Whether the large effect size of endovascular thrombectomy (EVT) for stroke due to large-vessel occlusion applies to stroke due to medium-vessel occlusion is unclear. In a multicenter, prospective, randomized, open-label trial with blinded outcome evaluation, we assigned patients with acute ischemic stroke due to medium-vessel occlusion who presented within 12 hours from the time that they were last known to be well and who had favorable baseline noninvasive brain imaging to receive EVT plus usual care or usual care alone. The primary outcome was the modified Rankin scale score (range, 0 [no symptoms] to 6 [death]) at 90 days, reported as the percentage of patients with a score of 0 or 1. A total of 530 patients from five countries were enrolled between April 2022 and June 2024, with 255 patients assigned to the EVT group and 275 to the usual-care group. Most patients (84.7%) had primary occlusions in a middle-cerebral-artery branch. A modified Rankin scale score of 0 or 1 at 90 days occurred in 106 of 255 patients (41.6%) in the EVT group and in 118 of 274 (43.1%) in the usual-care group (adjusted rate ratio, 0.95; 95% confidence interval [CI], 0.79 to 1.15; P = 0.61). Mortality at 90 days was 13.3% in the EVT group and 8.4% in the usual-care group (adjusted hazard ratio, 1.82; 95% CI, 1.06 to 3.12). Symptomatic intracranial hemorrhage occurred in 14 of 257 patients (5.4%) in the EVT group and in 6 of 272 (2.2%) in the usual-care group. Endovascular treatment for acute ischemic stroke due to medium-vessel occlusion within 12 hours did not lead to better outcomes at 90 days than usual care. (Funded by the Canadian Institutes for Health Research and Medtronic; ESCAPE-MeVO ClinicalTrials.gov number, NCT05151172.).

Background: We investigate whether the National Institutes of Health Stroke Scale (NIHSS) at 24 hours could serve as a primary outcome in acute ischemic stroke trials, and whether combining 90‐day modified Rankin Scale (mRS) and 24‐hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using endovascular treatment (EVT) as an exemplary study intervention. Methods: This was a post hoc analysis of pooled data from 7 randomized EVT trials. Twenty‐four‐hour NIHSS as a surrogate outcome for 90‐day mRS was assessed in a causal mediation model. A 7‐point ordinal NIHSS score was generated by grouping 24‐hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24‐hour NIHSS, ordinal 24‐hour NIHSS, 90‐day mRS, and a hierarchical outcome (win ratio) that combines 90‐day mRS and 24‐hour NIHSS. Results: A total of 1720 patients were included. Twenty‐four‐hour NIHSS mediated the association between EVT and 90‐day mRS and met criteria for a useful surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90‐day mRS (240) and ordinal 24‐hour NIHSS (242). In patients with baseline NIHSS <10 and ≥25, ordinal 24‐hour NIHSS resulted in the highest effect size. Conclusions: Twenty‐four‐hour NIHSS is a useful surrogate outcome for 90‐day mRS in patients with acute ischemic stroke undergoing EVT, with a similar EVT effect size compared with 90‐day mRS. It could potentially enhance detection of EVT benefit in patients with very low or high baseline NIHSS. An ordered hierarchical outcome could improve detection of EVT treatment effect.

The vast majority of patients with minor stroke achieve what are considered good or excellent outcomes on the modified Rankin Scale (0–1/0–2), yet many are dissatisfied with their outcomes. There is a need for a functional outcome measure tailored for minor stroke that better reflects the spectrum of clinical outcomes within this population. We developed the Canadian Outcome Scale for Minor Stroke (COSMOS) and performed an interrater and intrarater reliability study. COSMOS is a 7-point scale ranging from 0 (no symptoms) to 6 (loss of independence for an instrumental or basic activity of daily living or worse), which accounts for performance limitations and losses of a person’s hobbies or passions and of their employment, educational, service, or caregiving pursuits, besides just activities of daily living. One hundred test case vignettes were developed. Stroke physicians, fellows, and research nurses/staff were invited to review training materials and provide the COSMOS grade for 20 cases representing all COSMOS grades (0–6). After a minimum 2 weeks’ wash-out period, participants were asked to grade the same 20 cases again. Interrater and intrarater agreement were assessed using Cohen κ, weighted κ, percentage agreement, and intraclass correlation coefficient. Among 33 participants (18 attending physicians, 9 stroke fellows, and 6 research staff/nurses; median 12.5 years of experience), COSMOS had substantial interrater reliability (80.5% agreement [95% CI, 75.7%–85.3%]; Cohen κ, 0.77 [95% CI, 0.72–0.84]) and almost-perfect intrarater reliability overall (87.1% agreement [95% CI, 84.4%–89.7%]; Cohen κ, 0.85 [95% CI, 0.82–0.88]); weighted κ showed almost perfect agreement for both interrater (0.88 [95% CI, 0.85–0.92]) and intrarater reliability (0.92 [95% CI, 0.90–0.94]). The overall chance-adjusted simultaneous intrarater/interrater agreement using intraclass correlation coefficient was 0.95 (95% CI, 0.94–0.97). Results were similar with substantial to almost-perfect agreement when considering key subgroups based on position (attendings, fellows, research nurses/staff) and years of experience. In conclusion, the newly proposed COSMOS scale demonstrated substantial interrater and intrarater reliability. The scale merits further study in cohort studies and clinical trials of minor stroke.

