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OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection. MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications. RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses. CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.
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Ensaios Clínicos como Assunto , Seleção de Pacientes , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores Sexuais , Animais , Disparidades nos Níveis de Saúde , Projetos de Pesquisa , Interpretação Estatística de Dados , Disparidades em Assistência à Saúde , Sujeitos da Pesquisa , Identidade de Gênero , Fatores de RiscoRESUMO
OBJECTIVES: Central retinal artery occlusion (CRAO) is a stroke of the retina potentially amenable to intravenous thrombolysis (IVT). We aimed to determine feasibility of an emergency treatment protocol and risk profile of IVT for CRAO in a comprehensive stroke center (CSC). METHODS: We performed a retrospective, observational cohort study including patients with acute CRAO admitted to a CSC over 4 years. Patients are offered IVT if they present with acute vision loss of ≤ 20/200 in the affected eye, have no other cause of vision loss (incorporating a dilated ophthalmologic exam), and meet criteria akin to acute ischemic stroke. We collected socio-demographic data, triage data, time from onset to presentation, IVT candidacy, and rates of symptomatic intracranial hemorrhage (sICH)- or extracranial hemorrhage. RESULTS: 36 patients presented within the study period, mean (standard deviation (SD)) age of 70.7 (10), 52 % female, and median time (Q1, Q3) to ED presentation of 13.5 (4.3, 18.8) h. Patients within 4.5 h from onset presented more commonly directly to our ED (66.6 % vs 37.1 %, p = 0.1). Nine patients (25 %) presented within the 4.5 h window. Of those eligible, 7 (77 %) received IVT. There were no events of intracranial or extracranial hemorrhage. CONCLUSIONS: Our study confirmed that IVT for acute CRAO is feasible. We found a high rate of treatment with IVT of those eligible. However, because 75 % of patients presented outside the treatment window, continued educational efforts are needed to improve rapid triage to emergency departments to facilitate evaluation for possible candidacy with IVT.
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Isquemia Encefálica , AVC Isquêmico , Oclusão da Artéria Retiniana , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Isquemia Encefálica/terapia , Fibrinolíticos/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/etiologia , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/tratamento farmacológico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.
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Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Idoso , Feminino , AVC Isquêmico/tratamento farmacológico , Constrição Patológica/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Infarto Cerebral/complicações , Terapia Antiplaquetária Dupla , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , Fatores de Risco , RecidivaRESUMO
BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002). CONCLUSIONS: We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.
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Isquemia Encefálica , Embolia , Cardiopatias , Sistema de Registros , Acidente Vascular Cerebral , Troponina/sangue , Idoso , Biomarcadores , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Embolia/sangue , Embolia/etiologia , Feminino , Cardiopatias/sangue , Cardiopatias/etiologia , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.
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Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/efeitos adversos , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
PURPOSE: To quantify amide protein transfer (APT) effects in acidic ischemic lesions and assess the spatial-temporal relationship among diffusion, perfusion, and pH deficits in acute stroke patients. METHODS: Thirty acute stroke patients were scanned at 3 T. Quantitative APT (APT# ) effects in acidic ischemic lesions were measured using an extrapolated semisolid magnetization transfer reference signal technique and compared with commonly used MTRasym (3.5ppm) or APT-weighted parameters. RESULTS: The APT# images showed clear pH deficits in the ischemic lesion, whereas the MTRasym (3.5ppm) signals were slightly hypointense. The APT# contrast between acidic ischemic lesions and normal tissue in acute stroke patients was more than three times larger than MTRasym (3.5ppm) contrast (-1.45 ± 0.40% for APT# versus -0.39 ± 0.52% for MTRasym (3.5ppm), P < 4.6 × 10-4 ). Hypoperfused and acidic areas without an apparent diffusion coefficient abnormality were observed and assigned to an ischemic acidosis penumbra. Hypoperfused areas at normal pH were also observed and assigned to benign oligemia. Hyperintense APT signals were observed in a hemorrhage area in one case. CONCLUSIONS: The quantitative APT study using the extrapolated semisolid magnetization transfer reference signal approach enhances APT MRI sensitivity to pH compared with conventional APT-weighted MRI, allowing more reliable delineation of an ischemic acidosis in the penumbra. Magn Reson Med 78:871-880, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
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Amidas/química , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Algoritmos , Amidas/análise , Encéfalo/diagnóstico por imagem , Humanos , Concentração de Íons de Hidrogênio , Proteínas/química , PrótonsRESUMO
BACKGROUND AND PURPOSE: Hypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) at hospital arrival can be used to distinguish hypertensive ICH from non-hypertensive etiologies. PATIENTS AND METHODS: We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics including etiology were prospectively adjudicated by two attending neurologists. Using adjusted linear regression models, we compared first recorded systolic BPs (SBP) and mean arterial pressures (MAP) in patients with hypertensive vs. other ICH etiologies. We then used area under the ROC curve (AUC) analysis to determine the accuracy of admission BP in differentiating between hypertensive and non-hypertensive ICH. RESULTS: Of 311 patients in our cohort (mean age 70.6 ± 15.6, 50% male, 83% white), the most frequent ICH etiologies were hypertension (50%) and cerebral amyloid angiopathy (CAA; 22%). Mean SBP and MAP for patients with hypertensive ICH was 175.1 ± 32.9 mmHg and 120.4 ± 22.9 mmHg, respectively, compared to 156.4 ± 28.0 mmHg and 109.6 ± 20.3 mmHg in non-hypertensive ICH (p < .001). Adjusted models showed that hypertensive ICH patients had higher BPs than those with CAA (mean SBP difference 10.7 mmHg [95% CI 0.8-20.5]; mean MAP difference 8.1 mmHg [1.1-15.0]) and especially patients with other non-CAA causes (mean SBP difference 23.9 mmHg [15.3-32.4]; mean MAP difference 14.5 mmHg [8.5-20.6]). However, on a patient-level, arrival BP did not reliably discriminate between hypertensive and non-hypertensive etiologies (AUC 0.660 [0.599-0.720]). CONCLUSIONS: Arrival BP differs between hypertensive and non-hypertensive ICH but should not be used as a primary determinant of etiology, as hypertension may be implicated in various subtypes of ICH.
