Differentiating Carotid Terminus Occlusions into Two Distinct Populations Based on Willisian Collateral Status

BACKGROUND AND PURPOSE: The outcomes of acute internal carotid artery (ICA) terminus occlusions are poor. We classified ICA terminus occlusions into 2 groups according to the occlusion pattern of the circle of Willis and hypothesized that clinical outcomes would significantly differ between them. METHODS: Consecutive patients with acute ICA terminus occlusions evaluated by baseline computed tomographic angiography were enrolled. We investigated the occlusion patterns in the circle of Willis, retrospectively classified patients into simple ICA terminus occlusion (STO: with good Willisian collaterals from neighboring cerebral circulation) and complex ICA terminus occlusion (CTO: with one or more of A2 anterior cerebral artery, fetal posterior cerebral artery occlusion, or hypoplastic/absent contralateral A1: or with poor collaterals from anterior communicating artery) groups, and compared their baseline characteristics and outcomes. RESULTS: The STO group (n=58) showed smaller infarct volumes at 72 hours than the CTO group (n=34) (median, 81 mL [interquartile range, 38-192] vs. 414 mL [193-540], P<0.001) and more favorable outcomes (3-month modified Rankin Scale 0-3, 44.8% vs. 8.8%, P<0.001: 3-month mortality, 24.1% vs. 67.6%, P<0.001). In multivariable analyses, STO remained an independent predictor for favorable outcomes (odds ratio 6.1, P=0.010). CONCLUSIONS: Favorable outcomes in STO group suggested that the outcomes of acute ICA terminus occlusions depend on Willisian collateral status. Documenting the subtypes on computed tomographic angiography would help predict patient outcome

HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment

\ua9 2024 American Heart Association, Inc. BACKGROUND: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy. METHODS: Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614). RESULTS: In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879–0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886–0.944] and 0.909 [95% CI, 0.887–0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score &lt;10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations. CONCLUSIONS: The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2

Effect of Intracranial Atherosclerotic Disease on Endovascular Treatment for Patients with Acute Vertebrobasilar Occlusion

BACKGROUND AND PURPOSE: Although intracranial atherosclerotic disease is often encountered during endovascular treatment for acute vertebrobasilar occlusions, its clinical implication is not well-known. We aimed to evaluate whether intracranial atherosclerotic disease influences the clinical outcomes following endovascular treatment of acute vertebrobasilar occlusive stroke. MATERIALS AND METHODS: Fifty-one patients with acute vertebrobasilar occlusive stroke were included. The onset-to-groin puncture time was <12 hours, and aspiration- or stent-based thrombectomy was used as the primary treatment method. Following primary endovascular treatment, intracranial atherosclerotic disease (IAD group) was angiographically diagnosed when a fixed focal stenosis was observed at the occlusion site, whereas embolism (embolic group) was diagnosed if no stenosis was observed. Clinical and treatment variables were compared in both groups, and IAD was evaluated as a prognostic factor for clinical outcomes. RESULTS: The baseline NIHSS score tended to be lower (14 versus 22, P = .097) in the IAD group (n = 19) than in the embolic group (n = 32). The procedural time was longer in the IAD group (96 versus 61 minutes, P = .002), despite similar rates of TICI 2b-3 (89.5% versus 87.5%, P = 1.000). The NIHSS score at 7 days was higher (21 versus 8, P = .060) and poor outcomes (mRS 4-6 at 3 months) were more frequent in the IAD group (73.7% versus 43.8%, P = .038). IAD (odds ratio, 5.469: 95% CI, 1.09-27.58: P = .040) was independently associated with poor outcomes. CONCLUSIONS: An arterial occlusion related to IAD was associated with a longer procedural time and poorer clinical outcome. Further studies are warranted to elucidate the appropriate endovascular strategy

Temporal Changes in Care Processes and Outcomes for Endovascular Treatment of Acute Ischemic Stroke: Retrospective Registry Data from Three Korean Centers

BACKGROUND AND PURPOSE: The purpose of the current study is to evaluate the influence of temporal patterns related to the availability of new endovascular treatment (EVT) devices on care processes and outcomes among patients with AIS. MATERIALS AND METHODS: We enrolled 720 consecutive patients (January 2011 to May 2016) in a retrospective registry, ASIAN KR, from three Korean hospitals, who received EVT for acute ischemic stroke (AIS) caused by cervicocephalic arterial occlusions. We performed period-to-period analyses based on stent retriever reimbursement and the availability of second-generation direct-aspiration devices (Period 1: January 2011-July 2014 vs. Period 2: August 2014-May 2016): time metrics and outcomes were compared when the onset-to-puncture time was <720 min among patients with EVT for intracranial occlusion. RESULTS: Period 2 had better post-EVT outcomes (3-month modified Rankin Scale 0-2 or equal to prestroke score, 48.3% vs. 60.2%, P=0.004), more successful reperfusion rates (modified Treatment In Cerebral Ischemia 2b-3, 74.2% vs. 82.2%, P=0.019), fewer subarachnoid hemorrhages (modified Fisher grade 3-4, 5.5% vs. 2.0%, P=0.034) and lower hemorrhagic transformation rates (any intracerebral hemorrhage, 35.3 vs. 22.7%, P=0.001) than Period 1. Compared to Period 1, Period 2 had a shorter door-to-puncture time (median 109 vs. 90 min, P<0.001), but longer onset-to-door time (129 vs. 143 min, P=0.057). CONCLUSION: Recent temporal improvements in post-EVT AIS outcomes in Korea are likely due to a combination of enhanced hospital care processes and administration of newer thrombectomy devices

