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Background: Collateral circulation may modify the effect of neuroprotective therapies. We report a post hoc analysis of the URICO-ICTUS trial (NCT00860366) assessing the modifying treatment effect of pretreatment collaterals on clinical and radiological outcomes in patients with large-vessel acute ischemic stroke receiving uric acid therapy or placebo., Methods: URICO-ICTUS was a randomized clinical trial where 411 alteplase-treated patients also received uric acid 1,000 mg (n = 211) or placebo (n = 200) before the end of alteplase infusion. Herein, we included a nested study of 84 patients (placebo = 40, uric acid = 44) who had a pretreatment CT-angiography (CTA) showing a proximal arterial occlusion in the carotid territory. Excellent collaterals were defined as 100% collateral supply on pretreatment CTA. Regression models assessed the interaction between therapy (uric acid/placebo) and collaterals on the main outcome (ordinal modified Rankin Scale [mRS] shift at 90 days)., Results: Overall, excellent collaterals were associated with improved outcome. There was a significant interaction between therapy and pretreatment collaterals (p interaction = 0.02) for the prediction of improved mRS shift. The largest treatment contrast in favor of uric acid was found in patients with excellent collaterals (adjusted OR 9.2; 95% CI 1.23-68.6; p = 0.03)., Conclusions: Collectively, the study found that collaterals were associated with the neuroprotective effect of uric acid therapy highlighting the importance of assessing collateral status in neuroprotection trials., (© 2019 S. Karger AG, Basel.)

Background and Purpose: Computed tomographic (CT) high attenuation (HA) areas after endovascular therapy for acute ischemic stroke are a common finding indicative of blood-brain barrier disruption. Dual-energy CT allows an accurate differentiation between HA areas related to contrast staining (CS) or to brain hemorrhage (BH). We sought to evaluate the prognostic significance of the presence of CS and BH after endovascular therapy., Methods: A prospective cohort of 132 patients treated with endovascular therapy was analyzed. According to dual-energy CT findings, patients were classified into 3 groups: no HA areas (n=53), CS (n=32), and BH (n=47). The rate of new hemorrhagic transformations was recorded at follow-up neuroimaging. Clinical outcome was evaluated at 90 days with the modified Rankin Scale (poor outcome, 3-6)., Results: Poor outcome was associated with the presence of CS (odds ratio [OR], 11.3; 95% confidence interval, 3.34-38.95) and BH (OR, 10.4; 95% confidence interval, 3.42-31.68). The rate of poor outcome despite complete recanalization was also significantly higher in CS (OR, 9.7; 95% confidence interval, 2.55-37.18) and BH (OR, 15.1; 95% confidence interval, 3.85-59.35) groups, compared with the no-HA group. Patients with CS disclosed a higher incidence of delayed hemorrhagic transformation at follow-up (OR, 4.5; 95% confidence interval, 1.22-16.37) compared with no-HA patients., Conclusions: Blood-brain barrier disruption, defined as CS and BH on dual-energy CT, was associated with poor clinical outcomes in patients with stroke treated with endovascular therapies. Moreover, isolated CS was associated with delayed hemorrhagic transformation. These results support the clinical relevance of blood-brain barrier disruption in acute stroke., (© 2015 American Heart Association, Inc.)

Background: Current guidelines recommend withholding antithrombotic therapy (ATT) for at least 24 h in patients with acute ischemic stroke treated with thrombolytic therapy. Herein, we report a retrospective analysis of a single-centre experience on the safety and efficacy of antithrombotic therapy (ATT) started before or after 24 h of intravenous thrombolysis in a cohort of acute ischemic stroke patients., Methods: A total of 139 patients (Rapid ATT group) received antithrombotic therapy before 24 h of thrombolysis, and 33 patients (Standard ATT group) after 24 h. The brain parenchyma and vessel status were assessed using simple CT scan on admission, multimodal CT scan at the end of thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using the modified Rankin Scale (mRS) at day 90., Results: The two ATT groups had similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies, vessel-patency rates at the end of thrombolysis, and incidence of bleeding complications at follow up. At day 3, the Rapid ATT group had a non-significant improved vessel-patency rate than the Standard ATT group. At day 90, a greater proportion of patients in the rapid ATT group had shifted down the mRS, and had improved in the NIHSS score., Conclusions: ATT initiated before 24 h of intravenous thrombolytic therapy in acute stroke patients disclosed no safety concerns compared with a conventional antithrombotic therapy delay of 24 h and showed better functional outcome at follow up. The value of early initiation of ATT after thrombolysis deserves further assessment in randomized controlled trials.

Introduction: In up to one third of patients with mild stroke suitable to receive systemic thrombolysis the treatment is not administered because the treating physicians estimate a good spontaneous recovery. However, it is not settled whether the fate of these patients is equivalent to those who are thrombolysed., Methods: We analyzed 203 consecutive patients (134 men and 69 women, mean age 69±14 years) without premorbid disability and a NIHSS score ≤5 at admission [median 3 (IQR 2-4)]. Intravenous thrombolysis was administered within 4.5 hours from stroke onset (n = 119), or it was withheld (n = 84) whenever the treating physician predicted a spontaneous recovery. The baseline risk factors, clinical course, infarction volume, bleeding complications, and functional outcome at 3 months were analyzed and declared to a Web-based registry which was accessible to the local Health Authorities., Results: Expectedly, not thrombolysed patients had the mildest strokes at admission [median 2 (IQR 1-3.75)]. At day 2 to 5, the infarct volume on DWI-MRI was similar in both groups. There were no symptomatic cerebral bleedings in the study. An ordinal regression model adjusted for baseline stroke severity showed that thrombolysis was associated with a greater proportion of patients who shifted down on the modified Rankin Scale score at 3 months (OR 2.66; 95% CI 1.49-4.74, p = 0.001)., Conclusions: Intravenous thrombolysis seems to be safe in patients with mild stroke and may be associated with improved outcome compared with untreated patients. These results support the evaluation of the efficacy of intravenous thrombolysis in mild stroke patients in randomized clinical trials.