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Angiopatia Amiloide Cerebral , Hipertensão , Hemorragia Intracraniana Hipertensiva , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Hemorragia Cerebral/complicações , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hemorragia Intracraniana Hipertensiva/diagnóstico , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Older patients undergoing thrombectomy for emergent large vessel occlusion have worse outcomes. However, complete or near-complete reperfusion (modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2 c/3) is associated with improved outcomes compared with partial recanalisation (mTICI 2b). OBJECTIVE: To examine the relationship between outcomes and age separately for the mTICI 2c/3, 2b and 0-2a groups in patients undergoing thrombectomy for anterior circulation emergent large vessel occlusion. METHODS: Retrospective review of 157 consecutive patients undergoing thrombectomy at a single centre with an occlusion of the internal carotid artery (ICA), M1 or proximal M2 segments of the middle cerebral artery (MCA). Angiograms were graded in a blinded fashion. Patients were divided into three groups: mTICI 0-2a, mTICI 2b, and mTICI 2c/3. Demographics and workflow parameters were compared. Outcomes at 90 days were compared as a function of age, using both the conventional modified Rankin scale (mRs) and utility weighted mRs (UWmRs). RESULTS: There were 72, 61 and 24 patients in the mTICI 2c/3, 2b and 0-2a groups, respectively. Outcomes were significantly worse with increasing age for the mTICI 2b group, but not for the mTICI 0-2a and 2c/3 groups (P=0.0002). With increasing age, outcomes of the mTICI 2b group approached those of the mTICI 0-2a group. However, outcomes of the mTICI 2c/3 groups were similar for all ages. This association was present for both the original mRs and UWmRs. CONCLUSION: Increasing age was associated with worse outcomes for those with partial (mTICI 2b) recanalisation, not in patients with complete (mTICI 2c/3) recanalisation.
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Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/cirurgia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/cirurgia , Trombectomia/tendências , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Feminino , Humanos , Masculino , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/tendências , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Resultado do TratamentoRESUMO
Background and aims Baseline National Institutes of Health Stroke Scale (NIHSS) scores have frequently been used for prognostication after ischemic stroke. With the increasing utilization of acute stroke interventions, we aimed to determine whether baseline NIHSS scores are still able to reliably predict post-stroke functional outcome. Methods We retrospectively analyzed prospectively collected data from a high-volume tertiary-care center. We tested strength of association between NIHSS scores at baseline and 24 h with discharge NIHSS using Spearman correlation, and diagnostic accuracy of NIHSS scores in predicting favorable outcome at three months (defined as modified Rankin Scale 0-2) using receiver operating characteristic curve analysis with area under the curve. Results There were 1183 patients in our cohort, with median baseline NIHSS 8 (IQR 3-17), 24-h NIHSS 4 (IQR 1-11), and discharge NIHSS 2 (IQR 1-8). Correlation with discharge NIHSS was r = 0.60 for baseline NIHSS and r = 0.88 for 24-h NIHSS. Of all patients with follow-up data, 425/1037 (41%) had favorable functional outcome at three months. Receiver operating characteristic curve analysis for predicting favorable outcome showed area under the curve 0.698 (95% CI 0.664-0.732) for baseline NIHSS, 0.800 (95% CI 0.772-0.827) for 24-h NIHSS, and 0.819 (95% CI 0.793-0.845) for discharge NIHSS; 24 h and discharge NIHSS maintained robust predictive accuracy for patients receiving mechanical thrombectomy (AUC 0.846, 95% CI 0.798-0.895; AUC 0.873, 95% CI 0.832-0.914, respectively), while accuracy for baseline NIHSS decreased (AUC 0.635, 95% CI 0.566-0.704). Conclusion Baseline NIHSS scores are inferior to 24 h and discharge scores in predicting post-stroke functional outcomes, especially in patients receiving mechanical thrombectomy.
