hospital admission and 54,350 events resulting in only emergency department presentation. The events resulting in only emergency department presentation consisted of 25,941 events observed in Alberta and Ontario and a projection of 28,409 events across the rest of the country. CONCLUSIONS: We estimate a stroke event resulting in hospital or emergency department presentation occurs every 5 minutes in Canada.
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BACKGROUND AND PURPOSE: Numerous studies have shown longer pre-hospital and in-hospital workflow times and poorer outcomes in women after acute ischemic stroke (AIS) in general and after endovascular treatment (EVT) in particular. We investigated sex differences in acute stroke care of EVT patients over 5 years in a comprehensive Canadian provincial registry. METHODS: Clinical data of all AIS patients who underwent EVT between January 2017 and December 2022 in the province of Saskatchewan were captured in the Canadian OPTIMISE registry and supplemented with patient data from administrative data sources. Patient baseline characteristics, transport time metrics, and technical EVT outcomes between female and male EVT patients were compared. RESULTS: Three-hundred-three patients underwent EVT between 2017 and 2022: 144 (47.5%) women and 159 (52.5%) men. Women were significantly older (median age 77.5 [interquartile range: 66-85] vs.71 [59-78], p < 0.001), while men had more intracranial internal carotid artery occlusions (48/159 [30.2%] vs. 26/142 [18.3%], p = 0.03). Last-known-well to comprehensive stroke center (CSC)-arrival time (median 232 min [interquartile range 90-432] in women vs. 230 min [90-352] in men), CSC-arrival-to-reperfusion time (median 108 min [88-149] in women vs. 102 min [77-141] in men), reperfusion status (successful reperfusion 106/142 [74.7%] in women vs. 117/158 [74.1%] in men) as well as modified Rankin score at 90 days did not differ significantly. This held true after adjusting for baseline variables in multivariable analyses. CONCLUSION: While women undergoing EVT in the province of Saskatchewan were on average older than men, they were treated just as fast and achieved similar technical and clinical outcomes compared to men.
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INTRODUCTION: This study assesses experts' beliefs about important predictors of developing dementia in persons with mild cognitive impairment (MCI). METHODS: Structured expert elicitation, a methodology to quantify expert knowledge, was used to elicit the most important risk factors for developing dementia. We recruited 11 experts (6 neurologists, 3 geriatricians, and 2 psychiatrists). Ten experts fully participated in introductory meetings, two rounds of surveys, and discussion meetings. The data from these ten experts were utilized for this study. RESULTS: The expert elicitation identified age, CSF analysis, fluorodeoxyglucose-positron emission tomography (FDG-PET) findings, hippocampal atrophy, MoCA (or MMSE) score, parkinsonism, apathy, psychosis, informant report of cognitive symptoms, and global atrophy as the ten most important predictors of progressing to dementia in persons with MCI. DISCUSSION: Several dementia predictors are not routinely collected in existing registries, observational studies, or usual care. This might partially explain the low uptake of existing published dementia risk scores in clinical practice.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Atrofia , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Fluordesoxiglucose F18RESUMO
BACKGROUND: Randomized controlled trials for the use of alteplase in acute ischemic stroke have excluded or had little representation of patients with prestroke disability, and the benefit of alteplase in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with premorbid disability. METHODS: We performed a systematic review in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines and retrieved studies reporting intravenous thrombolysis (IVT) in patients with prestroke disability (modified Rankin Scale score, 3-5) with acute ischemic stroke, either compared with untreated patients or treated patients without premorbid disability. The primary outcome was the return to premorbid disability at 90 days. Secondary outcomes included rate and odds ratio of favorable functional outcome at 90 days (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Eight articles were included involving 103 988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared with those who did not receive IVT (odds ratio, 7.26 [95% CI, 2.51-21.02]). Mortality and rates of sICH were not significantly different between patients with disability treated with IVT and those not treated, although there were numerically more sICHs in the IVT group. Return to baseline function was not significantly different between patients with and without prestroke disability (odds ratio, 1.46 [95% CI, 0.75-2.83]). The rates of sICH were not significantly different in patients with and without premorbid disability. However, mortality was 3× higher in patients with premorbid disability than in those without premorbid disability (38.2% versus 12.6%). CONCLUSIONS: The use of IVT in patients with disability was associated with better outcomes compared with patients who did not receive IVT without statistically significant added risks of sICH or mortality. When compared with those without disability, there was no significant difference in the return to baseline function or sICH. High-quality data comparing treated versus untreated patients with premorbid disability are needed to clarify this issue. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Hemorragia Cerebral/etiologia , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.