Aspects correlates with Scandinavian Stroke Scale for predicting early neurological impairment

Objective: To investigate the correlation between the Alberta Program Early CT Score (ASPECTS) and the Scandinavian Stroke Scale (SSS) for the evaluation of neurological impairment in patients with acute stroke. Method: 59 patients with a first acute ischemic stroke were evaluated. The ASPECTS were evaluated by 2 neurologists at admission and by another neurologist after 48 hours. The NIHSS and SSS was applied to determinate stroke severity. Correlations and agreements were analysed statistically by Spearman and Kappa tests. Results: ASPECTS was correlated with National Institute of Health Stroke Scale (NIHSS) at admission (r = -0.52; p &lt; 0.001) and SSS (r = 0.50; p &lt; 0.001). The ASPECTS and SSS items were most correlated with arm (r = 0.52; p &lt; 0.001) and hand (r = 0.49; p &lt; 0.001) motor power, and speech (r = 0.51; p &lt; 0.001). The SSS of 25.5 shows sensitivity (68%) and specificity (72%) when associated with ASPECTS &lt;= 7. Conclusion: The SSS can predict worst neurological impairment when associated with lower values of ASPECTS.Objetivo: Investigar a relação entre o Alberta Program Early CT Score (ASPECTS) e a Scandinavian Stroke Scale (SSS) para avaliação da incapacidade neurológica de pacientes na fase aguda do acidente vascular cerebral (AVC). Método: 59 pacientes com diagnóstico de primeiro AVC foram avaliados. O ASPECTS foi avaliado por 2 neurologistas na admissão e por outro neurologista após 48 horas. O National Institute of Health Stroke Scale (NIHSS) e SSS foram aplicadas para determinar a gravidade do AVC. As correlação e concordâncias foram analisadas estatisticamente pelos testes de Spearman e Kappa. Resultados: ASPECTS foi correlacionado com o NIHSS na admissão (r = -0,52; p < 0,001) e SSS (r = 0,50; p < 0,001). O ASPECTS e os itens do SSS que mais se relacionaram foram força do braço (r = 0,52; p < 0,001), da mão (r = 0,49; p < 0,001) e fala (r = 0,51; p < 0,001). A pontuação da SSS de 25,5 mostrou sensibilidade (68%) e especificidade (72%) quando associado ao ASPECTS ≤ 7. Conclusão: A SSS pode predizer pior incapacidade neurológica quando associado a baixos valores do ASPECTS.Universidade de São Paulo, Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão PretoUniversidade Estadual Paulista, Departamento de Neurologia, Psicologia e Psiquiatria, Faculdade de Medicina de Botucat

Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial

Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130–140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target 150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24–36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24–36 h. Mean achieved systolic blood pressures over 1–24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24–36 h (0.3 [IQR 0.0–16.6] in the intensive group and 0.9 [0.0–12.5] in the guideline group; log Δmean −0.17, 95% CI −0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda

Associations of Early Systolic Blood Pressure Control and Outcome after Thrombolysis-Eligible Acute Ischemic Stroke: Results from the ENCHANTED Study

Background and Purpose: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. Methods: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. Results: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). Conclusions: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616

Assessment and Implication of Prognostic Imbalance in Randomized Controlled Trials with a Binary Outcome – A Simulation Study

Chance imbalance in baseline prognosis of a randomized controlled trial can lead to over or underestimation of treatment effects, particularly in trials with small sample sizes. Our study aimed to (1) evaluate the probability of imbalance in a binary prognostic factor (PF) between two treatment arms, (2) investigate the impact of prognostic imbalance on the estimation of a treatment effect, and (3) examine the effect of sample size (n) in relation to the first two objectives.We simulated data from parallel-group trials evaluating a binary outcome by varying the risk of the outcome, effect of the treatment, power and prevalence of the PF, and n. Logistic regression models with and without adjustment for the PF were compared in terms of bias, standard error, coverage of confidence interval and statistical power.For a PF with a prevalence of 0.5, the probability of a difference in the frequency of the PF≥5% reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5) leads to underestimating the strength of a moderate treatment effect, and the underestimate is independent of n when n is >50/arm. Adjusting for such PF increases statistical power. If the PF is weak (RR = 2), adjustment makes little difference in statistical inference. Conditional on a 5% imbalance of a powerful PF, adjustment reduces the likelihood of large bias. If an absolute measure of imbalance ≥5% is deemed important, including 1000 patients/arm provides sufficient protection against such an imbalance. Two thousand patients/arm may provide an adequate control against large random deviations in treatment effect estimation in the presence of a powerful PF.The probability of prognostic imbalance in small trials can be substantial. Covariate adjustment improves estimation accuracy and statistical power, and hence should be performed when strong PFs are observed