A New Therapeutic Strategy for Acute Ischemic Stroke: Sequential Combined Intravenous tPA-Tenecteplase for Proximal Middle Cerebral Artery Occlusion Based on First Results in 13 Consecutive Patients
Intravenous tissue plasminogen activator often fails to recanalize proximal middle cerebral artery (MCA-M1) occlusions. The clinical outcomes of these patients are strongly correlated with early arterial recanalization. The goal of this study was to present the results of patients with persistently occluded MCA-M1 occlusions after intravenous tissue plasminogen activator who were also treated with intravenous tenecteplase (TNK). TNK is a genetically engineered mutant tissue plasminogen activator. Forty patients with MCA-M1 occlusions were treated with full-dose (0.9 mg/kg) intravenous tissue plasminogen activator. After the intravenous tissue plasminogen activator infusion, 13 patients who had persistent MCA-M1 occlusion on MR angiography and met other inclusion criteria per study protocol received an intravenous bolus of TNK (0.1 mg/kg). Early neurological improvement, defined as a significant decline in National Institutes of Health Stroke Scale score 1 hour after intravenous TNK bolus, was seen in 6 patients. Significant neurological improvement, defined as a ≥4-point decrease in National Institutes of Health Stroke Scale score at 24 hours, was seen in 11 of 13 (85%) patients. MR angiography done after the intravenous TNK bolus showed 100% recanalization (2 Thrombolysis In Myocardial Ischemia 2 and 11 Thrombolysis In Myocardial Ischemia 3). Although one third of patients had intracerebral hemorrhage, no symptomatic intracerebral hemorrhage occurred. One of the 13 patients died, as a result of bronchopneumonia, during the 3 months after his stroke. At 3 months, 9 of 12 (69%) patients had good outcomes (modified Rankin Scale score 0/1). There are several limitations to this study, including a small sample size and no control group. However, these results suggest that the combination of intravenous TNK after intravenous tissue plasminogen activator for MCA-M1 occlusions may improve recanalization rates, be relatively safe, and improve outcome. Further studies are needed to confirm this promising result.
See p 1644.
The Importance of Size: Successful Recanalization by Intravenous Thrombolysis in Acute Anterior Stroke Depends on Thrombus Length
The authors of this study sought to determine if there is a limit to thrombus lengths in acute MCA stroke beyond which systemic thrombolysis fails to recanalize occluded arteries. The hyperdense MCA sign is a highly specific method to detect thrombotic clots on nonenhanced cranial CT. The use of thinner slice widths compared with standard CT protocols has previously been shown by this group to improve the accuracy of thrombus length quantification. For the current study, a retrospective case series was performed on a total of 138 patients over a 2-year period. Hyperdense MCA sign was detected on nonenhanced cranial CT scans with 2.5-mm slice width before intravenous thrombolysis and transcranial Doppler, MR angiography, or CT angiography were used after thrombolysis to assess for recanalization status. They report short clots (length <5 mm) are highly likely to be dissolved completely compared with larger clots (length >8 mm) in which recanalization was seen in <1% of cases. There are several limitations to this study, including its small sample size and retrospective analysis of the data. At the current time, catheter-based therapy should not replace intravenous thrombolysis in patients with large clots. However, further study is warranted to determine the best therapy in these cases.
See p 1775.
Does Impaired Cerebrovascular Reactivity Predict Stroke Risk in Asymptomatic Carotid Stenosis? A Prospective Substudy of the Asymptomatic Carotid Emboli Study
Carotid stenosis accounts for a large percentage of strokes. Randomized trials have demonstrated that carotid endarterectomy for asymptomatic carotid stenosis (ACS) results in a highly significant reduction in stroke. However, the cost-effectiveness and the risk–benefit ratios of carotid endarterectomy in this population, especially with current advances in medical management, have called this approach into question. It is important to identify which subset of patients with ACS is at particularly high risk of stroke, because those patients may benefit most from intervention. The Asymptomatic Carotid Emboli Study (ACES) was an international, multicenter, prospective study that examined whether asymptomatic embolic signals detected on transcranial Doppler in the ipsilateral MCA of patients with ≥70% ACS predicted future risk of stroke over a 2-year follow-up period. A subset of patients also received cerebrovascular reserve (CVR) measurements at baseline. This current substudy looks at the association between CVR and stroke risk in this patient population. One hundred six patients were recruited into the CVR substudy. Thirty-two of 106 (30.2%) patients had severely impaired CVR ipsilateral to the study artery. There were no ipsilateral strokes in the 106 subjects. One of 32 subjects with impaired CVR had a transient ischemic attack (TIA) in the ipsilateral territory and 1 of 74 subjects with preserved CVR had an ipsilateral TIA (P=0.515). There was a nonsignificant trend toward more secondary end points of any stroke/TIA in patients with severely impaired CVR. Embolic signals were associated with recurrent events in the whole ACES cohort. However, in this subgroup, there was no association between the presence of embolic signals and either any stroke or TIA or ipsilateral stroke or TIA (P=0.888). When a meta-analysis of 3 articles with the ACES data was performed, impaired CVR in ACS was significantly associated with an increased risk of ipsilateral stroke or TIA, ipsilateral stroke alone, any stroke, and any stroke/TIA. In summary, this study found no association between impaired CVR and recurrent ischemic events in ACS, but the study was underpowered due to a low event rate. Although the meta-analysis conducted suggests an association between impaired CVR and future stroke risk, there is insufficient data presently to justify the use of CVR in selecting patients with ACS for carotid endarterectomy.
See p 1550.
- © 2011 American Heart Association, Inc.
- A New Therapeutic Strategy for Acute Ischemic Stroke: Sequential Combined Intravenous tPA-Tenecteplase for Proximal Middle Cerebral Artery Occlusion Based on First Results in 13 Consecutive Patients
- The Importance of Size: Successful Recanalization by Intravenous Thrombolysis in Acute Anterior Stroke Depends on Thrombus Length
- Does Impaired Cerebrovascular Reactivity Predict Stroke Risk in Asymptomatic Carotid Stenosis? A Prospective Substudy of the Asymptomatic Carotid Emboli Study
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