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      Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke

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          Abstract

          Background and Purpose

          Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable.

          Methods

          We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0–1 and 0–2 respectively.

          Results

          We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (jos-2019-01648 P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19).

          Conclusions

          Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time results in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

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          Most cited references21

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          Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

          Harsh Khatri, Barry J. Broderick, S Yeatts … (2009)
          Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months. Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.
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            Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical Thrombectomy in Large-Vessel Occlusions

            Georgios Tsivgoulis, Aristeidis H. Katsanos, Peter Schellinger … (2018)
            Background and Purpose Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) prior to mechanical thrombectomy (MT), there are observational data questioning the efficacy of this approach. One of the main arguments in favour of IVT pretreatment is the potential for tPA-induced successful reperfusion (SR) before the onset of endovascular procedure. Methods We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and observational cohorts providing rates of SR with IVT in patients with LVO before the initiation of MT. We also performed subgroup analyses according to study type (RCTs vs. observational) and according to the inclusion per-protocol of patients with tandem (intracranial/extracranial) occlusions. Results We identified 13 eligible studies (7 RCTs & 6 observational cohorts), including 1561 AIS patients (median NIHSS score: 17) with LVO. SR following IVT and before MT was documented in 11% [95% confidence interval (95%CI): 7%–16%], with no difference among cohorts derived from RCTs and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I 2 >84%, p for Cochran Q<0.001). Higher tPA-induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%, 95%CI:11%–23%) compared to the rest (7%, 95%CI: 4%–11%;p for subgroup differences: 0.003). Conclusions Pretreatment with systemic thrombolysis in LVO patients eligible for MT results in SR in one out of ten cases, negating the need for additional endovascular reperfusion. Tandem occlusions appear to be the least responsive to IVT pretreatment.
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              Impact of onset-to-reperfusion time on stroke mortality: a collaborative pooled analysis.

              Mikael Mazighi, Saqib Chaudhry, Marc Ribó … (2013)
              Onset-to-reperfusion time has been reported to be associated with clinical prognosis. However, its impact on mortality remained to be assessed. Using a collaborative pooled analysis, we examined whether early mortality after successful endovascular treatment is time dependent.
              Article 0 comments Cited 47 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Stroke
                Journal ID (iso-abbrev): J Stroke
                Journal ID (publisher-id): JOS
                Title: Journal of Stroke
                Publisher: Korean Stroke Society
                ISSN (Print): 2287-6391
                ISSN (Electronic): 2287-6405
                Publication date (Print): January 2020
                Publication date (Electronic): 31 January 2020
                Volume: 22
                Issue: 1
                Pages: 130-140
                Affiliations
                [a ]Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA
                [b ]Second Department of Neurology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
                [c ]Department of Neurology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
                [d ]Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
                [e ]Department of Neuroscience, Hamad General Hospital, Doha, Qatar
                [f ]Division of Neurology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
                [g ]Vascular Neurology Program, Neurology Service, Department of Medicine, Clinica Alemana of Santiago, University of Desarrollo, Santiago, Chile
                [h ]Department of Emergency Medicine, Clinica Alemana of Santiago, University of Desarrollo, Santiago, Chile
                [i ]Department of Neurology, University Hospital Schleswig-Holstein, Campus Lubeck, Lübeck, Germany
                [j ]Department of Neurology, Sana Hospital Lubeck, Lübeck, Germany
                [k ]Neurology Department and International Clinical Research Center, St. Anne’s Hospital, Brno, Czech Republic
                [l ]Medical Faculty, Masaryk University, Brno, Czech Republic
                [m ]Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece
                [n ]Department of Hygiene, Epidemiology, and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
                [o ]Stroke Unit, Department of Neurological Sciences, LUNIC Laboratory, HUG, University Hospital and Medical Faculty of Geneva, Geneva, Switzerland
                [p ]Stroke Unit, Department of Neurology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Barcelona, Spain
                [q ]Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA
                [r ]Department of Cerebrovascular Disease, 115 The People Hospital, Ho Chi Minh, Vietnam
                [s ]Department of Neurology and Stroke Center, IdiPAZ Health Research Institute, La Paz University Hospital, Autonomous University of Madrid, Madrid, Spain
                [t ]Torrecardenas Hospital, University of Almeria School of Health Sciences, Almeria, Spain
                [u ]Stroke Unit, Department of Neurology, Brugmann University Hospital, Brussels, Belgium
                Author notes
                Correspondence: Andrei V. Alexandrov Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Suite 415, Memphis, TN 38163, USA Tel: +1-901-4486199 Fax: +1-901-4487440 E-mail: avalexandrov@ 123456att.net
                [*]

                These authors contributed equally to the manuscript as first author.

                Article
                Publisher ID: jos-2019-01648
                DOI: 10.5853/jos.2019.01648
                PMC ID: 7005347
                PubMed ID: 32027798
                SO-VID: ce2b7aad-a552-43af-b8f5-1df553f0a06b
                Copyright © Copyright © 2020 Korean Stroke Society
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 June 2019
                Date revision received : 23 September 2019
                Date accepted : 23 September 2019
                Categories
                Subject: Original Article

                Keywords: thrombolysis,stroke,reperfusion,outcomes
                Data availability:
                Keywords: thrombolysis, stroke, reperfusion, outcomes

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