The hemodynamic status within 24?h after intravenous thrombolysis predicts infarct growth in acute ischemic stroke

A rapid and complete recanalization of the occluded artery is the ideal goal when intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is administrated to patients with acute ischemic stroke, i.e., limiting the ongoing ischemia to achieve a better outcome. We explored the effect of complete versus partial recanalization of the occluded intracranial artery after IV thrombolysis on the infarct growth and evaluated the functional impact. Using diffusion-weighted (DWI) volumetric measurements before rt-PA administration (DWI(1)) and 24?h later (DWI(2)), we calculated the infarct growth in 36 consecutive patients with ischemic stroke treated with IV rt-PA, with the formula DWI(2)/DWI(1). Recanalization of the affected artery was assessed by transcranial Doppler (TCD) and magnetic resonance angiography (MRA) within 24?h of stroke onset. Three patients were eliminated from the analysis; 33?patients were fully analyzed (men: n?=?23; mean (SD) age: 72.4?±?16?years; time from stroke onset to rt-PA: 179?±?54?min; mean NIHSS score at admission: 17). Patients achieving full recanalization by TCD had a smaller infarct growth, compared to those who had a partial or persistent occlusion after thrombolysis: 1.86 versus 2.91 (P?=?0.017). This difference was not significant using MRA criteria: 2.01 versus 2.69 (P?=?0.193). In the regression analysis, complete recanalization by TCD was an independent predictor of infarct growth (P?=?0.045). Thus, complete recanalization measured by TCD within 24?h of IV thrombolysis was independently associated with smaller infarct growth.     

Doubts, fears and misconceptions. What is the future of thrombolysis in acute stroke?

Alteplase for acute ischemic stroke may be the first stroke intervention to have a significant public health impact. In February 1999, this therapy was conditionally licensed in Canada for acute ischemic stroke within three hours of symptom onset. However, considerable controversy exists regarding its safety, its wider applicability outside clinical trials, and its ultimate availability. In this article we review the thrombolytic literature, attempt to answer many of the concerns, provide new guidelines for its use, and cite the need for more information about whom we should and should not be treating with this therapy.     

What is the significance of leukoaraiosis in patients with acute ischemic stroke?

BACKGROUND: Leukoaraiosis (LA) may have specific clinical correlates in patients with stroke, but this is not well investigated, so that the significance of LA in patients with stroke remains unclear. METHODS: In a study of 2289 patients with a first-ever acute ischemic stroke, LA was noted in 149 by the use of baseline computed tomography of the brain. These patients were compared with the non-LA group. Statistical tests, including Fisher exact test or a chi(2) test, were used to compare variables, and a multivariate approach using stepwise logistic regression was performed. RESULTS: Patients with LA were significantly older (73.7 vs 62.7 years; P<. 001), and had a higher incidence of hypertension (72.5% vs 47.1%; P<. 001) and subcortical or lacunar infarction (40.3% vs 25.4% and 21.5% vs 8.0%, respectively; P<.001) on neuroimaging studies, compared with the non-LA group. The most common cause of stroke in the LA group was presumed to be small-artery disease associated with hypertension (46% vs 13.5% in the non-LA group). Age and hypertension were very strongly associated with LA (respective odds ratios [95% confidence intervals], 1.06 [1.04-1.08] and 2.33 [1.60-3. 39]). In addition to these risk factors, a close relationship was found between LA and nonsevere stenosis (<50%) of the internal carotid artery (odds ratio, 2.23 [95% confidence interval, 1.32-3. 76]), although the significance of this association remains speculative. The outcome at 1 month after stroke was similar in both groups. CONCLUSION: Our results provide further evidence that LA is related primarily to small-vessel disease.     

Life–threatening orolingual angioedema during thrombolysis in acute ischemic stroke

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %).Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.     

Can emergency department physicians safely and effectively initiate thrombolysis for acute ischemic stroke?

