The utility-weighted approach to analyzing the modified Rankin Scale (mRS) is increasingly being utilized in acute stroke clinical trials. This analytic approach assigns a patient-centered utility weight—the desirability or value of a health state to patients—to each level of the mRS. The utility-weighted-mRS analysis converts the mRS from a scale reflecting only the rank order of functional outcome after stroke into one that quantifies the value of each poststroke mRS health state from patients’ perspectives. The ability of the utility-weighted-mRS analysis to capture the unequal difference in patient health-related quality of life between each level of the mRS makes it an appealing patient-centered end point for acute stroke clinical trials. However, several concerns have historically raised skepticism regarding its value as a trial end point. Unfamiliarity with how utility weights are derived and used poses challenges to its use for shared decision-making between patients and clinicians. There are valid concerns that social, geographic, and demographic factors that differ between countries influence the mRS utility weights, so that use of uniform weights across all settings mildly reduces the precision of utility quantification, particularly in multinational stroke clinical trials. This narrative review aims to provide the clinical and research stroke community with a practical overview of key methodology in the utility-weighted-mRS analysis to aid in its interpretation, considers the advantages and challenges of using the utility-weighted-mRS analysis, and suggests future areas of study.

BACKGROUND:Minimally invasive surgical evacuation improved outcomes for patients with acute, spontaneous, lobar intracerebral hemorrhage (ICH) in the ENRICH trial (Early Minimally Invasive Removal of ICH). We determined the percentage of patients with ICH in a US population-based study eligible for minimally invasive surgical evacuation and projected the annual number of patients with ICH in the United States in 2020 eligible for this therapy. METHODS:We ascertained adults (aged ≥18 years) with acute (<24 hours from last known well), spontaneous ICH in Greater Cincinnati/Northern Kentucky in 2015. Cases were identified by the International Classification of Diseases codes, clinical data abstracted, and physician adjudicated. Location and volume of ICH were centrally adjudicated by neuroradiologists. We applied ENRICH trial criteria to calculate conservative and liberal estimates of the percentage of patients with (1) all ICH at any location and (2) lobar ICH eligible for minimally invasive surgical evacuation. We extrapolated our estimates to the 2020 US adult population using 2020 US census data. RESULTS:We identified 196 patients in Greater Cincinnati/Northern Kentucky in 2015 with acute, spontaneous ICH. After applying all criteria, 2.0% (n=5) of all patients with acute ICH (5.1%; n=5 lobar ICH) were eligible for minimally invasive surgical evacuation. The most common exclusion criteria were ICH volume <30 mL (60%) and prestroke modified Rankin Scale score >1 (52%). In liberal estimates, 2.6% to 3.6% (n=4-7) of all patients with acute ICH (4.1%-7.1% of lobar ICH) were eligible. We projected 1066 to 1848 patients of an estimated 72 283 adult patients with ICH in the United States in 2020 met eligibility criteria. CONCLUSIONS:Approximately 2% to 4% of patients with ICH in our population were eligible for minimally invasive surgical evacuation based on ENRICH criteria, which extrapolates to 1066 to 1848 patients with ICH in the United States annually. Future research is needed to determine whether indications for effective surgical therapy for ICH can be expanded.

Background Limited data exist regarding differences in ischemic stroke care across the care continuum between patients with and without prestroke disability. We investigated differences in in‐hospital and postdischarge ischemic stroke cause evaluation and treatment between patients with and without prestroke disability using population‐based data in the United States. Methods We ascertained all adult patients (≥18 years) hospitalized with acute ischemic stroke within the Greater Cincinnati/Northern Kentucky population between January 1, 2015, and December 31, 2015. We used univariate analyses and logistic regression to compare differences in acute ischemic stroke reperfusion therapies, stroke cause evaluation, prescription of secondary stroke prevention treatments, and rehabilitation between patients with prestroke disability (modified Rankin Scale score ≥2) and those without prestroke disability (modified Rankin Scale score 0–1). Results Of 2476 ischemic stroke patients, 1326 (53%) had prestroke disability. Prestroke disability was associated with lower odds of receiving thrombolysis (adjusted odds ratio [aOR], 0.43 [95% CI, 0.28–0.68], P<0.01) and endovascular thrombectomy (aOR, 0.32 [95% CI, 0.13–0.78], P<0.01). Patients with prestroke disability were less likely to receive complete in‐hospital stroke cause evaluation (aOR, 0.48 [95% CI, 0.33–0.69], P<0.01) and there were small differences in antiplatelet (84% versus 87%) and statin therapy (80% versus 86%) prescribed at discharge. Those with prestroke disability were more likely to receive in‐hospital (aOR, 2.6 [95% CI, 2.11–3.21], P<0.01) and postdischarge rehabilitative therapies (aOR, 2.27 [95% CI, 1.86–2.77], P<0.01). Conclusion Further research into factors driving medical decision‐making for patients with prestroke disability is needed to optimize the entire spectrum of ischemic stroke care for this population.