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Demência , AVC Isquêmico , Acidente Vascular Cerebral , American Heart Association , Demência/complicações , Demência/epidemiologia , Demência/terapia , Humanos , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica , Estados UnidosRESUMO
BACKGROUND: The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity. METHODS: We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔPaLVO) for each scale for mild (NIHSS 0-4), intermediate (NIHSS 5-9), moderate (NIHSS 10-14), and severe deficits (NIHSS≥15). RESULTS: Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔPaLVO in patients with mild deficits. Negative results achieved the highest ΔPaLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range. CONCLUSIONS: Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.
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Isquemia Encefálica , Serviços Médicos de Emergência , Acidente Vascular Cerebral , Humanos , Triagem/métodos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Serviços Médicos de Emergência/métodos , Índice de Gravidade de Doença , Isquemia Encefálica/diagnósticoRESUMO
BACKGROUND: Pandemics may promote hospital avoidance, and added precautions may exacerbate treatment delays for medical emergencies such as stroke. We sought to evaluate ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic. METHODS: We conducted a population-based study, using linked administrative and stroke registry data from Alberta to identify all patients presenting with stroke before the pandemic (Jan. 1, 2016 to Feb. 27, 2020) and in 5 periods over the first pandemic year (Feb. 28, 2020 to Mar. 31, 2021), reflecting changes in case numbers and restrictions. We evaluated changes in hospital admissions, emergency department presentations, thrombolysis, endovascular therapy, workflow times and outcomes. RESULTS: The study included 19 531 patients in the prepandemic period and 4900 patients across the 5 pandemic periods. Presentations for ischemic stroke dropped in the first pandemic wave (weekly adjusted incidence rate ratio [IRR] 0.54, 95% confidence interval [CI] 0.50 to 0.59). Population-level incidence of thrombolysis (adjusted IRR 0.50, 95% CI 0.41 to 0.62) and endovascular therapy (adjusted IRR 0.63, 95% CI 0.47 to 0.84) also decreased during the first wave, but proportions of patients presenting with stroke who received acute therapies did not decline. Rates of patients presenting with stroke did not return to prepandemic levels, even during a lull in COVID-19 cases between the first 2 waves of the pandemic, and fell further in subsequent waves. In-hospital delays in thrombolysis or endovascular therapy occurred in several pandemic periods. The likelihood of in-hospital death increased in Wave 2 (adjusted odds ratio [OR] 1.48, 95% CI 1.25 to 1.74) and Wave 3 (adjusted OR 1.46, 95% CI 1.07 to 2.00). Out-of-hospital deaths, as a proportion of stroke-related deaths, rose during 4 of 5 pandemic periods. INTERPRETATION: The first year of the COVID-19 pandemic saw persistently reduced rates of patients presenting with ischemic stroke, recurrent treatment delays and higher risk of in-hospital death in later waves. These findings support public health messaging that encourages care-seeking for medical emergencies during pandemic periods, and stroke systems should re-evaluate protocols to mitigate inefficiencies.
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COVID-19 , AVC Isquêmico , Alberta/epidemiologia , COVID-19/epidemiologia , COVID-19/terapia , Mortalidade Hospitalar , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , AVC Isquêmico/terapia , PandemiasRESUMO
BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) has been associated with various neurological and atypical head/eyes/ears/nose/throat (HEENT) manifestations. We sought to review the evidence for these manifestations. METHODS: In this systematic review and meta-analysis, we compiled studies published until March 31, 2021 that examined non-respiratory HEENT, central, and peripheral nervous system presentations in COVID-19 patients. We included 477 studies for qualitative synthesis and 59 studies for meta-analyses. RESULTS: Anosmia, ageusia, and conjunctivitis may precede typical upper/lower respiratory symptoms. Central nervous system (CNS) manifestations include stroke and encephalopathy, potentially with brainstem or cranial nerve involvement. MRI studies support CNS para-/postinfectious etiologies, but direct neuroinvasion seems very rare, with few cases detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the CNS. Peripheral nervous system (PNS) manifestations include muscle damage, Guillain-Barre syndrome (GBS), and its variants. There was moderate-to-high study heterogeneity and risk of bias. In random-effects meta-analyses, anosmia/ageusia was estimated to occur in 56% of COVID-19 patients (95% CI: 0.41-0.71, I2:99.9%), more commonly than in patients without COVID-19 (OR: 14.28, 95% CI: 8.39-24.29, I2: 49.0%). Neurological symptoms were estimated to occur in 36% of hospitalized patients (95% CI: 0.31-0.42, I2: 99.8%); ischemic stroke in 3% (95% CI: 0.03-0.04, I2: 99.2%), and GBS in 0.04% (0.033%-0.047%), more commonly than in patients without COVID-19 (OR[stroke]: 2.53, 95% CI: 1.16-5.50, I2: 76.4%; OR[GBS]: 3.43,1.15-10.25, I2: 89.1%). CONCLUSIONS: Current evidence is mostly from retrospective cohorts or series, largely in hospitalized or critically ill patients, not representative of typical community-dwelling patients. There remains a paucity of systematically gathered prospective data on neurological manifestations. Nevertheless, these findings support a high index of suspicion to identify HEENT/neurological presentations in patients with known COVID-19, and to test for COVID-19 in patients with such presentations at risk of infection.
