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Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

ABSTRACT: OBJECTIVE:To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke. METHODS:The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging. RESULTS:Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004). CONCLUSION:Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.

SUBMITTER: Mair G

PROVIDER: S-EPMC6282236 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

Mair Grant G von Kummer Rüdiger R Morris Zoe Z von Heijne Anders A Bradey Nick N Cala Lesley L Peeters André A Farrall Andrew J AJ Adami Alessandro A Potter Gillian G Sandercock Peter A G PAG Lindley Richard I RI Wardlaw Joanna M JM

Neurology 20181026 22

<h4>Objective</h4>To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.<h4>Methods</h4>The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue app ...[more]

PMID: 30366975

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Project description:Background and purposeAccurate long-term outcome prognostication in basilar artery occlusion strokes may guide clinical management in the subacute stage. We determine the prognostic value of the follow-up neurological examination using the National Institutes of Health stroke scale (NIHSS) and identify 24- to 48-hour NIHSS risk categories in basilar artery occlusion patients.MethodsParticipants of an observational registry of radiologically confirmed acute basilar artery occlusion (BASICS [Basilar Artery International Cooperation Study]) with prospectively collected 24- to 48-hour NIHSS and 1-month modified Rankin scale scores were included. Uni- and multivariable modeling were performed to identify independent predictors of poor outcome. Predictive powers of baseline and 24- to 48-hour NIHSS for poor outcome (modified Rankin scale, 4-6) and 1-month mortality were determined by receiver operating characteristic analyses. Classification and regression tree analysis was performed to identify risk groups.ResultsThree hundred seventy-six of 619 BASICS participants were included, of whom 65.4% had poor outcome. In multivariable analyses, 24- to 48-hour NIHSS (odds ratio=1.28 [1.21-1.35]), history of minor stroke (odds ratio=2.64 [1.04-6.74], time to treatment >6 hours (odds ratio=3.07 [1.35-6.99]), and age (odds ratio=1.02 [0.99-1.04]) were retained in the final model as predictors of poor outcome. Prognostic power of 24- to 48-hour NIHSS was higher than baseline NIHSS for 1-month poor outcome (area under the curve, 0.92 versus 0.75) and mortality (area under the curve, 0.85 versus 0.72). Classification and regression tree analysis identified five 24- to 48-hour NIHSS risk categories with poor outcome rates of 9.4% (NIHSS 0-4), 36% (NIHSS 5-11), 84.3% (NIHSS 12-22), 96.1% (NIHSS 23-27), and 100% (NIHSS≥28).ConclusionsTwenty-four- to 48-hour NIHSS accurately predicts 1-month poor outcome and mortality and represents a clinically valuable prognostic tool for the care of basilar artery occlusion patients.

Project description:BACKGROUND:In acute ischemic stroke, blood pressure (BP) tends to rise initially and fall to a baseline level within 24-48 hours. Previous studies reported several different effects of BPs during acute ischemic stroke on clinical outcomes, which was partly due to the different time intervals from stroke onset to BP measurement. METHODS:All patients with acute ischemic stroke (onset ≤3 hours) who lived independently before the stroke, were consecutively enrolled for a 62-month period. BPs at 0, 12, and 24 hours after admission were collected. A favorable outcome was defined as a modified Rankin Scale (mRS) score 0-2 at discharge. For different standards of BP management, patients were grouped and analyzed according to intravenous (IV) tissue plasminogen activator (tPA) treatment and favorable outcome. RESULTS:Among the 446 enrolled patients, 227 patients underwent IV tPA treatment and 216 had mRS score 0-2 at discharge. Patients with favorable outcomes had lower initial NIH Stroke Scale (NIHSS) scores, less frequent progressive neurological deficits, and lower systolic BP (SBP) 12 and 24 hours after admission than patients with unfavorable outcomes, regardless of whether they underwent tPA treatment or not (p <0.05). The BP decreased over a period of 24 hours after admission. In logistic regression analysis, the independent variables associated with favorable outcome were the initial NIHSS score, a progressive neurological deficit, a previous stroke, and the SBP 24 hours after admission in the patients who underwent tPA treatment and the initial NIHSS score and a progressive neurological deficit in the patients who did not undergo tPA treatment (p <0.05). CONCLUSIONS:The SBPs at 12 and 24 hours after admission were lower in acute stroke patients with favorable outcomes than in the other patients, regardless of whether the patients underwent tPA therapy and the SBP at 24 hours was an independent predictor of favorable outcomes among the patients who underwent tPA treatment.

Project description:Background and purpose: Early recognition and management of post-stroke dysphagia (PSD) based on MRI may reduce the incidence of complications. Combining clinical symptoms with applications of MRI, we aimed to identify the risk factors of PSD, develop a prediction scale with high accuracy and map key dysphagia brain areas. Methods: A total of 275 acute ischemic stroke patients were enrolled in this study, and 113 (41.1%) patients were diagnosed with PSD. All patients underwent the water-swallowing test (WST) and volume-viscosity swallow test (V-VST) within first 24 h following admission to assess swallowing. Vascular factors were evaluated and MRI brain scans were obtained within 3 days after symptom onset for each participant admitted to the hospital. T-test, chi-squared test and Fisher's exact test were used to investigate the associations of various patient characteristics with dysphagia, and multivariable logistic regression models were used to construct a prediction scale. Scale accuracy was assessed using receiver operating characteristic (ROC) analysis. We extracted white matter hyperintensities for each patient as potential brain lesions. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for dysphagia. Results: Risk factors related with PSD were older age, history of atrial fibrillation, higher fasting blood glucose, NIH stroke scale, TOAST classification, progressive stroke, middle cerebral artery lesion and anterior cerebral artery lesion. Three variables with most significant associations, including NIH stroke scale, TOAST classification and progressive stroke, combined with age and gender, were used to construct a dysphagia prediction scale with high accuracy (AUC = 0.86). VLSM identified left inferior parietal gyrus as a key brain region for PSD. Conclusion: Risk factors of PSD were identified and a predictive model of dysphagia was constructed intelligently and automatically. The left inferior parietal gyrus was identified as a key brain area for dysphagia, which provides a new symptom-based treatment target for early rehabilitation in the future.

Project description:Background and purposePrompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.MethodsIn this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.ResultsAlteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).ConclusionsThese exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.Clinical trial registration urlhttp://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

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Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

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Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

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