The Stroke Treatment Academic Industry Roundtable convened a workshop regarding artificial intelligence (AI) and innovative clinical trial designs during the Stroke Treatment Academic Industry Roundtable XIII meeting on March 28, 2025. This forum brought together stroke physicians and researchers, and industry representatives to discuss the current use and future opportunities for AI and novel trial designs in acute stroke trials. AI already plays a substantial role in the treatment of acute stroke with regards to imaging but is poised to have a much larger impact in clinical care and research trials over the coming years. The quality and understanding of the data are used to train the AI, the human element needed to ensure training is successful, and the clinician and trialist at the bedside, the humans "in the loop," will be necessary to maximize AI's effectiveness in clinical practice and trials. Platform trials address multiple scientific questions in an area of medicine simultaneously within the same trial structure by sharing controls across multiple interventions. While platform trials increase efficiency and potentially decrease the time needed to answer important clinical scientific questions, they also can introduce complexity to standard workflows. Future acute ischemic stroke clinical trials should incorporate elements of pragmatic and patient-centered trial design when possible. Pragmatic trials aim to assess the effectiveness of treatments when they are implemented into routine clinical care rather than under idealized conditions. AI models and platform, pragmatic, and patient-centered trial designs are new tools to answer important clinical questions, but understanding how they work, their best uses, and their limitations is critical for accelerating successful new treatments for stroke.

Background: Prehospital stroke triage scores aim to identify LVO patients who benefit from direct transport to high-level stroke centers for EVT by bypassing primary stroke centers. Patients with ICH may benefit from direct transport to high-level centers for neurologic intensive care and hematoma evacuation. Lobar ICH patients may particularly benefit as randomized clinical trial data suggest hematoma evacuation is more effective in these patients. We determined the ability of prehospital LVO triage scores to identify ICH patients and to discriminate lobar from non-lobar ICH. Methods: We identified ICH cases presenting to the ED in Greater Cincinnati/Northern Kentucky in 2005, 2010, and 2015. Cases were identified by ICD codes (ICD9 430-438, ICD10 G45-46, H34.11-12, I60-69), clinical data was extracted by a research nurse and adjudicated by physicians. The CSTAT and RACE scores were abstracted from the NIHSS. We calculated the proportion of ICH patients with a CSTAT ≥ 2 and a RACE ≥ 5, cut-offs used to bypass primary stroke centers, and the scores’ ability to distinguish lobar from non-lobar ICH. Results: We identified 904 ICH patients (median age 72, 54% female, 25% Black). CSTAT was ≥ 2 in 45% of all ICH patients while 27% had a RACE ≥ 5. These score cut-offs identified patients with more severe deficits (Table). Among patients with lobar ICH (n=391), 44% had a CSTAT ≥ 2 and 27% had a RACE ≥ 5. Results were similar for non-lobar ICH (n=473, 45% CSTAT ≥ 2 and 26% RACE ≥ 5). Both scores performed poorly in differentiating lobar from non-lobar ICH (CSTAT ≥ 2: sensitivity 0.44, specificity 0.55, AUC 0.52; RACE ≥ 5: sensitivity 0.27, specificity 0.74, AUC 0.53). Conclusion: Prehospital LVO triage scores identified fewer than half of all ICH patients and did not discriminate between lobar and non-lobar ICH. New prehospital triage scores are needed to identify all ICH patients, or perhaps ICH subgroups, along with LVO patients who benefit from direct transport to high-level stroke centers.

Endovascular mechanical thrombectomy (EVT) drastically reduces disability after acute ischemic stroke due to large‐vessel occlusion, but only a small proportion of patients with stroke are eligible for this powerful treatment. Several ongoing studies are aiming to expand the indications for EVT to further reduce disability after acute ischemic stroke for a larger proportion of patients suffering from large‐vessel occlusion stroke. Patients with preexisting disability, comprising ≈30% of all patients with acute ischemic stroke, were universally excluded from the landmark clinical trials that established EVT efficacy. These patients disproportionally suffer from accumulated disability after stroke, with substantial societal and economic impact. Further, there is significant heterogeneity in current practice of EVT among patients with preexisting disability. Establishing evidence‐based acute stroke treatments for this population is a priority. In this narrative review, we summarize the current literature regarding EVT in patients with preexisting disability. While doing so, we highlight key concepts regarding statistical analysis and discuss opportunities and challenges for future studies focusing on this vulnerable population.

