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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes the case of a 32-year-old man presenting with dense right hemiplegia and global aphasia caused by an acute left middle cerebral artery infarct that underwent successful endovascular therapy after being determined ineligible for intravenous tissue plasminogen activator. Clot transversion and balloon disruption followed by intra-arterial Alteplase resulted in successful re-canalization of his middle cerebral artery at 7 h 30 min. At 3 months post stroke, the patient had moderately severe expressive dysphasia but was mobilizing independently with normal right upper and lower limb strength. In conclusion, the 3 month outcome suggests that the therapeutic time window for endovascular therapy might exceed 6 h post stroke.
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PMID:Endovascular treatment of an acute left middle cerebral artery >6 h post stroke in a patient presenting with dysphasia and dense right hemiplegia. 1825 34

Treatment of acute ischaemic stroke aims to recanalize the occluded artery, salvage the at-risk brain tissue and thus minimize neurological sequelae. Efforts a decade ago have led to the only currently approved medical treatment for acute ischaemic stroke, i.e. intravenous alteplase given within 3 hours of stroke onset. Recanalization occurs in only one-half of the patients receiving alteplase, and only approximately 5% of all ischaemic stroke patients in industrialized countries receive this treatment. Studies are currently being carried out to determine whether intravenous alteplase would be safe and effective for up to 4.5 hours after ischaemic stroke onset, and whether it should be followed by an intra-arterial approach. Two novel thrombolytic drugs being studied for acute ischaemic stroke are desmoteplase and tenecteplase. Although the first trials were promising, the most recent evidence suggests that desmoteplase is not superior to placebo, even in carefully selected patients, in the 3- to 9-hour time window after stroke onset. Tenecteplase has only been studied for acute ischaemic stroke in a single noncontrolled, dose-finding trial in the 3-hour time window after stroke onset, which suggested a similar efficacy to that demonstrated in the historical data from the alteplase trials. A trial to compare the safety and efficacy of tenecteplase versus alteplase is ongoing. Safer and more effective thrombolytic drugs for the treatment of ischaemic stroke are thus being sought. Such agents will be welcome, but they are not here yet. While waiting we are likely to see the emergence of additive therapies, including ultrasound insonation, neuroprotective/regenerative agents and invasive intra-arterial techniques. Novel thrombolytic drugs, or other novel therapies, possess great potential to make a difference in the future, but the most urgent priority now is in the organization of stroke treatment in such a way that more patients receive the currently available optimal treatments.
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PMID:Novel thrombolytic drugs: will they make a difference in the treatment of ischaemic stroke? 1860 1

Ischemic stroke exacts a heavy toll in death and disability. Important progress have been made in terms of secondary prevention. Care of patients with acute stroke can also be improved. In 1996, the FDA approved Alteplase or rt-PA as a safe and effective treatment for stroke when given within 3 hours of the onset of neurological deficit. More than 10 years later, this treatment is still underused, mostly because of poor knowledge in the general population regarding stroke symptoms and implications, and inefficient emergency care and organisation. Organisation of primary stroke centers results in optimization in the care of patients with acute stroke, and improvement in outcomes, with reduction in death, dependency and need for institutional care.
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PMID:[Time is brain]. 1866 90

In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6 mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was approved for therapeutic use in the year 2006. t-PA induces thrombolysis in patients with acute ischemic stroke, and this method has gradually gained recognition among physicians and the general population. However, the number of patients who were treated using Alteplase is low (4,000-5,000 patients/year), and this figure accounts for only 2-3% of the annual number of cases of ischemic stroke. There is little doubt that Alteplase treatment is a potentially effective modality for some patients with acute ischemic stroke. The post-marketing surveillance of 4,749 Japanese patients treated using Alteplase showed that 33% of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patiens died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these results were comparable to those from other countries. The expansion of the therapeutic time window has been a matter of concern. The investigators of the European Cooperative Acute Stroke Study (ECASS) have reported that there was significant improvement in the clinical outcomes of patients with acute ischemie stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms. Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging (MRI) images have been used for selecting patients 3 h after the onset of symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed that local intra-arterial fibrinolysis is effective in patients with embolic MCA occlusion within 6 h of the onset of symptoms. Combining the initiation of intravenous t-PA administration with further intra-arterial fibrinolysis or mechanical thrombolectomy may improve the recanalization rate. Thrombolysis in combination with ultrasound-enhanced clot lysis is another attractive therapy. In Japan the neuroprotective agent edaravone (radical scavenger) is commonly used in combination with t-PA, and it is expected to decrease the hemorrhagic transformation after t-PA administration. Acute cerebral ischemic symptoms may occasionally precede thoracic aortic dissection. Thoracic aortic dissection after t-PA administration may prove to be fatal, and it is an important disorder that must be differentially diagnosed.
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PMID:[Thrombolysis by intravenous tissue plasminogen activator (t-PA)--current status and future direction]. 1917 6

