Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.

Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. Methods We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). Results The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P = 0.75). Conclusions Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.)

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Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke

Objective. —To evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. Design. —Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. Setting. —A total of 75 hospitals in 14 European countries. Patients. —A total of 620 patients with acute ischemic hemispheric stroke and moderate to severe neurologic deficit and without major early infarct signs on initial computed tomography (CT). Intervention. —Patients were randomized to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or placebo within 6 hours from the onset of symptoms. Outcome Measures. —Primary end points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days. Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS) at 90 days, and 30-day mortality. Tertiary end points included early neurologic recovery (SSS) and duration of in-hospital stay. Safety parameters included mortality and incidence of intracranial or extracranial hemorrhage. Results. —The distribution of demographic variables was similar among patients in the rt-PA and placebo treatment arms in both the intention-to-treat (ITT) analysis and the explanatory analysis for the target population (TP). A total of 109 patients (17.4%) were included in the trial despite major protocol violations but excluded from the TP. There was no difference in the primary end points in the ITT analysis, while the TP analysis revealed a significant difference in the RS in favor of rt-PA—treated patients (P Conclusions. —Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients. (JAMA. 1995;274:1017-1025)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=389723&pdfFileName=jama_274_13_023.pdf

Intravenous Thrombolysis With Recombinant Tissue Plasminogen Activator for Acute Hemispheric Stroke: The European Cooperative Acute Stroke Study (ECASS)

ContextIntravenous tissue-type plasminogen activator can be beneficial to some
patients when given within 3 hours of stroke onset, but many patients present
later after stroke onset and alternative treatments are needed.ObjectiveTo determine the clinical efficacy and safety of intra-arterial (IA)
recombinant prourokinase (r-proUK) in patients with acute stroke of less than
6 hours' duration caused by middle cerebral artery (MCA) occlusion.DesignPROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized,
controlled, multicenter, open-label clinical trial with blinded follow-up
conducted between February 1996 and August 1998.SettingFifty-four centers in the United States and Canada.PatientsA total of 180 patients with acute ischemic stroke of less than 6 hours'
duration caused by angiographically proven occlusion of the MCA and without
hemorrhage or major early infarction signs on computed tomographic scan.InterventionPatients were randomized to receive 9 mg of IA r-proUK plus heparin
(n = 121) or heparin only (n = 59).Main Outcome MeasuresThe primary outcome, analyzed by intention-to-treat, was based on the
proportion of patients with slight or no neurological disability at 90 days
as defined by a modified Rankin score of 2 or less. Secondary outcomes included
MCA recanalization, the frequency of intracranial hemorrhage with neurological
deterioration, and mortality.ResultsFor the primary analysis, 40% of r-proUK patients and 25% of control
patients had a modified Rankin score of 2 or less (P
= .04). Mortality was 25% for the r-proUK group and 27% for the control group.
The recanalization rate was 66% for the r-proUK group and 18% for the control
group (P<.001). Intracranial hemorrhage with neurological
deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of
control patients (P = .06).ConclusionDespite an increased frequency of early symptomatic intracranial hemorrhage,
treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke
caused by MCA occlusion significantly improved clinical outcome at 90 days.

https://jamanetwork.com/journals/jama/articlepdf/192156/JOC91323.pdf

Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial

Background and Purpose— For a biomarker to serve as an auxiliary or surrogate outcome measure, it must be tightly correlated with and causally related to functional clinical outcome. Vessel recanalization is a potential surrogate outcome marker for functional outcome in trials of thrombolytic and mechanical recanalization therapies in acute stroke, but the correlation of recanalization and clinical outcome has not been previously systematically reviewed. Methods— Through Medline search, we identified and abstracted recanalization and outcome data from all articles published between 1985 and 2002 that assessed vessel recanalization, either spontaneous or therapeutically induced, in acute ischemic stroke. Results— Fifty-three studies encompassing 2066 patients reported recanalization rates. Recanalization rates categorized according to intervention were: spontaneous (24.1%), intravenous fibrinolytic (46.2%), intra-arterial fibrinolytic (63.2%), combined intravenous–intra-arterial (67.5%), and mechanical (83...

The Impact of Recanalization on Ischemic Stroke Outcome A Meta-Analysis

An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke

Current research suggests that cerebral ischemia induces a cascade of pathophysiological reactions, with a massive influx of calcium into the neuron as the "final common pathway", resulting in catabolism and cell necrosis due to calcium overload. Treatment with calcium entry blockers, therefore, may be a new approach to arresting, and possibly preventing, destruction of cerebral tissue in stroke patients. The calcium entry blocker nimodipine was found to inhibit selectively spasms of the isolated cerebral arteries, produced either by depolarization or by receptor stimulation. In vivo experiments demonstrated that postischemic impairment of cerebral blood flow, which may be a major contributor to neuronal damage, is prevented. After encouraging, although not conclusive, results of a single-blind pilot study, further clinical studies were undertaken and a double-blind, placebo-controlled, multicenter study was conducted. The data from this study strongly suggest that patients with acute ischemic stroke benefit from treatment with 120 mg nimodipine, started with 24 h after onset, combined with a "standard" treatment, e. g., hemodilution by low molecular weight dextran. The conclusion so far is that calcium entry blockers such as nimodipine, may be useful in the treatment of patients with acute ischemic stroke.

New Trends in Diagnosis and Management of Stroke

Kopfschmerzen gehoren zu den haufigsten Befindlichkeitsstorungen. Sie werden wahrscheinlich nur noch von Ruckenschmerzen ubertroffen. Es ist daher nicht ungewohnlich, hin und wieder Kopfschmerzen zu haben.

Kopfschmerzen und Gesichtsneuralgien

Entwicklungsstorungen des Nervensystems kommen genetisch, als Folge von intrauterinen Infektionen und, heute am haufigsten, als Folge von Intoxikationen, der Uberdosierung von Medikamenten oder durch Alkohol zustande.

Klaus Poeck

Papers

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke

New Trends in Diagnosis and Management of Stroke

Kopfschmerzen und Gesichtsneuralgien

Entwicklungsstörungen und Fehlbildungen des Nervensystems

30 An open multicenter study of the safety and efficacy of various doses of rt-PA in acute stroke: Interim results