Background: Intracerebral hemorrhage (ICH) has the highest disability among stroke survivors. The Recovery and Outcomes from Stroke (ROSE) study (U01NS100417) utilized RNA sequencing (RNAseq) to identify biomarkers associated with poor outcome at 3 months. Methods: Supratentorial, non-moribund, ≥ 18 years of age, spontaneous ICH patients were prospectively recruited in a multi-center study. Whole blood was obtained at baseline (<15 days; RNA PAXgene tubes, Qiagen). 3-month outcomes were determined by modified Rankin Scale (mRS) 0-3 (good) vs 4-6 (poor). RNAseq libraries were constructed using the Illumina TruSeq Stranded Total RNA kit with Ribo-Zero, sequenced on an llumina NovaSeq 6000 platform using 1 x100 bp single end reads to generate 25-30 million reads at >90% >Q30 reads. Differential expression was tested using DESeq2 (negative binomial), adjusting for sequencing batch, age, sex, race, ICH volume, intraventricular hemorrhage, presenting Glasgow Coma Scale, and lobar vs non-lobar location. Pathway analyses and protein-protein interactions were computed on a set of genes (P < 0.0001) using STRING, Cytoscape, MCODE, and Reactome. Results: We analyzed baseline blood samples from 278 patients (N = 156 vs 122; good vs poor outcomes at 3 months). Multiple pathways were associated with poor outcome, including those involved in clot formation and cell-cell/cell-matrix interactions (not shown). The statistically most significant pathway was observed for transcripts involved in neutrophil activation and degranulation. Conclusion: Variation in mRNA expression pathways associated with inflammation, coagulation and cellular interactions were associated with poor outcome after controlling for severity measures.

Background Rates of dual antiplatelet therapy (DAPT) after high‐risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost‐effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS. Methods and Results We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost‐effectiveness ratio <$100 000 per quality‐adjusted life year was considered cost‐effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality‐adjusted life years compared with current national treatment rates. A QI intervention was cost‐effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1‐time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost‐effective in the base case. Conclusions Increasing DAPT use after TIAMIS with a QI intervention is cost‐effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.

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Introduction Recurrent infarcts to the internal carotid artery territory in the setting of a corresponding occlusion raises concern for carotid stump syndrome. Over time, robust anastomoses may develop between the patent ipsilateral external carotid artery and the anterior circulation distal to the site of occlusion. A carotid stump’s disturbance of flow uncommonly can form emboli that travel via retrograde flow from the occluded internal carotid artery to the ipsilateral external carotid artery and its collaterals. Stenosis of the external carotid artery in such patients can be a source of atheroembolism or hypoperfusion. We describe a case of external carotid stenting with carotid stump coil occlusion. Methods We present a case report. Verbal consent to share this information was obtained directly from the patient. Results A 75‐year‐old man with aortic stenosis, atrial arrhythmia, multiple prior bi‐hemispheric strokes, on aspirin and clopidogrel, presented with left facial droop, arm weakness, and slurred speech. Magnetic resonance imaging revealed embolic appearing strokes in the right middle cerebral artery territory (Figure 1A). Cerebral angiography revealed complete occlusion of the right internal carotid artery with perfusion of the right middle cerebral artery by external carotid artery anastomoses, and the external carotid was found to be stenosed proximally. Digital subtraction angiography revealed right external carotid – middle cerebral artery anastomoses via the right sphenopalatine artery, middle meningeal artery, internal maxillary artery, and ophthalmic collaterals (Figure 1B). The patient underwent coiling of the right internal carotid artery stump (Figure 1C) followed by stenting of the right external carotid using a 9 mm x 40 mm Cordis precise Pro stent. Post‐stenting angiogram demonstrated good apposition of the stent to the parent vessel walls and improvement of flow into the right external carotid and intracranial circulation (Figure 1D). The patient was treated with aspirin and ticagrelor for 3 months. Repeat imaging at follow up did not show further embolic episodes, with improvement in the patient’s deficits. After three months, he was continued on aspirin alone. Conclusion In patients with an occluded internal carotid artery and recurrent embolic infarcts ipsilateral to the side of the occlusion, carotid stump syndrome may be considered. In this case, we believe the patient’s carotid occlusion served as a nidus for emboli formation, or that there was atheroembolism from the stenosed external carotid artery despite adherence to dual antiplatelet therapy. By coiling the stump, we addressed a possible source of emboli, and stenting of the proximal external carotid optimized anterograde flow and prevented further atheroembolism. Our case showcases an interventional neuroradiology approach to carotid stump emboli and external carotid artery stenosis.

