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Introduction: The THRIVE score and the THRIVE-c calculation are validated ischemic stroke outcome prediction tools based on patient variables that are readily available at initial presentation. Randomized controlled trials (RCTs) have demonstrated the benefit of endovascular treatment (EVT) for many patients with large vessel occlusion (LVO), and pooled data from these trials allow for adaptation of the THRIVE-c calculation for use in shared clinical decision making regarding EVT. Methods: To extend THRIVE-c for use in the context of EVT, we extracted data from the Virtual International Stroke Trials Archive (VISTA) from 7 RCTs of EVT. Models were built in a randomly selected development cohort using logistic regression that included the predictors from THRIVE-c: age, NIH Stroke Scale (NIHSS) score, presence of hypertension, diabetes mellitus, and/or atrial fibrillation, as well as randomization to EVT and, where available, the Alberta Stroke Program Early CT Score (ASPECTS). Results: Good outcome was achieved in 366/787 (46.5%) of subjects randomized to EVT and in 236/795 (29.7%) of subjects randomized to control (P Conclusion: THRIVE-EVT may be used alongside the original THRIVE-c calculation to improve outcome probability estimation for patients with acute ischemic stroke, including patients with or without LVO, and to model the potential improvement in outcomes with EVT for an individual patient based on variables that are available at initial presentation. Online calculators for THRIVE-c estimation are available at www.thrivescore.org and www.mdcalc.com/thrive-score-for-stroke-outcome .

Background: The CHANCE-2 study compared 3 weeks of aspirin–ticagrelor to aspirin–clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin–ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown. Methods: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty. Results: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY. Conclusion: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin–ticagrelor compared to standard-of-care aspirin–clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

Background Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better. Aims We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome. Methods We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24–48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24–48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between “discrepant cases” – those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV – and “non-discrepant cases”. Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome. Results Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement ( p = 0.39, p = 0.81, respectively, for PIV ≤ 7 mL/mRS ≥ 3). Pre-treatment factors independently associated with small-PIV/mRS ≥ 3 included older age ( p = 0.010), cancer, and vascular risk-factors; post-treatment factors included 48-h NIHSS ( p = 0.007) and post-stroke complications ( p = 0.026). Absence of vascular risk-factors ( p = 0.004), CT-based lentiform nucleus sparing ( p = 0.002), lower 24-hour NIHSS ( p = 0.001), and absence of complications ( p = 0.013) were associated with large-PIV/mRS ≤ 2. Sensitivity analyses yielded similar results. Conclusions Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01778335 .

Rationale Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. Aim The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume—Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. Methods and design REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. Study outcomes Primary—Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary—Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. Conclusion REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

Background Determining mechanisms of secondary stroke injury related to cerebral blood flow and the severity of microvascular injury contributing to edema and blood-brain barrier breakdown will be critical for the development of adjuvant therapies for revascularization treatment. Aim To characterize the heterogeneity of the ischemic lesion using quantitative T2 imaging along with diffusion-weighted magnetic resonance imaging (DWI) within five hours of treatment. Methods Quantitative T2 magnetic resonance imaging was acquired within 5 h (baseline) and at 24 h (follow-up) of stroke treatment in 29 patients. Dynamic contrast enhanced permeability imaging was performed at baseline in a subgroup of patients. Absolute volume change and lesion percent change was determined for the quantitative T2, DWI, and absolute volume change sequences. A Gaussian process with RRELIEFF feature selection algorithm was used for prediction of relative quantitative T2 and DWI lesion growth, baseline and follow-up quantitative T2/DWI lesion ratios, and also NIHSS at 24 h and change in NIHSS from admission to 24 h. Results In n = 27 patients, median (interquartile range) lesion percent change was 114.8% (48.9%, 259.1%) for quantitative T2, 48.2% (−12.6%, 179.6%) for absolute volume change, and 62.7% (26.3%, 230.9%) for DWI, respectively. Our model, consisting of baseline NIHSS, CT ASPECTS, and systolic blood pressure, showed a strong correlation with quantitative T2 percent change (cross correlation R2 = 0.80). There was a strong predictive ability for quantitative T2/DWI lesion ratio at 24 h using baseline NIHSS and last seen normal to 24 h magnetic resonance imaging time (cross correlation R2 = 0.93). Baseline dynamic contrast enhanced permeability was moderately correlated to the baseline quantitative T2 values (rho = 0.38). Conclusion Quantitative T2 imaging provides critical information for development of therapeutic approaches that could ameliorate microvascular damage during ischemia reperfusion.

Background Manual segmentations of intracranial hemorrhage on non-contrast CT images are the gold-standard in measuring hematoma growth but are prone to rater variability. Aims We demonstrate that a convex optimization-based interactive segmentation approach can accurately and reliably measure intracranial hemorrhage growth. Methods Baseline and 16-h follow-up head non-contrast CT images of 46 subjects presenting with intracranial hemorrhage were selected randomly from the ANNEXA-4 trial imaging database. Three users semi-automatically segmented intracranial hemorrhage to measure hematoma volume for each timepoint using our proposed method. Segmentation accuracy was quantitatively evaluated compared to manual segmentations by using Dice similarity coefficient, Pearson correlation, and Bland–Altman analysis. Intra- and inter-rater reliability of the Dice similarity coefficient and intracranial hemorrhage volumes and volume change were assessed by the intraclass correlation coefficient and minimum detectable change. Results Among the three users, the mean Dice similarity coefficient, Pearson correlation, and mean difference ranged from 76.79% to 79.76%, 0.970 to 0.980 ( p Conclusions We spatially and volumetrically validate a novel interactive segmentation method for delineating intracranial hemorrhage on head non-contrast CT images. Good spatial overlap, excellent volume correlation, and good repeatability suggest its usefulness for measuring intracranial hemorrhage volume and volume change on non-contrast CT images.

Background and Purpose The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods The initial construct validity of miFUNCTION was established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect of endovascular treatment. Results The pilot study showed moderate inter-observer agreement (k = 0.585, p Conclusions miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

Background A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. Aims Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. Methods Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. Results For patients with poor recanalization (modified thrombolysis in cerebral infarction Conclusion Despite best efforts to recanalize the ischemic brain, early diffusion-weighted imaging lesion growth still occurs. Treatment trials in stroke should consider early diffusion-weighted imaging lesion growth as a surrogate outcome measure to significantly reduce sample sizes.

Background and purpose Ischemic stroke patients must be transferred to comprehensive stroke centers for endovascular treatment, but this transfer can be interpreted post hoc as “futile” if patients do not ultimately undergo the procedure or have a poor outcome. We posit that transfer decisions must instead be evaluated in terms of appropriateness at the time of decision-making. Methods We propose a classification schema for Appropriateness of Transfer for Endovascular Thrombectomy based on patient, logistic, and center characteristics. Results The classification outline characteristics of patients that are 1. Appropriate for transfer for endovascular treatment; 2. Inappropriate for transfer; and 3. Appropriate for transfer for higher level of care. Conclusions Appropriate transfer decisions for endovascular treatment are significant for patient outcomes. A more nuanced understanding of transfer decision-making and a classification for such transfers can help minimize inappropriate transfers in acute stroke.