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      Is Open Access

      Wake-up stroke: Dawn of a new era

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          Abstract

          Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one-fourth of ischemic stroke patients. These patients are not considered for thrombolytic therapy based on time designation of their symptom onset as per the current guidelines. Observational studies have investigated the pathophysiology and suggested actual onset of symptoms to be approximate to the awakening time for these patients. Use of advanced imaging modalities in these patients tends to identify favorable patient profiles for thrombolysis. Results of the ongoing trials will likely beckon a seminal juncture in stroke therapy and deliver critical modifications in the current treatment guidelines for thrombolysis in this substantial, yet neglected, group of stroke patients. In this article, we have reviewed the predisposing factors, preferred imaging modalities and various ongoing thrombolytic and endovascular trials to date for patients with unclear time of symptom onset or who wake up with stroke symptoms.

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          Obstructive sleep apnoea and its cardiovascular consequences.

          T. Douglas Bradley, John S. Floras (2009)
          Obstructive sleep apnoea (OSA) is a common disorder in which repetitive apnoeas expose the cardiovascular system to cycles of hypoxia, exaggerated negative intrathoracic pressure, and arousals. These noxious stimuli can, in turn, depress myocardial contractility, activate the sympathetic nervous system, raise blood pressure, heart rate, and myocardial wall stress, depress parasympathetic activity, provoke oxidative stress and systemic inflammation, activate platelets, and impair vascular endothelial function. Epidemiological studies have shown significant independent associations between OSA and hypertension, coronary artery disease, arrhythmias, heart failure, and stroke. In randomised trials, treating OSA with continuous positive airway pressure lowered blood pressure, attenuated signs of early atherosclerosis, and, in patients with heart failure, improved cardiac function. Current data therefore suggest that OSA increases the risk of developing cardiovascular diseases, and that its treatment has the potential to diminish such risk. However, large-scale randomised trials are needed to determine, definitively, whether treating OSA improves cardiovascular outcomes.
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            Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.

            Gregory W Albers, Vincent Thijs, Lawrence Wechsler … (2006)
            To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved. Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile. For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.
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              Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

              Stephen M Davis, Geoffrey Donnan, Mark W. Parsons … (2008)
              Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Brain Circ
                Journal ID (iso-abbrev): Brain Circ
                Journal ID (publisher-id): BC
                Title: Brain Circulation
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 2394-8108
                ISSN (Electronic): 2455-4626
                Publication date (Print): Apr-Jun 2016
                Publication date (Electronic): 13 July 2016
                Volume: 2
                Issue: 2
                Pages: 72-79
                Affiliations
                [1] Department of Neurology, UCLA, Los Angeles, CA, USA
                Author notes
                Address for correspondence: Dr. David S Liebeskind, Department of Neurology, UCLA, Los Angeles, CA, USA. E-mail: davidliebeskind@ 123456yahoo.com
                Article
                Publisher ID: BC-2-72
                DOI: 10.4103/2394-8108.186266
                PMC ID: 6126251
                PubMed ID: 30276276
                SO-VID: bc1a02fc-3f48-43ca-9e01-146d4e5a942f
                Copyright © Copyright: © 2016 Brain Circulation
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Date received : 03 May 2016
                Date revision received : 08 June 2016
                Date accepted : 12 June 2016
                Categories
                Subject: Review Article

                Keywords: diffusion-fluid-attenuated inversion recovery mismatch,multimodal imaging,wake-up stroke
                Data availability:
                Keywords: diffusion-fluid-attenuated inversion recovery mismatch, multimodal imaging, wake-up stroke

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