Japan Alteplase Clinical Trial (J-ACT), a prospective multicenter clinical trial, demonstrated good clinical outcome in patients treated with 0.6 mg/kg of alteplase, being similar to that with 0.9 mg/kg of alteplase in the National Institute of Neurological Disorders and Stroke (NINDS) study. On that basis, intravenous aplteplase therapy was approved in Japan in October, 2005. This therapy resulted in better efficacy and similar safety in our stroke care unit (SCU) as compared to J-ACT or other clinical studies performed outside Japan. Our nation-wide survey demonstrated that the approval of the therapy resulted in dramatic changes in the processes of management for acute stroke patients. Preliminary results of the post-marketing surveillance study of alteplase in Japan suggested similar efficacy and safety profiles of the therapy to those reported by a European study, Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). There are several limitations and problems in the therapy that will be overcome by new therapeutic strategies including the development of new-generation therombolytic agents having longer therapeutic time window, applications of magnetic resonance imaging techniques, and combination therapies with neuroprotective agents, sonothrombolysis, intraarterial application of the agent, or mechanical thrombectomy.
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PMID:[New era has begun since the approval of thrombolytic therapy for acute ischemic stroke in Japan]. 1919 7

In the present study, we used a modification of the rabbit small clot embolic stroke model (RSCEM), a multiple infarct ischemia model to achieve reperfusion (REP) through the internal carotid artery (ICA) following small clot embolization. We determined if increasing regional cortical blood flow (RCBF) following an embolic stroke is beneficial to neurological outcome. We compared this to cerebral reperfusion induced by the administration of the thrombolytic Tenecteplase (TNK, 1.5 mg/kg, IV bolus) in the presence or absence of REP. In this study, we also measured the incidence of ICH following REP and thrombolytic treatment. Following embolization, RCBF was reduced to 48-55% of baseline. When REP was induced by removal of a CCA ligature, RCBF initially increased to 185% of baseline. REP (P(50)=1.18+/-0.43 mg) had no effect on embolization-induced behavior measured 24 h following embolization compared to control (P(50)=1.01+/-0.48 mg). However, TNK treatment (2-hours post-embolization) in the absence or presence of REP (initiated 2 h following embolization) significantly (p<0.05) increased the group P(50) to 2.92+/-0.55 mg and 2.42+/-0.40 mg, respectively. In addition, ICH was increased in the REP (42%, p<0.05) and REP-TNK (35%, p>0.05) group compared to either the control group (5.5%) or TNK group (10%). This study show that reperfusion of ICA can increase RCBF following embolization, but this is not associated with improved neurological outcome measured using quantal analysis. However, TNK administration significantly increased behavioral outcome when given 2 h following embolization; an increase that is not affected by combining TNK with REP.
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PMID:Effect of internal carotid artery reperfusion in combination with Tenecteplase on clinical scores and hemorrhage in a rabbit embolic stroke model. 1964 97

The US Food and Drug Administration (FDA) approved the use of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in 1996, on the basis of the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study. IV rt-PA therapy at a dose of 0.9 mg/kg has been approved internationally for the treatment of hyperacute ischemic stroke. After a dose comparison study using duteplase and a multicenter study using a single dose of alteplase (Japan Alteplase Clinical Trial: J-ACT), the administration of IV rt-PA therapy at a dose of 0.6 mg/kg was approved in Japan in 2005. Immediately after the approval, the Japan Stroke Society published the Japanese guidelines for this low-dose therapy. Two years after the approval in Japan, the outcome of IV rt-PA therapy in Japan was observed to be comparable to that of NINDS rt-PA therapy and to those published in studies based in Western nations. Several trials have reported predictors of unfavorable outcome for IV rt-PA therapy. Patients with severe strokes (higher NIHSS score, coma), higher age at disease onset, aortic arch dissection, higher blood pressure, higher blood sugar, occlusion of the internal carotid artery (ICA) or tandem lesion of the left ICA and right middle cerebral artery (MCA), or the presence of major early ischemic changes as observed upon computed tomography (CT) or magnetic resonance imaging (MRI), showed a greater probability for unfavorable response to treatment. The results of the randomised 2008 trial conducted by the third European Cooperative Acute Stroke Study (ECASS III) suggested that treatment with IV rt-PA administered 3-4.5 hours after symptom onset can still induce significant improvement in clinical outcomes after an acute ischemic stroke as opposed to a placebo. MRI-based thrombolysis might be safer than standard CT-based thrombolysis. A combination of reperfusion therapies, IV rt-PA and sonothrombolysis, neuroprotective agents or antiplatelet agents may be effective. However, currently available data do not provide conclusive evidence for the safety or efficacy of these combination therapies. Patients having ICA occlusion may require alternatives including a higher dose of alteplase, combined IV/IA thrombolysis, or possibly mechanical thrombectomy by using a thrombus-removal device.
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PMID:[Prospects of thrombolytic therapy for acute ischemic stroke]. 1980 99

