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Background: The likelihood of severe disability and death increases with each recurrent stroke. Repeated intravenous (IV) thrombolysis remains one of the therapeutic options when secondary prevention fails; however, its effects after recurrent stroke are largely unknown. The aim of the present review was to assess the risks and benefits of IV re-thrombolysis after recurrent stroke as compared with IV thrombolysis after index stroke., Methods: We identified 8 patients who repeated IV thrombolysis after recurrent stroke from among the 615 consecutive stroke patients who received IV thrombolysis at our Stroke Unit and 22 cases of IV re-thrombolysed patients extracted for the literature review of case reports and case series., Results: After excluding the 6 patients treated with endovascular procedures, we included in the analyses 21 patients for which we had data on pre-stroke functional status and baseline neurological severity for each stroke event and post-treatment functional status for each IV thrombolysis. We compared second (n=21) and third (n=3) IV thrombolytic treatments with first IV thrombolytic treatments (n=21). Also, we compared IV thrombolytic re-treatments ≤3 months from previous IV thrombolysis (n=10) with those >3 months (n=14). No significant differences in the rate of intracranial hemorrhage with neurological deterioration, mortality and restitution of the pre-existing functional status were observed in the comparative analyses., Conclusions: IV re-thrombolysis may be safe and effective when recurrent stroke occurs after a period of complete neurologic regression lasting at least 24h or minor disability (mRS score ≤2) lasting at least 3 months since the previous stroke., (Copyright © 2014 Elsevier B.V. All rights reserved.)

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.

The onset of non-lacunar stroke symptoms has a circadian variation, with a higher risk in the early morning hours and lower risk during the nighttime period, but this circadian distribution has not been clearly established on the effect of intravenous (IV) thrombolysis. The aim of the present study was to assess whether the time interval based on time of Alteplase IV infusion may influence the effect of treatment in patients with non-lacunar stroke. We conducted an analysis on prospectively collected data of 476 non-lacunar stroke patients treated with IV thrombolysis. To identify a possible circadian variation in the effect of Alteplase IV infusion, we used the following outcome measures: major neurological improvement (NIH stroke scale [NIHSS] score decrease of ≤8 points from baseline or NIHSS score of 0 at 24 h), and hemorrhagic transformation according to European Cooperative Acute Stroke Study trial definition within 24 h. Multivariate analysis showed that ORs for major neurological improvement were lower in patients who started IV thrombolysis in the 6 AM-noon interval (OR 0.35, 95% CI 0.16-0.74, p = 0.006) and noon-6 PM interval (OR 0.40, 95% CI 0.20-0.81, p = 0.010), whereas ORs for hemorrhagic transformation were lower in patients who started IV thrombolysis in the noon-6 PM interval (OR 0.29, 95% CI 0.12-0.67, p = 0.004) and in the 6 PM-midnight interval (OR 0.26, 95% CI 0.11-0.62, p = 0.002), compared with midnight-6 AM interval. The effect of Alteplase IV infusion could show a circadian variation in patients with non-lacunar stroke. After comparison with the midnight-6 AM interval, thrombolysis could be more safe from noon to midnight, and less effective from 6 AM to 6 PM.

CHA2DS2-VASc score influences the outcome in stroke patients with or without atrial fibrillation (AF). We assessed whether the risk stratification based on the prestroke CHA2DS2-VASc score may predict the response to intravenous (IV) thrombolysis in stroke patients. We conducted an analysis on prospectively collected data of 516 consecutive AF and non-AF patients treated with IV thrombolysis. Outcome measures were major improvement (NIH Stroke Scale [NIHSS] ≤8 points from baseline or NIHSS score 0) and deterioration (death or NIHSS ≥1 points from baseline) or no improvement (NIHSS score equivalent to baseline) at 24 h; excellent (modified Rankin Scale [mRS] score ≤1) and unfavorable outcome (mRS score >2) at 3 months. Multivariate analysis showed that ORs for major improvement and excellent outcome were lower in patients with intermediate risk (CHA2DS2-VASc = 1) (OR 0.39, 95 % CI 0.16-0.92, p = 0.032; OR 0.10, 95 % CI 0.02-0.56, p = 0.009), moderately high risk (CHA2DS2-VASc = 2) (OR 0.43, 95 % CI 0.19-0.96, p = 0.040; OR 0.16, 95 % CI 0.03-0.76, p = 0.022), and very high risk (CHA2DS2-VASc > 3) (OR 0.31, 95 % CI 0.15-0.65, p = 0.002; OR 0.17, 95 % CI 0.04-0.81, p = 0.026), whereas ORs for deterioration or no improvement and unfavorable outcome were higher only in patients with very high risk (OR 4.26, 95 % CI 1.24-14.65, p = 0.021; OR 9.26, 95 % CI 1.15-74.65, p = 0.037), compared with low risk (CHA2DS2-VASc = 0). Low-risk level based on the prestroke CHA2DS2-VASc score was predictor of effective response to IV thrombolysis. Very high-risk level was predictor of failed response, compared with low-risk level.

Background: The current European license for Alteplase in acute ischemic stroke excludes the patients who have neoplasm with increased bleeding, but this criterion is not clearly defined. The aim of the present study is to assess whether intravenous (IV) thrombolysis is safe and effective in patients with current non-malignant neoplasm in absence of metastatic disease or other additional risk factors of bleeding., Methods: We reviewed the clinical characteristics of 11 thrombolysed patients with current malignant neoplasm. We decided to treat only patients who did not have one or more of the following additional risk factors of bleeding: metastatic malignant disease; recent bleeding; documented hemorrhagic diathesis, also including baseline normal platelet count, activated partial thromboplastin time and prothrombin time value; and anticoagulant treatment on admission., Results: Cancer was diagnosed before IV thrombolysis in 9 patients, while non-metastatic malignant disease was incidentally detected after IV thrombolysis in 2 patients. None of the patients showed severe hemorrhagic complications. At 7days, all patients that showed a reduction of 4 points or more in the National Institutes of Health Stroke Scale from baseline were asymptomatic. At 3months, functional outcome was favorable in 7 (73%) patients., Conclusions: Our experience suggests that IV thrombolysis does not appear to increase the risk of hemorrhagic complications in current non-metastatic cancer patients in absence of additional risk factors of bleeding. In addition, these patients showed clinical improvement after IV thrombolysis, although replication of our findings in a randomized controlled trial is required to confirm our results., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis., Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death., Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007)., Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.