Assuntos
Ageusia , COVID-19 , Síndrome de Guillain-Barré , Doenças do Sistema Nervoso , Acidente Vascular Cerebral , Anosmia/epidemiologia , Anosmia/etiologia , COVID-19/complicações , Síndrome de Guillain-Barré/complicações , Humanos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Faringe , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2 , Acidente Vascular Cerebral/complicaçõesRESUMO
Informed consent is a key concept to ensure patient autonomy in clinical trials and routine care. The coronavirus disease 2019 (COVID-19) pandemic has complicated informed consent processes, due to physical distancing precautions and increased physician workload. As such, obtaining timely and adequate patient consent has become a bottleneck for many clinical trials. However, this challenging situation might also present an opportunity to rethink and reappraise our approach to consent in clinical trials. This viewpoint discusses the challenges related to informed consent during the COVID-19 pandemic, whether it could be acceptable to alter current consent processes under these circumstances, and outlines a possible framework with predefined criteria and a system of checks and balances that could allow for alterations of existing consent processes to maximize patient benefit under exceptional circumstances such as the COVID-19 pandemic without undermining patient autonomy.
Assuntos
COVID-19 , Consentimento Livre e Esclarecido/normas , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Idoso , COVID-19/epidemiologia , Humanos , Masculino , Acidente Vascular Cerebral/epidemiologia , Fatores de TempoRESUMO
Infarct volume in acute ischemic stroke is closely linked with clinical outcome, with larger infarct volumes being associated with a worse prognosis. Small iatrogenic infarcts, which can occur as a result of surgical or endovascular procedures, are often only seen on diffusion-weighted MR imaging. They often do not lead to any overtly appreciable clinical deficits, hence the term covert or silent infarcts. There is relative paucity of data on the clinical impact of periprocedural hyperintense diffusion-weighted MR imaging lesions, partly because they commonly remain undiagnosed. Clearly, a better understanding of iatrogenic periprocedural diffusion-weighted MR imaging lesions and their clinical significance is needed. In this article, we describe the current limitations of our understanding of the significance of iatrogenic diffusion-weighted MR imaging lesions using exemplary data from the ENACT trial (Safety and Efficacy of NA-1 in Patients With Iatrogenic Stroke After Endovascular Aneurysm Repair) and outline a framework for how to investigate their clinical impact.
Assuntos
Encéfalo/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Doença Iatrogênica , AVC Isquêmico/cirurgia , Imagem de Difusão por Ressonância Magnética , Humanos , AVC Isquêmico/diagnóstico por imagemRESUMO
Physicians often base their decisions to offer acute stroke therapies to patients around the question of whether the patient will benefit from treatment. This has led to a plethora of attempts at accurate outcome prediction for acute ischemic stroke treatment, which have evolved in complexity over the years. In theory, physicians could eventually use such models to make a prediction about the treatment outcome for a given patient by plugging in a combination of demographic, clinical, laboratory, and imaging variables. In this article, we highlight the importance of considering the limits and nuances of outcome prediction models and their applicability in the clinical setting. From the clinical perspective of decision-making about acute treatment, we argue that it is important to consider 4 main questions about a given prediction model: (1) what outcome is being predicted, (2) what patients contributed to the model, (3) what variables are in the model (considering their quantifiability, knowability at the time of decision-making, and modifiability), and (4) what is the intended purpose of the model? We discuss relevant aspects of these questions, accompanied by clinically relevant examples. By acknowledging the limits of outcome prediction for acute stroke therapies, we can incorporate them into our decision-making more meaningfully, critically examining their contents, outcomes, and intentions before heeding their predictions. By rigorously identifying and optimizing modifiable variables in such models, we can be empowered rather than paralyzed by them.