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Isquemia Encefálica/diagnóstico , Valor Preditivo dos Testes , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Many factors may potentially complicate the stroke recovery process, including persistently impaired level of consciousness (LOC)-whether from residual stroke effects or from superimposed delirium. We aimed to determine the degree to which impaired LOC at hospital discharge is associated with outcomes after ischemic stroke. METHODS: We conducted a single-center retrospective cohort study using prospectively-collected data from 2015 to 2017, collecting total NIHSS-LOC score at discharge as well as subscores for responsiveness (LOC-R), orientation questions (LOC-Q), and command-following (LOC-C). We determined associations between LOC scores and 3-month outcome using logistic regression, with discharge location (skilled nursing facility [SNF] vs. inpatient rehabilitation) representing a pre-specified secondary outcome. RESULTS: We identified 1003 consecutive patients with ischemic stroke who survived to discharge, of whom 32% had any LOC scoreâ¯>â¯0. Total LOC score at discharge was associated with unfavorable 3-month outcome (OR 4.9 [95% CI 2.4-9.8] for LOCâ¯=â¯1; OR 8.0 [2.7-23.9] for LOCâ¯=â¯2-3; OR 6.3 [2.1-18.5] for LOCâ¯=â¯4-5; all patients with LOCâ¯=â¯6-7 had poor outcomes), as were subscores for LOC-R (OR 5.3 [1.3-21.2] for LOC-Râ¯=â¯1; all patients with LOC-Râ¯=â¯2-3 had poor outcomes) and LOC-Q (OR 4.1 [2.1-8.3] for LOC-Qâ¯=â¯1; OR 4.9 [1.8-13.5] for LOC-Qâ¯=â¯2). Total LOC score (OR 2.6 [1.3-5.3] for LOCâ¯=â¯1; OR 3.1 [1.2-8.2] for LOCâ¯=â¯2-3) and LOC-Q (OR 3.3 [1.6-6.6] for LOC-Qâ¯=â¯1; OR 3.4 [1.3-9.0] for LOC-Qâ¯=â¯2) were also associated with discharge to SNF rather than to inpatient rehabilitation. CONCLUSIONS: The presence of impaired consciousness or disorientation at discharge is associated with markedly worse outcomes after ischemic stroke. Further studies are necessary to determine the separate effects of residual stroke-related LOC changes and those caused by superimposed delirium.
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Isquemia Encefálica/terapia , Estado de Consciência , Alta do Paciente , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Instituições de Cuidados Especializados de Enfermagem , Acidente Vascular Cerebral/epidemiologia , Reabilitação do Acidente Vascular Cerebral , Resultado do TratamentoRESUMO
OBJECTIVE: To determine to what degree stroke mimics skew clinical outcomes and the potential effects of incorrect stroke diagnosis. METHODS: This retrospective analysis of data from 2005 to 2014 included IV tissue plasminogen activator (tPA)-treated adults with clinical suspicion for acute ischemic stroke who were transferred or admitted directly to our 2 hub hospitals. Primary outcome measures compared CT-based spoke hospitals' and MRI-based hub hospitals' mimic rates, hemorrhagic transformation, follow-up modified Rankin Scale (mRS), and discharge disposition. Secondary outcomes were compared over time. RESULTS: Of the 725 thrombolysis-treated patients, 29% were at spoke hospitals and 71% at hubs. Spoke hospital patients differed from hubs by age (mean 62 ± 15 vs 72 ± 15 years, p < 0.0001), risk factors (atrial fibrillation, 17% vs 32%, p < 0.0001; alcohol consumption, 9% vs 4%, p = 0.007; smoking, 23% vs 13%, p = 0.001), and mimics (16% vs 0.6%, p < 0.0001). Inclusion of mimics resulted in better outcomes for spokes vs hubs by mRS ≤1 (40% vs 27%, p = 0.002), parenchymal hematoma type 2 (3% vs 7%, p = 0.037), and discharge home (47% vs 37%, p = 0.01). Excluding mimics, there were no significant differences. Comparing epochs, spoke stroke mimic rate doubled (9%-20%, p = 0.03); hub rate was unchanged (0%-1%, p = 0.175). CONCLUSIONS: Thrombolysis of stroke mimics is increasing at our CT-based spoke hospitals and not at our MRI-based hub hospitals. Caution should be used in interpreting clinical outcomes based on large stroke databases when stroke diagnosis at discharge is unclear. Inadvertent reporting of treated stroke mimics as strokes will artificially elevate overall favorable clinical outcomes with additional downstream costs to patients and the health care system.