Background:Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. Methods:We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. Results:From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. Conclusions:For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

To describe a comprehensive review of the epidemiology, pathophysiology, and treatment of stroke in the era of COVID-19.COVID-19 is associated with myriad neurological disorders, including cerebrovascular disease. While ischemic stroke is the most common, COVID-19 is associated with an increased risk of intracranial hemorrhage, arterial dissection, posterior reversible encephalopathy syndrome, and cerebral venous sinus thrombosis. In this review, we discuss the epidemiology, pathophysiology, and treatment of stroke due to COVID-19. In addition, we describe how COVID-19 has changed the landscape of stroke systems of care and the effect this has had on patients with cerebrovascular disease.While COVID-19 is associated with a heightened risk of stroke, the pandemic has led to advances in stroke systems of care that may reduce the long-term burden of stroke.

Introduction: The cost effectiveness of smoking-cessation interventions after ischemic stroke and TIA has not been evaluated. We performed a cost-effectiveness analysis of smoking-cessation interventions in this population. Methods: We constructed a decision tree model to compare brief counseling alone to 3 interventions: varenicline, any pharmacotherapy with intensive counseling, and monetary incentives. Direct health care costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a 5-year horizon. Estimates and variance for the base case (42% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. Using standard techniques, we calculated incremental cost-effectiveness ratios (ICER) and net-monetary benefits (NMB). An intervention was considered cost effective if the ICER was less than the standard willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) or when the NMB was maximized. Sensitivity analyses and a probabilistic Monte Carlo simulation modeled the impact of parameter uncertainty, including for the base case cessation rate and costs and effectiveness of interventions (TreeAge Pro). Results: All three interventions were cost effective based on the ICER: varenicline - $7,422/QALY, pharmacotherapy with counseling - $14,550/QALY, and monetary incentives - $23,280/QALY. In one-way sensitivity analyses, interventions costing up to $1,729 remained cost-effective. In a two-way sensitivity analysis varying the cost and effectiveness of smoking-cessation interventions, all three interventions were cost effective based on NMB (Figure). In 10,000 Monte Carlo simulations, smoking-cessation interventions were cost effective 90% of the time, as compared to brief counseling alone. Conclusion: Smoking-cessation strategies are cost effective in secondary prevention after stroke and TIA.

To perform a cost-effectiveness analysis of smoking-cessation interventions after ischemic stroke and TIA.

Introduction: Reductions in hospital visits for stroke have been seen during the COVID-19 pandemic, partly reflecting perceived risks of in-hospital care. We recently implemented an evidence-based protocol for outpatient rapid evaluation of transient and minor, non-disabling stroke symptoms for patients seeking care 24 hours after symptom onset. We present our early experience through the pandemic. Methods: We conducted a retrospective review of patients evaluated in the RESCUE-TIA ( R apid E valuation of minor S troke and C erebrovasc U lar E vents including TIA ) clinic from December 2019-August 2020. The clinic sees patients with TIA symptoms or with fixed, non-disabling deficits seeking care > 24 hours after symptom onset. We introduced telemedicine in March 2020. Magnetic resonance brain and vascular imaging is available within 24 hours of visit. We summarized patient characteristics and quality data with standard descriptive statistics. Results: A total of 21 patients were seen in the RESCUE-TIA clinic, including 15 patients during the height of the pandemic in NY; 67% were seen by telemedicine. The median age was 75 years (interquartile range [IQR], 61-82), and 71% were women. The median NIH Stroke Score for patients with minor stroke was 0 (IQR, 0-1), and the median ABCD 2 score for TIA patients was 3 (IQR, 2-3). Median time from symptom onset to evaluation was 3 days (IQR, 2.5-17.5). Median time from evaluation to laboratory diagnostics was 8 hours (IQR, 2-21), and to completion of imaging was 1 day (IQR, 0-5). Outpatient telemetry commenced in a median of 5 days (IQR, 1-9), and echocardiography was completed in a median of 8 days (IQR, 0-10). One patient was referred to the emergency room for a carotid occlusion. Final diagnoses were TIA (n=12), ischemic stroke (n=5), transient global amnesia (n=2), migraine (n=1), and non-aneurysmal, distal subarachnoid hemorrhage (n=1). Secondary prevention was initiated or optimized in 94% of TIA and stroke patients. Recurrent TIA occurred in 1 patient after 67 days, and ischemic stroke occurred in 1 patient 55 days after TIA. Conclusion: Timely outpatient evaluation of patients with recent TIA and minor, non-disabling stroke is feasible and may be useful during the pandemic, especially during emergency room crowding.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients' care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Neurologic complications of COVID-19 are not well described. We report 2 patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.