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      Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke

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          Abstract

          Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse.

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          European Stroke Organisation (ESO)- European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke.

          Guillaume Turc, Pervinder Bhogal, Urs Fischer … (2019)
          Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT.
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            Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan.

            Makoto Sasaki, Akira Ogawa, Takashi Inoue … (2007)
            The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset. Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index. The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level (P=0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P=0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group (P=0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group (P=1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively (P=0.206). The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.
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              Hemorrhagic Transformations after Thrombectomy: Risk Factors and Clinical Relevance

              Alexandra S. Gersing, Claus Zimmer, Christian Maegerlein … (2017)
              Background: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke, potentially associated with clinical deterioration. We attempted to identify risk factors and evaluated clinical relevance of minor and major HTs following endovascular thrombectomy (ET) in isolated middle cerebral artery (MCA) occlusions. Methods: This is a retrospective single-center analysis of 409 patients with isolated MCA occlusion treated with ET. Patients' and procedural characteristics, severity of HT according to the European Cooperative Acute Stroke Study criteria, and clinical outcomes were analyzed. Multivariate logistic regression models with standard retention criteria (p < 0.1) were used to determine risk factors and clinical relevance of HT. Results are shown as adjusted OR (aOR) and respective 95% CIs. Good neurologic short-term outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score <5 at the day of discharge. Results: Of 299 patients included, hemorrhagic infarction (HI) was detected in 87 patients, while 13 patients developed parenchymal hematoma (PH). Higher age (aOR 0.970, 95% CI 0.947-0.993, p = 0.012), eligibility for intravenous recombinant tissue plasminogen activator (IV rtPA; aOR 0.512, 95% CI 0.267-0.982, p = 0.044), and complete recanalization (TICI 3, aOR 0.408, 95% CI 0.210-0.789, p = 0.008) were associated with a lower risk of HI. Risk factors for HI included higher admission NIHSS score (aOR 1.080, 95% CI 1.010-1.153, p = 0.024) and higher admission glucose levels (aOR 1.493, 95% CI 1.170-1.904, p = 0.001). Further, female sex tended to be associated with a lower risk of HI (aOR 0.601, 95% CI 0.316-1.143, p = 0.121), while a statistical trend was observable for proximal MCA occlusion (aOR 1.856, 95% CI 0.945-3.646, p = 0.073) and a history of hypertension (aOR 2.176, 95% CI 0.932-5.080, p = 0.072) to increase risk of HI. Longer intervals from symptom onset to first digital subtraction angiography runs (aOR 1.013, 95% CI 1.003-1.022, p = 0.009), lower preinterventional Alberta Stroke Program Early CT score (aOR 0.536, 95% CI 0.307-0.936, p = 0.028) and wake-up stroke (aOR 18.540, 95% CI 1.352-254.276, p = 0.029) were associated with PH. Both, PH and HI were independently associated with lower rates of good neurologic outcome (aOR 0.086, 95% CI 0.008-0.902, p = 0.041 and aOR 0.282, 95% CI 0.131-0.606, p = 0.001). Conclusion: Risk of HI following MCA occlusion and subsequent ET is mainly determined by factors influencing infarct severity. Good recanalization results seem to be protective against subsequent HI. Our results support the notion that occurrence of PH after ET is time dependent and risk increases with more extensive early ischemic damage. Both, HI and PH do not seem to be facilitated by bridging therapy with IV rtPA or the use of oral anticoagulants, but were independently associated with more severe neurologic disability. These results support the notion that HI is not a “benign” imaging sign.
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                Author and article information

                Journal
                Title: JAMA Neurology
                Abbreviated Title: JAMA Neurol
                Publisher: American Medical Association (AMA)
                ISSN (Print): 2168-6149
                Publication date (Electronic): December 09 2019
                Affiliations
                [1 ]University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
                [2 ]University Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
                [3 ]Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland
                Article
                DOI: 10.1001/jamaneurol.2019.4192
                PMC ID: 6902179
                PubMed ID: 31816018
                SO-VID: 814f16f3-19f5-4a4e-b232-4ccf463bd5df
                Copyright © © 2019
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