After the success of the 1995 National Institutes of Neurological Disorders and Stroke (NINDS) study using intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA, alteplase) within 3 hours in acute stroke, this therapy was approved worldwide and has been a standard therapy for acute stroke patients. In Japan, IV alteplase at a dose of 0.6 mg/kg was approved in 2005 after a multicenter study using this low dose of alteplase (Japan Alteplase Clinical Trial [J-ACT]). IV rt-PA can drastically improve stroke outcomes. However, more than half of treated patients are not independent in the chronic stage. In addition, the therapeutic time window was so limited that many stroke patients do not have a chance to receive the therapy. In 2008, European Cooperative Acute Stroke Study III showed that IV rt-PA administered between 3 and 4.5 hours after stroke onset significantly improved clinical outcomes in stroke patients; the success resulted in the renewal of recommendation in guidelines in Europe, Canada, and the United States. Several therapeutic strategies, including endovascular therapy, sonothrombolysis, and neuroprotective therapy, may improve the efficacy of IV rt-PA.
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PMID:[Intravenous rt-PA therapy for acute ischemic stroke: efficacy and limitations]. 2003 Feb 14

Alteplase (tissue plasminogen activator, tPA) is currently the only FDA-approved treatment that can be given to acute ischemic stroke (AIS) patients if patients present within 3 h of an ischemic stroke. After 14 years of alteplase clinical research, evidence now suggests that the therapeutic treatment window can be expanded 4.5 h, but this is not formally approved by the FDA. Even though there remains a significant risk of intracerebral hemorrhage associated with alteplase administration, there is an increased chance of favorable outcome with tPA treatment. Over the last 30 years, the use of preclinical models has assisted with the search for new effective treatments for stroke, but there has been difficulty with the translation of efficacy from animals to humans. Current research focuses on the development of new and potentially useful thrombolytics, neuroprotective agents, and devices which are also being tested for efficacy in preclinical and clinical trials. One model in particular, the rabbit small clot embolic stroke model (RSCEM) which was developed to test tPA for efficacy, remains the only preclinical model used to gain FDA approval of a therapeutic for stroke. Correlative analyses from existing preclinical translational studies and clinical trials indicate that there is a therapeutic window ratio (ARR) of 2.43-3 between the RSCEM and AIS patients. In conclusion, the RSCEM can be used as an effective translational tool to gauge the clinical potential of new treatments.
Transl Stroke Res 2010 Jun
PMID:Translational stroke research using a rabbit embolic stroke model: a correlative analysis hypothesis for novel therapy development. 2053 48

The aim of the present study was to identify factors associated with functional outcome, mortality, and symptomatic intracranial hemorrhage (sICH) in patients from the Japan Alteplase Clinical Trial (J-ACT) data set with ischemic stroke treated with intravenous (IV) 0.6 mg/kg alteplase within 3 hours after onset. The patient sample comprised 103 patients from the J-ACT, a multicenter, single-dose, open-label cohort study conducted to verify the efficacy and safety of IV 0.6 mg/kg alteplase in treating acute hemispheric stroke. The effects of 21 patient baseline characteristics on a favorable outcome (as evaluated by modified Rankin scale [mRS] score of 0-1 after 3 months), death within 3 months, and incidence of sICH within 36 hours after the start of treatment were examined by univariate analysis and stepwise logistic regression analysis. The baseline characteristics associated with a favorable outcome in univariate analysis included age and National Institutes of Health Stroke Scale (NIHSS) score. The factors associated with death included age and the NIHSS score. No factors were significantly associated with sICH. In stepwise logistic regression analysis, age and NIHSS score significantly predicted both favorable outcome and death. No factors significantly predicted sICH. Age and baseline NIHSS score were independent predictors for both favorable outcome and death. Although these factors are consistent with those found to be predictors in studies on IV 0.9 mg/kg alteplase, there were no factors predicting outcomes specific for IV 0.6 mg/kg alteplase.
J Stroke Cerebrovasc Dis 2011 Nov
PMID:Factors predicting outcome in stroke patients treated with 0.6 mg/kg alteplase: evidence from the Japan Alteplase Clinical Trial (J-ACT). 2071 35


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