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Background and purpose: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. Methods: Pulse pressure variability was calculated from 24‐h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST‐ER) trial. The outcomes of interest were the pre‐specified efficacy and safety end‐points of CLOTBUST‐ER. All associations were adjusted for potential confounders in multivariable regression models. Results: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24‐h neurological improvement and 90‐day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90‐day mortality (P < 0.001). Every 5‐mmHg increase in the 24‐h PP variability was independently associated with a 36% decrease in the likelihood of 90‐day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52–0.80) and a 60% increase in the odds of 90‐day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23–2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. Conclusions: Increased PP variability appears to be independently associated with adverse short‐term and long‐term functional outcomes of AIS patients treated with IVT. [ABSTRACT FROM AUTHOR]

Background and purpose There are concerns that systemic thrombolysis might not achieve clinically important outcome amongst chronic heart failure ( CHF) patients with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on the outcome of acute stroke patients who received thrombolysis. Methods A non-randomized cohort analysis was conducted using data obtained from the Virtual International Stroke Trials Archive. The association of outcome amongst CHF patients with thrombolysis treatment was described using the modified Rankin scale (m RS) distribution at day 90, stratified by the presence of atrial fibrillation. Dichotomized outcomes were considered as a secondary end-point. Results 5677 patients were identified, of whom 2366 (41.7%) received thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%) received thrombolysis. The presence of CHF was associated with a negative impact on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI) 0.62-0.87), P < 0.001]. However, thrombolysis treatment was associated with favourable functional outcome using ordinal mRS, irrespective of CHF status, after adjustment for age and baseline National Institutes of Health Stroke Scale [OR 1.44 (95% CI 1.04-2.01, P = 0.029) for CHF patients versus OR 1.50 (95% CI 1.36-1.66, P < 0.001) for non-CHF patients]. CHF patients had higher mortality at day 90 than non-CHF patients. There was no significant difference for recurrent stroke or symptomatic intracerebral haemorrhage within 7 days of the initial stroke between CHF and thrombolysis groups. Conclusions Chronic heart failure was associated with a worse outcome with or without thrombolysis. However, acute stroke patients who received thrombolysis had more favourable outcome regardless of CHF status, compared with their untreated peers. Our findings should reassure clinicians considering systemic thrombolysis treatment in hyperacute ischaemic stroke patients with CHF. [ABSTRACT FROM AUTHOR]

Background and Purpose: The authors establish accuracy parameters of a broad diagnostic battery for bedside transcranial Doppler (TCD) to detect flow changes due to internal carotid artery (ICA) stenosis or occlusion.Methods: The authors prospectively studied consecutive patients with stroke or transient ischemic attack referred for TCD. TCD was performed and interpreted at bedside using a standard insonation protocol. A broad diagnostic battery included major criteria: collateral flow signals, abnormal siphon or terminal carotid signals, and delayed systolic flow acceleration in the middle cerebral artery. Minor criteria included a unilateral decrease in pulsatility index (< or = 0.6 or < or = 70% of contralateral side), flow diversion signs, and compensatory velocity increase. Angiography or carotid duplex ultrasound (CDU) was used to grade the degree of carotid stenosis using North American criteria. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD findings were determined.Results: Seven hundred and twenty patients underwent TCD, of whom 517 (256 men and 261 women) had angiography and/or CDU within 8.8 +/- 0.9 days. Age was 63.1 +/- 15.7 years. For a 70% to 99% carotid stenosis or occlusion, TCD had sensitivity of 79.4%, specificity of 86.2%, PPV of 57.0%, NPV of 94.8%, and accuracy of 84.7%. For a 50% to 99% carotid stenosis or occlusion, TCD had sensitivity of 67.5%, specificity of 83.9%, PPV of 54.5%, NPV of 90.0%, and accuracy of 81.6%. TCD detected intracranial carotid lesions with 84.9% accuracy and extracranial carotid lesions with 84.4% accuracy (sensitivity of 88% and 79%, specificity of 85% and 86%, PPV of 24% and 54%, and NPV of 99% and 95%, respectively). The prevalence of the ophthalmic artery flow reversal was 36.4% in patients with > or = 70% stenosis or occlusion. If present, this finding indicated a proximal ICA lesion location in 97% of these patients.Conclusions: In symptomatic patients, bedside TCD can accurately detect flow changes consistent with hemodynamically significant ICA obstruction; however, TCD should not be a substitute for direct carotid evaluation. Because TCD is sensitive and specific for a > or = 70% carotid stenosis or occlusion in both extracranial and intracranial carotid segments, it can be used as a complementary test to refine other imaging findings and detect tandem lesions. [ABSTRACT FROM AUTHOR]

Aims: Neurologic impairment following ischemic injury complicates the quality of life for stroke survivors. Xenon (Xe) has favorable neuroprotective properties to modify stroke. Xe delivery is hampered by a lack of suitable administration strategies. We have developed Xe-containing echogenic liposomes (Xe-ELIP) for systemic Xe delivery. We investigated the time window for Xe-ELIP therapeutic effect and the most efficacious dose for neuroprotection. Molecular mechanisms for Xe neuroprotection were investigated., Methods: Xenon-containing echogenic liposomes were created by a previously developed pressurization-freezing method. Following right middle cerebral artery occlusion (2 h), animals were treated with Xe-ELIP at 2, 3, or 5 h to determine time window of therapeutic effect. The neuroprotectant dosage for optimal effect was evaluated 3 h after stroke onset. Expression of brain-derived neurotrophic factor (BDNF), protein kinase B (Akt), and mitogen-activated protein kinases (MAPK) was determined., Results: Xenon-containing echogenic liposomes administration for up to 5 h after stroke onset reduced infract size. Treatment groups given 7 and 14 mg/kg of Xe-ELIP reduced infarct size. Behavioral outcomes corresponded to changes in infarct volume. Xe-ELIP treatment reduced ischemic neuronal cell death via activation of both MAPK and Akt. Elevated BDNF expression was shown following Xe-ELIP delivery., Conclusion: This study demonstrates the therapeutic efficacy of Xe-ELIP administered within 5 h after stroke onset with an optimal dosage range of 7-14 mg/kg for maximal neuroprotection., (© 2013 John Wiley & Sons Ltd.)