OBJECTIVE: To review the clinical outcomes of stroke patients treated with IV tissue plasminogen activator (tPA; alteplase) in a community setting and to compare outcomes when treatment was initiated by a neurologist or an emergency department (ED) physician in telephone consultation with a neurologist and radiologist. METHODS: Clinical information was prospectively collected for 43 stroke patients treated with IV tPA (alteplase) within a five-hospital network of affiliated community hospitals. Blinded 3-month outcomes were obtained with telephone interview or patient visit. RESULTS: Excellent functional recovery measured by a Modified Rankin score of 0 to 1 (42%), symptomatic intracerebral hemorrhages (7%), and mortality (16.3%) were similar to those reported by National Institute of Neurological Disorders and Stroke (39%, 7.7%, 17.3%). After initial screening by an ED physician, 20 patients were directly examined by a stroke neurologist who then prescribed tPA. Twenty-three patients received tPA prescribed by an ED physician after telephone consultation with a neurologist and review of the head CT by a radiologist. Functional outcome, symptomatic intracerebral bleeding rate, and mortality rate were similar between these groups. Door-to-needle time was similar. Protocol deviations were much higher when ED physicians prescribed the tPA compared to when neurologists did (30% versus 5%). These protocol deviations were reduced with staff education. CONCLUSIONS: The clinical results of the National Institute of Neurological Disorders and Stroke tPA Stroke Trial were replicated in this small series of patients treated in a community setting. Outcomes were similar whether the prescribing physician was a neurologist or an ED physician.     

Does smoking influence outcome after intravenous thrombolysis for acute ischaemic stroke?

Background and purpose:  It remains uncertain whether current smoking influences outcome in patients with acute ischaemic stroke.
Objectives:  To evaluate the effect of current smoking in routinely tissue plasminogen activator (tPA)-treated stroke patients on the 3-month functional outcome and the occurrence of symptomatic intracerebral hemorrhage (ICH).
Methods:  We analyzed data from a single stroke care unit registry of 345 consecutive patients with ischaemic stroke, treated with tPA. Logistic regression models were used to assess if smoking was independently associated with 3-months good outcome defined as a modified Rankin Scale score of ≤2, and the occurrence of symptomatic ICH.
Results:  In the multivariable models, smoking was not associated with a good outcome or a decreased risk of symptomatic ICH.
Conclusion:  Current smoking did not affect functional outcome at 3 months or the risk of symptomatic ICH in patients routinely treated with tPA for ischaemic stroke.     

Diabetes and previous stroke: hazards for intravenous thrombolysis?

Background and purpose: Alteplase licensing approval in Europe does not advocate intravenous thrombolysis (IVT) for diabetic ischaemic stroke (IS) patients with previous cerebral infarction (PCI). Our aim was to assess whether concomitant diabetes mellitus (DM) and PCI are associated with symptomatic intracerebral haemorrhage (SICH) and poor outcome after IVT. Methods: Multicentre prospective registry, which included consecutive IVT‐treated, acute IS patients from January 2003 to December 2010. The frequency of SICH (SITS‐MOST criteria) and 3‐month outcomes (mRS) were compared between the following groups: (i) diabetic patients with PCI (DM+/PCI+); (ii) diabetic patients without PCI (DM+/PCI?); (iii) non‐diabetic patients with PCI (DM?/PCI+); and (iv) patients without diabetes or PCI (DM?/PCI?). Results: A total of 1475 patients were included. Thirty‐four patients (2.3%) had known DM and PCI, 258 (17.5%) were diabetics without PCI, and 119 (8.1%) had a PCI and no DM. Thirty‐six patients (2.6%) developed SICH, with no differences between groups (P = 985). Fifteen (40.9%) DM+/PCI+ patients, 113 (46.5%) DM+/PCI? patients, 47 (42%) DM?/PCI+ patients and 414 (40.9%) DM?/PCI? patients had mRS ≥ 3 at 3 months (P = 427). The presence neither of DM nor of PCI, nor their combination, had any impact on the risk of SICH or on outcome at 3 months after adjusting for age, stroke severity and glucose levels on admission. Conclusions: Acute IS diabetic patients with PCI who were treated with IVT had similar outcomes to patients without such history, with no increase in the rates of SICH. Thus, they should not be excluded from IVT only on the basis of DM and PCI.     

Hyperdense middle cerebral artery sign: can it be used to select intra-arterial versus intravenous thrombolysis in acute ischemic stroke?