Background: The endovascular approach has emerged as standard therapy for many intracranial aneurysms (IAs) to prevent hemorrhage, yet its long-term durability varies considerably. The aim of this study was to evaluate the safety and effectiveness of an initially deliberate endovascular approach regarding IA hemorrhage rates over a long-term follow-up period. Methods: This retrospective single-center study included all consecutive patients with endovascularly treated IAs who presented between January 2008 and December 2020 with a follow-up of at least 12 months. The primary endpoint was the proportion of patients with long-term IA hemorrhage rates and reperfusion. The secondary endpoint was treatment-related morbidity and mortality. Independent risk factors for IA reperfusion over the long term were analyzed using multivariate logistic regression. Results: Endovascular treatment was the therapy of choice for 333 patients with IAs, among whom 188 (57%) experienced rupture upon presentation. Complete coiling (Raymond I) was noted in 162 (49%) of the patients, with primary supportive devices being used in 51 (15%) patients. After a median (±SD) follow-up time of 34 ± 41 months (range 12–265 months), IA reperfusion was noted in 158 (47%), necessitating retreatment in 105 (32%) of the patients. Over the long term, hemorrhage was noted in four (1%) patients. Multivariate analysis revealed aneurysmal multilobarity (HR 1.8, 95%CI 1.2–2.7; p = 0.004) and a patient age of ≥50 years (HR 1.7, 95% CI 1.1–2.5, p = 0.01) as independent predictors of reperfusion over time. Intervention-related morbidity was noted in 16 (4.8%) patients, namely, thrombosis formation and contrast extravasation in 8 (2.4%) patients each, while no intervention-induced mortality was observed. Conclusion: In the long term, the hemorrhage rate in patients with IA with an initially more conservative endovascular approach is low. Therefore, a deliberate endovascular treatment approach might be justified.

BACKGROUND: Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiological phenotypes. We compared different methods of estimating infarct growth rate in patients with acute ischemic stroke undergoing thrombectomy using multimodal computed tomography (CT) stroke imaging. METHODS: Secondary analysis of the international ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) which evaluated the effect of nerinetide in patients with large vessel occlusion undergoing thrombectomy. Infarct growth rate was estimated leveraging each component of multimodal stroke CT imaging: (1) 10 minus baseline Alberta Stroke Program Early CT Score (ASPECTS) divided by hours elapsed from symptom onset on noncontrast CT (ASPECTS decay per hour); (2) collateral status on multiphase CT angiography (mCTA), and (3) hypoperfusion intensity ratio on CT perfusion. Patients were dichotomized into intermediate and slow progressors (since fast progressors were likely to be excluded from ESCAPE-NA1 based on trial enrollment criteria) according to median ASPECTS decay, presence of good versus moderate/poor mCTA collaterals, and median hypoperfusion intensity ratio, respectively. Associations between progressor phenotypes and 90-day modified Rankin Scale score were assessed across neuroimaging modalities using adjusted logistic regression analyses. RESULTS: Among 1105 patients enrolled in ESCAPE-NA1 between 2017 and 2019, 619 (56.0%) were assessed for progressor phenotypes using noncontrast CT, 1084 (98.1%) with mCTA, and 415 (37.6%) with CT perfusion. Median ASPECTS decay per hour was 1.05 (interquartile range, 0.05–1.85), 188/1084 (17%) patients had good collateral status on mCTA, and the median hypoperfusion intensity ratio was 0.44 (interquartile range, 0.28–0.59). Intermediate progressors showed worse functional outcomes compared with slow progressors only in CT perfusion strata: adjusted common odds ratio for modified Rankin Scale ordinal shift analysis of 1.69 (95% CI, 1.14–2.49). No significant association between progressor phenotypes and 90-day modified Rankin Scale was seen when the noncontrast CT and the mCTA approaches were used. CONCLUSIONS: Stroke progressor phenotypes based on CT perfusion criteria (using the hypoperfusion intensity ratio approach) were associated with clinical outcomes, while stroke progressor phenotypes based on noncontrast CT (ASPECTS decay) and mCTA (collateral status) criteria were not.

Acute ischemic stroke patients with mild deficits (National Institutes of Health Stroke Scale [NIHSS] of 0–5) but confirmed large vessel occlusions (LVO) present a clinical challenge for endovascular thrombectomy (EVT) decisions due to limited evidence and the absence of clear guidelines. A Delphi consensus was conducted at the 2024 5T (Teamwork, Training, Technology, Technique, Transport) Think Tank conference with 40 international stroke experts. Following a systematic literature review, three iterative Delphi rounds were employed to explore EVT decision-making in strokes due to LVO with low NIHSS. Data were collected through surveys and in-person discussions, focusing on disability evaluation, imaging markers, procedural risk, and outcome scales. Consensus was achieved on key factors influencing EVT decisions. Experts emphasized the importance of symptom-specific disability (e.g., aphasia, vision loss) over NIHSS scores alone. Early neurological deterioration (END) was perceived as main concern in this patient population. Imaging markers such as proximal occlusion, poor collaterals, and large penumbra were expected to be predictors of END. The anticipated technical difficulty and patient-specific factors, such as independence and quality of life, also guided decisions. The Potential of rtPA for Ischemic Strokes With Mild Symptoms (PRISMS) trial definition of disabling deficits and the 9-level modified Rankin Scale were favored as outcome measures for future studies. EVT decisions for acute ischemic strokes with mild deficit but proven LVO require nuanced, individualized approaches beyond NIHSS thresholds. Disability assessment, imaging-based risk evaluation, and patient-centered discussions are critical for optimizing outcomes, emphasizing the need for further research and standardized guidelines.