ImportanceThe role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.ObjectiveTo evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.Design, Setting, and ParticipantsThis retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well.InterventionsEndovascular thrombectomy or medical management (control).Main Outcomes and MeasuresPrimary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)–weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts.ResultsOf 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02).Conclusions and RelevanceIn this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Objective This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits ‐ Intra‐Arterial (EXTEND‐IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND‐IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri) were compared to those who received primary MM (MMpri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)‐matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90‐day modified Rankin Scale = 0–2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26–96] ml vs MMpri: 40 [14–76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2–5] vs MMpri: 3 [2–4], p < 0.001). Functional independence was similar (EVTpri: 77.4% vs MMpri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82–2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri: 16.3% vs MMpri: 1.3%, p < 0.001) and neurological worsening (EVTpri: 19.6% vs MMpri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri: 77.4% vs MMpri: 72.7%, aOR = 1.68, 95% CI = 1.01–2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri: 77.4% vs MMpri: 83.3%, aOR = 0.39, 95% CI = 0.12–1.34, p = 0.13) without target mismatch (pinteraction = 0.06). Similar findings were observed in a propensity score‐matched subpopulation. Interpretation Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364–378

Outcome after intraarterial therapy (IAT) for acute ischemic stroke remains variable, suggesting that improved patient selection is needed to better identify patients likely to benefit from treatment. The authors evaluate the predictive accuracies of the Houston IAT (HIAT) and the Totaled Health Risks in Vascular Events (THRIVE) scores in an independent cohort and review the existing literature detailing additional predictive factors to be used in patient selection for IAT. They reviewed their center's endovascular records from January 2004 to July 2010 and identified patients who had acute ischemic stroke and underwent IAT. They calculated individual HIAT and THRIVE scores using patient age, admission National Institutes of Health Stroke Scale (NIHSS) score, admission glucose level, and medical history. The scores' predictive accuracies for good outcome (discharge modified Rankin Scale score ≤ 3) were analyzed using receiver operating characteristics analysis. The THRIVE score predicts poor outcome after IAT with reasonable accuracy and may perform better than the HIAT score. Nevertheless, both measures may have significant clinical utility; further validation in larger cohorts that accounts for differences in patient demographic characteristics, variation in time-to-treatment, and center preferences with respect to IAT modalities is needed. Additional patient predictive factors have been reported but not yet incorporated into predictive scales; the authors suggest the need for additional data analysis to determine the independent predictive value of patient admission NIHSS score, age, admission hyperglycemia, patient comorbidities, thrombus burden, collateral flow, time to treatment, and baseline neuroimaging findings.

Stroke is the leading cause of disability and the third leading cause of death in the US, affecting more than 700,000 individuals each year. 1 Moreover, the economic toll of stroke is profound, costing more than $33 billion annually in direct health care fees and an additional $21 billion in losses secondary to present treatment method inefficacies. 1 Unfortunately there are few effective stroke therapies currently available.Cell death in stroke is potentiated through a cascade of cytotoxins. In focal cerebral ischemia, cytotoxins travel past the immediate ischemic core and cause bystander cell death in the penumbra. 2 While the ischemic core is generally believed to be unsalvageable, penumbral damage may be ameliorated if an effective intervention is instituted in a timely manner. 1 To this end, research and development of therapeutic agents have focused on preserving the ischemic penumbra and limiting secondary injury following the initial insult. ABSTRACT:Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue. Although the precise mechanism is unclear, the presence of reactive aldehydes produced through polyamine metabolism, such as 3-aminopropanal and acrolein, have been shown to correlate with the incidence of cerebral vasospasm, disruption of oxidative metabolism and mitochondrial functioning, and disturbance of cellular calcium ion channels. Regulation of the polyamine metabolic pathway, therefore, may have the potential to limit injury following cerebral ischemia. To this end, we review this pathway in detail with an emphasis on clinical applicability.RÉSUMÉ: Le rôle du métabolisme de la polyamine dans le dommage neurologique dû à l'ischémie cérébrale. L'accident vasculaire cérébral (AVC) est une cause importante de morbidité et de mortalité aux États-Unis. Les dommages secondaires suite à l'accident initial contribuent significativement à l'issue défavorable. Des recherches antérieures ont démontré que le métabolisme de certaines polyamines comme la spermine, la spermidine et la putrescine est élevé dans le parenchyme ischémique, ce qui provoque une augmentation de la concentration de leurs métabolites. Les métabolites des polyamines sont généralement cytotoxiques, ce qui provoque des lésions neuronales pendant la pénombre ischémique suivant l'AVC et l'expansion de la zone infarcisée. Bien que le mécanisme précis ne soit pas clair, il a été démontré qu'il existe une corrélation entre la présence d'aldéhydes réactifs résultant du métabolisme de polyamines comme le 3-aminopropanal et l'acroléine, et l'incidence de vasospasme cérébral, l...