BACKGROUND: Stroke patients with a hyperdense middle cerebral artery sign (HMCAS) may respond less favorably to intravenous (IV) thrombolysis. OBJECTIVE: To compare outcomes of patients with and without early CT findings treated with IV versus intra-arterial (IA) recombinant tissue plasminogen activator (rtPA). METHODS: Initial and 24-hour CT scans of the head were evaluated in 83 consecutive stroke patients (66 on IV rtPA, 17 on IA rtPA). Time permitting, a CT angiogram was performed immediately after the initial CT scan to ascertain major cerebral artery occlusion. Demographics and etiological stroke subtype, times to thrombolysis and CT scan, baseline (prethrombolysis) and 24-hour National Institutes of Health stroke scale (NIHSS) score, discharge NIHSS score and 90-day modified Rankin scale (mRS) were recorded. The initial CT of these patients was examined for early signs of stroke. The 24-hour scan was reviewed for the presence of infarct, hemorrhage and persistence of HCMAS. RESULTS: A favorable outcome, indicated by a significant improvement in the discharge NIHSS score, was noted with IA rtPA, irrespective of the presence (p = 0.001) or absence (p = 0.01) of HCMAS. A less favorable outcome in discharge NIHSS score was noted with IV rtPA in patients with HCMAS (p = not significant) than those without the sign (p < 0.001). A similar proportion of patients with HCMAS exhibited a neurological improvement at 24 h as those without the sign in the IA rtPA group (p = 0.9). However, a smaller proportion of patients with HCMAS exhibited a neurological improvement at 24 h than those without the sign in the IV rtPA group (p = 0.005). The results were similar using 90-day mRS 相似文献   

Acute seizures in acute ischemic stroke: does thrombolysis have a role to play?

Seizures appear at stroke presentation, during the acute phase or as a late complication of stroke. Thrombolysis has not been investigated as a risk factor despite its potential neurotoxic effect. We try to identify risk factors for seizures during the acute phase of ischemic stroke in a cohort including thrombolysed patients. We undertook a case–control study at a single stroke center using data from Acute Stroke Registry and Analyse of Lausanne (ASTRAL). Patients with seizure occurring during the first 7 days following stroke were retrospectively identified. Bi-variable and multivariable statistical analyses were applied to compare cases and randomly selected controls. We identified 28 patients experiencing from seizures in 2,327 acute ischemic strokes (1.2 %). All seizures occurred during the first 72 h. Cortical involvement, thrombolysis with rt-PA, arterial recanalization, and higher initial NIHSS were statistically associated with seizures in univariated analysis. Backward linear regression identified cortical involvement (OR 7.53, 95 % CI 1.6–35.2, p < 0.01) and thrombolysis (OR 4.6, 95 % CI 1.6–13.4, p = 0.01) as being independently associated with seizure occurrence. Overall, 3-month outcome measured by the modified Rankin scale (mRS) was comparable in both groups. In the subgroup of thrombolysed patients, outcome was significantly worse at 3 months in the seizure group with 9/12 (75 %) patients with mRS ≥3, compared to 6/18 (33.3 %) in the seizure-free group (p = 0.03). Acute seizures in acute ischemic stroke were relatively infrequent. Cortical involvement and thrombolysis with rt-PA are the principal risk factors. Seizures have a potential negative influence on clinical outcome in thrombolysed patients.     

Trials of thrombolysis in acute ischemic stroke: does the choice of primary outcome measure really matter?

BACKGROUND AND PURPOSE: Controversy regarding the risks and benefits of thrombolysis has not been helped by the perception that some trials were "positive" and others "negative" on their primary outcome measure of either "good" or "poor" functional outcome. We wondered whether the definition of good or poor functional outcome might have contributed to this perception, and what effect altering the definition might have on the individual trials and on the systematic review of all the trials combined. METHODS: We analyzed data on functional outcome, extracted from the randomized trials of thrombolysis in acute ischemic stroke, according to good (modified Rankin scale scores of 0 to 1 versus 2 to 6) and poor (modified Rankin 0 to 2 versus 3 to 6) functional outcome, to determine the effects of thrombolysis. RESULTS: Twelve trials (4342 patients, treated up to 6 hours after stroke) contributed to this analysis. Overall, there was no difference in the estimate of treatment effect between the 2 definitions (modified Rankin 0 to 2 versus 3 to 6, and 0 to 1 versus 2 to 6 [ORs 0.83 and 0.79, respectively]). However, the apparent "success" of several individual trials did alter. CONCLUSIONS: We should not place undue emphasis on the results of individual trials, when a change of a single point on the Rankin scale can make the difference between "success" and "failure." Overall, by either analysis, there was a significant benefit in patients treated with thrombolysis up to 6 hours after stroke.